Ravanel P, Taillandier G, Tissut M, Benoit-Guyod J L
Ecotoxicol Environ Saf. 1985 Jun;9(3):300-20. doi: 10.1016/0147-6513(85)90048-x.
Twenty-three chlorinated monophenols were investigated for their uncoupling and inhibitory properties on plant mitochondria. All the studied compounds had uncoupling properties but their activity was submitted to quantitative changes from 1- to 400-fold, according to the substitution. They also had inhibitory properties on the electron transfer at a level located upstream to the quinone pool. Three inhibitory types could be recognized: (a) chlorophenols inhibiting similarly the oxidation of every type of substrate (NADH, succinate, alpha-ketoglutarate, at pH 7.2; malate, at pH 7.5), (b) chlorophenols inhibiting first complex I, and (c) chlorophenols inhibiting first complex II. In this last case, the presence of substituents at the 2 and 6 positions increases selectively the inhibition of succinate oxidation. A quantitative structure activity relationship (QSAR) study was undertaken and showed that a good correlation appeared between the steric parameter, 1 chi v, and the inhibitory properties with NADH as substrate. This result could be explained by the binding of the chlorinated phenols with NADH dehydrogenase whose position, on the external surface of the mitochondrial membrane, is favorable to good accessibility of the xenobiotic. Equations for inhibitory properties with other substrates were clearly different. The relation between the uncoupling activity and the studied parameters was more complex but a good correlation occurred with the steric parameter (sigma D, A) and the electronic parameter sigma. Neither log P nor sigma alone gave equations of good quality. These results suggest a competition between the chlorophenol mobility in the inner membrane, necessary for uncoupling, and binding with different proteins in the same membrane on which the inhibitory activity is dependent.
对23种氯化单酚对植物线粒体的解偶联和抑制特性进行了研究。所有研究的化合物都具有解偶联特性，但根据取代情况，其活性有1至400倍的定量变化。它们对醌池上游水平的电子传递也具有抑制特性。可识别出三种抑制类型：(a) 对每种底物（pH 7.2时的NADH、琥珀酸、α-酮戊二酸；pH 7.5时的苹果酸）氧化具有相似抑制作用的氯酚，(b) 首先抑制复合体I的氯酚，以及(c) 首先抑制复合体II的氯酚。在最后一种情况下，2位和6位取代基的存在选择性地增加了对琥珀酸氧化的抑制作用。进行了定量构效关系（QSAR）研究，结果表明，空间参数1 chi v与以NADH为底物时的抑制特性之间存在良好的相关性。这一结果可以通过氯化酚与NADH脱氢酶的结合来解释，NADH脱氢酶位于线粒体外膜表面，有利于外源化合物的良好可及性。与其他底物的抑制特性方程明显不同。解偶联活性与所研究参数之间的关系更为复杂，但与空间参数（sigma D, A）和电子参数sigma存在良好的相关性。单独的log P或sigma都不能给出高质量的方程。这些结果表明，内膜中氯酚的流动性（解偶联所必需）与同一膜中不同蛋白质的结合之间存在竞争，而抑制活性取决于这些蛋白质。
