Ab initio investigation of interactions between models of membrane-active compounds and polar groups of membranes: complexes involving amine, ether, amide, phosphate, and carboxylate.
Ab initio investigation of interactions between models of membrane-active compounds and polar groups of membranes: complexes involving amine, ether, amide, phosphate, and carboxylate.
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从头算研究膜活性化合物模型和膜极性基团之间的相互作用：涉及胺、醚、酰胺、磷酸盐和羧酸盐的复合物。
DOI：
10.1002/jps.2600800409
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发表时间：
1991
影响因子：
3.8
通讯作者：
Scheiner,S
中科院分区：
文献类型：
--
作者：
Remko,M;Scheiner,S
用从头算(mini-1)分子轨道计算方法研究了抗心律失常药与细胞膜极性基团之间的氢键和质子转移，甲胺阳离子、二甲醚和N-甲基乙酰胺作为抗心律失常药美西律和托卡胺的缔合中心。选择甲酸盐和磷酸阴离子、甲胺阳离子和甲酰胺作为膜极性基团的模型。质子化的甲胺与甲酸盐和磷酸阴离子形成非常强的络合物。然而，甲酸盐CoO-基团是比磷酸PO-4基团更好的质子受体。研究了比水合作用对HCOO-…中质子势函数的影响+HNH2CH3和H2PO4…+HNH2 CH3系统。在平衡距离RO…下计算的质子势函数N，只有一个最小值。Long erRO…的从头计算N=0.275 nm距离表示双极小势。不断增加的水化作用稳定了对应于带电O-…的第二个最小值+HN结构。含有托卡胺和美西律的酰胺和醚基以及膜的质子化伯胺基团的络合物相对较弱。最弱的氢键是由药物的氨基(处于中性和电离状态)与多肽基形成的。
Ab initio (MINI-1) molecular orbital calculations were performed on model systems to investigate the hydrogen bonds and proton transfer between antiarrhythmics and polar groups of the cell membrane, Methylamine cation, dimethyl ether, and N-methylacetamide served as models of associative sites for the antiarrhythmics mexiletine and tocainide. Formate and phosphate anions, the methylamine cation, and formamide were chosen as models for the membrane polar groups. Protonated methylamine forms a very strong complex with the formate and phosphate anions. However, the formate COO-group is a better proton acceptor than the phosphate PO-4group. The effect of specific hydration on the proton potential functions was investigated in the HCOO-…+HNH2CH3and H2PO4…+HNH2CH3systems. The proton potential functions, calculated at the equilibrium distancesRO…N, with a single minimum were found. The ab initio calculations at the longerRO…N= 0.275 nm distance indicate double-minimum potentials. The increasing hydration stabilizes a second minimum corresponding to the charged O-…+HN structures. The complexes involving the amide and ether groups of tocainide and mexiletine and the protonated primary amine group of the membrane are considerably weaker. The weakest hydrogen bonds are formed by the amine group of the drug (in its neutral and ionized state) with the peptide group.