Co-reporter:Carmelo Sgarlata, Alessandro Giuffrida, Evan R. Trivedi, Vincent L. Pecoraro, and Giuseppe Arena
Inorganic Chemistry May 1, 2017 Volume 56(Issue 9) pp:4771-4771
Publication Date(Web):April 17, 2017
DOI:10.1021/acs.inorgchem.6b03043
Metallacrown complexes capable of sequestering dianions, as shown in the solid state, also exist in aqueous solution at neutral pH, as demonstrated by calorimetric and mass spectrometric data. The driving forces for the formation of these dimeric complexes in solution strongly depend on the chain length of the guest rather than its degree of unsaturation.
Co-reporter:Ivana Martinić, Svetlana V. Eliseeva, Tu N. Nguyen, Vincent L. Pecoraro, and Stéphane Petoud
Journal of the American Chemical Society June 28, 2017 Volume 139(Issue 25) pp:8388-8388
Publication Date(Web):June 14, 2017
DOI:10.1021/jacs.7b01587
Sensitive detection of cell necrosis is crucial for the determination of cell viability. Because of its high resolution at the cellular level and sensitivity, optical imaging is highly attractive for identifying cell necrosis. However, challenges associated with this technique remain present such as the rapid photobleaching of several types of organic fluorophores and/or the interference generated by biological autofluorescence. Herein, we synthesized novel biologically compatible Zn2+/Ln3+ metallacrowns (MCs) that possess attractive near-infrared (NIR) emission and are highly photostable. In addition, these MCs have the ability to label differentially necrotic HeLa cells from living cells. This work is also the first demonstration of (i) the use of the NIR emission arising from a single lanthanide(III) cation for optical biological imaging of cells under single photon excitation, (ii) the first example of a lanthanide(III)-based NIR-emitting probe that can be targeted to a specific type of cell.
Co-reporter:Ivana Martinić;Svetlana V. Eliseeva;Tu N. Nguyen;Frédéric Foucher;David Gosset;Frances Westall;Stéphane Petoud
Chemical Science (2010-Present) 2017 vol. 8(Issue 9) pp:6042-6050
Publication Date(Web):2017/08/21
DOI:10.1039/C7SC01872J
Cell fixation is an essential approach for preserving cell morphology, allowing the targeting and labelling of biomolecules with fluorescent probes. One of the key requirements for more efficient fluorescent labelling is the preservation of cell morphology, which usually requires a combination of several fixation techniques. In addition, the use of a counter stain is often essential to improve the contrast of the fluorescent probes. Current agents possess significant limitations, such as low resistance toward photobleaching and sensitivity to changes in the microenvironment. Luminescent Ln3+ ‘encapsulated sandwich’ metallacrowns (MCs) overcome these drawbacks and offer complementary advantages. In particular, they emit sharp emission bands, possess a large difference between excitation and emission wavelengths and do not photobleach. Herein, MCs formed with pyrazinehydroxamic acid (Ln3+[Zn(II)MCpyzHA], Ln3+ = Yb, Nd) were used, combined with near-infrared (NIR) counter staining and fixation agents for HeLa cells upon an initial five minute exposure to UV-A light. The validity and quality of the cell fixation were assessed with Raman spectroscopy. Analysis of the NIR luminescence properties of these MCs was performed under different experimental conditions, including in a suspension of stained cells. Moreover, the high emission intensity of Ln3+[Zn(II)MCpyzHA] in the NIR region allows these MCs to be used for imaging with standard CCD cameras installed on routine fluorescence microscopes. Finally, the NIR-emitting Ln3+[Zn(II)MCpyzHA] compounds combine, within a single molecule, features such as cell fixation and staining abilities, good photostability and minimal sensitivity of the emission bands to the local microenvironment, and they are highly promising for establishing the next generation of imaging agents with a single biodistribution.
Co-reporter:Leela Ruckthong, Melissa L. Zastrow, Jeanne A. Stuckey, and Vincent L. Pecoraro
Journal of the American Chemical Society 2016 Volume 138(Issue 36) pp:11979-11988
Publication Date(Web):August 17, 2016
DOI:10.1021/jacs.6b07165
Preorganization and predisposition are important molecular recognition concepts exploited by nature to obtain site-specific and selective metal binding to proteins. While native structures containing an MS3 core are often unavailable in both apo- and holo-forms, one can use designed three-stranded coiled coils (3SCCs) containing tris-thiolate sites to evaluate these concepts. We show that the preferred metal geometry dictates the degree to which the cysteine rotamers change upon metal complexation. The Cys ligands in the apo-form are preorganized for binding trigonal pyramidal species (Pb(II)S3 and As(III)S3) in an endo conformation oriented toward the 3SCC C-termini, whereas the cysteines are predisposed for trigonal planar Hg(II)S3 and 4-coordinate Zn(II)S3O structures, requiring significant thiol rotation for metal binding. This study allows assessment of the importance of protein fold and side-chain reorientation for achieving metal selectivity in human retrotransposons and metalloregulatory proteins.
Co-reporter:Monika Stachura, Saumen ChakrabortyAlexander Gottberg, Leela Ruckthong, Vincent L. Pecoraro, Lars Hemmingsen
Journal of the American Chemical Society 2016 Volume 139(Issue 1) pp:79-82
Publication Date(Web):December 14, 2016
DOI:10.1021/jacs.6b11525
Nanosecond ligand exchange dynamics at metal sites within proteins is essential in catalysis, metal ion transport, and regulatory metallobiochemistry. Herein we present direct observation of the exchange dynamics of water at a Cd2+ binding site within two de novo designed metalloprotein constructs using 111mCd perturbed angular correlation (PAC) of γ-rays and 113Cd NMR spectroscopy. The residence time of the Cd2+-bound water molecule is tens of nanoseconds at 20 °C in both proteins. This constitutes the first direct experimental observation of the residence time of Cd2+ coordinated water in any system, including the simple aqua ion. A Leu to Ala amino acid substitution ∼10 Å from the Cd2+ site affects both the equilibrium constant and the residence time of water, while, surprisingly, the metal site structure, as probed by PAC spectroscopy, remains essentially unaltered. This implies that remote mutations may affect metal site dynamics, even when structure is conserved.
Co-reporter:Chun Y. Chow; Svetlana V. Eliseeva; Evan R. Trivedi; Tu N. Nguyen; Jeff W. Kampf; Stéphane Petoud
Journal of the American Chemical Society 2016 Volume 138(Issue 15) pp:5100-5109
Publication Date(Web):March 25, 2016
DOI:10.1021/jacs.6b00984
Luminescent lanthanide(III)-based molecular scaffolds hold great promises for materials science and for biological applications. Their fascinating photophysical properties enable spectral discrimination of emission bands that range from the visible to the near-infrared (NIR) regions. In addition, their strong resistance to photobleaching makes them suitable for long duration or repeated biological experiments using a broad range of sources of excitation including intense and focalized systems such as lasers (e.g., confocal microscopy). A main challenge in the creation of luminescent lanthanide(III) complexes lies in the design of a ligand framework that combines two main features: (i) it must include a chromophoric moiety that possesses a large molar absorptivity and is able to sensitize several different lanthanide(III) ions emitting in the visible and/or in the near-infrared, and (ii) it must protect the Ln3+ cation by minimizing nonradiative deactivation pathways due to the presence of −OH, −NH and −CH vibrations. Herein, a new family of luminescent Ga3+/Ln3+ metallacrown (MC) complexes is reported. The MCs with the general composition [LnGa4(shi)4(C6H5CO2)4(C5H5N) (CH3OH)] (Ln-1, Ln = Sm3+–Yb3+) were synthesized in a one pot reaction using salicylhydroxamic acid (H3shi) with Ga3+ and Ln3+ nitrates as reagents. The molecular structure of [DyGa4(shi)4(C6H5CO2)4(C5H5N) (CH3OH)] was obtained by X-ray analysis of single crystals and shows that the complex is formed as a [12-MCGa(III)shi-4] core with four benzoate molecules bridging the central Dy3+ ion to the Ga3+ ring metals. The powder X-ray diffraction analysis demonstrates that all other isolated complexes are isostructural. The extended analysis of the luminescence properties of these complexes, excited by the electronic states of the chromophoric ligands, showed the presence of characteristic, sharp f–f transitions that can be generated not only in the NIR (Sm, Dy, Ho, Er, Yb) but also in the visible (Sm, Eu, Tb, Dy, Tm). All Ln-1 complexes possess very high quantum yield values with respect to other literature compounds, indicating a good sensitization efficiency of the [12-MCGa(III)shi-4] scaffold. Especially, as of today, the Yb-1 complex exhibits the highest NIR quantum yield reported for a lanthanide(III) complex containing C–H bonds with a value of 5.88(2)% in the solid state. This work is a significant step forward toward versatile, easily prepared luminescent lanthanide(III) complexes suitable for a variety of applications including highly in demand biological imaging, especially in the NIR domain.
Co-reporter:Chun Y. Chow, Régis Guillot, Eric Rivière, Jeff W. Kampf, Talal Mallah, and Vincent L. Pecoraro
Inorganic Chemistry 2016 Volume 55(Issue 20) pp:10238-10247
Publication Date(Web):October 4, 2016
DOI:10.1021/acs.inorgchem.6b01404
The structural characterization and magnetic properties of three related 9-metallacrown-3 (9-MC-3) structures are reported. Each of these iron complexes is shown to exhibit significant magnetic refrigerant properties. FeIII(acetate)3[9-MCFeIIIN(shi)-3](MeOH)3·MeOH·7H2O (1-OAc) and FeIII(benzoate)3[9-MCFeIIIN(shi)-3](MeOH)3·MeOH·4H2O (1-OBz) are structurally analogous tetranuclear iron(III) clusters which exhibit drastically different magnetic properties, due to differences in intermolecular and intramolecular π interactions which affect superexchange. 1-OAc displays a magnetocaloric effect with a maximum entropy change of −ΔSm = 15.4 J kg–1 K–1 at T = 3 K and an applied field change of μoΔH = 7 T, whereas 1-OBz exhibits a maximum −ΔSm = 7.4 J kg–1 K–1 at T = 7 K and μoΔH = 7 T and displays an inverse magnetocaloric effect at lower temperatures and field changes. 1-OAc has −ΔSm values comparable to those of other Fe-based MCE materials and displays a significant MCE at lower applied fields, with −ΔSm = 11.2 J kg–1 K–1 at 3 K and μoΔH = 3 T. The tetranuclear core of 1 may be linked with isophthalate to form an octanuclear FeIII2(isophthalate)3[9-MCFeIIIN(shi)-3]2 dimer (2) that crystallizes in a honeycomb packing arrangement and exhibits solvation-dependent magnetic properties. The MCE for this molecule ranges from −ΔSm = 9.9 J kg–1 K–1 at T = 5 K and μoΔH = 7 T, when the pores of the material are highly occupied with solvent, to −ΔSm = 5.4 J kg–1 K–1, when the system is fully desolvated.
Co-reporter:Thaddeus T. Boron III, Jacob C. Lutter, Connor I. Daly, Chun Y. Chow, Andrew H. Davis, Arunpatcha Nimthong-Roldán, Matthias Zeller, Jeff W. Kampf, Curtis M. Zaleski, and Vincent L. Pecoraro
Inorganic Chemistry 2016 Volume 55(Issue 20) pp:10597-10607
Publication Date(Web):October 5, 2016
DOI:10.1021/acs.inorgchem.6b01832
A family of DyX4M(12-MCMnIII(N)shi-4) compounds were synthesized and magnetically characterized (X = salicylate, acetate, benzoate, trimethylacetate, M = NaI or KI). The bridging ligands were systematically varied while keeping the remainder of the MC-geometry constant. The type of monovalent cation, necessary for charge balance, was also altered. The dc magnetization and susceptibility of all compounds were similar across the series. Regardless of the identity of the countercation, the Dy(Hsal)4M 12-MC-4 compounds were the only compounds to show frequency-dependent ac magnetic susceptibility, a hallmark of single-molecule magnetism. This indicates that the nature of the bridging ligand in the 12-MCMnIII(N)shi-4 compounds strongly affects the out-of-phase magnetic properties. The SMM behavior appears to correlate with the pKa of the bridging ligand.
Co-reporter:Dr. Corrado Atzeri; Luciano Marchiò;Dr. Chun Y. Chow;Dr. Jeff W. Kampf; Vincent L. Pecoraro;Dr. Matteo Tegoni
Chemistry - A European Journal 2016 Volume 22( Issue 19) pp:6482-6486
Publication Date(Web):
DOI:10.1002/chem.201600562
Abstract
A 12-metallacrown-4 (MC) complex was designed and employed as the building block in the synthesis of coordination polymers, one of which is the first permanently porous MC architecture. The connection of the four-fold symmetric MC subunits by CuII nodes led to the formation of 2D layers of metallacrowns. Channels are present in the crystalline architecture, which exhibits permanent porosity manifested in N2 and CO2 uptake capacity.
Co-reporter:Catherine S. Mocny and Vincent L. Pecoraro
Accounts of Chemical Research 2015 Volume 48(Issue 8) pp:2388
Publication Date(Web):August 3, 2015
DOI:10.1021/acs.accounts.5b00175
The major advances in molecular and structural biology and automated peptide and DNA synthesis of the 1970s and 1980s generated fertile conditions in the 1990s for the exploration of designed proteins as a new approach for inorganic chemists to generate biomolecular mimics of metalloproteins. This Account follows the development of the TRI peptide family of three-stranded coiled coils (3SCC) and α3D family of three-helix bundles (3HB) as scaffolds for the preparation of metal binding sites within de novo designed constructs. The 3SCC were developed using the concept of a heptad repeat (abcdefg) putting hydrophobes in the a and d positions. The TRI peptides contain four heptads with capping glycines. Via substitution of leucine hydrophobes, metal ligands can be introduced into the a or d sites in order to bind metals.First, the ability to use cysteine-substituted 3SCC aggregates to impose higher or lower coordination numbers on Hg(II) and Cd(II) or matching the coordination preferences of As(III) and Pb(II) is discussed. Then, methods to develop dual site peptides capable of discriminating metals based on their type (e.g., Cd(II) vs Pb(II)), their preference for a vs d sites, and then their coordination number is described.Once these principles of metal site differentiation are described, we shift to building dual site peptides using both cysteine and histidine metal binding sites. This approach provides a construct with both a Hg(II) structural and a Zn(II) hydrolytic center, the latter of which is capable of hydrating CO2. With these Zn(II) proteins, we consider the relative importance of the location of the catalytic center along the primary sequence of the peptide and show that only minor perturbations in catalytic efficiencies are observed based on metal location. We then assess the feasibility of preparing enzymes competent to reduce nitrite with copper centers in a histidine-rich environment. As part of this discussion, we examine the influence of surface residues on catalyst reduction potentials and catalytic efficiencies.We end describing approaches to prepare asymmetric proteins that can incorporate acid–base catalysts or water channels. In this respect, we highlight modifications of a helix–turn–helix–turn–helix motif called α3D and show how this 3HB can be modified to bind heavy metals or to make Zn(II) centers, which are active hydrolytic catalysts. A comparison is made to the comparable parallel 3SCC.
Co-reporter:Chun Y. Chow, Hélène Bolvin, Victoria E. Campbell, Régis Guillot, Jeff W. Kampf, Wolfgang Wernsdorfer, Frédéric Gendron, Jochen Autschbach, Vincent L. Pecoraro and Talal Mallah
Chemical Science 2015 vol. 6(Issue 8) pp:5087-5087
Publication Date(Web):26 Jun 2015
DOI:10.1039/C5SC90037A
Correction for ‘Assessing the exchange coupling in binuclear lanthanide(III) complexes and the slow relaxation of the magnetization in the antiferromagnetically coupled Dy2 derivative’ by Chun Y. Chow et al., Chem. Sci., 2015, 6, 4148–4159.
Co-reporter:Chun Y. Chow, Hélène Bolvin, Victoria E. Campbell, Régis Guillot, Jeff W. Kampf, Wolfgang Wernsdorfer, Frédéric Gendron, Jochen Autschbach, Vincent L. Pecoraro and Talal Mallah
Chemical Science 2015 vol. 6(Issue 7) pp:4148-4159
Publication Date(Web):07 May 2015
DOI:10.1039/C5SC01029B
We report here the synthesis and the investigation of the magnetic properties of a series of binuclear lanthanide complexes belonging to the metallacrown family. The isostructural complexes have a core structure with the general formula [Ga4Ln2(shi3−)4(Hshi2−)2(H2shi−)2(C5H5N)4(CH3OH)x(H2O)x]·xC5H5N·xCH3OH·xH2O (where H3shi = salicylhydroxamic acid and Ln = GdIII1; TbIII2; DyIII3; ErIII4; YIII5; YIII0.9DyIII0.16). Apart from the Er-containing complex, all complexes exhibit an antiferromagnetic exchange coupling leading to a diamagnetic ground state. Magnetic studies, below 2 K, on a single crystal of 3 using a micro-squid array reveal an opening of the magnetic hysteresis cycle at zero field. The dynamic susceptibility studies of 3 and of the diluted DyY 6 complexes reveal the presence of two relaxation processes for 3 that are due to the excited ferromagnetic state and to the uncoupled DyIII ions. The antiferromagnetic coupling in 3 was shown to be mainly due to an exchange mechanism, which accounts for about 2/3 of the energy gap between the antiferro- and the ferromagnetic states. The overlap integrals between the Natural Spin Orbitals (NSOs) of the mononuclear fragments, which are related to the magnitude of the antiferromagnetic exchange, are one order of magnitude larger for the Dy2 than for the Er2 complex.
Co-reporter:Alison G Tebo, Vincent L Pecoraro
Current Opinion in Chemical Biology 2015 Volume 25() pp:65-70
Publication Date(Web):April 2015
DOI:10.1016/j.cbpa.2014.12.034
•α-Helical de novo designed proteins are versatile scaffolds.•The primary coordination sphere confers significant hydrolytic or redox catalytic activity.•Secondary coordination sphere engineering is required for enhancing reactivity.Three-helix bundles and coiled-coil motifs are well-established de novo designed scaffolds that have been investigated for their metal-binding and catalytic properties. Satisfaction of the primary coordination sphere for a given metal is sufficient to introduce catalytic activity and a given structure may catalyze different reactions dependent on the identity of the incorporated metal. Here we describe recent contributions in the de novo design of metalloenzymes based on three-helix bundles and coiled-coil motifs, focusing on non-heme systems for hydrolytic and redox chemistry.
Co-reporter:Jefferson S. Plegaria; Matteo Duca; Cédric Tard; Thomas J. Friedlander; Aniruddha Deb; James E. Penner-Hahn
Inorganic Chemistry 2015 Volume 54(Issue 19) pp:9470-9482
Publication Date(Web):September 18, 2015
DOI:10.1021/acs.inorgchem.5b01330
Using de novo protein design, we incorporated a copper metal binding site within the three-helix bundle α3D (Walsh et al. Proc. Natl. Acad. Sci. U.S.A. 1999, 96, 5486–5491) to assess whether a cupredoxin center within an α-helical domain could mimic the spectroscopic, structural, and redox features of native type-1 copper (CuT1) proteins. We aimed to determine whether a CuT1 center could be realized in a markedly different scaffold rather than the native β-barrel fold and whether the characteristic short Cu–S bond (2.1–2.2 Å) and positive reduction potentials could be decoupled from the spectroscopic properties (ε600 nm = 5000 M–1 cm–1) of such centers. We incorporated 2HisCys(Met) residues in three distinct α3D designs designated core (CR), chelate (CH), and chelate-core (ChC). XAS analysis revealed a coordination environment similar to reduced CuT1 proteins, producing Cu–S(Cys) bonds ranging from 2.16 to 2.23 Å and Cu–N(His) bond distances of 1.92–1.99 Å. However, Cu(II) binding to the CR and CH constructs resulted in tetragonal type-2 copper-like species, displaying an intense absorption band between 380 and 400 nm (>1500 M–1 cm–1) and A|| values of (150–185) × 10–4 cm–4. The ChC construct, which possesses a metal-binding site deeper in its helical bundle, yielded a CuT1-like brown copper species, with two absorption bands at 401 (4429 M–1 cm–1) and 499 (2020 M–1 cm–1) nm and an A|| value ∼30 × 10–4 cm–4 greater than its native counterparts. Electrochemical studies demonstrated reduction potentials of +360 to +460 mV (vs NHE), which are within the observed range for azurin and plastocyanin. These observations showed that the designed metal binding sites lacked the necessary rigidity to enforce the appropriate structural constraints for a Cu(II) chromophore (EPR and UV–vis); however, the Cu(I) structural environment and the high positive potential of CuT1 centers were recapitulated within the α-helical bundle of α3D.
Co-reporter:Alison G. Tebo, Lars Hemmingsen and Vincent L. Pecoraro
Metallomics 2015 vol. 7(Issue 12) pp:1555-1561
Publication Date(Web):19 Oct 2015
DOI:10.1039/C5MT00228A
Members of the ArsR/SmtB family of transcriptional repressors, such as CadC, regulate the intracellular levels of heavy metals like Cd(II), Hg(II), and Pb(II). These metal sensing proteins bind their target metals with high specificity and affinity, however, a lack of structural information about these proteins makes defining the coordination sphere of the target metal difficult. Lingering questions as to the identity of Cd(II) coordination in CadC are addressed via protein design techniques. Two designed peptides with tetrathiolate metal binding sites were prepared and characterized, revealing fast exchange between CdS3O and CdS4 coordination spheres. Correlation of 111mCd PAC spectroscopy and 113Cd NMR spectroscopy suggests that Cd(II) coordinated to CadC is in fast exchange between CdS3O and CdS4 forms, which may provide a mechanism for rapid sensing of heavy metal contaminants by this regulatory protein.
Co-reporter:Jefferson S. Plegaria, Stephen P. Dzul, Erik R. P. Zuiderweg, Timothy L. Stemmler, and Vincent L. Pecoraro
Biochemistry 2015 Volume 54(Issue 18) pp:2858-2873
Publication Date(Web):March 19, 2015
DOI:10.1021/acs.biochem.5b00064
De novo protein design is a biologically relevant approach that provides a novel process in elucidating protein folding and modeling the metal centers of metalloproteins in a completely unrelated or simplified fold. An integral step in de novo protein design is the establishment of a well-folded scaffold with one conformation, which is a fundamental characteristic of many native proteins. Here, we report the NMR solution structure of apo α3DIV at pH 7.0, a de novo designed three-helix bundle peptide containing a triscysteine motif (Cys18, Cys28, and Cys67) that binds toxic heavy metals. The structure comprises 1067 NOE restraints derived from multinuclear multidimensional NOESY, as well as 138 dihedral angles (ψ, φ, and χ1). The backbone and heavy atoms of the 20 lowest energy structures have a root mean square deviation from the mean structure of 0.79 (0.16) Å and 1.31 (0.15) Å, respectively. When compared to the parent structure α3D, the substitution of Leu residues to Cys enhanced the α-helical content of α3DIV while maintaining the same overall topology and fold. In addition, solution studies on the metalated species illustrated metal-induced stability. An increase in the melting temperatures was observed for Hg(II), Pb(II), or Cd(II) bound α3DIV by 18–24 °C compared to its apo counterpart. Further, the extended X-ray absorption fine structure analysis on Hg(II)-α3DIV produced an average Hg(II)–S bond length at 2.36 Å, indicating a trigonal T-shaped coordination environment. Overall, the structure of apo α3DIV reveals an asymmetric distorted triscysteine metal binding site, which offers a model for native metalloregulatory proteins with thiol-rich ligands that function in regulating toxic heavy metals, such as ArsR, CadC, MerR, and PbrR.
Co-reporter:Jefferson S. Plegaria
Israel Journal of Chemistry 2015 Volume 55( Issue 1) pp:85-95
Publication Date(Web):
DOI:10.1002/ijch.201400146
Abstract
De novo protein design is a biologically relevant approach used to study the active centers of native metalloproteins. In this review, we will first discuss the design process in achieving α3D, a de novo designed three-helix bundle peptide with a well-defined fold. We will then cover our recent work in functionalizing the α3D framework by incorporating a tris(cysteine) and tris(histidine) motif. Our first design contains the thiol-rich sites found in metalloregulatory proteins that control the levels of toxic metal ions (Hg, Cd, and Pb). The latter design recapitulates the catalytic site and activity of a natural metalloenzyme carbonic anhydrase. The review will conclude with future design goals aimed at introducing an asymmetric metal-binding site in the α3D framework.
Co-reporter:Joseph Jankolovits, Jeff W. Kampf, Vincent L. Pecoraro
Chinese Chemical Letters 2015 Volume 26(Issue 4) pp:444-448
Publication Date(Web):April 2015
DOI:10.1016/j.cclet.2015.01.017
In the assembly of metallacrowns for molecular recognition, luminescence, and molecular magnetism applications, substituting the ring ion can have profound effects on the structure, stability, and physical properties of the inorganic macrocycle. The assembly of Zn(II) metallacrowns with an α-amino hydroxamic acid ligand (pheHA) was investigated to compare the assembly behavior with the well studied metallacrowns containing Cu(II) and Ni(II). Electrospray ionization mass spectrometry reveals that the benchmark species Zn5(pheHA)42+ and LnZn5(pheHA)53+ assemble in pyridine, which is consistent with the behavior of Cu(II) and Ni(II). A LnZn4(pheHA)43+ species is also observed in a 1:1 DMF-pyridine mixture. An unprecedented La(III)[16-MCZn(II),pheHA,HpheHA-6]5+ complex was crystallographically characterized that possesses unusual C2 symmetry. These results provide insights into the design of functional metallacrowns through ring ion substitution.The chiral ligand l-phenylalanine hydroxamic acid is shown to assemble the metallacrowns Zn(II)[12-MCZn,pheHA-4]2+, Ln(III)[15-MCZn(II),pheHA-5]3+, and Ln(III)[12-MCZn(II),pheHA-4]3+ using electrospray ionization mass spectrometry. A La(III)[16-MCZn(II),pheHA,HpheHA-6]5+ was crystallographically characterized that uniquely possesses protonated hydroxamate ligands and lower rotationally symmetry than conventional lanthanide metallacrowns.
Co-reporter:Fangting Yu, Virginia M. Cangelosi, Melissa L. Zastrow, Matteo Tegoni, Jefferson S. Plegaria, Alison G. Tebo, Catherine S. Mocny, Leela Ruckthong, Hira Qayyum, and Vincent L. Pecoraro
Chemical Reviews 2014 Volume 114(Issue 7) pp:3495
Publication Date(Web):March 24, 2014
DOI:10.1021/cr400458x
Co-reporter:Evan R. Trivedi ; Svetlana V. Eliseeva ; Joseph Jankolovits ; Marilyn M. Olmstead ; Stéphane Petoud
Journal of the American Chemical Society 2014 Volume 136(Issue 4) pp:1526-1534
Publication Date(Web):January 10, 2014
DOI:10.1021/ja4113337
Near-infrared (NIR) luminescent lanthanide complexes hold great promise for practical applications, as their optical properties have several complementary advantages over organic fluorophores and semiconductor nanoparticles. The fundamental challenge for lanthanide luminescence is their sensitization through suitable chromophores. The use of the metallacrown (MC) motif is an innovative strategy to arrange several organic sensitizers at a well-controlled distance from a lanthanide cation. Herein we report a series of lanthanide “encapsulated sandwich” MC complexes of the form Ln3+[12-MCZn(II),quinHA-4]2[24-MCZn(II),quinHA-8] (Ln3+[Zn(II)MCquinHA]) in which the MC framework is formed by the self-assembly of Zn2+ ions and tetradentate chromophoric ligands based on quinaldichydroxamic acid (quinHA). A first-generation of luminescent MCs was presented previously but was limited due to excitation wavelengths in the UV. We report here that through the design of the chromophore of the MC assembly, we have significantly shifted the absorption wavelength toward lower energy (450 nm). In addition to this near-visible inter- and/or intraligand charge transfer absorption, Ln3+[Zn(II)MCquinHA] exhibits remarkably high quantum yields, long luminescence lifetimes (CD3OD; Yb3+, QLnL = 2.88(2)%, τobs = 150.7(2) μs; Nd3+, QLnL = 1.35(1)%, τobs = 4.11(3) μs; Er3+, QLnL = 3.60(6)·10–2%, τobs = 11.40(3) μs), and excellent photostability. Quantum yields of Nd3+ and Er3+ MCs in the solid state and in deuterated solvents, upon excitation at low energy, are the highest values among NIR-emitting lanthanide complexes containing C–H bonds. The versatility of the MC strategy allows modifications in the excitation wavelength and absorptivity through the appropriate design of the ligand sensitizer, providing a highly efficient platform with tunable properties.
Co-reporter:Michael R. Azar, Thaddeus T. Boron III, Jacob C. Lutter, Connor I. Daly, Kelcie A. Zegalia, Ruthairat Nimthong, Gregory M. Ferrence, Matthias Zeller, Jeff W. Kampf, Vincent L. Pecoraro, and Curtis M. Zaleski
Inorganic Chemistry 2014 Volume 53(Issue 3) pp:1729-1742
Publication Date(Web):January 13, 2014
DOI:10.1021/ic402865p
The inclusion of LnIII ions into the 12-MC-4 framework generates the first heterotrimetallic complexes of this molecular class. The controllable and deliberate preparations of these compounds are demonstrated through 12 crystal structures of the LnIIIMI(OAc)4[12-MCMnIII(N)shi-4](H2O)4·6DMF complex, where OAc– is acetate, shi3- is salicylhydroximate, and DMF is N,N-dimethylformamide. Compounds 1–12 have MI as NaI, and LnIII can be PrIII (1), NdIII (2), SmIII (3), EuIII (4), GdIII (5), TbIII (6), DyIII (7), HoIII (8), ErIII (9), TmIII (10), YbIII (11), and YIII (12). An example with MI = KI and LnIII = DyIII is also reported (DyIIIK(OAc)4[12-MCMnIII(N)shi-4](DMF)4·DMF (14)). When LaIII, CeIII, or LuIII is used as the LnIII ions to prepare the LnIIINaI(OAc)4[12-MCMnIII(N)shi-4] complex, the compound Na2(OAc)2[12-MCMnIII(N)shi-4](DMF)6·2DMF·1.60H2O (13) results. For compounds 1–12, the identity of the LnIII ion affects the 12-MCMnIII(N)shi-4 framework as the largest LnIII, PrIII, causes an expansion of the 12-MCMnIII(N)shi-4 framework as demonstrated by the largest metallacrown cavity radius (0.58 Å for 1 to 0.54 Å for 11), and the PrIII causes the 12-MCMnIII(N)shi-4 framework to be the most domed structure as evident in the largest average angle about the axial coordination of the ring MnIII ions (103.95° for 1 to 101.69° for 11). For 14, the substitution of KI for NaI does not significantly affect the 12-MCMnIII(N)shi-4 framework as many of the structural parameters such as the metallacrown cavity radius (0.56 Å) fall within the range of compounds 1–12. However, the use of the larger KI ion does cause the 12-MCMnIII(N)shi-4 framework to become more planar as evident in a smaller average angle about the axial coordination of the ring MnIII ions (101.35°) compared to the analogous DyIII/NaI (7) complex (102.40°). In addition to broadening the range of structures available through the metallacrown analogy, these complexes allow for the mixing and matching of a diverse range of metals that might permit the fine-tuning of molecular properties where one day they may be exploited as magnetic materials or luminescent agents.
Co-reporter:Joseph Jankolovits, Jeff. W. Kampf, and Vincent L. Pecoraro
Inorganic Chemistry 2014 Volume 53(Issue 14) pp:7534-7546
Publication Date(Web):June 23, 2014
DOI:10.1021/ic500832u
Solvent dependence in the assembly of coordination driven macrocycles is a poorly understood phenomenon. This work presents the solvent dependent assembly of 8 lanthanide metallacrowns (LnMCs) in solution using picoline hydroxamic acid (picHA), Zn(II), and Ln(III) ions. ESI-MS and single-crystal X-ray crystallography reveal the selective assembly of LnZn4(picHA)43+, LnZn5(picHA)53+, LnZn8(picHA)83+, LnZn12(picHA)123+, LnZn16(picHA)163+, Ln2Zn3(picHA)44+, Ln2Zn7–9(picHA)8–10, and Ln4Zn4–5(picHA)8–9 complexes in five different solvents. The coordination preferences of the hard Ln(III) ion and relatively soft Zn(II) ion dictate the solvent selectivity in this system. The LnMCs assemble with open or closed Zn(II) and/or Ln(III) coordination sites based on the behavior of the solvent as an ancillary ligand. This structural promiscuity is attributed to the symmetry incompatible building blocks, which generate assemblies with substantial geometric strain such that no clear thermodynamic minimum exists between the different LnMCs. These LnMCs assemble from a Zn5(picHA)42+ intermediate, which is monitored using 1H NMR and ESI-MS to assess the stability of the complexes and possible assembly pathways based on kinetic considerations. LnMC assemblies that can be generated through central metal substitution reactions such as the LnZn4(picHA)43+, LnZn5(picHA)53+, and LnZn8(picHA)83+ effectively reach equilibrium after 24 h at room temperature. In contrast, LnMCs that must disrupt the Zn5L42+ structure to assemble, such as the LnZn16L163+, reach equilibrium after heating for 24 h at 65 °C. A pathway for LnMC assembly is presented where the Zn5L42+ is the key intermediate based on these reaction data and shared structural motifs in the complexes. These results correlate solvent dependent assembly to the building block geometry, highlighting synthetic approaches for generating novel complexes.
Co-reporter:Melissa L. Zastrow and Vincent L. Pecoraro
Biochemistry 2014 Volume 53(Issue 6) pp:
Publication Date(Web):February 7, 2014
DOI:10.1021/bi4016617
Zinc is an essential element required for the function of more than 300 enzymes spanning all classes. Despite years of dedicated study, questions regarding the connections between primary and secondary metal ligands and protein structure and function remain unanswered, despite numerous mechanistic, structural, biochemical, and synthetic model studies. Protein design is a powerful strategy for reproducing native metal sites that may be applied to answering some of these questions and subsequently generating novel zinc enzymes. From examination of the earliest design studies introducing simple Zn(II)-binding sites into de novo and natural protein scaffolds to current studies involving the preparation of efficient hydrolytic zinc sites, it is increasingly likely that protein design will achieve reaction rates previously thought possible only for native enzymes. This Current Topic will review the design and redesign of Zn(II)-binding sites in de novo-designed proteins and native protein scaffolds toward the preparation of catalytic hydrolytic sites. After discussing the preparation of Zn(II)-binding sites in various scaffolds, we will describe relevant examples for reengineering existing zinc sites to generate new or altered catalytic activities. Then, we will describe our work on the preparation of a de novo-designed hydrolytic zinc site in detail and present comparisons to related designed zinc sites. Collectively, these studies demonstrate the significant progress being made toward building zinc metalloenzymes from the bottom up.
Co-reporter:Dr. Virginia M. Cangelosi;Dr. Aniruddha Deb; James E. Penner-Hahn ; Vincent L. Pecoraro
Angewandte Chemie International Edition 2014 Volume 53( Issue 30) pp:7900-7903
Publication Date(Web):
DOI:10.1002/anie.201404925
Abstract
Protein design will ultimately allow for the creation of artificial enzymes with novel functions and unprecedented stability. To test our current mastery of nature’s approach to catalysis, a ZnII metalloenzyme was prepared using de novo design. α3DH3 folds into a stable single-stranded three-helix bundle and binds ZnII with high affinity using His3O coordination. The resulting metalloenzyme catalyzes the hydration of CO2 better than any small molecule model of carbonic anhydrase and with an efficiency within 1400-fold of the fastest carbonic anhydrase isoform, CAII, and 11-fold of CAIII.
Co-reporter:Dr. Virginia M. Cangelosi;Dr. Aniruddha Deb; James E. Penner-Hahn ; Vincent L. Pecoraro
Angewandte Chemie 2014 Volume 126( Issue 30) pp:8034-8037
Publication Date(Web):
DOI:10.1002/ange.201404925
Abstract
Protein design will ultimately allow for the creation of artificial enzymes with novel functions and unprecedented stability. To test our current mastery of nature’s approach to catalysis, a ZnII metalloenzyme was prepared using de novo design. α3DH3 folds into a stable single-stranded three-helix bundle and binds ZnII with high affinity using His3O coordination. The resulting metalloenzyme catalyzes the hydration of CO2 better than any small molecule model of carbonic anhydrase and with an efficiency within 1400-fold of the fastest carbonic anhydrase isoform, CAII, and 11-fold of CAIII.
Co-reporter:Fangting Yu ; James E. Penner-Hahn
Journal of the American Chemical Society 2013 Volume 135(Issue 48) pp:18096-18107
Publication Date(Web):November 1, 2013
DOI:10.1021/ja406648n
Enzymatic reactions involving redox processes are highly sensitive to the local electrostatic environment. Despite considerable effort, the complex interactions among different influential factors in native proteins impede progress toward complete understanding of the structure–function relationship. Of particular interest is the type 2 copper center Cu(His)3, which may act as an electron transfer center in peptidylglycine α-hydroxylating monooxygenase (PHM) or a catalytic center in copper nitrite reductase (CuNiR). A de novo design strategy is used to probe the effect of modifying charged amino acid residues around, but not directly bound to, a Cu(His)3 center embedded in three-stranded coiled coils (TRI-H)3 [TRI-H = Ac-G WKALEEK LKALEEK LKALEEK HKALEEK G-NH2]. Specifically, the peptide TRI-EH (=TRI-HK22E) alters an important lysine to glutamate just above the copper binding center. With a series of TRI-EH peptides mutated below the metal center, we use a variety of spectroscopies (EPR, UV–vis, XAS) to show a direct impact on the protonation equilibria, copper binding affinities, reduction potentials, and nitrite reductase activities of these copper–peptide complexes. The potentials at a specific pH vary by 100 mV, and the nitrite reductase activities range over a factor of 4 in rates. We also observe that the affinities, potentials, and catalytic activities are strongly influenced by the pH conditions (pH 5.8–7.4). In general, Cu(II) affinities for the peptides are diminished at low pH values. The interplay among these factors can lead to a 200 mV shift in reduction potential across these peptides, which is determined by the pH-dependent affinities of copper in both oxidation states. This study illustrates the strength of de novo protein design in elucidating the influence of ionizable residues on a particular redox system, an important step toward understanding the factors that govern the properties of this metalloenzyme with a goal of eventually improving the catalytic activity.
Co-reporter:Melissa L. Zastrow
Journal of the American Chemical Society 2013 Volume 135(Issue 15) pp:5895-5903
Publication Date(Web):March 21, 2013
DOI:10.1021/ja401537t
While metalloprotein design has now yielded a number of successful metal-bound and even catalytically active constructs, the question of where to put a metal site along a linear, repetitive sequence has not been thoroughly addressed. Often several possibilities in a given sequence may exist that would appear equivalent but may in fact differ for metal affinity, substrate access, or protein dynamics. We present a systematic variation of active site location for a hydrolytically active ZnHis3O site contained within a de novo-designed three-stranded coiled coil. We find that the maximal rate, substrate access, and metal-binding affinity are dependent on the selected position, while catalytic efficiency for p-nitrophenyl acetate hydrolysis can be retained regardless of the location of the active site. This achievement demonstrates how efficient, tailor-made enzymes which control rate, pKa, substrate and solvent access (and selectivity), and metal-binding affinity may be realized. These findings may be applied to the more advanced de novo design of constructs containing secondary interactions, such as hydrogen-bonding channels. We are now confident that changes to location for accommodating such channels can be achieved without location-dependent loss of catalytic efficiency. These findings bring us closer to our ultimate goal of incorporating the secondary interactions we believe will be necessary in order to improve both active site properties and the catalytic efficiency to be competitive with the native enzyme, carbonic anhydrase.
Co-reporter:Melissa L. Zastrow, Vincent L. Pecoraro
Coordination Chemistry Reviews 2013 Volume 257(17–18) pp:2565-2588
Publication Date(Web):September 2013
DOI:10.1016/j.ccr.2013.02.007
Metalloenzymes efficiently catalyze some of the most important and difficult reactions in nature. For many years, coordination chemists have effectively used small molecule models to understand these systems. More recently, protein design has been shown to be an effective approach for mimicking metal coordination environments. Since the first designed proteins were reported, much success has been seen for incorporating metal sites into proteins and attaining the desired coordination environment but until recently, this has been with a lack of significant catalytic activity. Now there are examples of designed metalloproteins that, although not yet reaching the activity of native enzymes, are considerably closer. In this review, we highlight work leading up to the design of a small metalloprotein containing two metal sites, one for structural stability (HgS3) and the other a separate catalytic zinc site to mimic carbonic anhydrase activity (ZnN3O). The first section will describe previous studies that allowed for a high affinity thiolate site that binds heavy metals in a way that stabilizes three-stranded coiled coils. The second section will examine ways of preparing histidine-rich environments that lead to metal-based hydrolytic catalysts. We will also discuss other recent examples of the design of structural metal sites and functional metalloenzymes. Our work demonstrates that attaining the proper first coordination geometry of a metal site can lead to a significant fraction of catalytic activity, apparently independent of the type of secondary structure of the surrounding protein environment. We are now in a position to begin to meet the challenge of building a metalloenzyme systematically from the bottom-up by engineering and analyzing interactions directly around the metal site and beyond.Highlights► De novo metalloprotein design. ► Structural metal sites: Hg(II) binding to α-helical coiled coils. ► Hydrolytic catalysis by a de novo designed Zn(II) metalloprotein. ► Redox catalysis by a de novo designed Cu(I/II) metalloprotein. ► De novo designed binuclear metal sites.
Co-reporter:Joseph Jankolovits, Jeff W. Kampf, and Vincent L. Pecoraro
Inorganic Chemistry 2013 Volume 52(Issue 9) pp:5063-5076
Publication Date(Web):April 11, 2013
DOI:10.1021/ic302831u
Two intermediates in the assembly of lanthanide metallacrowns (MCs) of divalent transition metals and ligands in the picoline hydroxamic acid (picHA)/α-amino hydroxamic acid family were synthesized and crystallographically characterized. Structures of the elusive MII[12-MCMII,L-4]2+ were obtained with M = Ni, Zn and L = picHA, quinaldic hydroxamic acid. Consistent with previous calculations, the complex is highly concave, particularly with Zn(II). ESI-MS and 1H NMR reveal that the complexes retain their structure in solution. The Zn(II) analogue reacts with Ln(III) ions to form LnIII[15-MCZn(II),picHA-5]3+ in pyridine. The greater stability of ZnII[12-MCZn(II),picHA-4]2+ relative to the Cu(II) and Ni(II) analogues is inferred and attributed to the square-pyramidal Zn(II) ions being complementary with the concave MC topology. A Zn4(picHA)2(OAc)4(DMF)2 species bearing a tetranuclear [6-MCZnII,picHA-2] motif was also isolated. A mechanism for MII[12-MCMII,L-4]2+ formation is proposed on the basis of structural analysis of tetranuclear [6-MCMII,L-2] complexes. These results contribute to the goal of controlling the reactivity of intermediates in the assembly of lanthanide MCs, and coordination driven macrocycles in general, to prepare complexes with greater stability or enhanced physical properties.
Co-reporter:Benedikt Lassalle-Kaiser ; Thaddeus T. Boron III; Vera Krewald ; Jan Kern ; Martha A. Beckwith ; Mario U. Delgado-Jaime ; Henning Schroeder ; Roberto Alonso-Mori ; Dennis Nordlund ; Tsu-Chien Weng ; Dimosthenis Sokaras ; Frank Neese ; Uwe Bergmann ; Vittal K. Yachandra ; Serena DeBeer ; Vincent L. Pecoraro ;Junko Yano
Inorganic Chemistry 2013 Volume 52(Issue 22) pp:12915-12922
Publication Date(Web):October 25, 2013
DOI:10.1021/ic400821g
The protonation state of oxo bridges in nature is of profound importance for a variety of enzymes, including the Mn4CaO5 cluster of photosystem II and the Mn2O2 cluster in Mn catalase. A set of dinuclear bis-μ-oxo-bridged MnIV complexes in different protonation states was studied by Kβ emission spectroscopy to form the foundation for unraveling the protonation states in the native complex. The valence-to-core regions (valence-to-core XES) of the spectra show significant changes in intensity and peak position upon protonation. DFT calculations were performed to simulate the valence-to-core XES spectra and to assign the spectral features to specific transitions. The Kβ2,5 peaks arise primarily from the ligand 2p to Mn 1s transitions, with a characteristic low energy shoulder appearing upon oxo-bridge protonation. The satellite Kβ″ peak provides a more direct signature of the protonation state change, since the transitions originating from the 2s orbitals of protonated and unprotonated μ-oxo bridges dominate this spectral region. The energies of the Kβ″ features differ by ∼3 eV and thus are well resolved in the experimental spectra. Additionally, our work explores the chemical resolution limits of the method, namely, whether a mixed (μ-O)(μ-OH2) motif can be distinguished from a symmetric (μ-OH)2 one. The results reported here highlight the sensitivity of Kβ valence-to-core XES to single protonation state changes of bridging ligands, and form the basis for further studies of oxo-bridged polymetallic complexes and metalloenzyme active sites. In a complementary paper, the results from X-ray absorption spectroscopy of the same MnIV dimer series are discussed.
Co-reporter:Vera Krewald ; Benedikt Lassalle-Kaiser ; Thaddeus T. Boron III; Christopher J. Pollock ; Jan Kern ; Martha A. Beckwith ; Vittal K. Yachandra ; Vincent L. Pecoraro ; Junko Yano ; Frank Neese ;Serena DeBeer
Inorganic Chemistry 2013 Volume 52(Issue 22) pp:12904-12914
Publication Date(Web):October 25, 2013
DOI:10.1021/ic4008203
In nature, the protonation of oxo bridges is a commonly encountered mechanism for fine-tuning chemical properties and reaction pathways. Often, however, the protonation states are difficult to establish experimentally. This is of particular importance in the oxygen evolving complex of photosystem II, where identification of the bridging oxo protonation states is one of the essential requirements toward unraveling the mechanism. In order to establish a combined experimental and theoretical protocol for the determination of protonation states, we have systematically investigated a series of Mn model complexes by Mn K pre-edge X-ray absorption spectroscopy. An ideal test case for selective bis-μ-oxo-bridge protonation in a Mn dimer is represented by the system [MnIV2(salpn)2(μ-OHn)2]n+. Although the three species [MnIV2(salpn)2(μ-O)2], [MnIV2(salpn)2(μ-O)(μ-OH)]+ and [MnIV2(salpn)2(μ-OH)2]2+ differ only in the protonation of the oxo bridges, they exhibit distinct differences in the pre-edge region while maintaining the same edge energy. The experimental spectra are correlated in detail to theoretically calculated spectra. A time-dependent density functional theory approach for calculating the pre-edge spectra of molecules with multiple metal centers is presented, using both high spin (HS) and broken symmetry (BS) electronic structure solutions. The most intense pre-edge transitions correspond to an excitation of the Mn 1s core electrons into the unoccupied orbitals of local eg character (dz2 and dxy based in the chosen coordinate system). The lowest energy experimental feature is dominated by excitations of 1s-α electrons, and the second observed feature is primarily attributed to 1s-β electron excitations. The observed energetic separation is due to spin polarization effects in spin-unrestricted density functional theory and models final state multiplet effects. The effects of spin polarization on the calculated Mn K pre-edge spectra, in both the HS and BS solutions, are discussed in terms of the strength of the antiferromagnetic coupling and associated changes in the covalency of Mn–O bonds. The information presented in this paper is complemented with the X-ray emission spectra of the same compounds published in an accompanying paper. Taken together, the two studies provide the foundation for a better understanding of the X-ray spectroscopic data of the oxygen evolving complex (OEC) in photosystem II.
Co-reporter:Joseph Jankolovits, Annabel D. Cutland Van-Noord, Jeff W. Kampf and Vincent L. Pecoraro
Dalton Transactions 2013 vol. 42(Issue 27) pp:9803-9808
Publication Date(Web):22 May 2013
DOI:10.1039/C3DT50535A
Secondary sphere interactions from proximal phenyl side chains control the anion selectivity of dimeric Ln(III)[15-MCCu(II),α-aminoHA-5]3+ metallocavitands. CH–O interactions, which are only possible with certain side chains, are sufficient for overcoming an intrinsic energy barrier to binding saturated dicarboxylates in hydrophobic compartments.
Co-reporter:Fangting Yu, Vincent L. Pecoraro
Polyhedron 2013 64() pp: 99-105
Publication Date(Web):
DOI:10.1016/j.poly.2013.02.074
Co-reporter:Dr. Marek &x141;uczkowski;Dr. Brian A. Zeider;Alia V. H. Hinz;Dr. Monika Stachura;Dr. Saumen Chakraborty; Lars Hemmingsen;Dr. David L. Huffman; Vincent L. Pecoraro
Chemistry - A European Journal 2013 Volume 19( Issue 27) pp:9042-9049
Publication Date(Web):
DOI:10.1002/chem.201204184
Abstract
Although metal ion homeostasis in cells is often mediated through metallochaperones, there are opportunities for toxic metals to be sequestered through the existing transport apparatus. Proper trafficking of CuI in human cells is partially achieved through complexation by HAH1, the human metallochaperone responsible for copper delivery to the Wilson and Menkes ATPase located in the trans-Golgi apparatus. In addition to binding copper, HAH1 strongly complexes HgII, with the X-ray structure of this complex previously described. It is important to clarify the solution behavior of these systems and, therefore, the binding of HgII to HAH1 was probed over the pH range 7.5 to 9.4 using 199Hg NMR, 199mHg PAC and UV–visible spectroscopies. The metal-dependent protein association over this pH range was examined using analytical gel-filtration. It can be concluded that at pH 7.5, HgII is bound to a monomeric HAH1 as a two coordinate, linear complex (HgS2), like the HgII–Atx1 X-ray structure (PDB ID: 1CC8). At pH 9.4, HgII promotes HAH1 association, leading to formation of HgS3 and HgS4 complexes, which are in exchange on the μs–ns time scale. Thus, structures that may represent central intermediates in the process of metal ion transfer, as well as their exchange kinetics have been characterized.
Co-reporter:Joseph Jankolovits, Jeff W. Kampf, Vincent L. Pecoraro
Polyhedron 2013 52() pp: 491-499
Publication Date(Web):
DOI:10.1016/j.poly.2012.08.046
Co-reporter:Saumen Chakraborty ; Olga Iranzo ; Erik R. P. Zuiderweg
Journal of the American Chemical Society 2012 Volume 134(Issue 14) pp:6191-6203
Publication Date(Web):March 6, 2012
DOI:10.1021/ja210510g
An important factor that defines the toxicity of elements such as cadmium(II), mercury(II), and lead(II) with biological macromolecules is metal ion exchange dynamics. Intriguingly, little is known about the fundamental rates and mechanisms of metal ion exchange into proteins, especially helical bundles. Herein, we investigate the exchange kinetics of Cd(II) using de novo designed three-stranded coiled-coil peptides that contain metal complexing cysteine thiolates as a model for the incorporation of this ion into trimeric, parallel coiled coils. Peptides were designed containing both a single Cd(II) binding site, GrandL12AL16C [Grand = AcG-(LKALEEK)5-GNH2], GrandL26AL30C, and GrandL26AE28QL30C, as well as GrandL12AL16CL26AL30C with two Cd(II) binding sites. The binding of Cd(II) to any of these sites is of high affinity (KA > 3 × 107 M–1). Using 113Cd NMR spectroscopy, Cd(II) binding to these designed peptides was monitored. While the Cd(II) binding is in extreme slow exchange regime without showing any chemical shift changes, incremental line broadening for the bound 113Cd(II) signal is observed when excess 113Cd(II) is titrated into the peptides. Most dramatically, for one site, L26AL30C, all 113Cd(II) NMR signals disappear once a 1.7:1 ratio of Cd(II)/(peptide)3 is reached. The observed processes are not compatible with a simple “free-bound” two-site exchange kinetics at any time regime. The experimental results can, however, be simulated in detail with a multisite binding model, which features additional Cd(II) binding site(s) which, once occupied, perturb the primary binding site. This model is expanded into differential equations for five-site NMR chemical exchange. The numerical integration of these equations exhibits progressive loss of the primary site NMR signal without a chemical shift change and with limited line broadening, in good agreement with the observed experimental data. The mathematical model is interpreted in molecular terms as representing binding of excess Cd(II) to surface Glu residues located at the helical interfaces. In the absence of Cd(II), the Glu residues stabilize the three-helical structure though salt bridge interactions with surface Lys residues. We hypothesize that Cd(II) interferes with these surface ion pairs, destabilizing the helical structure, and perturbing the primary Cd(II) binding site. This hypothesis is supported by the observation that the Cd(II)-excess line broadening is attenuated in GrandL26AE28QL30C, where a surface Glu(28), close to the metal binding site, was changed to Gln. The external binding site may function as an entry pathway for Cd(II) to find its internal binding site following a molecular rearrangement which may serve as a basis for our understanding of metal complexation, transport, and exchange in complex native systems containing α-helical bundles.
Co-reporter:Joseph Jankolovits ; Choong-Sun Lim ; Gellert Mezei ; Jeff W. Kampf
Inorganic Chemistry 2012 Volume 51(Issue 8) pp:4527-4538
Publication Date(Web):February 6, 2012
DOI:10.1021/ic202347j
Dimeric Ln3+[15-metallacrown-5] compartments selectively recognize carboxylates through guest binding to host metal ions and intermolecular interactions with the phenyl side chains. A systematic study is presented on how the size, selectivity, and number of encapsulated guests in the dimeric containers is influenced by the Ln3+[15-metallacrownCu(II)-5] ligand side chain and central metal. Compartments of varying heights were assembled from metallacrowns with S-phenylglycine hydroxamic acid (pgHA), S-phenylalanine hydroxamic acid (pheHA), and S-homophenylalanine hydroxamic acid (hpheHA) ligands. Guests that were examined include the fully deprotonated forms of terephthalic acid, isonicotinic acid, and bithiophene dicarboxylic acid (btDC). X-ray crystallography reveals that the side-chain length constrains the maximum and minimum length guest that can be encapsulated in the compartment. Compartments with heights ranging from 9.7 to 15.2 Å are formed with different phenyl side chains that complex 4.3–9.2 Å long guests. Up to five guests are accommodated in Ln3+[15-metallacrownCu(II)-5] compartments depending on steric effects from the host side chains. The nine-coordinate La3+ central metal promotes the encapsulation of multiple guests, while the eight-coordinate Gd3+ typically binds only one dicarboxylate. Electrospray ionization mass spectrometry reveals that the dimerization phenomenon occurs beyond the solid state, suggesting that these containers can be utilized in solid-state and solution applications.
Co-reporter:Joseph T. Grant ; Joseph Jankolovits
Inorganic Chemistry 2012 Volume 51(Issue 15) pp:8034-8041
Publication Date(Web):May 2, 2012
DOI:10.1021/ic300110g
Supramolecular hosts that bind guests reversibly are investigated for potential catalysis and separations applications. Chiral Ln3+[15-Metallacrown-5] metallocavitands bind carboxylate guests in hydrophobic cavities generated by their ligand side chains. A thermodynamic study on Gd3+[15-metallacrown-5] hosts with ligands bearing phenyl side chains containing 0, 1, and 2 methylene spacers (1-pgHA, 1-pheHA, 1-hpheHA, respectively) is presented to quantitatively assess how guest affinity and chiral selectivity can be enhanced through changes to the ligand side chain. Guest binding affinity was measured with cyclic voltammetry using ferrocene carboxylate as a redox probe. Ka values between ferrocene carboxylate and 1-pgHA and 1-pheHA were 4800 ± 400 M–1 and 4400 ± 700 M–1, respectively. Significantly stronger binding affinity of 12100 ± 700 M–1 was measured with 1-hpheHA, a result of the longer side-chains more completely encapsulating the guest. A similar trend was observed with benzoate. The side chain also influenced enantioselectivity, as KS/KR values of up to 2.2 ± 0.6 were measured. The side chain dependent guest binding supports the development of highly selective Ln3+[15-Metallacrown-5] hosts for use in catalysis and separations through careful ligand design.
Co-reporter:Choong-Sun Lim, Matteo Tegoni, Tamás Jakusch, Jeff W. Kampf, and Vincent L. Pecoraro
Inorganic Chemistry 2012 Volume 51(Issue 21) pp:11533-11540
Publication Date(Web):October 17, 2012
DOI:10.1021/ic3013798
The calcium metallacrown Ca(II)[15-MCCu(II)N(Trpha)-5]2+ was obtained by self-assembly of CaII, CuII, and tryptophanhydroxamic acid. Its X-ray structure shows that the core calcium ion is well-encapsulated in the five oxygen cavity of the metallacrown scaffold. The kinetics of Ca–Ln core metal substitution was studied by visible spectrophotometry by addition of LnIII nitrate to solutions of Ca(II)[15-MCCu(II)N(Trpha)-5]2+ in methanol solution at pH 6.2 (LnIII = LaIII, NdIII, GdIII, DyIII, ErIII) to obtain the corresponding Ln(III)[15-MCCu(II)N(Trpha)-5]3+ complexes on the hours time scale. The reaction is first order in the two reactants (second order overall) with different rate constants across the lanthanide series. In particular, the rate for the Ca–Ln substitution decreases from LaIII to GdIII and then increases slightly from GdIII to ErIII. This substitution reaction occurs with second order rate constants ranging from 0.1543(3) M–1 min–1 for LaIII to 0.0720(6) M–1 min–1 for GdIII. By means of the thermodynamic log K constants for the same reaction previously reported, the rate constants for the inverse Ln–Ca substitution were also determined. In this study, we demonstrated that the substitution reaction proceeds through a direct metal substitution and does not involve the disassembly of the MC scaffold. These observations in concert allow the proposition of a hypothesis that the dimension of the core metals play the major role in determining the rate constants of the substitution reaction. In particular, the largest lanthanides, which do not require complete encapsulation in the MC cavity, displace the CaII ion faster, whereas in the back reaction CaII displaces the smaller lanthanides faster as they interact relatively weakly with the metallacrown oxygen cavity.
Co-reporter:Dr. Giuseppe Zampella;Dr. Kosh P. Neupane;Dr. Luca DeGioia;Dr. Vincent L. Pecoraro
Chemistry - A European Journal 2012 Volume 18( Issue 7) pp:2040-2050
Publication Date(Web):
DOI:10.1002/chem.201102786
Abstract
The toxicity of heavy metals, which is associated with the high affinity of the metals for thiolate rich proteins, constitutes a problem worldwide. However, despite this tremendous toxicity concern, the binding mode of AsIII and PbII to proteins is poorly understood. To clarify the requirements for toxic metal binding to metalloregulatory sensor proteins such as AsIII in ArsR/ArsD and PbII in PbrR or replacing ZnII in δ-aminolevulinc acid dehydratase (ALAD), we have employed computational and experimental methods examining the binding of these heavy metals to designed peptide models. The computational results show that the mode of coordination of AsIII and PbII is greatly influenced by the steric bulk within the second coordination environment of the metal. The proposed basis of this selectivity is the large size of the ion and, most important, the influence of the stereochemically active lone pair in hemidirected complexes of the metal ion as being crucial. The experimental data show that switching a bulky leucine layer above the metal binding site by a smaller alanine residue enhances the PbII binding affinity by a factor of five, thus supporting experimentally the hypothesis of lone pair steric hindrance. These complementary approaches demonstrate the potential importance of a stereochemically active lone pair as a metal recognition mode in proteins and, specifically, how the second coordination sphere environment affects the affinity and selectivity of protein targets by certain toxic ions.
Co-reporter:Matteo Tegoni;Manuela Bersellini;Fangting Yu;James E. Penner-Hahn
PNAS 2012 Volume 109 (Issue 52 ) pp:21234-21239
Publication Date(Web):2012-12-26
DOI:10.1073/pnas.1212893110
One of the ultimate objectives of de novo protein design is to realize systems capable of catalyzing redox reactions on substrates.
This goal is challenging as redox-active proteins require design considerations for both the reduced and oxidized states of
the protein. In this paper, we describe the spectroscopic characterization and catalytic activity of a de novo designed metallopeptide
Cu(I/II)(TRIL23H)3+/2+, where Cu(I/II) is embeded in α-helical coiled coils, as a model for the CuT2 center of copper nitrite reductase. In Cu(I/II)(TRIL23H)3+/2+, Cu(I) is coordinated to three histidines, as indicated by X-ray absorption data, and Cu(II) to three histidines and one
or two water molecules. Both ions are bound in the interior of the three-stranded coiled coils with affinities that range
from nano- to micromolar [Cu(II)], and picomolar [Cu(I)]. The Cu(His)3 active site is characterized in both oxidation states, revealing similarities to the CuT2 site in the natural enzyme. The species Cu(II)(TRIL23H)32+ in aqueous solution can be reduced to Cu(I)(TRIL23H)3+ using ascorbate, and reoxidized by nitrite with production of nitric oxide. At pH 5.8, with an excess of both the reductant
(ascorbate) and the substrate (nitrite), the copper peptide Cu(II)(TRIL23H)32+ acts as a catalyst for the reduction of nitrite with at least five turnovers and no loss of catalytic efficiency after 3.7
h. The catalytic activity, which is first order in the concentration of the peptide, also shows a pH dependence that is described
and discussed.
Co-reporter:Choong-Sun Lim ; Joseph Jankolovits ; Peng Zhao ; Jeff W. Kampf
Inorganic Chemistry 2011 Volume 50(Issue 11) pp:4832-4841
Publication Date(Web):May 3, 2011
DOI:10.1021/ic102579t
Chiral Ln(III)[15-metallacrown-5] complexes with phenyl side chains have been shown to encapsulate aromatic carboxylates reversibly in their hydrophobic cavities. Given the importance of selective guest binding for applications of supramolecular containers in synthesis, separations, and materials design, the affinity of Gd(III)[15-metallacrownCu(II), l-pheHA-5] hosts for a series of chiral carboxylate guests with varying substitutions on the α-carbon (phenylalanine, N-acetyl-phenylalanine, phenyllactate, mandelate, methoxyphenylacetate) has been investigated. Differential binding of S- and R-phenylalanine was revealed by X-ray crystallography, as the S-enantiomer exclusively forms associative hydrogen bonds with oxygen atoms in the metallacrown ring. Selective guest binding in solution was assessed with isothermal titration calorimetry, which measures the sequential guest binding in the hydrophobic cavity first and the hydrophilic face of the host, and a cyclic voltammetry assay, which quantifies guest binding strength in the hydrophobic cavity of the host exclusively. In solution, the Gd(III)[15-metallacrownCu(II), l-pheHA-5] hydrophobic cavity exhibits modest chiral selectivity for enantiomers of phenylalanine (KS/KR = 2.4) and mandelate (KS/KR = 1.22). Weak binding constants of ∼100 M–1 were measured for neutral and −1 charged carboxylates with hydrophilic functional groups (ammonium, N-acetyl, methyl ether). Weaker binding relative to the unsubstituted guests is attributed to unfavorable interactions between the hydrophilic functionalities of the guest and the hydrophobic cavity of the host. In contrast, binding constants greater than 2000 M–1 were measured for α-hydroxy analogues phenyllactate and mandelate. The significantly increased affinity likely arises from the guests being bound as a −2 anion upon metal-assisted deprotonation in the Gd(III)[15-metallacrownCu(II), l-pheHA-5] cavity. It is established that guest binding affinity in the hydrophobic cavity of the host follows the general trend of neutral zwitterion < monoanion < dianion, with hydrophilic functional groups decreasing the binding affinity. These results have broad implications for the development of metallacrowns as supramolecular catalysts or in chiral separations.
Co-reporter:Curtis M. Zaleski, Choong-Sun Lim, Annabel D. Cutland-Van Noord, Jeff W. Kampf, and Vincent L. Pecoraro
Inorganic Chemistry 2011 Volume 50(Issue 16) pp:7707-7717
Publication Date(Web):July 18, 2011
DOI:10.1021/ic200740h
Twenty crystal structures of the LnIII[15-MCCuII(N)pheHA-5]3+ complex, where pheHA = phenylalanine hydroxamic acid and where LnIII = YIII and LaIII–TmIII, except PmIII, with the nitrate and/or hydroxide anion are used to assess the effect of the central metal ion on the metallacrown structure. Each LnIII[15-MCCuII(N)pheHA-5]3+ complex is amphiphilic with a hydrophobic side consisting of the phenyl groups of the pheHA ligand and a side without the aromatic residues. Three general structures are observed for the LnIII[15-MCCuII(N)pheHA-5]3+ complexes. In the Type 1 structures, the central metal ion does not bind a nitrate anion on the metallacrown’s hydrophobic face, and two adjacent metallacrowns dimerize through their phenyl groups producing a hydrophobic compartment. In the Type 2 structures, the central metal ion binds a nitrate in a bidentate fashion on the hydrophobic face. There are two distinct types of Type 2 metallacrowns, designated A and B. Type 2A metallacrowns have a water molecule bound to the central metal ion on the hydrophilic face, while Type 2B metallacrowns have a monodentate nitrate ion bound on the hydrophilic face to the central metal ion. The Type 2 metallacrowns also dimerize via the phenyl groups to form a hydrophobic compartment. In Type 3 structures, the central metal ion binds a nitrate in a bidentate fashion on the hydrophobic side, but instead of forming dimers, the metallacrowns pack in a helical arrangement to give either P or M one-dimensional helices. Regardless of the type of metallacrown, the overall trend observed is that as the LnIII ion crystal radius increases, the metallacrown cavity radius also increases while the metallacrown becomes more planar. This conclusion is demonstrated by a decrease in the oxime oxygen distances to the oxime oxygen mean plane and a decrease in the ring CuII distances to the CuII mean plane as the metallacrown cavity radius increases and the lanthanide crystal radius increases. In addition, a decrease in the Ooxime–CuII–Noxime–Ooxime torsion (dihedral) angles is also observed as the metallacrown cavity radius and the lanthanide crystal radius both increase. These observations help explain the thermodynamic preferences for LnIII ions within this class of metallacrowns and may be used to design compartments capable of binding guests in different orientations within chiral, soft solids.
Co-reporter:Curtis M. Zaleski ; Simon Tricard ; Ezra C. Depperman ; Wolfgang Wernsdorfer ; Talal Mallah ; Martin L. Kirk
Inorganic Chemistry 2011 Volume 50(Issue 22) pp:11348-11352
Publication Date(Web):October 21, 2011
DOI:10.1021/ic2008792
The magnetic behavior of the pentanuclear complex of formula MnII(O2CCH3)2[12-MCMnIII(N)shi-4](DMF)6, 1, was investigated using magnetization and magnetic susceptibility measurements both in the solid state and in solution. Complex 1 has a nearly planar structure, made of a central MnII ion surrounded by four peripheral MnIII ions. Solid state variable-field dc magnetic susceptibility experiments demonstrate that 1 possesses a low value for the total spin in the ground state; fitting appropriate expressions to the data results in antiferromangetic coupling both between the peripheral MnIII ions (J = −6.3 cm–1) and between the central MnII ion and the MnIII ones (J′ = −4.2 cm–1). In order to obtain a reasonable fit, a relatively large single ion magnetic anisotropy (D) value of 1 cm–1 was necessary for the central MnII ion. The single crystal magnetization measurements using a microsquid array display a very slight opening of the hysteresis loop but only at a very low temperature (0.04 K), which is in line with the ac susceptibility data where a slow relaxation of the magnetization occurs just around 2 K. In frozen solution, complex 1 displays a frequency dependent ac magnetic susceptibility signal with an energy barrier to magnetization reorientation (E) and relaxation time at an infinite temperature (τo) of 14.7 cm–1 and 1.4 × 10–7 s, respectively, demonstrating the single molecule magnetic behavior in solution.
Co-reporter:Kosh P. Neupane, Vincent L. Pecoraro
Journal of Inorganic Biochemistry 2011 Volume 105(Issue 8) pp:1030-1034
Publication Date(Web):August 2011
DOI:10.1016/j.jinorgbio.2011.04.010
207Pb NMR spectroscopy can be used to monitor the binding of Pb(II) to thiol rich biological small molecules such as glutathione and to zinc finger proteins. The UV/visible (UV/Vis) absorption band centered at 334 nM and the observed 207Pb signal in 207Pb NMR (δ ~ 5750 ppm) indicate that glutathione binds Pb(II) in a trigonal pyramidal geometry (PbS3) at pH 7.5 or higher with a 1:3 molar ratio of Pb(II) to GSH. While previous studies using UV/Vis and extended X-ray absorption fine structure (EXAFS) spectroscopy were interpreted to show that the zinc binding domain from HIV nucleocapsid protein (HIV-CCHC) binds Pb(II) in a single PbS3 environment, the more sensitive 207Pb NMR spectra (at pH 7.0, 1:1 molar ratio) provide compelling evidence for the presence of two PbS3 structures (δ - 5790 and 5744 ppm), one of which is more stable at high temperatures. It has previously been proposed that the HIV-CCHH peptide does not fold properly to afford a PbS2N motif, because histidine does not bind to Pb(II). These predictions are confirmed by the present studies. These results demonstrate the applicability of 207Pb NMR to biomolecular structure determination in proteins with cysteine binding sites for the first time.207Pb NMR of His → Gly substituted zinc binding domain of HIV retrovirus nucleocapsid protein (HIV-CCGC) showing the peptide folded in two conformations.
Co-reporter:Joseph Jankolovits;Dr. Christopher M. Andolina;Dr. Jeff W. Kampf; Kenneth N. Raymond; Vincent L. Pecoraro
Angewandte Chemie International Edition 2011 Volume 50( Issue 41) pp:9660-9664
Publication Date(Web):
DOI:10.1002/anie.201103851
Co-reporter:Saumen Chakraborty;Dr. Joslyn YudenfreundKravitz; Peter W. Thulstrup; Lars Hemmingsen; William F. DeGrado; Vincent L. Pecoraro
Angewandte Chemie 2011 Volume 123( Issue 9) pp:2097-2101
Publication Date(Web):
DOI:10.1002/ange.201006413
Co-reporter:Saumen Chakraborty;Dr. Joslyn YudenfreundKravitz; Peter W. Thulstrup; Lars Hemmingsen; William F. DeGrado; Vincent L. Pecoraro
Angewandte Chemie 2011 Volume 123( Issue 9) pp:
Publication Date(Web):
DOI:10.1002/ange.201100297
Co-reporter:Saumen Chakraborty;Dr. Joslyn YudenfreundKravitz; Peter W. Thulstrup; Lars Hemmingsen; William F. DeGrado; Vincent L. Pecoraro
Angewandte Chemie International Edition 2011 Volume 50( Issue 9) pp:2049-2053
Publication Date(Web):
DOI:10.1002/anie.201006413
Co-reporter:Saumen Chakraborty;Dr. Joslyn YudenfreundKravitz; Peter W. Thulstrup; Lars Hemmingsen; William F. DeGrado; Vincent L. Pecoraro
Angewandte Chemie International Edition 2011 Volume 50( Issue 9) pp:
Publication Date(Web):
DOI:10.1002/anie.201100297
Co-reporter:Saumen Chakraborty ; Debra S. Touw ; Anna F. A. Peacock ; Jeanne Stuckey
Journal of the American Chemical Society 2010 Volume 132(Issue 38) pp:13240-13250
Publication Date(Web):September 8, 2010
DOI:10.1021/ja101812c
Over the past two decades, designed metallopeptides have held the promise for understanding a variety of fundamental questions in metallobiochemistry; however, these dreams have not yet been realized because of a lack of structural data to elaborate the protein scaffolds before metal complexation and the resultant metalated structures which ultimately exist. This is because there are few reports of structural characterization of such systems either in their metalated or nonmetalated forms and no examples where an apo structure and the corresponding metalated peptide assembly have both been defined by X-ray crystallography. Herein we present X-ray structures of two de novo designed parallel three-stranded coiled coils (designed using the heptad repeat (a → g)) CSL9C (CS = Coil Ser) and CSL19C in their nonmetalated forms, determined to 1.36 and 2.15 Å resolutions, respectively. Leucines from either position 9 (a site) or 19 (d site) are replaced by cysteine to generate the constructs CSL9C and CSL19C, respectively, yielding thiol-rich pockets at the hydrophobic interior of these peptides, suitable to bind heavy metals such as As(III), Hg(II), Cd(II), and Pb(II). We use these structures to understand the inherent structural differences between a and d sites to clarify the basis of the observed differential spectroscopic behavior of metal binding in these types of peptides. Cys side chains of (CSL9C)3 show alternate conformations and are partially preorganized for metal binding, whereas cysteines in (CSL19C)3 are present as a single conformer. Zn(II) ions, which do not coordinate or influence Cys residues at the designed metal sites but are essential for forming X-ray quality crystals, are bound to His and Glu residues at the crystal packing interfaces of both structures. These “apo” structures are used to clarify the changes in metal site organization between metalated As(CSL9C)3 and to speculate on the differential basis of Hg(II) binding in a versus d peptides. Thus, for the first time, one can establish general rules for heavy metal binding to Cys-rich sites in designed proteins which may provide insight for understanding how heavy metals bind to metallochaperones or metalloregulatory proteins.
Co-reporter:Olga Iranzo ; Saumen Chakraborty ; Lars Hemmingsen
Journal of the American Chemical Society 2010 Volume 133(Issue 2) pp:239-251
Publication Date(Web):December 16, 2010
DOI:10.1021/ja104433n
Herein we report how de novo designed peptides can be used to investigate whether the position of a metal site along a linear sequence that folds into a three-stranded α-helical coiled coil defines the physical properties of Cd(II) ions in either CdS3 or CdS3O (O-being an exogenous water molecule) coordination environments. Peptides are presented that bind Cd(II) into two identical coordination sites that are located at different topological positions at the interior of these constructs. The peptide GRANDL16PenL19IL23PenL26I binds two Cd(II) as trigonal planar 3-coordinate CdS3 structures whereas GRANDL12AL16CL26AL30C sequesters two Cd(II) as pseudotetrahedral 4-coordinate CdS3O structures. We demonstrate how for the first peptide, having a more rigid structure, the location of the identical binding sites along the linear sequence does not affect the physical properties of the two bound Cd(II). However, the sites are not completely independent as Cd(II) bound to one of the sites (113Cd NMR chemical shift of 681 ppm) is perturbed by the metalation state (apo or [Cd(pep)(Hpep)2]+ or [Cd(pep)3]−) of the second center (113Cd NMR chemical shift of 686 ppm). GRANDL12AL16CL26AL30C shows a completely different behavior. The physical properties of the two bound Cd(II) ions indeed depend on the position of the metal center, having pKa2 values for the equilibrium [Cd(pep)(Hpep)2]+ → [Cd(pep)3]− + 2H+ (corresponding to deprotonation and coordination of cysteine thiols) that range from 9.9 to 13.9. In addition, the L26AL30C site shows dynamic behavior, which is not observed for the L12AL16C site. These results indicate that for these systems one cannot simply assign a “4-coordinate structure” and assume certain physical properties for that site since important factors such as packing of the adjacent Leu, size of the intended cavity (endo vs exo) and location of the metal site play crucial roles in determining the final properties of the bound Cd(II).
Co-reporter:Matteo Tegoni, Michele Furlotti, Manuel Tropiano, Choong Sun Lim and Vincent L. Pecoraro
Inorganic Chemistry 2010 Volume 49(Issue 11) pp:5190-5201
Publication Date(Web):April 29, 2010
DOI:10.1021/ic100315u
The equilibria for core Ca2+ replacement by Ln3+ in copper(II) 15-MC-5 complexes have been investigated using a series of visible spectrophotometric titrations of calcium(II) metallacrowns ({CaII[15-MCCuII(N)(L)-5]}2+) with Ln3+ ions (H2L = pheha, (S)-α-phenylalaninehydroxamic acid, or trpha, (S)-α-tryptophanhydroxamic acid). These studies allowed the determination of the equilibrium constants for the reaction {CaII[15-MCCuII(N)(L)-5]}2+ + Ln3+ → {LnIII[15-MCCuII(N)(L)-5]}3+ + Ca2+ in methanol/water 9:1 (Ln3+ = La3+, Gd3+, Dy3+, Er3+) or 99:1 (Ln3+ = La3+, Nd3+, Gd3+, Dy3+, Er3+, Yb3+), respectively. The log K for these reactions decreases with increasing atomic number of the lanthanide(III), ranging from 6.1 to 3.91 in methanol/water 9:1. The same behavior is observed in methanol/water 99:1, although the constants are uniformly lower (log K = 4.09−2.52). A significant thermodynamic selectivity was observed for the later lanthanides (Gd3+−Yb3+) while a smaller selectivity is present throughout the beginning of the series (La3+−Gd3+). This observation has been interpreted on the basis of the size correspondence between the metal ions and the metallacrown cavity. The overall stability of the {CaII[15-MCCuII(N)(L)-5]}2+ in methanol/water 9:1 has been determined by pH-spectrophotometric titrations with HCl. The resulting log K values are 63.46(12) and 65.05(13) for pheha and trpha, respectively (Ca2+ + 5Cu2+ + 5HL− = {CaII[15-MCCuII(N)(L)-5]}2+ +5H+). The stability of both the La3+ and Ca2+ 15-metallacrown-5 complexes in the presence of high Na+ concentrations has also been demonstrated by spectophotometric studies. Based upon these observations, the preference of the 15-MC-5 for Ca2+ complexation compared to crown ethers has been quantitatively demonstrated for the first time.
Co-reporter:Thaddeus T. Boron ; III; Jeff W. Kampf
Inorganic Chemistry 2010 Volume 49(Issue 20) pp:9104-9106
Publication Date(Web):September 17, 2010
DOI:10.1021/ic101121d
We describe the synthesis and magnetic properties of a unique mixed 3d−4f 14-metallacrown-5 complex. This is the first metallacrown family to feature μ-O and μ-OH bridges as well as to incorporate a LnIII ion into the ring. Alternating-current SQUID magnetometry of the Tb, Dy, and Ho derivatives reveals slow magnetic relaxation, a hallmark property of single-molecule magnets. For the Dy structure (4), an effective energy barrier Ueff of 16.7 K and a relaxation time of 4.9 × 10−8 s were calculated. Because of the relatively small total spin, this behavior most likely results from a large magnetoanisotropy, which is controlled through geometric constraints.
Co-reporter:Choong-Sun Lim Dr.;Joseph Jankolovits;JeffW. Kampf Dr. ;VincentL. Pecoraro
Chemistry – An Asian Journal 2010 Volume 5( Issue 1) pp:46-49
Publication Date(Web):
DOI:10.1002/asia.200900612
Co-reporter:Choong-Sun Lim Dr.;Joseph Jankolovits;JeffW. Kampf Dr. ;VincentL. Pecoraro
Chemistry – An Asian Journal 2010 Volume 5( Issue 1) pp:
Publication Date(Web):
DOI:10.1002/asia.200990045
Co-reporter:Joseph Jankolovits;JeffW. Kampf Dr.;Stephen Maldonado ;VincentL. Pecoraro
Chemistry - A European Journal 2010 Volume 16( Issue 23) pp:6786-6796
Publication Date(Web):
DOI:10.1002/chem.200903015
Abstract
A novel competitive binding assay was implemented to monitor the binding of a redox inactive substrate to a redox inactive metallacrown host based on its competition with ferrocene carboxylate (FcC−) using cyclic voltammetry (CV). First, the binding of FcC− to LnIII[15-MC-5] (LnMC) hosts was characterized by cyclic voltammetry. It was shown that the voltammetric half wave potentials, E1/2, shifted to more positive potentials upon the addition of LnMC. The explicit dependence of E1/2 with the concentration of LnMC was used to determine the association constants for the complex. The FcC− binding strength decreased with larger central lanthanide metals in the LnMC hosts, and substantially weaker binding was observed with LaIII. X-ray crystallography revealed that the hydrophobic host cavity incompletely encapsulated FcC− when the guest was bound to the nine-coordinate LaIII, suggesting the LnMC’s ligand side chains play a substantial role in guest recognition. With knowledge of the MC-FcC− solution thermodynamics, the binding affinity of a redox inactive guest was then assessed. Addition of sodium benzoate to a LnMC and FcC− mixture resulted in E1/2 shifting back to the value observed for FcC− in the absence of LnMC. The association constants between benzoate and LnMC’s were calculated via the competitive binding approach. Comparison with literature values suggests this novel assay is a viable method for determining association constants for host–guest systems that exhibit the proper electrochemical behavior. Notably, this CV competitive binding approach does not require the preparation of a modified electrode or a tethered guest, and thus can be generalized to a number of host–guest systems.
Co-reporter:Joseph Jankolovits;JeffW. Kampf Dr.;Stephen Maldonado ;VincentL. Pecoraro
Chemistry - A European Journal 2010 Volume 16( Issue 23) pp:
Publication Date(Web):
DOI:10.1002/chem.201090108
Co-reporter:Dr. Kosh P. Neupane ;Dr. Vincent L. Pecoraro
Angewandte Chemie 2010 Volume 122( Issue 44) pp:8353-8356
Publication Date(Web):
DOI:10.1002/ange.201004429
Co-reporter:Dr. Kosh P. Neupane ;Dr. Vincent L. Pecoraro
Angewandte Chemie International Edition 2010 Volume 49( Issue 44) pp:8177-8180
Publication Date(Web):
DOI:10.1002/anie.201004429
Co-reporter:Choong-Sun Lim, Jeff W. Kampf and Vincent L. Pecoraro
Inorganic Chemistry 2009 Volume 48(Issue 12) pp:5224-5233
Publication Date(Web):May 8, 2009
DOI:10.1021/ic9001829
The reaction of l-phenylalanine hydroxamic acid (H2l-pheHA) with copper(II) and lanthanide(III) salts yields 15-Metallacrown-5 structures of the general composition Ln(X)n[Cu(II)(l-pheHA)]5(3−n)+ where X can represent a wide variety of anions. With five copper ions and one central lanthanide ion, the Ln[15-MC-5] complexes have multiple positions where these anionic guests may bind to the metallacrown host. In addition, these metallacrowns are amphiphilic, containing one face that is primarily hydrophobic (due to the five benzyl side chains which are oriented upon the same face of the molecule) and a face that is hydrophilic which has no impediment to solvent access. While it has been known that aromatic carboxylates bind preferentially to the hydrophobic face and short chain aliphatic carboxylates bind preferentially to the hydrophilic face, there have been no quantitative assessments of the stability of these host−guest complexes. Using Isothermal Calorimetry (ITC) we have determined the binding constants for several carboxylate anions to a variety of metallacrown complexes. The affinities of anions that coordinate to the lanthanide ion on the hydrophobic face are related to the hydrophobicities of the guests, with higher binding strength observed for the more hydrophobic carboxylates. Central metal such as La(III) or Nd(III) which are nine coordinate are able to accommodate two guests on the hydrophobic side; however, central metals such as Gd(III) or Dy(III) which are eight coordinate are limited to encapsulating one guest into the hydrophobic pocket. A second guest, bound to the hydrophilic face is often observed with these 8-coordinate lanthanides. The significantly weaker second binding constant between benzoate and Gd(III)[15-MC-5] supports the model that the second benzoate binds to the central metal through the hydrophilic side. Unlike the Gd(III)[15-MC-5], the higher binding constant of the second benzoate with La(III)[15-MC-5] is consistent with the crystallographic model which shows that the second guest binds to the hydrophobic side.
Co-reporter:Anna F. A. Peacock, Olga Iranzo and Vincent L. Pecoraro
Dalton Transactions 2009 (Issue 13) pp:2271-2280
Publication Date(Web):16 Jan 2009
DOI:10.1039/B818306F
Advances in protein chemistry and molecular and structural biology have empowered modern chemists to build complex biological architectures using a “first principles” approach, which is known as de novoprotein design. In this Perspective we demonstrate how simple three-stranded α-helical constructs can be prepared by the sole consideration of the primary amino acid sequence of a peptide. With these well defined systems, we then demonstrate that metal binding cavities can be carved out of the hydrophobic cores of these aggregates in order to bind metal ions such as cadmium with well defined coordination geometries. Examples will be given of homoleptic CdS3 complexes, CdS3O sites and proteins which contain equilibrium mixtures of these two species. We will provide a description of a strategy that allows us to build heterochromic peptides (small proteins that complex two metals in nearly identical environments but which result in different physical properties and allow for metal site selectivity). We conclude with a new class of designed peptides, diastereopeptides, which can exploit changes in amino acid chirality to control metal ion coordination number and lead to an alternative path towards heterochromic systems. The constructs described herein represent the initial steps of preparing protein structures that may simultaneous contain structural and catalytic metal binding centers. These studies inform the community on a developing field, which promises new opportunities for the study of bioinorganic chemistry.
Co-reporter:Jessica Gätjens, Christopher S. Mullins, Jeff W. Kampf, Pierre Thuéry and Vincent L. Pecoraro
Dalton Transactions 2009 (Issue 1) pp:51-62
Publication Date(Web):09 Oct 2008
DOI:10.1039/B809453E
We have synthesised and characterised a series of new CoII complexes (1–4, 6, 7) and one new ZnII complex (5) employing N3- and N3O-donor ligands [biap: N,N-bis(2-ethyl-5-methyl-imidazol-4-ylmethyl)amino-propane, KBPZG: potassium N,N-bis(3,5-dimethylpyrazolylmethyl) glycinate, KBPZA: potassium N,N-bis(3,5-dimethylpyrazolylmethyl) alaninate, KBiPrPZG: potassium N,N-bis(3,5-di-iso-propylpyrazolylmethyl) glycinate, and KB(tBuM)PZG: potassium N,N-bis(3-methyl-5-tert-butyl-pyrazolylmethyl)glycinate] as structural models of the metalloenzyme α-amino-β-carboxymuconic-ε-semialdehyde decarboxylase (ACMSD). These complexes were characterised by several techniques including X-ray crystallographic analysis, X-band EPR, and mass spectrometry (ESI-MS). The crystal structures of 1, 2, 6, 7 revealed that they exist as mononuclear Co(II) complexes with trigonal-bipyramidal geometry in the solid state. Compounds 3 and 5 form infinite polymeric chains of CoII or ZnII complexes, respectively, linked by the pendant carboxylate arms of the BPZG− ligand. By comparing the degree of distortion in the penta-coordinate complexes, defined by the Addison-parameter τ, with the value determined for the five-coordinate centres found in the active site of ACMSD, it could be seen that complexes 5 and 7 are very good matches for the geometry of the zinc(II) centre in monomer A of the native enzyme. All complexes could be seen as model compounds for the active site of the enzyme ACMSD, where the Co(II) complexes reflected the structural flexibility found in case of two histidine (His177 and His228) residues found in the active site of the enzyme.
Co-reporter:Jessica Gätjens, Jeff W. Kampf, Vincent L. Pecoraro
Inorganica Chimica Acta 2009 Volume 362(Issue 3) pp:878-886
Publication Date(Web):20 February 2009
DOI:10.1016/j.ica.2008.02.006
Bernhard Lippert has contributed significantly to the understanding of metallamacrocyclic complexes with low valent, late transition metals. In particular, he has pioneered the preparation of metallacalixarenes such as 12-MC-3 and 16-MC-4 structure types. In this article, we provide the preparation of a new 16-MC-4, [Mn4Br4(B(tBuM)PZG)4] [Mn(HOCO2)2], complex made with the ligand potassium N,N-bis(3-methyl-5-tert-butylpyrazolylmethyl)glycinate (KB(tBuM)PZG). In addition to being the first 16-MC-4 that is composed of manganese, this complex is the first example of a transition metal [Mn(II)] being captured in the interior cavity of the 16-MC-4. We discuss how our ligand design leads to the isolated structure due to the steric bulk that has been appended to the pyrazole ligand.Rather than forming a discrete mononuclear species, the sterically encumbered ligand potassium N,N-bis(3-methyl-5-tert-butylpyrazolylmethyl)glycinate (KB(tBuM)PZG) reacts with Mn(II) to form what is best described as a Mn(II)(HCO3)2[16-MC-4] complex. This pentanuclear Mn(II) complex is the first 16-MC-4 to contain manganese and the only 16-MC-4 to capture a transition metal ion in the cavity. Each of the two “hinge” bicarbonates serve to sequester the central Mn(II) as well as bridge two of the four ring Mn(II) ions that form the metallacrown. This binding mode could model the interaction of bicarbonate with the photosynthetic Mn4Ca water oxidizing cluster.
Co-reporter:AnnaF.A. Peacock Dr.;JeanneA. Stuckey ;VincentL. Pecoraro
Angewandte Chemie 2009 Volume 121( Issue 40) pp:7507-7510
Publication Date(Web):
DOI:10.1002/ange.200902166
Co-reporter:AnnaF.A. Peacock Dr.;JeanneA. Stuckey ;VincentL. Pecoraro
Angewandte Chemie 2009 Volume 121( Issue 40) pp:
Publication Date(Web):
DOI:10.1002/ange.200990212
Co-reporter:Olga Iranzo Dr.;Tamas Jakusch Dr.;Kyung-Hoon Lee Dr.;Lars Hemmingsen ;VincentL. Pecoraro
Chemistry - A European Journal 2009 Volume 15( Issue 15) pp:3761-3772
Publication Date(Web):
DOI:10.1002/chem.200802105
Co-reporter:AnnaF.A. Peacock Dr.;JeanneA. Stuckey ;VincentL. Pecoraro
Angewandte Chemie International Edition 2009 Volume 48( Issue 40) pp:7371-7374
Publication Date(Web):
DOI:10.1002/anie.200902166
Co-reporter:AnnaF.A. Peacock Dr.;JeanneA. Stuckey ;VincentL. Pecoraro
Angewandte Chemie International Edition 2009 Volume 48( Issue 40) pp:
Publication Date(Web):
DOI:10.1002/anie.200990210
Co-reporter:Vincent L. Pecoraro ;Wen-Yuan Hsieh
Inorganic Chemistry 2008 Volume 47(Issue 6) pp:1765-1778
Publication Date(Web):March 10, 2008
DOI:10.1021/ic7017488
Significant progress in the understanding of biological water oxidation has occurred during the past 25 years. Today we have a somewhat clearer description of the structure of the Mn4Ca cluster and an idea of the appropriate oxidation states for the enzyme during catalysis. At issue is the mechanism of water oxidation. Depending on one’s belief of the manganese ion oxidation levels at the catalytically active S4 configuration, one can invoke a variety of different processes that could lead to water oxidation. We have suggested that the most likely process is the nucleophilic attack of a water bound to calcium (or manganese) onto a highly electrophilic MnV═O center. In this Article, we explore the difficulties of preparing MnV in dimeric systems and the even more arduous task of definitively assigning oxidation states to such highly reactive species.
Co-reporter:Marciela Scarpellini ; Jessica Gätjens ; Ola J. Martin △; Jeff W. Kampf ; Suzanne E. Sherman △
Inorganic Chemistry 2008 Volume 47(Issue 9) pp:3584-3593
Publication Date(Web):April 10, 2008
DOI:10.1021/ic701953g
In view of the biological and commercial interest in models for Oxalate Decarboxylases (OxDC) and Oxalate Oxidases (OxOx), we have synthesized and characterized three new MnII complexes (1−3) employing N3O-donor amino-carboxylate ligands (TCMA, 1,4,7-triazacyclononane-N-acetic acid; KiPr2TCMA, potassium 1,4-diisopropyl-1,4,7-triazacyclononane-N-acetate; and KBPZG, potassium N,N-bis(3,5-dimethylpyrazolyl methyl)glycinate). These complexes were characterized by several techniques including X-ray crystallographic analysis, X-band electron paramagnetic resonance (EPR), electrospray ionization mass spectrometry (ESI-MS), and cyclic voltammetry. The crystal structures of 1 and 3 revealed that both form infinite polymeric chains of MnII complexes linked by the pendant carboxylate arms of the TCMA− and the BPZG− ligands in a syn-antipattern. Complex 2 crystallizes as a mononuclear MnII cation, six-coordinate in a distorted octahedral geometry. Although complexes 1 and 3 crystallize as polymeric chains, all compounds present the same N3O-donor set atoms around the metal center as observed in the crystallographically characterized OxDC and OxOx. Moreover, complex 2 also contains two water molecules coordinated to the Mn center as observed in the active site of OxDC and OxOx. ESI-MS spectrometry, combined with EPR, were useful techniques to establish that complexes 1−3 are present as mononuclear MnII species in solution. Finally, complexes 1−3 are able to model the resting state active sites, with special attention focused on complex 2 which provides the first exact first coordination sphere ligand structural model for the resting states of both OxDC and OxOx.
Co-reporter:Curtis M. Zaleski ; ; Tsu-Chen Weng ; ; Catherine Dendrinou-Samara ; ; Maria Alexiou ; ; Paraskevi Kanakaraki ; ; Wen-Yuan Hsieh ; ; Jeff Kampf ; ; James E. Penner-Hahn ; ; Vincent L. Pecoraro ; ;Dimitris P. Kessissoglou ;
Inorganic Chemistry 2008 Volume 47(Issue 14) pp:6127-6136
Publication Date(Web):June 7, 2008
DOI:10.1021/ic702109c
Two tetranuclear Mn complexes with an average Mn oxidation state of +2.5 have been prepared. These valence isomers have been characterized by a combination of X-ray crystallography, X-ray absorption spectroscopy, and magnetic susceptibility. The Mn II 3Mn IV tetramer has the Mn ions arranged in a distorted tetrahedron, with an S = 6 ground spin state, dominated by ferromagnetic exchange among the manganese ions. The Mn II 2Mn III 2 tetramer also has a distorted tetrahedral arrangement of Mn ions but shows magnetic behavior, suggesting that it is a single-molecule magnet. The X-ray absorption near-edge structure (XANES) spectra for the two complexes are similar, suggesting that, while Mn XANES has sufficient sensitivity to distinguish between trinuclear valence isomers (Alexiou et al. Inorg. Chem. 2003, 42, 2185), similar distinctions are difficult for tetranuclear complexes such as that found in the photosynthetic oxygen-evolving complex.
Co-reporter:Marek Łuczkowski ; Monika Stachura ; Virgil Schirf ; Borries Demeler ; Lars Hemmingsen
Inorganic Chemistry 2008 Volume 47(Issue 23) pp:10875-10888
Publication Date(Web):October 28, 2008
DOI:10.1021/ic8009817
A de novo protein design strategy provides a powerful tool to elucidate how heavy metals interact with proteins. Cysteine derivatives of the TRI peptide family (Ac-G(LKALEEK)4G-NH2) have been shown to bind heavy metals in an unusual trigonal geometry. Our present objective was to design binding sites in α-helical scaffolds that are able to form higher coordination number complexes with Cd(II) and Hg(II). Herein, we evaluate the binding of Cd(II) and Hg(II) to double cysteine substituted TRI peptides lacking intervening leucines between sulfurs in the heptads. We compare a -Cysd-X-X-X-Cysa- binding motif found in TRIL12CL16C to the more common -Cysa-X-X-Cysd- sequence of native proteins found in TRIL9CL12C. Compared to TRI, these substitutions destabilize the helical aggregates, leading to mixtures of two- and three-stranded bundles. The three-stranded coiled coils are stabilized by the addition of metals. TRIL9CL12C forms distorted tetrahedral complexes with both Cd(II) and Hg(II), as supported by UV−vis, CD, 113Cd NMR, 199Hg NMR and 111mCd PAC spectroscopy. Additionally, these signatures are very similar to those found for heavy metal substituted rubredoxin. These results suggest that in terms of Hg(II) binding, TRIL9CL12C can be considered as a good mimic of the metallochaperone HAH1, that has previously been shown to form protein dimers. TRIL12CL16C has limited ability to generate homoleptic tetrahedral complexes (Cd(SR)42−). These type of complexes were identified only for Hg(II). However, the spectroscopic signatures suggest a different geometry around the metal ion, demonstrating that effective metal sequestration into the hydrophobic interior of the bundle requires more than simply adding two sulfur residues in adjacent layers of the peptide core. Thus, proper design of metal binding sites must also consider the orientation of cysteine sidechains in a vs d positions of the heptads.
Co-reporter:Anna F. A. Peacock;Lars Hemmingsen
PNAS 2008 Volume 105 (Issue 43 ) pp:16566-16571
Publication Date(Web):2008-10-28
DOI:10.1073/pnas.0806792105
Here, we report a previously undescribed approach for controlling metal ion coordination geometry in biomolecules by reorientating
amino acid side chains through substitution of L- to D-amino acids. These diastereopeptides allow us to manipulate the spatial
orientation of amino acid side chains to alter the sterics of metal binding pockets. We have used this approach to design
the de novo metallopeptide, Cd(TRIL12LDL16C)3−, which is an example of Cd(II) bound to 3 L-Cys as exclusively trigonal CdS3, as characterized by a combination of 113Cd NMR and 111mCd PAC spectroscopy. We subsequently show that the physical properties of such a site, such as the high pKa2 for Cd(II) binding of 15.1, is due to the nature of the coordination number and not the ligating group. Further more this
approach allowed for the design of a construct, GRANDL12LDL16CL26AL30C, capable of independently binding 2 equivalents of Cd(II) to 2 very similar Cys sites as exclusively 3- and 4-,
CdS3 and CdS3O, respectively. Demonstrating that we are capable of controlling the Cd(II) coordination number in these 2 sites solely by
varying the nature of a noncoordinating second coordination sphere amino acid, with D-leucine and L-alanine resulting in exclusively
3- and 4-coordinate structures, respectively. Cd(II) was found to selectively bind to the 4-coordinate CdS3O site, demonstrating that a protein can be designed that displays metal-binding selectivity based solely on coordination
number control and not on the chemical identity of coordinating ligands.
Co-reporter:Gellert Mezei, Jeff W. Kampf, Shilie Pan, Kenneth R. Poeppelmeier, Byron Watkins and Vincent L. Pecoraro
Chemical Communications 2007 (Issue 11) pp:1148-1150
Publication Date(Web):10 Jan 2007
DOI:10.1039/B614024F
Upon crystallization in high yields, metallacrowns form compartments that are capable of asymmetrically encapsulating three isonicotinate guests.
Co-reporter:Tereza Afrati, Curtis M. Zaleski, Catherine Dendrinou-Samara, Gellert Mezei, Jeff W. Kampf, Vincent L. Pecoraro and Dimitris P. Kessissoglou
Dalton Transactions 2007 (Issue 25) pp:2658-2668
Publication Date(Web):24 Apr 2007
DOI:10.1039/B700902J
The use of di-2-pyridyl ketone oxime (Hpko)/X−
“blends” (X− = OH−, Cl−, ClO4−) in copper chemistry has yielded neutral binuclear and cationic trinuclear, pentanuclear or hexanuclear complexes. Various synthetic procedures have led to the synthesis of compounds [Cu5(pko)7]·[ClO4]3·2CH3OH·2H2O (1), [Cu3(pko)3(OH)(Cl)]2[Ph4B]2·4DMF·2H2O (2), [Cu2(pko)4] (3), {[Cu6(pko)6ClO4(CH3CN)6][Cu6(pko)6(ClO4)3(CH3CN)4]}·8ClO4·14CH3CN·H2O (4). The structures of the complexes have been determined by single-crystal X-ray crystallography.
Co-reporter:Gellert Mezei, Jeff W. Kampf and Vincent L. Pecoraro
New Journal of Chemistry 2007 vol. 31(Issue 3) pp:439-446
Publication Date(Web):08 Feb 2007
DOI:10.1039/B615273B
Five new dicarboxylic acid-functionalized pseudorotaxanes, comprised of a bis(1,5-naphtho)-38-crown-10 ring-component and a N,N′-di(n-carboxyalkyl)-4,4′-bipyridinium dihexafluorophosphate (n = 4 or 5, alkyl = butyl or pentyl) rod-component, have been synthesized and characterized by UV-Vis and 1H-NMR spectroscopic, ESI-MS and/or X-ray crystallographic methods. Depending on the temperature of crystallization and the molar ratio between the N,N′-di(4-carboxybutyl)-4,4′-bipyridinium rod and the crown ether, three different polymorphs were obtained. In the case of the N,N′-di(5-carboxypentyl)-4,4′-bipyridinium rod, two different pseudorotaxane-structures were obtained at different temperatures and in the presence of one or two different counterions. The latter one is an unprecedented example of a pseudorotaxane in which the bipyridinium rod is not sandwiched in-between the crown ether ring’s two naphthalene units, as expected, but forms intermolecular π–π interactions with neighboring pseudorotaxanes.
Co-reporter:Choong-Sun Lim;Annabel Cutl Van Noord;Jeff W. Kampf
European Journal of Inorganic Chemistry 2007 Volume 2007(Issue 10) pp:
Publication Date(Web):26 FEB 2007
DOI:10.1002/ejic.200700054
15-MC-5 complexes associate in the solid state to form chiral compartments capable of binding guests. Using small molecular yardsticks, we are able to assess the size restrictions of these structures. Dicarboxylate guests that are too short to span the GdIII ions are stabilized by solvates that hydrogen bond to the uncoordinated carboxylate, while guests that are too long destroy the weakly associated structure. We also demonstrate that all that is required for guest encapsulation is unsaturation of the chain connection carboxylates rather than necessitating the presence of aromaticity. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Co-reporter:Olga Iranzo Dr.;Peter W. Thulstrup ;Seung-baek Ryu;Lars Hemmingsen ;Vincent L. Pecoraro
Chemistry - A European Journal 2007 Volume 13(Issue 33) pp:
Publication Date(Web):25 OCT 2007
DOI:10.1002/chem.200701208
The use of de novo designed peptides is a powerful strategy to elucidate HgII–protein interactions and to gain insight into the chemistry of HgII in biological systems. Cysteine derivatives of the designed α-helical peptides of the TRI family [Ac-G-(LaKbAcLdEeEfKg)4-G-NH2] bind HgII at high pH values and at peptide/HgII ratios of 3:1 with an unusual trigonal thiolate coordination mode. The resulting HgII complexes are good water-soluble models for HgII binding to the protein MerR. We have carried out a parallel study using 199Hg NMR and 199mHg perturbed angular correlation (PAC) spectroscopy to characterize the distinct species that are generated under different pH conditions and peptide TRI L9C/HgII ratios. These studies prove for the first time the formation of [Hg{(TRI L9C)2-(TRI L9CH)}], a dithiolate–HgII complex in the hydrophobic interior of the three-stranded coiled coil (TRI L9C)3. 199Hg NMR and 199mHg PAC data demonstrate that this dithiolate–HgII complex is different from the dithiolate [Hg(TRI L9C)2], and that the presence of third α-helix, containing a protonated cysteine, breaks the symmetry of the coordination environment present in the complex [Hg(TRI L9C)2]. As the pH is raised, the deprotonation of this third cysteine generates the trigonal thiolate–HgII complex Hg(TRI L9C)3− on a timescale that is slower than the NMR timescale (0.01–10 ms). The formation of the species [Hg{(TRI L9C)2(TRI L9CH)}] is the result of a compromise between the high affinity of HgII to form dithiolate complexes and the preference of the peptide to form a three-stranded coiled coil.
Co-reporter:Vincent L. Pecoraro;Jeanne A. Stuckey;Christer E. Nordman;Debra S. Touw
PNAS 2007 Volume 104 (Issue 29 ) pp:11969-11974
Publication Date(Web):2007-07-17
DOI:10.1073/pnas.0701979104
Arsenic, a contaminant of water supplies worldwide, is one of the most toxic inorganic ions. Despite arsenic's health impact,
there is relatively little structural detail known about its interactions with proteins. Bacteria such as Escherichia coli have evolved arsenic resistance using the Ars operon that is regulated by ArsR, a repressor protein that dissociates from
DNA when As(III) binds. This protein undergoes a critical conformational change upon binding As(III) with three cysteine residues.
Unfortunately, structures of ArsR with or without As(III) have not been reported. Alternatively, de novo designed peptides can bind As(III) in an endo configuration within a thiolate-rich environment consistent with that proposed
for both ArsR and ArsD. We report the structure of the As(III) complex of Coil Ser L9C to a 1.8-Å resolution, providing x-ray
characterization of As(III) in a Tris thiolate protein environment and allowing a structural basis by which to understand
arsenated ArsR.
Co-reporter:Olga Iranzo Dr.;Chris Cabello;Vincent L. Pecoraro
Angewandte Chemie 2007 Volume 119(Issue 35) pp:
Publication Date(Web):28 AUG 2007
DOI:10.1002/ange.200790171
Heterochromie bezeichnet die genetisch bedingte Verschiedenfarbigkeit der Augen mancher Individuen. Analog unterscheiden sich die physikalischen Eigenschaften nahezu identischer Metallbindungsstellen in heterochromen Peptiden, für die V. L. Pecoraro et al. in ihrer Zuschrift auf S. 6808 ff. ein Beispiel vorstellen, nach der Metallbindung. Das Titelbild zeigt ein de novo entworfenes heterochromes Peptid, das zwei CdII-Ionen in unterschiedlichen Koordinationsgeometrien bindet.
Co-reporter:Olga Iranzo Dr.;Chris Cabello;Vincent L. Pecoraro
Angewandte Chemie International Edition 2007 Volume 46(Issue 35) pp:
Publication Date(Web):20 JUN 2007
DOI:10.1002/anie.200701729
Molecular recognition and control of the physical properties of metal ions are major challenges in metalloprotein design. The newly designed peptide Grand L16PenL26AL30C binds two CdII ions, each with a different coordination geometry—trigonal planar or pseudotetrahedral (see picture; Cd purple, S yellow, O blue). The physical properties of the two centers, such as site selectivity and pH dependence of binding, differ as well.
Co-reporter:Olga Iranzo Dr.;Chris Cabello;Vincent L. Pecoraro
Angewandte Chemie International Edition 2007 Volume 46(Issue 35) pp:
Publication Date(Web):28 AUG 2007
DOI:10.1002/anie.200790171
Heterochromia is a genetic condition that causes individuals to have eyes of different colors. In the same way, nearly identical metal-binding sites in heterochromic peptides, an example of which is presented by V. L. Pecoraro and co-workers in their Communication on page 6688 ff., display different physical properties after metal binding. The cover picture shows a de novo designed heterochromic peptide that binds two CdII ions, each with a different coordination geometry.
Co-reporter:Olga Iranzo Dr.;Chris Cabello;Vincent L. Pecoraro
Angewandte Chemie 2007 Volume 119(Issue 35) pp:
Publication Date(Web):20 JUN 2007
DOI:10.1002/ange.200701729
Molekulare Erkennung und gezielt einstellbare physikalische Eigenschaften der Metallionen zählen zu den großen Herausforderungen beim Metalloprotein-Design. Das neuartige Peptid Grand L16PenL26AL30C bindet zwei CdII-Ionen mit unterschiedlicher Koordinationsgeometrie – trigonal planar oder pseudotetraedrisch (siehe Bild; Cd violett, S gelb, O blau). Die physikalischen Eigenschaften der beiden Zentren, z. B. Ortsselektivität und pH-Abhängigkeit der Bindung, unterscheiden sich ebenfalls.
Co-reporter:Kyung-Hoon Lee Dr.;Chris Cabello;Lars Hemmingsen ;E. Neil G. Marsh
Angewandte Chemie 2006 Volume 118(Issue 18) pp:
Publication Date(Web):5 APR 2006
DOI:10.1002/ange.200504548
Wie unnatürlich: Peptide der TRI-Familie können durch Austausch nur eines Aminosäurerestes in der Primärsequenz die Koordinationszahl eines Metallzentrums kontrollieren. Der Ersatz eines Cysteinrestes durch Penicillamin führt zu dreifach koordinierten CdIIS3-Komplexen, während bei Alanin-Substitution eines Leucinrestes vierfach koordiniertes CdIIS3O resultiert (siehe Schema).
Co-reporter:Kyung-Hoon Lee Dr.;Chris Cabello;Lars Hemmingsen ;E. Neil G. Marsh
Angewandte Chemie International Edition 2006 Volume 45(Issue 18) pp:
Publication Date(Web):5 APR 2006
DOI:10.1002/anie.200504548
It isn't natural: TRI peptides can selectively control the coordination number of a metal center by changing only one of the amino acids in the primary sequence. Replacement of the cysteine residue with penicillamine leads to a three-coordinate complex CdIIS3, whereas substitution of alanine for leucine gives four-coordinate CdS3O (see scheme).
Co-reporter:Curtis M. Zaleski;Ezra C. Depperman;Jeff W. Kampf Dr.;Martin L. Kirk
Angewandte Chemie International Edition 2004 Volume 43(Issue 30) pp:
Publication Date(Web):20 JUL 2004
DOI:10.1002/anie.200454013
The largest known Dy–Mn complex is [DyIII6MnIII4MnIV2(H2shi)4(Hshi)2(shi)10] (H3shi is salicylhydroxamic acid; see stereopicture). The Dy ions are arranged in a nearly planar hexagonal ring and are capped on opposite sides by a MnIII2MnIV trimer. This mixed-metal topology provides a new structure class for the examination of interesting magnetic phenomena of individual molecules.
Co-reporter:Curtis M. Zaleski;Ezra C. Depperman;Jeff W. Kampf Dr.;Martin L. Kirk
Angewandte Chemie 2004 Volume 116(Issue 30) pp:
Publication Date(Web):20 JUL 2004
DOI:10.1002/ange.200454013
Der größte bekannte Dy-Mn-Komplex ist [DyIII6MnIII4MnIV2(H2shi)4(Hshi)2(shi)10] (H3shi=Salicylhydroxamsäure; siehe Stereobild). Die Dysprosiumionen bilden einen nahezu planaren Sechsring, wobei zwei von ihnen durch MnIII2MnIV-Trimere überdacht sind. Diese Topologie bietet eine neue Strukturklasse, an der interessante magnetische Phänomene von Einzelmolekülen untersucht werden können.
Co-reporter:T. M. Rajendiran, Martin L. Kirk, Ika A. Setyawati, M. Tyler Caudle, Jeff W. Kampf and Vincent L. Pecoraro
Chemical Communications 2003 (Issue 7) pp:824-825
Publication Date(Web):05 Mar 2003
DOI:10.1039/B212684M
Binuclear manganese complexes Mn2(III/IV)(dtsalpn)2DCBI, 1, Mn2(III/III)(dtsalpn)2HDCBI, 2, containing the ligand dicarboxyimidazole (DCBI) have been prepared in order to address the issue of imidazole bridged and ferromagnetically coupled Mn sites in high oxidation states of the OEC in Photosystem II (PS II). Temperature dependent magnetic susceptibility studies of 1 indicates that the interaction between the two Mn(III)/Mn(IV) ions is ferromagnetic (J = + 1.4 cm−1). Variable temperature EPR spectra of 1 shows that a g = 2 multiline is as an excited state signal corresponding to S =1/2.
Co-reporter:Wojciech Lesniak, John Mc Laren, Wesley R Harris, Vincent L Pecoraro, Jochen Schacht
Carbohydrate Research 2003 Volume 338(Issue 24) pp:2853-2862
Publication Date(Web):21 November 2003
DOI:10.1016/j.carres.2003.08.005
A simple method for the separation of the major components of commercial gentamicin sulfate (C-1, C-1a, C-2, C-2a) by high-performance liquid chromatography (HPLC) on an analytical and a semipreparative scale was developed. The method utilized ion-pair reversed-phase chromatography, isocratic elution with an aqueous solution containing 9% trifluroacetic acid and 2.5% acetonitrile as the mobile phase at a flow rate of 2 and 9 mL/min for analytical and semipreparative columns, respectively. Detection was carried out at 213 nm without derivatization. The protonation pattern of the separated gentamicins was determined by potentiometry and 15N and 1H NMR. The full proton NMR assignment for gentamicin C-1 was obtained through the use of 1H 1D and 2D 1H–1H COSY measurements.A simple method for the separation of the major components of commercial gentamicin by HPLC was developed. The protonation pattern of the separated gentamicins was determined by potentiometry, 15N and 1H NMR. The full proton NMR assignment for gentamicin C-1 was achieved through the use of 1H 1D and 2D 1H–1H COSY measurements.
Co-reporter:Catherine Dendrinou-Samara Dr.;Maria Alexiou;Curtis M. Zaleski;Jeff W. Kampf Dr.;Martin L. Kirk ;Dimitris P. Kessissoglou
Angewandte Chemie 2003 Volume 115(Issue 32) pp:
Publication Date(Web):13 AUG 2003
DOI:10.1002/ange.200351246
Ein Metallacryptat mit 26 Manganzentren in zwei Oxidationsstufen wird bei der Reaktion von Mangan(II)-chlorid mit Natriumhydroxid, Di-(2-pyridyl)-ketonoxim und Natriumazid erhalten (siehe Bild; 4 MnII: gold und 22 MnIII: grün, blau und violett). In ac-SQUID-Messungen zeigt die Komplexverbindung Einzelmolekül-Magnetismus.
Co-reporter:James A. Johnson;Jeff W. Kampf Dr.
Angewandte Chemie 2003 Volume 115(Issue 5) pp:
Publication Date(Web):30 JAN 2003
DOI:10.1002/ange.200390125
L- oder D-Norvalinhydroxamsäuren bilden in einstufigen Reaktionen mit Acetat-, Chlorid- und CuII-Ionen selbstorganisierte Metallahelicate, die zwanzig asymmetrische Kohlenstoff- und vier asymmetrische Metallzentren enthalten. Es wurden enantiomerenreine Komplexe von über 3 nm Länge isoliert, die aus doppelsträngigen helicalen Oligomeren mit entweder P- oder M-Helizität bestehen (siehe Bild).
Co-reporter:Catherine Dendrinou-Samara Dr.;Maria Alexiou;Curtis M. Zaleski;Jeff W. Kampf Dr.;Martin L. Kirk ;Dimitris P. Kessissoglou
Angewandte Chemie International Edition 2003 Volume 42(Issue 32) pp:
Publication Date(Web):13 AUG 2003
DOI:10.1002/anie.200351246
Crypt analysis: The reaction of manganese(II) chloride with sodium hydroxide, di-(2-pyridyl)-ketonoxime, and sodium azide yields a metallacryptate consisting of 26 manganese centers, namely, four MnII (see picture; gold spheres) and 22 MnIII ions (green, aqua, and blue spheres). Results obtained from ac SQUID magnetic studies indicate that this molecule displays single-molecule magnetic behavior.
Co-reporter:Vincent L. Pecoraro;Brian T. Farrer
PNAS 2003 Volume 100 (Issue 7 ) pp:3760-3765
Publication Date(Web):2003-04-01
DOI:10.1073/pnas.0336055100
A detailed kinetic analysis of metal encapsulation by a de novo-designed protein is described. The kinetic mechanism of Hg(II) encapsulation in the three-stranded coiled coil formed by
the peptide CH3CO-G LKALEEK CKALEEK LKALEEK G-NH2 (Baby L9C) is derived by global analysis. The mechanism involves rapid initial collapse of two peptides by Hg(II) forming
Hg(Baby L9C-H)2 with a linear thiolato Hg(II) bound to the cysteine sulfur atoms. Here, Baby L9C-H denotes Baby L9C with the cysteine thiol deprotonated. Addition of the third peptide, forming the three-stranded coiled coil,
is the rate-determining step and results in an intermediate state involving two separate species. One of the species, termed
the properly folded intermediate, undergoes rapid deprotonation of the third cysteine thiol, yielding the desired three-stranded
coiled coil with an encapsulated trigonal thiolato Hg(II). The other species, termed the misfolded intermediate, rearranges
in an experimentally distinguishable step to the properly folded intermediate. The order of the reaction involving the addition
of the third peptide with respect to the concentration of Baby L9C indicates that addition of the third helix only occurs
through reaction of Hg(Baby L9C-H)2 and Baby L9C that is unassociated with a coiled coil. Temperature dependence of the reaction afforded activation parameters
for both the addition of the third helix (ΔH‡ = 20(2) kcal/mol; ΔS‡ = 40(5) cal/mol K) and the rearrangement of the misfolded intermediate steps (ΔH‡ = 23(2) kcal/mol; ΔS‡ = 27(5) cal/mol K). The mechanism is discussed with regard to metalloprotein folding and metalloprotein design.
Co-reporter:James A. Johnson;Jeff W. Kampf Dr.
Angewandte Chemie International Edition 2003 Volume 42(Issue 5) pp:
Publication Date(Web):30 JAN 2003
DOI:10.1002/anie.200390157
Both L- or D-norvaline hydroxamic acids undergo one-step reactions with acetate, chloride, and CuII ions to form self-assembled metallahelicates that contain 20 chiral carbon and four chiral metal centers. Enantiopure complexes of over three nanometers in length, and composed of either P- or M-type double-stranded helical oligomers (see scheme), have been isolated.
Co-reporter:Thomas S. Smith II, Russell LoBrutto, Vincent L. Pecoraro
Coordination Chemistry Reviews 2002 Volume 228(Issue 1) pp:1-18
Publication Date(Web):17 May 2002
DOI:10.1016/S0010-8545(01)00437-4
Co-reporter:Annabel D. Cutl-Van Noord;Jeff W. Kampf Dr.
Angewandte Chemie 2002 Volume 114(Issue 24) pp:
Publication Date(Web):12 DEC 2002
DOI:10.1002/ange.200290009
Die Konfiguration des Liganden bestimmt die Struktur der Helix: Koordination einer Kette aus [15]Metallakrone-5-Komplexen mit Phenylalaninhydroxamsäure-Grundgerüst resultiert in einer amphiphilen Metallohelix mit 41-Schraubenachse. Die Verwendung des L-Isomers der Säure ergibt die rechtshändige Helix (siehe linke Struktur), während das D-Isomer zur Spiegelbildstruktur führt.
Co-reporter:Annabel D. Cutl-Van Noord;Jeff W. Kampf Dr.
Angewandte Chemie International Edition 2002 Volume 41(Issue 24) pp:
Publication Date(Web):12 DEC 2002
DOI:10.1002/anie.200290010
The chirality of the ligand determines the nature of the helix: Coordination of a chain of [15]metallacrown-5 complexes based on phenylalanine hydroxamic acid results in an amphiphilic metallohelix with a 41 screw axis. The use of the L isomer of the acid gives the right-handed helix (see left structure) while the D isomer gives the mirror image structure.
Co-reporter:Annabel D. Cutl;Roneil G. Malkani;Jeff W. Kampf;Vincent L. Pecoraro
Angewandte Chemie 2000 Volume 112(Issue 15) pp:
Publication Date(Web):2 AUG 2000
DOI:10.1002/1521-3757(20000804)112:15<2801::AID-ANGE2801>3.0.CO;2-B
Co-reporter:Charles F Yocum, Vincent L Pecoraro
Current Opinion in Chemical Biology 1999 Volume 3(Issue 2) pp:182-187
Publication Date(Web):1 April 1999
DOI:10.1016/S1367-5931(99)80031-3
Developments in manganese biochemistry have centered on the discovery of new manganese enzymes, X-ray analysis of binuclear manganese enzymes, and the discovery of new spectroscopic signatures for the oxygen-evolving complex. Despite these gains, many questions regarding the structure, composition and redox state of the oxygen-evolving complex remain unanswered.
Co-reporter:Jefferson S. Plegaria, Christian Herrero, Annamaria Quaranta, Vincent L. Pecoraro
Biochimica et Biophysica Acta (BBA) - Bioenergetics (May 2016) Volume 1857(Issue 5) pp:522-530
Publication Date(Web):May 2016
DOI:10.1016/j.bbabio.2015.09.007
Co-reporter:Kosh P. Neupane, Vincent L. Pecoraro
Journal of Inorganic Biochemistry (August 2011) Volume 105(Issue 8) pp:1030-1034
Publication Date(Web):1 August 2011
DOI:10.1016/j.jinorgbio.2011.04.010
207Pb NMR spectroscopy can be used to monitor the binding of Pb(II) to thiol rich biological small molecules such as glutathione and to zinc finger proteins. The UV/visible (UV/Vis) absorption band centered at 334 nM and the observed 207Pb signal in 207Pb NMR (δ ~ 5750 ppm) indicate that glutathione binds Pb(II) in a trigonal pyramidal geometry (PbS3) at pH 7.5 or higher with a 1:3 molar ratio of Pb(II) to GSH. While previous studies using UV/Vis and extended X-ray absorption fine structure (EXAFS) spectroscopy were interpreted to show that the zinc binding domain from HIV nucleocapsid protein (HIV-CCHC) binds Pb(II) in a single PbS3 environment, the more sensitive 207Pb NMR spectra (at pH 7.0, 1:1 molar ratio) provide compelling evidence for the presence of two PbS3 structures (δ - 5790 and 5744 ppm), one of which is more stable at high temperatures. It has previously been proposed that the HIV-CCHH peptide does not fold properly to afford a PbS2N motif, because histidine does not bind to Pb(II). These predictions are confirmed by the present studies. These results demonstrate the applicability of 207Pb NMR to biomolecular structure determination in proteins with cysteine binding sites for the first time.207Pb NMR of His → Gly substituted zinc binding domain of HIV retrovirus nucleocapsid protein (HIV-CCGC) showing the peptide folded in two conformations.Download full-size image
Co-reporter:Fangting Yu, Vincent L. Pecoraro
Polyhedron (12 November 2013) Volume 64() pp:99-105
Publication Date(Web):12 November 2013
DOI:10.1016/j.poly.2013.02.074
•First direct evidence of a manganyl species in the mixed-valent [Mn(2-OH Salpn)]2 series.•The use of a mechanistic probe to demonstrate the formation of a fleeting intermediate MnIVMnVO.•Directly relevant to the chemistry that might occur during photosynthetic water oxidation.High-valent Mn species are key intermediates in the oxygen evolving complex in photosystem II. In some mechanisms, the MnVO moiety is proposed to be a critical species at the final step of oxygen production. This work reports the use of a mechanistic probe 2-methyl-1-phenylpropan-2-yl hydroperoxide (MPPH) to distinguish the formation of MnIVMnIV(OH) and MnIVMnVO species. We demonstrate that a dimeric Mn complex [MnIIIMnIV(2-OH-3,5-diClsalpn)]+ reacts with MPPH, leading to the production of the O–O bond heterolysis product. In this process, the Mn complex transforms into a transient MnIVMnVO species, which undergoes comproportionation rapidly.We use a mechanistic probe 2-methyl-1-phenylpropan-2-yl hydroperoxide (MPPH) to investigate the formation of a transient manganyl species in a dimeric Mn complex, which is a synthetic model for the oxygen evolving complex in photosystem II. We have obtained the first direct evidence of a manganyl species in the mixed-valent [Mn(2-OH Salpn)]2 series.Download full-size image
Co-reporter:Chun Y. Chow, Hélène Bolvin, Victoria E. Campbell, Régis Guillot, Jeff W. Kampf, Wolfgang Wernsdorfer, Frédéric Gendron, Jochen Autschbach, Vincent L. Pecoraro and Talal Mallah
Chemical Science (2010-Present) 2015 - vol. 6(Issue 8) pp:NaN5087-5087
Publication Date(Web):2015/06/26
DOI:10.1039/C5SC90037A
Correction for ‘Assessing the exchange coupling in binuclear lanthanide(III) complexes and the slow relaxation of the magnetization in the antiferromagnetically coupled Dy2 derivative’ by Chun Y. Chow et al., Chem. Sci., 2015, 6, 4148–4159.
Co-reporter:Joseph Jankolovits, Annabel D. Cutland Van-Noord, Jeff W. Kampf and Vincent L. Pecoraro
Dalton Transactions 2013 - vol. 42(Issue 27) pp:NaN9808-9808
Publication Date(Web):2013/05/22
DOI:10.1039/C3DT50535A
Secondary sphere interactions from proximal phenyl side chains control the anion selectivity of dimeric Ln(III)[15-MCCu(II),α-aminoHA-5]3+ metallocavitands. CH–O interactions, which are only possible with certain side chains, are sufficient for overcoming an intrinsic energy barrier to binding saturated dicarboxylates in hydrophobic compartments.
Co-reporter:Anna F. A. Peacock, Olga Iranzo and Vincent L. Pecoraro
Dalton Transactions 2009(Issue 13) pp:NaN2280-2280
Publication Date(Web):2009/01/16
DOI:10.1039/B818306F
Advances in protein chemistry and molecular and structural biology have empowered modern chemists to build complex biological architectures using a “first principles” approach, which is known as de novoprotein design. In this Perspective we demonstrate how simple three-stranded α-helical constructs can be prepared by the sole consideration of the primary amino acid sequence of a peptide. With these well defined systems, we then demonstrate that metal binding cavities can be carved out of the hydrophobic cores of these aggregates in order to bind metal ions such as cadmium with well defined coordination geometries. Examples will be given of homoleptic CdS3 complexes, CdS3O sites and proteins which contain equilibrium mixtures of these two species. We will provide a description of a strategy that allows us to build heterochromic peptides (small proteins that complex two metals in nearly identical environments but which result in different physical properties and allow for metal site selectivity). We conclude with a new class of designed peptides, diastereopeptides, which can exploit changes in amino acid chirality to control metal ion coordination number and lead to an alternative path towards heterochromic systems. The constructs described herein represent the initial steps of preparing protein structures that may simultaneous contain structural and catalytic metal binding centers. These studies inform the community on a developing field, which promises new opportunities for the study of bioinorganic chemistry.
Co-reporter:Gellert Mezei, Jeff W. Kampf, Shilie Pan, Kenneth R. Poeppelmeier, Byron Watkins and Vincent L. Pecoraro
Chemical Communications 2007(Issue 11) pp:NaN1150-1150
Publication Date(Web):2007/01/10
DOI:10.1039/B614024F
Upon crystallization in high yields, metallacrowns form compartments that are capable of asymmetrically encapsulating three isonicotinate guests.
Co-reporter:Catherine Dendrinou-Samara, Curtis M. Zaleski, Andri Evagorou, Jeff W. Kampf, Vincent L. Pecoraro and Dimitris P. Kessissoglou
Chemical Communications 2003(Issue 21) pp:NaN2669-2669
Publication Date(Web):2003/09/30
DOI:10.1039/B309439A
Reaction of Mn(ClO4)2 with di-pyridyl ketone oxime, (2-py)2CNOH, gives the novel cluster [MnII4MnIII6MnIV2(μ4-O)2(μ3-O)4(μ3-OH)4(μ3-OCH3)2(pko)12](OH)(ClO4)3 1. It is the only example of a 24-MC-8, and the first metallacrown with ring metal ions in three different oxidation states. Magnetic measurements show antiferromagnetic behavior.
Co-reporter:Tereza Afrati, Curtis M. Zaleski, Catherine Dendrinou-Samara, Gellert Mezei, Jeff W. Kampf, Vincent L. Pecoraro and Dimitris P. Kessissoglou
Dalton Transactions 2007(Issue 25) pp:NaN2668-2668
Publication Date(Web):2007/04/24
DOI:10.1039/B700902J
The use of di-2-pyridyl ketone oxime (Hpko)/X−
“blends” (X− = OH−, Cl−, ClO4−) in copper chemistry has yielded neutral binuclear and cationic trinuclear, pentanuclear or hexanuclear complexes. Various synthetic procedures have led to the synthesis of compounds [Cu5(pko)7]·[ClO4]3·2CH3OH·2H2O (1), [Cu3(pko)3(OH)(Cl)]2[Ph4B]2·4DMF·2H2O (2), [Cu2(pko)4] (3), {[Cu6(pko)6ClO4(CH3CN)6][Cu6(pko)6(ClO4)3(CH3CN)4]}·8ClO4·14CH3CN·H2O (4). The structures of the complexes have been determined by single-crystal X-ray crystallography.
Co-reporter:Jessica Gätjens, Christopher S. Mullins, Jeff W. Kampf, Pierre Thuéry and Vincent L. Pecoraro
Dalton Transactions 2009(Issue 1) pp:NaN62-62
Publication Date(Web):2008/10/09
DOI:10.1039/B809453E
We have synthesised and characterised a series of new CoII complexes (1–4, 6, 7) and one new ZnII complex (5) employing N3- and N3O-donor ligands [biap: N,N-bis(2-ethyl-5-methyl-imidazol-4-ylmethyl)amino-propane, KBPZG: potassium N,N-bis(3,5-dimethylpyrazolylmethyl) glycinate, KBPZA: potassium N,N-bis(3,5-dimethylpyrazolylmethyl) alaninate, KBiPrPZG: potassium N,N-bis(3,5-di-iso-propylpyrazolylmethyl) glycinate, and KB(tBuM)PZG: potassium N,N-bis(3-methyl-5-tert-butyl-pyrazolylmethyl)glycinate] as structural models of the metalloenzyme α-amino-β-carboxymuconic-ε-semialdehyde decarboxylase (ACMSD). These complexes were characterised by several techniques including X-ray crystallographic analysis, X-band EPR, and mass spectrometry (ESI-MS). The crystal structures of 1, 2, 6, 7 revealed that they exist as mononuclear Co(II) complexes with trigonal-bipyramidal geometry in the solid state. Compounds 3 and 5 form infinite polymeric chains of CoII or ZnII complexes, respectively, linked by the pendant carboxylate arms of the BPZG− ligand. By comparing the degree of distortion in the penta-coordinate complexes, defined by the Addison-parameter τ, with the value determined for the five-coordinate centres found in the active site of ACMSD, it could be seen that complexes 5 and 7 are very good matches for the geometry of the zinc(II) centre in monomer A of the native enzyme. All complexes could be seen as model compounds for the active site of the enzyme ACMSD, where the Co(II) complexes reflected the structural flexibility found in case of two histidine (His177 and His228) residues found in the active site of the enzyme.
Co-reporter:Chun Y. Chow, Hélène Bolvin, Victoria E. Campbell, Régis Guillot, Jeff W. Kampf, Wolfgang Wernsdorfer, Frédéric Gendron, Jochen Autschbach, Vincent L. Pecoraro and Talal Mallah
Chemical Science (2010-Present) 2015 - vol. 6(Issue 7) pp:NaN4159-4159
Publication Date(Web):2015/05/07
DOI:10.1039/C5SC01029B
We report here the synthesis and the investigation of the magnetic properties of a series of binuclear lanthanide complexes belonging to the metallacrown family. The isostructural complexes have a core structure with the general formula [Ga4Ln2(shi3−)4(Hshi2−)2(H2shi−)2(C5H5N)4(CH3OH)x(H2O)x]·xC5H5N·xCH3OH·xH2O (where H3shi = salicylhydroxamic acid and Ln = GdIII1; TbIII2; DyIII3; ErIII4; YIII5; YIII0.9DyIII0.16). Apart from the Er-containing complex, all complexes exhibit an antiferromagnetic exchange coupling leading to a diamagnetic ground state. Magnetic studies, below 2 K, on a single crystal of 3 using a micro-squid array reveal an opening of the magnetic hysteresis cycle at zero field. The dynamic susceptibility studies of 3 and of the diluted DyY 6 complexes reveal the presence of two relaxation processes for 3 that are due to the excited ferromagnetic state and to the uncoupled DyIII ions. The antiferromagnetic coupling in 3 was shown to be mainly due to an exchange mechanism, which accounts for about 2/3 of the energy gap between the antiferro- and the ferromagnetic states. The overlap integrals between the Natural Spin Orbitals (NSOs) of the mononuclear fragments, which are related to the magnitude of the antiferromagnetic exchange, are one order of magnitude larger for the Dy2 than for the Er2 complex.
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