Research School of Chemistry, College of Science, The Australian National University, Canberra, ACT, 0200, Australia.
School of Mathematical and Physical Sciences, Faculty of Science, University of Technology Sydney, Sydney, NSW, 2007, Australia.
Org Biomol Chem. 2022 Dec 21;21(1):132-139. doi: 10.1039/d2ob02049a.
Aryl-urea substituted fatty acids are protonophores and mitochondrial uncouplers that utilise a urea-based synthetic anion transport moiety to carry out the protonophoric cycle. Herein we show that replacement of the urea group with carbamate, a functional group not previously reported to possess anion transport activity, produces analogues that retain the activity of their urea counterparts. Thus, the aryl-carbamate substituted fatty acids uncouple oxidative phosphorylation and inhibit ATP production by collapsing the mitochondrial proton gradient. Proton transport proceeds self-assembly of the deprotonated aryl-carbamates into membrane permeable dimeric species, formed by intermolecular binding of the carboxylate group to the carbamate moiety. These results highlight the anion transport capacity of the carbamate functional group.
芳基脲取代脂肪酸是质子载体和线粒体解偶联剂，它们利用基于脲的合成阴离子转运部分来进行质子载体循环。在此，我们表明，用先前未报道具有阴离子转运活性的氨基甲酸酯取代脲基团，会产生保留其脲对应物活性的类似物。因此，芳基氨基甲酸酯取代的脂肪酸通过崩解线粒体质子梯度来解偶联氧化磷酸化并抑制 ATP 的产生。质子通过去质子化的芳基氨基甲酸酯自组装成膜可渗透的二聚体物种来运输，该二聚体物种通过羧酸盐基团与氨基甲酸酯部分的分子间结合形成。这些结果突出了氨基甲酸酯官能团的阴离子转运能力。
