BIOTHERMODYNAMIC STUDIES OF THE SOLVATION AND CLUSTERING OF NONIONIC AMPHIPHILES

长期目标：本研究的最终目的是提高我们对非离子两亲体在水和其他溶剂环境中自聚集可能影响生物化学和生物物理过程的能量学和途径的理解。具体目的：我们建议继续积累非离子两亲体和水的混合物的热力学数据。我们将主要关注那些在文献中信息最少的系统的混合焓。我们还将测量相同的两亲化合物和惰性溶剂庚烷的混合物的量热和体积性质。我们最近的研究清楚地表明，在惰性环境中形成不稳定的反胶束聚集。我们将继续发展策略来分析这些二元系统的过剩热力学性质和建立构效关系。我们计划将测量的混合焓与非离子两亲体溶剂化能的分子模型估计相关联。我们也希望通过两亲体+水的混合物来扩展我们早期对疏水代谢物的增溶作用的研究。健康相关性：有机物质，包括代谢物和治疗剂，在生命系统中的作用方式部分取决于其官能团的性质，部分取决于其聚集模式和修饰溶剂结构的方式。我们的目的是确定修饰两亲分子结构对溶剂化簇的稳定性和这种簇纳入疏水代谢物的能力的影响。

Long Term Goals: The ultimate purpose of this research is to improve upon our understanding of the manner in which the self-aggregation of non-ionic amphiphiles in water and other solvent environments might influence the energetics and pathways of biochemical and biophysical processes. Specific Aims: We propose to continue to accumulate thermodynamic data for mixtures of non-ionic amphiphiles and water. There will a major focus on the enthalpies of mixing of those systems for which there is the least amount of information in the literature. We will also measure calorimetric and volumetric properties of mixtures of the same amphiphiles and the inert solvent heptane. Our recent studies give a clear indication of the formation of labile reverse micellar aggregation in the inert environment. We shall continue to develop strategies for analyzing the excess thermodynamic properties of these binary systems and for the establishment of structure-activity relationships. We plan to correlate the measured enthalpies of mixing with molecular modelling estimates of the energies of solvation of the non-ionic amphiphiles. We also wish to extend our earlier studies of the solubilization of hydrophobic metabolites by amphiphile+ water mixtures. Health Relatedness: The manner in which organic substances, including metabolites and therapeutic agents, perform in living systems is partly dictated by the nature of their functional groups and partly by their patterns of aggregation and the manner in which modify solvent structures. Our aim is to determine the effects of modifying the amphiphile's molecular structure upon the stability of the solvated clusters and the ability of such clusters to incorporate hydrophobic metabolites.