Woznichak M M, Overcast J D, Robertson K, Neumann H M, May S W
School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia 30332, USA.
Arch Biochem Biophys. 2000 Jul 15;379(2):314-20. doi: 10.1006/abbi.2000.1893.
Peroxynitrite, a reactive cytotoxic species generated by the reaction of superoxide with nitric oxide, rapidly oxidizes phenylaminoethyl selenide (PAESe) and its para-substituted derivatives with second-order rate constants ranging from 900 to 3000 M(-1) s(-1) at neutral pH (pH 7.0) and 25 degrees C. These values are approximately 3 x 10(4) times greater than the corresponding rate constants for the reactions of selenides with hydrogen peroxide. The peroxynitrite reaction was also studied at alkaline pH. HPLC analysis confirms that both the peroxynitrite and hydrogen peroxide reactions produced the corresponding phenylaminoethyl selenoxide (PAESeO) as the sole selenium-containing product, with a stoichiometry of 1 mol of PAESe oxidized per 1 mol of PAESeO formed per 1 mol of oxidant reacted. The influence of para-substituents on the rate constants was investigated using Hammett plots; in both cases the data are consistent with an S(N)2-type mechanism, wherein the selenium atom acts as the nucleophile. Our results provide further evidence that organoselenium compounds may play a protective role in the defense against the many reactive oxidizing species produced in cellular metabolism.
过氧亚硝酸根是超氧化物与一氧化氮反应生成的一种具有细胞毒性的活性物质，在中性pH值（pH 7.0）和25℃条件下，它能迅速氧化苯氨基乙基硒化物（PAESe）及其对位取代衍生物，二级反应速率常数在900至3000 M⁻¹ s⁻¹之间。这些值比硒化物与过氧化氢反应的相应速率常数大约大3×10⁴倍。还研究了碱性pH条件下过氧亚硝酸根的反应。高效液相色谱分析证实，过氧亚硝酸根和过氧化氢反应均生成相应的苯氨基乙基亚硒酸盐（PAESeO）作为唯一含硒产物，化学计量比为每反应1摩尔氧化剂，每形成1摩尔PAESeO会氧化1摩尔PAESe。使用哈米特图研究了对位取代基对速率常数的影响；在两种情况下，数据都与SN2型机理一致，其中硒原子作为亲核试剂。我们的结果进一步证明，有机硒化合物在抵御细胞代谢过程中产生的多种活性氧化物质方面可能发挥保护作用。
