Co-reporter:Xiaobing Yang;Fangzhong Hu;Yang Wang;Chiming Yang;Xiaomao Zou;Jiahui Liu;Qichun Zhang
Chemical Communications 2017 vol. 53(Issue 54) pp:7497-7500
Publication Date(Web):2017/07/04
DOI:10.1039/C7CC03308G
A novel protocol to prepare multi-substituted dihydrofuropyridine and dihydropyrrolopyridine derivatives from KOH-catalyzed reactions between readily available N-propargylic β-enaminones and arylaldehydes or N-sulfonyl imines has been developed in moderate to good yields.
Co-reporter:Chao Zhang, Bingyang Han, Zichen Xu, Chi Ming Yang
Tetrahedron Letters 2016 Volume 57(Issue 1) pp:85-89
Publication Date(Web):6 January 2016
DOI:10.1016/j.tetlet.2015.11.063
A competitive formation of ‘anti’ symmetric di-CuII and ‘syn’ non-symmetric decarboxylated di-CuII complexes was established from a systematic study of CuII binding to aminocarboxylate-based bis-glycinamide ligands featuring a His/His dyad, due to the Δ–Λ interconversion of backbone conformation which gave rise to anti versus syn binding for the 2nd CuII. The findings provide a facile strategy for the investigation of novel di-CuII mimics.
Co-reporter:Chi Ming Yang
Dalton Transactions 2011 vol. 40(Issue 12) pp:3008-3027
Publication Date(Web):17 Feb 2011
DOI:10.1039/C0DT00237B
Metal-site Trp/His interactions are crucial to diverse metalloprotein functions. This paper presents a study using metal-motif mimicry to capture and dissect the static and transient components of physicochemical properties underlying the Trp/His aromatic side-chain noncovalent interactions across the first- and second-coordination spheres of biometal ions. Modular biomimetic constructs, EDTA-(L-Trp, L-His) or EWH and DTPA-(L-Trp, L-His) or DWH, featuring a function-significant Trp/His pair, enabled extracting the putative hydrophobic/hydrophilic aromatic interactions surrounding metal centers. Fluorescence, circular dichroism (CD) spectroscopic titrations and ESI mass spectrometry demonstrated that both the constructs stoichiometrically bind to Ca2+, Co2+, Cu2+, Ni2+, Mn2+, Zn2+, Cd2+, and Fe2+, and such binding was strongly coupled to stereospecific side-chain structure reorientations of the Trp indole and His imidazole rings. A mechanistic dichotomy corresponding to the participation of the indole unit in the binding event was revealed by a scaffold-platform correlation of steady-state fluorescence-response landscape, illuminating that secondary-coordination-sphere ligand cation-π interactions were immediately followed by subsequent transient physicochemical processes including through-space energy transfer, charge transfer and/or electron transfer, depending on the type of metals. The fluorescence quenching of Trp side chain by 3d metal ions can be ascribed to through-space d-π interactions. While the fluorescence titration was capable of illuminating a two-component energetic model, clean isosbestic/isodichroic points in the CD titration spectra indicated that the metallo-constructs, such as Cu2+-EWH complex, fold thermodynamically by means of a two-state equilibrium. Further, the metal-ion dependence of Trp conformational variation in the modular architecture of metal-bound scaffolds was evidenced unambiguously by the CD spectra and supported by MMFF calculations; both were capable of distinguishing between the coordination geometry and the preference for metal binding mode. The study thus helps understand how aromatic rings around metal-sites have unique capabilities through the control of the spatiotemporal distribution of noncovalent interaction elements to achieve diverse chemical functionality.
Co-reporter:Dr. Chi Ming Yang ;Jie Zhang
Chemistry - A European Journal 2010 Volume 16( Issue 35) pp:10854-10865
Publication Date(Web):
DOI:10.1002/chem.200903149
Abstract
Metal-binding scaffolds incorporating a Trp/His-paired epitope are instrumental in giving novel insights into the physicochemical basis of functional and mechanistic versatility conferred by the Trp–His interplay at a metal site. Herein, by coupling biometal site mimicry and 1H and 13C NMR spectroscopy experiments, modular constructs EDTA-(L-Trp, L-His) (EWH; EDTA=ethylenediamino tetraacetic acid) and DTPA-(L-Trp, L-His) (DWH; DTPA=diethylenetriamino pentaacetic acid) were employed to dissect the static and transient physicochemical properties of hydrophobic/hydrophilic aromatic interactive modes surrounding biometal centers. The binding feature and identities of the stoichiometric metal-bound complexes in solution were investigated by using 1H and 13C NMR spectroscopy, which facilitated a cross-validation of the carboxylate, amide oxygen, and tertiary amino groups as the primary ligands and indole as the secondary ligand, with the imidazole (Im) N3 nitrogen being weakly bound to metals such as Ca2+ owing to a multivalency effect. Surrounding the metal centers, the stereospecific orientation of aromatic rings in the diastereoisomerism is interpreted with the Ca2+–EWH complex. With respect to perturbed Trp side-chain rotamer heterogeneity, drastically restricted Trp side-chain flexibility and thus a dynamically constrained rotamer interconversion due to π interactions is evident from the site-selective 13C NMR spectroscopic signal broadening of the Trp indolyl C3 atom. Furthermore, effects of Trp side-chain fluctuation on indole/Im orientation were the subject of a 2D NMR spectroscopy study by using the Ca2+-bound state; a CH2(indolyl)/CH5(Im+) connectivity observed in the NOESY spectra captured direct evidence that the NH1 of the Ca2+–Im+ unit interacted with the pyrrole ring of the indole unit in Ca2+-bound EWH but not in DWH, which is assignable to a moderately static, anomalous, T-shaped, interplanar π+–π stacking alignment. Nevertheless, a comparative 13C NMR spectroscopy study of the two homologous scaffolds revealed that the overall response of the indole unit arises predominantly from global attractions between the indole ring and the entire positively charged first coordination sphere. The study thus demonstrates the coordination-sphere/geometry dependence of the Trp/His side-chain interplay, and established that π interactions allow 13C NMR spectroscopy to offer a new window for investigating Trp rotamer heterogeneity near metal-binding centers.
Co-reporter:Chi Ming Yang Dr.;Xueying Li;Wei Wei;Yitong Li;Zhengjuan Duan;Jianyu Zheng Dr.;Tai Huang
Chemistry - A European Journal 2007 Volume 13(Issue 11) pp:
Publication Date(Web):3 JAN 2007
DOI:10.1002/chem.200600661
Detailed physicochemical features inherent in the dynamic cation–π interactions of aromatic amino acid side chains in the secondary coordination spheres around metal ions were extracted and mapped by intrinsic tyrosine fluorescence titration experiments with two homologous, artificially engineered metal-binding scaffolds which mimic metal-binding sites in metalloproteins. A newly formulated method for the treatment of fluorescence titration data allows straightforward assessment of both the magnitudes and properties of metal-chelation-assisted cation–aromatic interactions (K2) underlying a proposed two-step metallosupramolecular association process. The unprecedented linear platform-motif correlations between the two contrasting scaffolds in their changes in tyrosine fluorescence on binding of 3d metal cations help to elucidate the properties of general cation–arene recognition corresponding to the metal-responsive characteristics of the second-shell Tyr residue surrounding the metal-binding sites in the supramolecular context, and thereby define a new noncovalent design principle for metal-ion recognition in aqueous solution. As supported by NMR spectroscopic and ESI-MS analyses and molecular mechanics force field calculations, the systematic study exemplifies the concept of using steady-state tyrosine fluorescence as a powerful tool for comprehensive descriptions of cation–π interactions in the extended environment of a metal-binding site. We established that the physicochemical properties pertaining to indirect metal–arene interactions are highly dependent on the electronic properties of the metal ions. This work suggests that second-shell cation-π interactions may play more diverse roles, including modulation of structure, reactivity, and function of metal-binding sites, than the previously well-established direct cation–π interactions involving hard cations (e.g., alkali metal ions). Moreover, such a study will continue to complement theoretical predications and/or the early experimental investigations in organic solvents.
Co-reporter:Yitong Li and Chi Ming Yang
Chemical Communications 2003 (Issue 23) pp:2884-2885
Publication Date(Web):22 Oct 2003
DOI:10.1039/B310543A
Cooperative interactions between metal ions and bivalent tryptophan side chain are identified in water by fluorescence quenching of a designed novel receptor, EDTA-bis(L-tryptophan methyl ester), supplemented by a circular dichroism study; results revealed that the receptor is capable of distinguishing a variety of metal ions on the basis of their abilities in quenching tryptophan fluorescence and the relative magnitude of these interactions is Cu2+
∼ Fe2+ >> Co2+ > Ni2+ >> Mn2+ > Zn2+ > La3+ > Al3+.
Co-reporter:Xiaobing Yang, Fangzhong Hu, Yang Wang, Chiming Yang, Xiaomao Zou, Jiahui Liu and Qichun Zhang
Chemical Communications 2017 - vol. 53(Issue 54) pp:NaN7500-7500
Publication Date(Web):2017/06/12
DOI:10.1039/C7CC03308G
A novel protocol to prepare multi-substituted dihydrofuropyridine and dihydropyrrolopyridine derivatives from KOH-catalyzed reactions between readily available N-propargylic β-enaminones and arylaldehydes or N-sulfonyl imines has been developed in moderate to good yields.
Co-reporter:Chi Ming Yang
Dalton Transactions 2011 - vol. 40(Issue 12) pp:NaN3027-3027
Publication Date(Web):2011/02/17
DOI:10.1039/C0DT00237B
Metal-site Trp/His interactions are crucial to diverse metalloprotein functions. This paper presents a study using metal-motif mimicry to capture and dissect the static and transient components of physicochemical properties underlying the Trp/His aromatic side-chain noncovalent interactions across the first- and second-coordination spheres of biometal ions. Modular biomimetic constructs, EDTA-(L-Trp, L-His) or EWH and DTPA-(L-Trp, L-His) or DWH, featuring a function-significant Trp/His pair, enabled extracting the putative hydrophobic/hydrophilic aromatic interactions surrounding metal centers. Fluorescence, circular dichroism (CD) spectroscopic titrations and ESI mass spectrometry demonstrated that both the constructs stoichiometrically bind to Ca2+, Co2+, Cu2+, Ni2+, Mn2+, Zn2+, Cd2+, and Fe2+, and such binding was strongly coupled to stereospecific side-chain structure reorientations of the Trp indole and His imidazole rings. A mechanistic dichotomy corresponding to the participation of the indole unit in the binding event was revealed by a scaffold-platform correlation of steady-state fluorescence-response landscape, illuminating that secondary-coordination-sphere ligand cation-π interactions were immediately followed by subsequent transient physicochemical processes including through-space energy transfer, charge transfer and/or electron transfer, depending on the type of metals. The fluorescence quenching of Trp side chain by 3d metal ions can be ascribed to through-space d-π interactions. While the fluorescence titration was capable of illuminating a two-component energetic model, clean isosbestic/isodichroic points in the CD titration spectra indicated that the metallo-constructs, such as Cu2+-EWH complex, fold thermodynamically by means of a two-state equilibrium. Further, the metal-ion dependence of Trp conformational variation in the modular architecture of metal-bound scaffolds was evidenced unambiguously by the CD spectra and supported by MMFF calculations; both were capable of distinguishing between the coordination geometry and the preference for metal binding mode. The study thus helps understand how aromatic rings around metal-sites have unique capabilities through the control of the spatiotemporal distribution of noncovalent interaction elements to achieve diverse chemical functionality.
