Williams D H, Searle M S, Mackay J P, Gerhard U, Maplestone R A
University Chemical Laboratory, Cambridge, United Kingdom.
Proc Natl Acad Sci U S A. 1993 Feb 15;90(4):1172-8. doi: 10.1073/pnas.90.4.1172.
An approach toward the estimation of binding constants for organic molecules in aqueous solution is presented, based upon a partitioning of the free energy of binding. Consideration is given to polar and hydrophobic contributions and to the entropic cost of rotor restrictions and bimolecular associations. Several parameters (derived from an analysis of entropy changes upon the melting of crystals and from the binding of cell wall peptide analogues to the antibiotic ristocetin A) which may be useful guides to a crude understanding of binding phenomena are presented: (i) amide-amide hydrogen bond strengths of -(1 to 7) +/- 2 kJ.mol-1, (ii) a hydrophobic effect of -0.2 +/- 0.05 kJ.mol-1.A-2 of hydrocarbon removed from exposure to water in the binding process, and (iii) free energy costs for rotor restrictions of 3.5-5.0 kJ.mol-1. The validity of the parameters for hydrogen bond strengths is dependent on the validity of the other two parameters. The phenomenon of entropy/enthalpy compensation is considered, with the conclusion that enthalpic barriers to dissociations will result in larger losses in translational and rotational entropy in the association step. The dimerization of some vancomycin group antibiotics is strongly exothermic (-36 to -51 kJ.mol-1) and is promoted by a factor of 50-100 by a disaccharide attached to ring 4 (in vancomycin and eremomycin) and by a factor of ca. 1000 by an amino-sugar attached to the benzylic position of ring 6 in eremomycin. The dimerization process (which, as required for an exothermic association, appears to be costly in entropy) may be relevant to the mode of action of the antibiotics.
本文提出了一种基于结合自由能分配来估算水溶液中有机分子结合常数的方法。考虑了极性和疏水作用，以及转子限制和双分子缔合的熵成本。给出了几个参数（这些参数源自对晶体熔化时熵变的分析以及细胞壁肽类似物与抗生素瑞斯托菌素A的结合），它们可能有助于粗略理解结合现象：（i）酰胺-酰胺氢键强度为-(1至7)±2 kJ·mol⁻¹，（ii）在结合过程中，每从暴露于水中去除1 Ų的烃，疏水效应为-0.2±0.05 kJ·mol⁻¹，（iii）转子限制的自由能成本为3.5 - 5.0 kJ·mol⁻¹。氢键强度参数的有效性取决于其他两个参数的有效性。考虑了熵/焓补偿现象，得出的结论是，解离的焓垒将导致缔合步骤中平移和旋转熵的更大损失。一些万古霉素类抗生素的二聚化是强烈放热的（-36至-51 kJ·mol⁻¹），并且在万古霉素和埃瑞霉素中，连接在4位环上的二糖可将其促进50 - 100倍，在埃瑞霉素中，连接在6位环苄基位置的氨基糖可将其促进约1000倍。二聚化过程（由于放热缔合的需要，其在熵方面似乎成本高昂）可能与抗生素的作用方式有关。
