Department of Chemistry and Biochemistry, The University of Arizona , P.O. Box 210041, Tucson, Arizona 85721, United States.
J Am Chem Soc. 2014 Mar 12;136(10):4012-8. doi: 10.1021/ja500087m. Epub 2014 Feb 26.
Reductive cleavage of disulfide bonds is an important step in many biological and chemical processes. Whether cleavage occurs stepwise or concertedly with electron transfer is of interest. Also of interest is whether the disulfide bond is reduced directly by intermolecular electron transfer from an external reducing agent or mediated intramolecularly by internal electron transfer from another redox-active moiety elsewhere within the molecule. The electrochemical reductions of 4,4'-bipyridyl-3,3'-disulfide (1) and the di-N-methylated derivative (2(2+)) have been studied in acetonitrile. Simulations of the cyclic voltammograms in combination with DFT (density functional theory) computations provide a consistent model of the reductive processes. Compound 1 undergoes reduction directly at the disulfide moiety with a substantially more negative potential for the first electron than for the second electron, resulting in an overall two-electron reduction and rapid cleavage of the S-S bond to form the dithiolate. In contrast, compound 2(2+) is reduced at less negative potential than 1 and at the dimethyl bipyridinium moiety rather than at the disulfide moiety. Most interesting, the second reduction of the bipyridinium moiety results in a fast and reversible intramolecular two-electron transfer to reduce the disulfide moiety and form the dithiolate. Thus, the redox-active bipyridinium moiety provides a low energy pathway for reductive cleavage of the S-S bond that avoids the highly negative potential for the first direct electron reduction. Following the intramolecular two-electron transfer and cleavage of the S-S bond the bipyridinium undergoes two additional reversible reductions at more negative potentials.
二硫键的还原裂解是许多生物和化学过程中的重要步骤。裂解是逐步发生还是与电子转移协同发生，这一点很有意思。此外，感兴趣的还有二硫键是否直接通过来自外部还原剂的分子间电子转移还原，或者是否通过分子内来自分子内其他氧化还原活性部分的内部电子转移来还原。已经在乙腈中研究了 4,4'-联吡啶-3,3'-二硫化物（1）和二-N-甲基化衍生物（2(2+)）的电化学还原。循环伏安图的模拟与 DFT（密度泛函理论）计算相结合，提供了还原过程的一致模型。化合物 1 在二硫键部分直接还原，第一个电子的还原电位比第二个电子的还原电位负得多，导致总共有两个电子的还原和 S-S 键的快速裂解，形成二硫醇盐。相比之下，化合物 2(2+)的还原电位比 1 更负，并且在二甲基联吡啶鎓部分而不是二硫键部分还原。最有趣的是，联吡啶鎓部分的第二次还原导致快速可逆的分子内两电子转移，还原二硫键部分并形成二硫醇盐。因此，氧化还原活性的联吡啶鎓部分为 S-S 键的还原裂解提供了一条低能量途径，避免了第一个直接电子还原的高负电位。在分子内两电子转移和 S-S 键裂解之后，联吡啶鎓在更负的电位下经历两个额外的可逆还原。
