MTA-DE Redox and Homogeneous Catalytic Reaction Mechanisms Research Group , University of Debrecen , H-4032 Debrecen , Hungary.
Department of Inorganic and Analytical Chemistry , University of Debrecen , H-4032 Debrecen , Hungary.
Inorg Chem. 2019 Jan 22;58(2):1414-1424. doi: 10.1021/acs.inorgchem.8b02952. Epub 2019 Jan 8.
Detailed equilibrium and spectroscopic characterization of the complex formation processes of the nickel binding loop in NiSOD and its related fragments is reported in the slightly acidic-alkaline pH range. The N-terminally free and protected nonapeptides HCDLPCGVY-NH (NiSODM), HCDLACGVY-NH (NiSODM), and Ac-HCDLPCGVY-NH (NiSODM) and the N-terminally shortened analogues HCDL-NH and HCA-NH were synthesized, and their nickel(II) complexes were studied by potentiometric and several spectroscopic techniques. EPR spectroscopy was also used to assign the coordinating donor sites after the in situ oxidation of nickel(II) complexes. The terminal amino groups are the primary metal binding sites for nickel(II) ion in NiSODM and NiSODM, resulting in the high nickel(II) binding affinity of this peptide via the formation of a square-planar, (NH,N,S,S) or (NH,NN,S) coordinated species in a wide pH range. The latter coordination sphere prevents the formation of the active structure of NiSOD under physiological pH, reflecting the crucial role of proline in nickel(II) binding. In situ oxidation of the Ni(II) complexes yielded Ni(III) transient species in the case of nonapeptides. The square-pyramidal coordination environment with axial imidazole ligation provides the active structure of the oxidized form of NiSOD in the case of N-terminally free peptides. Consequently, these ligands are promising candidates for modeling NiSOD. The acylation of the amino terminus significantly reduces the nickel(II) binding affinity of the nonapeptide, while the oxidation results in coordination isomers.
详细的平衡和光谱学研究了 NiSOD 及其相关片段中镍结合环的形成过程，该研究在微酸性-碱性 pH 范围内进行。合成了无 N 端保护的九肽 HCDLPCGVY-NH（NiSODM）、HCDLACGVY-NH（NiSODM）和 Ac-HCDLPCGVY-NH（NiSODM）以及 N 端缩短的类似物 HCDL-NH 和 HCA-NH，并通过电位法和多种光谱技术研究了它们的镍（II）配合物。EPR 光谱也用于在原位氧化镍（II）配合物后分配配位供体部位。末端氨基是 NiSODM 和 NiSODM 中镍（II）离子的主要金属结合位点，通过形成平面正方形（NH，N，S，S）或（NH，NN，S）配位物种，在很宽的 pH 范围内实现该肽对镍（II）的高结合亲和力。后者的配位球阻止了 NiSOD 在生理 pH 下形成活性结构，反映了脯氨酸在镍（II）结合中的关键作用。在原位氧化 Ni(II)配合物时，非肽会产生 Ni(III)瞬态物种。轴向咪唑配位的平面四方配位环境为无 N 端自由肽的 NiSOD 氧化形式提供了活性结构。因此，这些配体是模拟 NiSOD 的有前途的候选物。氨基末端的酰化会显著降低九肽的镍（II）结合亲和力，而氧化则会导致配位异构体。
