López-Alarcón C, Navarrete P, Camargo C, Squella J A, Núñez-Vergara L J
Laboratory of Biolectrochemistry, Laboratory of Organic Synthesis and Molecular Modeling, Faculty of Chemical and Pharmaceutical Sciences, University of Chile, P.O. Box 233, Santiago, Chile.
Chem Res Toxicol. 2003 Feb;16(2):208-15. doi: 10.1021/tx025579o.
A series of C4-substituted 1,4-dihydropyridines (DHP) with either secondary or tertiary nitrogen in the dihydropyridine ring were synthesized. All of these compounds together with some commercial DHP derivatives were tested for potential scavenger effects toward alkyl, alkylperoxyl radicals, and ABTS radical cation in aqueous media at pH 7.4. Kinetic rate constants were assessed either by UV/vis spectroscopy or GC/MS techniques. Tested compounds reacted faster toward alkylperoxyl radicals and ABTS radical cation than alkyl ones. N-Ethyl-substituted DHPs showed the lowest reactivity. Kinetic results were compared with either trolox or nisoldipine. Using deuterium kinetic isotope effect studies, we have proved that the hydrogen of the 1-position of the DHP ring is involved in the proposed mechanism. This fact is mostly noticeable in the case of alkyl radicals. In all cases, the respective pyridine derivative was detected as the main product of the reaction.
合成了一系列在二氢吡啶环中含有仲氮或叔氮的C4-取代的1,4-二氢吡啶（DHP）。所有这些化合物以及一些市售的DHP衍生物在pH 7.4的水性介质中，针对烷基、烷基过氧自由基和ABTS自由基阳离子的潜在清除作用进行了测试。动力学速率常数通过紫外/可见光谱法或气相色谱/质谱技术进行评估。测试的化合物对烷基过氧自由基和ABTS自由基阳离子的反应速度比对烷基自由基的反应速度更快。N-乙基取代的DHP显示出最低的反应活性。将动力学结果与生育三烯酚或尼索地平进行了比较。通过氘动力学同位素效应研究，我们证明了DHP环1位的氢参与了所提出的反应机制。这一事实在烷基自由基的情况下最为明显。在所有情况下，相应的吡啶衍生物被检测为反应的主要产物。
