Shearer Jason, Schmitt Jennifer C, Clewett Heather S
Department of Chemistry, University of Nevada, 1664 North Virginia Street, Reno, Nevada 89557, United States.
J Phys Chem B. 2015 Apr 30;119(17):5453-61. doi: 10.1021/acs.jpcb.5b02640. Epub 2015 Apr 16.
Nickel-containing superoxide dismutases (NiSODs) are bacterial metalloenzymes that catalyze the disproportionation of O2(-). These enzymes take advantage of a redox-active nickel cofactor, which cycles between the Ni(II) and Ni(III) oxidation states, to catalytically disprotorptionate O2(-). The Ni(II) center is ligated in a square planar N2S2 coordination environment, which, upon oxidation to Ni(III), becomes five-coordinate following the ligation of an axial imidazole ligand. Previous studies have suggested that metallopeptide-based mimics of NiSOD reduce O2(-) through a proton-coupled electron transfer (PCET) reaction with the electron derived from a reduced Ni(II) center and the proton from a protonated, coordinated Ni(II)-S(H(+))-Cys moiety. The current work focuses on the O2(-) reduction half-reaction of the catalytic cycle. In this study we calculate the vibronic coupling between the reactant and product diabatic surfaces using a semiclassical formalism to determine if the PCET reaction is proceeding through an adiabatic or nonadiabatic proton tunneling process. These results were then used to calculate H/D kinetic isotope effects for the PCET process. We find that as the axial imidazole ligand becomes more strongly associated with the Ni(II) center during the PCET reaction, the reaction becomes more nonadiabatic. This is reflected in the calculated H/D KIEs, which moderately increase as the reaction becomes more nonadiabatic. Furthermore, the results suggest that as the axial ligand becomes less Lewis basic the observed reaction rate constants for O2(-) reduction should become faster because the reaction becomes more adiabatic. These conclusions are in-line with experimental observations. The results thus indicate that variations in the axial donor's ability to coordinate to the nickel center of NiSOD metallopeptide-based mimics will strongly influence the fundamental nature of the O2(-) reduction process.
含镍超氧化物歧化酶（NiSODs）是一类细菌金属酶，可催化超氧阴离子（O2(-)）的歧化反应。这些酶利用一种氧化还原活性镍辅因子，该辅因子在Ni(II)和Ni(III)氧化态之间循环，以催化超氧阴离子的歧化反应。Ni(II)中心在平面正方形N2S2配位环境中配位，氧化为Ni(III)后，随着轴向咪唑配体的配位，变为五配位。先前的研究表明，基于金属肽的NiSOD模拟物通过质子耦合电子转移（PCET）反应还原超氧阴离子，电子来源于还原的Ni(II)中心，质子来源于质子化的、配位的Ni(II)-S(H(+))-半胱氨酸部分。目前的工作聚焦于催化循环中的超氧阴离子还原半反应。在本研究中，我们使用半经典形式计算反应物和产物非绝热表面之间的振动电子耦合，以确定PCET反应是通过绝热还是非绝热质子隧穿过程进行。然后利用这些结果计算PCET过程的H/D动力学同位素效应。我们发现，在PCET反应过程中，随着轴向咪唑配体与Ni(II)中心的结合变得更强，反应变得更加非绝热。这反映在计算得到的H/D动力学同位素效应中，随着反应变得更加非绝热，该效应适度增加。此外，结果表明，随着轴向配体的路易斯碱性降低，观察到的超氧阴离子还原反应速率常数应该会加快，因为反应变得更加绝热。这些结论与实验观察结果一致。因此，结果表明，轴向供体与基于NiSOD金属肽模拟物的镍中心配位能力的变化将强烈影响超氧阴离子还原过程的基本性质。
