Co-reporter:Ao Li;Rahul Yadav;Jessica K. White;Mackenzie K. Herroon;Brian P. Callahan;Izabela Podgorski;Claudia Turro;Emily E. Scott
Chemical Communications 2017 vol. 53(Issue 26) pp:3673-3676
Publication Date(Web):2017/03/28
DOI:10.1039/C7CC01459G
New Ru(II)-caged abiraterone complexes were synthesized that exhibit strong absorption in the visible region and release the steroidal CYP17A1 inhibitor abiraterone upon exposure to low energy visible light in buffer and prostate cancer cells. Photoinduced release results in abiraterone binding to its CYP17A1 target in an inhibitory mode.
Co-reporter:Ao Li, Jessica K. White, Karan Arora, Mackenzie K. Herroon, Philip D. Martin, H. Bernhard Schlegel, Izabela Podgorski, Claudia Turro, and Jeremy J. Kodanko
Inorganic Chemistry 2016 Volume 55(Issue 1) pp:10-12
Publication Date(Web):December 15, 2015
DOI:10.1021/acs.inorgchem.5b02600
Three complexes of the general formula [Ru(TPA)L2](PF6)2 [TPA = tris(2-pyridylmethyl)amine], where L = pyridine (1), nicotinamide (2), and imidazole (3), were prepared and characterized spectroscopically. X-ray crystallographic data were obtained for 1 and 3. Complexes 1–3 show strong absorption in the visible region and selective release of heterocycles upon irradiation with visible light. Time-dependent density functional theory calculations are consistent with the presence of singlet metal-to-ligand charge-transfer bands in the visible region in 1–3. Caged heterocycles 1–3 are highly stable in solution in the dark, including in cell growth media. Cell viability data show no signs of toxicity of 1–3 against PC-3 cells at concentrations up to 100 μM under light and dark conditions, consistent with Ru(TPA) acting as a nontoxic and effective photocaging group for aromatic heterocycles.
Co-reporter:Karan Arora, Jessica K. White, Rajgopal Sharma, Shivnath Mazumder, Philip D. Martin, H. Bernhard Schlegel, Claudia Turro, and Jeremy J. Kodanko
Inorganic Chemistry 2016 Volume 55(Issue 14) pp:6968-6979
Publication Date(Web):June 29, 2016
DOI:10.1021/acs.inorgchem.6b00650
Four complexes of the general formula [Ru(L)(CH3CN)2](PF6)2, [L = TPA (5), MeTPA (6), Me2TPA (7), and Me3TPA (8)] [TPA = tris[(pyridin-2-yl)methyl]amine, where methyl groups were introduced consecutively onto the 6-position of py donors of TPA, were prepared and characterized by various spectroscopic techniques and mass spectrometry. While 5 and 8 were isolated as single stereoisomers, 6 and 7 were isolated as mixtures of stereoisomers in 2:1 and 1.5:1 ratios, respectively. Steric effects on ground state stability and thermal and photochemical reactivities were studied for all four complexes using 1H NMR and electronic absorption spectroscopies and computational studies. These studies confirmed that the addition of steric bulk accelerates photochemical and thermal nitrile release.
Co-reporter:Rajgopal Sharma, Jessica D. Knoll, Nicholas Ancona, Phillip D. Martin, Claudia Turro, and Jeremy J. Kodanko
Inorganic Chemistry 2015 Volume 54(Issue 4) pp:1901-1911
Publication Date(Web):January 22, 2015
DOI:10.1021/ic502791y
Ruthenium-based photocaging groups have important applications as biological tools and show great potential as therapeutics. A method was developed to rapidly synthesize, screen, and identify ruthenium-based caging groups that release nitriles upon irradiation with visible light. A diverse library of tetra- and pentadentate ligands was synthesized on polystyrene resin. Ruthenium complexes of the general formula [Ru(L)(MeCN)n]m+ (n = 1–3, m = 1–2) were generated from these ligands on solid phase and then cleaved from resin for photochemical analysis. Data indicate a wide range of spectral tuning and reactivity with visible light. Three complexes that showed strong absorbance in the visible range were synthesized by solution phase for comparison. Photochemical behavior of solution- and solid-phase complexes was in good agreement, confirming that the library approach is useful in identifying candidates with desired photoreactivity in short order, avoiding time-consuming chromatography and compound purification.
Co-reporter:Rajgopal Sharma, Jessica D. Knoll, Philip D. Martin, Izabela Podgorski, Claudia Turro, and Jeremy J. Kodanko
Inorganic Chemistry 2014 Volume 53(Issue 7) pp:3272-3274
Publication Date(Web):March 24, 2014
DOI:10.1021/ic500299s
Ruthenium(II) tris(2-pyridylmethyl)amine (TPA) is an effective caging group for nitriles that provides high levels of control over the enzyme activity with light. Two caged nitriles were prepared, [Ru(TPA)(MeCN)2](PF6)2 (1) and [Ru(TPA)(3)2](PF6)2 (2), where 3 is the cathepsin K inhibitor Cbz-Leu-NHCH2CN, and characterized by various spectroscopic techniques and mass spectrometry. Both 1 and 2 show the release of a single nitrile within 20 min of irradiation with 365 nm light. Complex 2 acts as a potent, photoactivated inhibitor of human cathepsin K. IC50 values were determined for 2 and 3. Enzyme inhibition for 2 was enhanced by a factor of 89 upon exposure to light, with IC50 values of 63 nM (light) and 5.6 μM (dark).
Co-reporter:Dr. Tomasz Respondek;Rajgopal Sharma;Mackenzie K. Herroon;Dr. Robert N. Garner;Dr. Jessica D. Knoll;Eric Cueny; Claudia Turro;Dr. Izabela Podgorski; Jeremy J. Kodanko
ChemMedChem 2014 Volume 9( Issue 6) pp:1306-1315
Publication Date(Web):
DOI:10.1002/cmdc.201400081
Abstract
Light-activated inhibition of cathepsin activity was demonstrated in a cell-based assay. Inhibitors of cathepsin K, Cbz-Leu-NHCH2CN (2) and Cbz-Leu-Ser(OBn)-CN (3), were caged within the complexes cis-[Ru(bpy)2(2)2]Cl2 (4) and cis-[Ru(bpy)2(3)2](BF4)2 (5) (bpy=2,2′-bipyridine) as 1:1 mixtures of Δ and Λ stereoisomers. Complexes 4 and 5 were characterized by 1H NMR, IR, and UV/Vis spectroscopies and electrospray mass spectrometry. Photochemical experiments confirm that 4 releases two molecules of 2 upon exposure to visible light for 15 min, whereas release of 3 by 5 requires longer irradiation times. IC50 determinations against purified cathepsin K under light and dark conditions with 4 and 5 confirm that inhibition is enhanced from 35- to 88-fold, respectively, upon irradiation with visible light. No apparent toxicity was observed for 4 in the absence or presence of irradiation in bone marrow macrophage (BMM) or PC3 cells, as determined by MTT assays, at concentrations up to 10 μM. Compound 5 is well tolerated at lower concentrations (<1 μM), but does show growth-inhibitory effects at higher concentrations. Confocal microscopy experiments show that 4 decreases intracellular cathepsin activity in osteoclasts with light activation. These results support the further development of caged nitrile-based inhibitors as chemical tools for investigating spatial aspects of proteolysis within living systems.
Co-reporter:Tomasz Respondek, Eric Cueny, and Jeremy J. Kodanko
Organic Letters 2012 Volume 14(Issue 1) pp:150-153
Publication Date(Web):December 13, 2011
DOI:10.1021/ol202939g
Cumyl ester is an optimal C-terminal protecting group for glycine benzophenone imine in asymmetric alkylation reactions catalyzed by Cinchona chiral phase-transfer catalysts. High levels of enantioselectivity have been obtained (up to 94% ee) with this substrate, which provides an attractive alternative to the analogous tert-butyl ester. N-terminal imines and the C-terminal esters can be cleaved from alkylation products by hydrogenolysis, while maintaining acid-labile side chain protecting groups.
Co-reporter:Jai Prakash
Inorganic Chemistry 2012 Volume 51(Issue 4) pp:2689-2698
Publication Date(Web):February 8, 2012
DOI:10.1021/ic2026736
Synthetic Co(III) complexes containing N5 donor sets undergo glutathionylation to generate biomimetic species of glutathionylcobalamin (GSCbl), an important form of cobalamin (Cbl) found in nature. For this study, a new Co(III) complex was synthesized derived from the polypyridyl pentadentate N5 ligand N4PyCO2Me (1). The compound [Co(N4PyCO2Me)Cl]Cl2 (3) was characterized by X-ray crystallography, UV–vis, IR, 1H NMR, and 13C NMR spectroscopies and mass spectrometry (HRMS). Reaction of 3 with glutathione (GSH) in H2O generates the biomimetic species [Co(N4PyCO2Me)(SG)]2+ (5), which was generated in situ and characterized by UV–vis and 1H NMR spectroscopies and HRMS. 1H NMR and UV–vis spectroscopic data are consistent with ligation of the cysteine thiolate of GSH to the Co(III) center of 5, as occurs in GSCbl. Kinetic analysis indicated that the substitution of chloride by GS– occurs by a second-order process [k1 = (10.1 ± 0.7) × 10–2 M–1 s–1]. The observed equilibrium constant for formation of 5 (Kobs = 870 ± 50 M–1) is about 3 orders of magnitude smaller than for GSCbl. Reaction of the Co(III) complex [Co(Bn-CDPy3)Cl]Cl2 (4) with GSH generates glutathionylated species [Co(Bn-CDPy3)(GS)]2+ (6), analogous to 5. Glutathionylation of 4 occurs at a similar rate [k2 = (8.4 ± 0.5) × 10–2 M–1 s–1], and the observed equilibrium constant (Kobs = 740 ± 47 M–1) is slightly smaller than for 5. Glutathionylation showed a significant pH dependence, where rates increased with pH. Taken together, these results suggest that glutathionylation is a general reaction for Co(III) complexes related to Cbl.
Co-reporter:Jai Prakash, Sara M. Schmitt, Q. Ping Dou and Jeremy J. Kodanko
Metallomics 2012 vol. 4(Issue 2) pp:174-178
Publication Date(Web):15 Dec 2011
DOI:10.1039/C2MT00131D
Polypyridyl pentadentate ligands N4Py (1) and Bn-TPEN (2), along with their respective iron complexes, have been investigated for their ability to inhibit the purified 20S proteasome. Results demonstrated that the iron complexes of both ligands are potent inhibitors of the 20S proteasome (IC50 = 9.2 μM for [FeII(OH2)(N4Py)]2+ (3) and 4.0 μM for [FeII(OH2)(Bn-TPEN)]2+ (4)). Control experiments showed that ligand 1 or FeII alone showed no inhibition, whereas 2 was moderately active (IC50 = 96 μM), suggesting that iron, when bound to these ligands, plays a key role in proteasome inhibition. Results from time-dependent inactivation studies suggest different modes of action for the iron complexes. Time-dependent decay of proteasome activity was observed upon incubation in the presence of 4, which accelerated in the presence of DTT, suggesting reductive activation of O2 and oxidation of the 20S proteasome as a mode of action. In contrast, loss of 20S proteasome activity was not observed with 3 over time, suggesting inhibition through direct binding of the iron complex to the enzyme. Inhibition of the 20S proteasome by 4 was not blocked by reactive oxygen species scavengers, consistent with a unique oxidant being responsible for the time-dependent inhibition observed.
Co-reporter:Jian Zuo;Sara M. Schmitt;Zhen Zhang;Jai Prakash;Yuhua Fan;Caifeng Bi;Q. Ping Dou
Journal of Cellular Biochemistry 2012 Volume 113( Issue 8) pp:2567-2575
Publication Date(Web):
DOI:10.1002/jcb.24132
Abstract
X-linked inhibitor of apoptosis protein (XIAP), inhibits the initiation and execution phases of the apoptotic pathway. XIAP is the most potent member of the inhibitor of apoptosis protein (IAP) family of the endogenous caspase inhibitors. Therefore, targeting XIAP may be a promising strategy for the treatment of apoptosis-resistant malignancies. In this study, we systematically studied the relationships of chemical structures of several novel ligands to their zinc (Zn)-binding ability, molecular target XIAP, and tumor cell death-inducing activity. We show that treatment of PC-3 prostate cancer and MDA-MB-231 breast cancer cells with these membrane-permeable Zn-chelators with different Zn affinities results in varying degrees of XIAP depletion. Following decreased level of XIAP expression, we also show apoptosis-related caspase activation and cellular morphological changes upon treatment with strong Zn-chelators N4Py and BnTPEN. Addition of Zn has a full protective effect on the cells treated with these chelators, while iron (Fe) addition has only partial protection that, however, can be further increased to a comparable level of protection as Zn by inhibition of ROS generation, indicating that cell death effects mediated by Fe- but not Zn-complexes involve redox cycling. These findings suggest that strong Zn-chelating agents may be useful in the treatment of apoptosis-resistant human cancers. J. Cell. Biochem. 113: 2567–2575, 2012. © 2012 Wiley Periodicals, Inc.
Co-reporter:Tomasz Respondek ; Robert N. Garner ; Mackenzie K. Herroon ; Izabela Podgorski ; Claudia Turro
Journal of the American Chemical Society 2011 Volume 133(Issue 43) pp:17164-17167
Publication Date(Web):October 5, 2011
DOI:10.1021/ja208084s
A novel method for caging protease inhibitors is described. The complex [RuII(bpy)2(1)2](PF6)2 (2) was prepared from the nitrile-based peptidomimetic inhibitor Ac-Phe-NHCH2CN (1). 1H NMR, UV–vis, and IR spectroscopic and mass spectrometric data confirmed that 2 equiv of inhibitor 1 bind to RuII through the nitrile functional group. Complex 2 shows excellent stability in aqueous solution in the dark and fast release of 1 upon irradiation with visible light. As a result of binding to the RuII center, the nitriles of complex 2 are caged, and 2 does not act as a potent enzyme inhibitor. However, when 2 is irradiated, it releases 1, which inhibits the cysteine proteases papain and cathepsins B, K and L up to 2 times more potently than 1 alone. Ratios of the IC50 values in the dark versus in the light ranged from 6:1 to 33:1 for inhibition by 2 against isolated enzymes and in human cell lysates, confirming that a high level of photoinduced enzyme inhibition can be obtained using this method.
Co-reporter:Jai Prakash and Jeremy J. Kodanko
Inorganic Chemistry 2011 Volume 50(Issue 9) pp:3934-3945
Publication Date(Web):April 6, 2011
DOI:10.1021/ic102320j
Oxidative inactivation of the serine proteases trypsin and chymotrypsin by nonheme iron complexes is described. The nonheme ligands N4Py (1) and derivative 3CG-N4Py (2), which contains a pendant guanidinium group, were used as ligands for iron. Ferryl (FeIVO) species derived from these ligands, [FeIV(O)(N4Py)]2+ (7) and [FeIV(O)(3CG-N4Py)]3+ (8), inactivate trypsin and chymotrypsin by the oxidation of amino acid side chains. Ferryl 8 is most effective with chymotrypsin (IC50 value of 26 μM for 8 vs 119 μM for 7). IC50 values of 71 and 54 μM were obtained for trypsin with 7 and 8, respectively. Amino acid analysis confirmed that residues cysteine, tyrosine, and tryptophan are oxidized under these conditions. Trypsin is inactivated preferentially over chymotrypsin under catalytic conditions, where the enzyme was pulsed with H2O2 in the presence of ferrous complexes [FeII(OH2)(N4Py)]2+(5) and [FeII(Cl)(3CG-N4Py)]2+ (6). Control experiments support the action of a unique oxidant, other than ferryls or hydroxyl radicals, under these conditions, where tyrosine residues are targeted selectively.
Co-reporter:Casey S. Jackson ; Sara Schmitt ; Q. Ping Dou
Inorganic Chemistry 2011 Volume 50(Issue 12) pp:5336-5338
Publication Date(Web):May 27, 2011
DOI:10.1021/ic200676s
Photoactivated carbon monoxide (CO) release by the iron carbonyl complex [FeII(CO)(N4Py)](ClO4)2 (1) is described. Compound 1 is a low-spin ferrous complex that is highly stable and soluble in aerobic aqueous solutions. CO release was studied by the substitution of MeCN for CO, which displays saturation kinetics, and by the transfer of CO to deoxymyoglobin, which is slow in the dark but fast upon irradiation with UV light (365 nm). Compound 1 is active against PC-3 prostate cancer cells and shows potent photoinduced cytotoxicity. In addition, the iron carbonyl complex was attached to a short peptide toward the goal of tissue or cell-specific delivery.
Co-reporter:Ahmed I. Abouelatta, Jason A. Sonk, Mirvat M. Hammoud, Danielle M. Zurcher, Joshua J. McKamie, H. Bernhard Schlegel and Jeremy J. Kodanko
Inorganic Chemistry 2010 Volume 49(Issue 11) pp:5202-5211
Publication Date(Web):May 11, 2010
DOI:10.1021/ic100322p
Synthesis and characterization of metal complexes of the chiral tripyridyldiamine ligand Bn-CDPy3 (1), derived from trans-1,2-diaminocyclohexane, are described, along with theoretical studies that support the experimental data. These studies confirm that a single coordination geometry, out of five possible, is favored for octahedral complexes of the type [M(Bn-CDPy3)Cl], where M equals Co(III), Fe(II), and Zn(II). A combination of X-ray crystallographic and NMR spectroscopic methods was used to define the structures of the complexes [Co(Bn-CDPy3)Cl]Cl2 (5), [Fe(Bn-CDPy3)Cl]X (X = FeCl4, Cl, ClO4, 6−8), and [Zn(Bn-CDPy3)Cl]2ZnCl4 (9) in the solid state and in solution. Experimental and theoretical data indicate that the most stable coordination geometry for all complexes possesses the Cl group trans to a basic amine donor and three pyridyl donors adopting the mer geometry, with two pyridyl N-donors adopting a coplanar geometry with respect to the M−Cl bond and the third pyridyl donor perpendicular to that axis. Calculations indicate that the ability to favor a single geometry is born from the chiral ligand, which prefers to be in a single conformation in metal complexes due to steric interactions and electronic factors. Calculated structures of the complexes were used to locate key interactions among the various diastereomeric complexes that are proposed to create an energetic preference for the coordination geometry observed in the metal complexes of 1.
Co-reporter:Ashley A. Campanali, Timothy D. Kwiecien, Lew Hryhorczuk and Jeremy J. Kodanko
Inorganic Chemistry 2010 Volume 49(Issue 11) pp:4759-4761
Publication Date(Web):May 6, 2010
DOI:10.1021/ic100439n
The mechanism of glutathione (GSH) oxidation by a nonheme ferryl species has been investigated. The reaction of [FeIV(O)(N4Py)]2+ (1) with GSH in an aqueous solution leads to the rapid formation of a green intermediate, characterized as the low-spin ferric complex [FeIII(SG)(N4Py)]2+ (2) by UV−vis and electron paramagnetic resonance spectroscopies and by high-resolution time-of-flight mass spectrometry. Intermediate 2 decays to form the final products [FeII(OH2)(N4Py)]2+ and the disulfide GSSG over time. The overall reaction was fit to a three-step process involving rapid quenching of the ferryl by GSH, followed by the formation and decay of 2, which are both second-order processes.
Co-reporter:Casey S. Jackson and Jeremy J. Kodanko
Metallomics 2010 vol. 2(Issue 6) pp:407-411
Publication Date(Web):06 May 2010
DOI:10.1039/C003414B
Polypyridyl ligands were investigated for their ability to bind and mobilize iron(II) from ferritin in aqueous solution. Association constants with iron(II) (pFeII) were determined for the pentadentate ligands N4Py (pFeII = 14.4) and Bn-TPEN (pFeII = 13.7) using a competition method with the hexadentate ligand TPEN (pFeII = 14.6, 0.1 M KNO3). Ferrous complexes were formed using the polypyridyl ligands and ferritin as the sole iron source in the presence of reductant. The observed rates of iron mobilization from ferritin were dependent on reductant and were higher in the presence of ascorbate than dithiothreitol. TPEN, N4Py and Bn-TPEN demonstrated comparable and in some cases faster rates and higher levels of iron mobilization when compared to the iron(II) chelator 1,10-phenanthroline, particularly at low concentrations of chelator.
Co-reporter:A. R. Ekkati;A. A. Campanali;A. I. Abouelatta;M. Shamoun;S. Kalapugama
Amino Acids 2010 Volume 38( Issue 3) pp:747-751
Publication Date(Web):2010 March
DOI:10.1007/s00726-009-0279-y
N-Acetyl-AA(amino acid)-NHtBu derivatives of all 20 naturally occurring amino acids have been synthesized. Syntheses were performed via solution-phase methodology with yields that allow for access to gram quantities of substrates, in most cases. Syntheses include the coupling of a hindered amine, tert-butylamine, with each amino acid, either directly or in two steps using an activated ester isolated as an intermediate. The introduction of protecting groups was necessary in some cases. The development of synthetic sequences to access challenging substrates, such as the one derived from asparagine, are discussed.
Co-reporter:Ahmed I. Abouelatta ; Ashley A. Campanali ; Anil R. Ekkati ; Mark Shamoun ; Suneth Kalapugama
Inorganic Chemistry 2009 Volume 48(Issue 16) pp:7729-7739
Publication Date(Web):July 13, 2009
DOI:10.1021/ic900527c
Kinetic and mechanistic studies detailing the oxidation of substrates derived from the 20 natural amino acids by the ferryl complex [FeIV(O)(N4Py)]2+ are described. Substrates of the general formula Ac-AA-NHtBu were treated with the ferryl complex under identical conditions ([Ac-AA-NHtBu] = 10 mM, [Fe] = 1 mM, 1:1 H2O/CH3CN), and pseudo-first-order rate constants were obtained. Relative rate constants calculated from these data illustrated the five most reactive substrates; in order of decreasing reactivity were those derived from Cys, Tyr, Trp, Met, and Gly. Second-order rate constants were determined for these substrates by varying substrate concentration under pseudo-first-order conditions. Substrates derived from the other natural amino acids did not display significant reactivity, accelerating decomposition of the ferryl complex at a rate less than 10 times that of the control reaction with no substrate added. Ferryl decomposition rates changed in D2O/CD3CN for the Cys, Tyr, and Trp substrates, giving deuterium kinetic isotope effects of 4.3, 29, and 5.2, respectively, consistent with electron-transfer, proton-transfer (Cys and Trp), or hydrogen atom abstraction (Tyr) mechanisms. Decomposition rates for [FeIV(O)(N4Py)]2+ in the presence of the Met and Gly substrates were identical in H2O/CH3CN versus D2O/CD3CN solvents. A deuterium kinetic isotope effect of 4.8 was observed with the labeled substrate 2,2-d2-Ac-Gly-NHtBu, consistent with [FeIV(O)(N4Py)]2+ abstracting an α-hydrogen atom from Ac-Gly-NHtBu and generating a glycyl radical. Abstraction of α-hydrogen atoms from amino acid substrates other than Gly and oxidation of side chains contained in the amino acids other than Cys, Tyr, Trp, and Met were slow by comparison.
Co-reporter:Nitinkumar D. Jabre ; Lew Hryhorczuk
Inorganic Chemistry 2009 Volume 48(Issue 17) pp:8078-8080
Publication Date(Web):July 31, 2009
DOI:10.1021/ic9013653
The formation of a synthetic ferryl−peptide conjugate and mechanistic studies that elucidate its mode of decomposition are presented. A ferryl species is generated from a ligand−dipeptide conjugate 4. The ferryl species [FeIV(4)(O)]2+, noted as compound 5, was characterized by UV−vis spectroscopy and by high-resolution electrospray mass spectrometry. The ferryl−peptide conjugate 5 is stable for over 1 h at room temperature. Ester derivatives of 5 decay at different rates, consistent with the remote ester group controlling the stability of the ferryl. The kinetic isotope effect value (4.5) and ρ = −1.3 observed with ester derivatives suggest that the mechanism for decomposition of 5 follows a hydrogen-atom-transfer pathway. The formation and decay of 5 was fit to a two-step process, with the decay being unimolecular with respect to the ferryl 5.
Co-reporter:Mirvat M. Hammoud, Joshua J. McKamie, Mary Jane Heeg and Jeremy J. Kodanko
Dalton Transactions 2008 (Issue 36) pp:4843-4845
Publication Date(Web):30 Jul 2008
DOI:10.1039/B810980J
Synthesis of the tripyridyldiamine Bn-CDPy3, a chiral pentadentate ligand, and characterization of its low-spin Co(III) complex [Co(Bn-CDPy3)Cl]Cl2 by X-ray crystallography, 1H NMR, 13C NMR, IR and UV-vis spectroscopy as well as molar conductivity and mass spectrometry, is described.
Co-reporter:Ao Li, Rahul Yadav, Jessica K. White, Mackenzie K. Herroon, Brian P. Callahan, Izabela Podgorski, Claudia Turro, Emily E. Scott and Jeremy J. Kodanko
Chemical Communications 2017 - vol. 53(Issue 26) pp:NaN3676-3676
Publication Date(Web):2017/03/07
DOI:10.1039/C7CC01459G
New Ru(II)-caged abiraterone complexes were synthesized that exhibit strong absorption in the visible region and release the steroidal CYP17A1 inhibitor abiraterone upon exposure to low energy visible light in buffer and prostate cancer cells. Photoinduced release results in abiraterone binding to its CYP17A1 target in an inhibitory mode.
Co-reporter:Matthew Huisman, Jessica K. White, Veronica G. Lewalski, Izabela Podgorski, Claudia Turro and Jeremy J. Kodanko
Chemical Communications 2016 - vol. 52(Issue 85) pp:NaN12593-12593
Publication Date(Web):2016/10/06
DOI:10.1039/C6CC07083C
Photochemical control over irreversible inhibition was shown using Ru(II)-caged inhibitors of cathepsin L. Levels of control were dependent on where the Ru(II) complex was attached to the organic inhibitor, reaching >10:1 with optimal placement. A new strategy for photoreleasing Ru(II) fragments from inhibitor–enzyme conjugates is also reported.
Co-reporter:Mirvat M. Hammoud, Joshua J. McKamie, Mary Jane Heeg and Jeremy J. Kodanko
Dalton Transactions 2008(Issue 36) pp:NaN4845-4845
Publication Date(Web):2008/07/30
DOI:10.1039/B810980J
Synthesis of the tripyridyldiamine Bn-CDPy3, a chiral pentadentate ligand, and characterization of its low-spin Co(III) complex [Co(Bn-CDPy3)Cl]Cl2 by X-ray crystallography, 1H NMR, 13C NMR, IR and UV-vis spectroscopy as well as molar conductivity and mass spectrometry, is described.
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