Schäfer G, Trebst A, Büchel K H
Z Naturforsch C Biosci. 1975 Mar-Apr;30(2):183-9.
2-anilino-1,3,4-thiadiazoles carrying various substituents in the 5-position as well as in the benzene-ring were synthesized. The compounds were tested with rat-liver-mitochondria and with spinach-chloroplasts and revelaed to be potent uncouplers of both, oxidative and photosynthetic phosphorylation, with pI50-values rangeing from 6.79 to 4.05. At higher concentrations all compounds are inhibitors of the Hill-reaction. In mitochondria a fair correlation exists between pKa of the acidic NH-group and the uncoupling activity; a maximum is obtained around pKa equals 6.8, whereas in chloroplasts activity is shifted to more acid pKa-values. The compounds meet the requirements for uncouplers according to the chemi-osmotic theory, being lipophilic weak acids. N-methylation causes total loss of activity in mitochondrial oxidative phosphorylation. The ingibitory action on photosynthetic electron transport is located within photosystem II. This latter activity is almost independent of substituent effects in contrast to uncoupling of either respiratory- or photo-phosphorylation.
合成了在5位以及苯环上带有各种取代基的2-苯胺基-1,3,4-噻二唑。用大鼠肝线粒体和菠菜叶绿体对这些化合物进行了测试，结果表明它们是氧化磷酸化和光合磷酸化的有效解偶联剂，其半数抑制浓度（pI50）值在6.79至4.05之间。在较高浓度下，所有化合物都是希尔反应的抑制剂。在线粒体中，酸性NH基团的pKa与解偶联活性之间存在良好的相关性；在pKa约为6.8时达到最大值，而在叶绿体中，活性转移到酸性更强的pKa值。根据化学渗透理论，这些化合物符合解偶联剂的要求，是亲脂性弱酸。N-甲基化导致线粒体氧化磷酸化活性完全丧失。对光合电子传递的抑制作用位于光系统II内。与呼吸或光合磷酸化的解偶联作用相反，后一种活性几乎与取代基效应无关。
