Nagy Peter I, Erhardt Paul W
Center for Drug Design and Development, College of Pharmacy, The University of Toledo, Toledo, OH 43606-3390, USA.
J Phys Chem B. 2005 Mar 31;109(12):5855-72. doi: 10.1021/jp045570q.
Monte Carlo simulations have been performed to explore the solution structure of ethyl, isopropyl, isobutyl, and tertiary butyl alcohols in pure water, pure acetonitrile, and different mixtures of the two solvents. The explicit solvent studies in NpT ensembles at T = 298 K illustrate that the solute "discriminates" the solvent's components and that the composition of the first solvation shell differs from that of the bulk solution. Since the polarizable continuum dielectric method (PCM) does not presently model the solvation of molecules with both polar and apolar sites in mixed protic solvents, we suggest a direction for further program development wherein a continuum dielectric method would accept more than one solvent and the solute sites would be solvated by user-defined solvent components. The prevailing solvation model will be determined upon the lowest free energy calculated for a particular solvation pattern of the solute having a specific conformational/tautomeric state. Characterization of equilibrium hydrogen-bond formation becomes a complicated problem that depends on the chemical properties of the solute and its conformation, as well as upon the varying nature of the first solvation shell. For example, while the number of hydrogen bonds to secondary and tertiary alcohol solutes are nearly constant in pure water and in water-acetonitrile mixtures with at least 50% water content, the number of hydrogen bonds to primary alcohols gradually decreases for most of their conformations when acetonitrile content is increased. Nonetheless, the calculations indicate that O-H...O(water) hydrogen bonds are still possible in a small fraction of the arrangements for the solution models with water content of 30% or less. The isopentene solute does not form any observable hydrogen bonds, despite having an electron-rich, double-bond site.
已进行蒙特卡罗模拟，以探究乙醇、异丙醇、异丁醇和叔丁醇在纯水、纯乙腈以及这两种溶剂的不同混合物中的溶液结构。在298K的NpT系综中进行的显式溶剂研究表明，溶质“区分”溶剂的成分，并且第一溶剂化层的组成与本体溶液不同。由于目前极化连续介质介电方法（PCM）无法对在混合质子溶剂中同时具有极性和非极性位点的分子的溶剂化进行建模，我们提出了进一步程序开发的方向，即连续介质介电方法将接受不止一种溶剂，并且溶质位点将由用户定义的溶剂成分进行溶剂化。占主导地位的溶剂化模型将根据为具有特定构象/互变异构状态的溶质的特定溶剂化模式计算出的最低自由能来确定。平衡氢键形成的表征成为一个复杂的问题，它取决于溶质的化学性质及其构象，以及第一溶剂化层的变化性质。例如，虽然在纯水和水含量至少为50%的水 - 乙腈混合物中，与仲醇和叔醇溶质形成的氢键数量几乎恒定，但当乙腈含量增加时，对于大多数构象，与伯醇形成的氢键数量会逐渐减少。尽管如此，计算表明，对于水含量为30%或更低的溶液模型，在一小部分排列中，O - H...O（水）氢键仍然是可能的。异戊烯溶质尽管有一个富电子的双键位点，但不会形成任何可观察到的氢键。
