Institute for BioComplexity and Informatics and Department for Biological Sciences, University of Calgary, 2500 University Drive, Calgary, AB, Canada T2N 1N4.
J Phys Chem B. 2010 May 20;114(19):6401-8. doi: 10.1021/jp908339j.
The partitioning of a substrate from one phase into another is a complex process with widespread applications: from chemical technology to the pharmaceutical industry. One particularly well-known and well-studied example is 2-bromo-2-chloro-1,1,1-trifluoroethane (halothane) trafficking through the lipid bilayer. Halothane is a model volatile anesthetic known to impact functions of model lipid bilayers, altering the structure and thickness upon its partitioning from the bulk phase. A number of theoretical and experimental investigations suggest the importance of electronic polarizability, determining a preference for halothane to partition in the interfacial systems as in lipid bilayers or binary solvents. The recently published protocol for the development of polarizable force fields based on the classical Drude model has provided fresh impetus to efforts directed at understanding the molecular principles governing complex thermodynamics of the hydrophobic hydration. Here, molecular simulations were combined with free energy simulations to study solvation of halothane in polarizable water and methanol. The absolute free energy of halothane solvation in different solvents (water, methanol, and n-hexane) has been evaluated for additive and polarizable models. It was found that both additive and polarizable models provide an adequate description of the halothane solvation in high-dielectric (polar) solvents such as water, but explicit accounting for electronic polarization is imperative for a correct description of the solvation thermodynamics in nonpolar systems. To study halothane dynamics in binary mixtures, all-atom molecular dynamics (MD) simulations for halothane-methanol mixtures in a wide range of concentrations were performed alongside an analysis of structural organization, dynamics, and thermodynamic properties to dissect the molecular determinants of the halothane solvation in polar and amphiphilic liquids such as methanol. Additionally, a theoretical test of the hypothesis on the weak hydrogen bonding of halothane and methanol in the condensed phase is provided, which was presented on the basis of spectroscopic analysis of the C-H vibrations in different gas-phase complexes. The simulations performed in the condensed phase suggest that hydrophobic interactions between halothane and methanol play a dominant role in preferential solvation.
从一相到另一相的底物分配是一个复杂的过程，具有广泛的应用：从化学技术到制药工业。一个特别著名和研究充分的例子是 2-溴-2-氯-1,1,1-三氟乙烷（氟烷）通过脂质双层的运输。氟烷是一种已知影响模型脂质双层功能的挥发性麻醉剂，在其从主体相分配时会改变结构和厚度。许多理论和实验研究表明，电子极化率的重要性决定了氟烷优先分配在界面体系中，如在脂质双层或二元溶剂中。最近发表的基于经典 Drude 模型的极化力场开发方案为理解控制疏水水合复杂热力学的分子原理提供了新的动力。在这里，分子模拟与自由能模拟相结合，研究了氟烷在可极化水中和甲醇中的溶剂化。在不同溶剂（水、甲醇和正己烷）中，评估了氟烷溶剂化的绝对自由能，包括加性和极化模型。结果表明，加性和极化模型都能对氟烷在高介电（极性）溶剂（如水）中的溶剂化提供适当的描述，但要正确描述非极性体系的溶剂化热力学，必须明确考虑电子极化。为了研究氟烷在二元混合物中的动力学，在广泛的浓度范围内进行了氟烷-甲醇混合物的全原子分子动力学（MD）模拟，并对结构组织、动力学和热力学性质进行了分析，以剖析氟烷在甲醇等极性和两亲性液体中的溶剂化的分子决定因素。此外，还提供了对氟烷和甲醇在凝聚相中弱氢键假说的理论检验，该假说基于不同气相复合物中 C-H 振动的光谱分析。在凝聚相中进行的模拟表明，氟烷和甲醇之间的疏水相互作用在优先溶剂化中起主导作用。
