申请人前期发现聚乙二醇构建的拥挤环境诱导脂肪酸酐自催化水解出现了异常链长依赖现象，因此进一步探索其背后的热力学机制是一个很有意义的科学问题。本项目从构建不同类型大分子拥挤环境入手，系统研究拥挤环境内在物理性质变化、脂肪酸囊泡组装及二者协同诱导脂肪酸酐水解动力学过程中的焓、熵、自由能变化及交互影响的驱动力差异，试图揭示大分子拥挤诱导不同结构脂肪酸酐自催化水解反应的热力学本源。长期以来，大分子拥挤效应研究集中在其对蛋白质、核酸结构变化及酶催化反应的影响，尚未关注其控制小分子自组装及化学反应；而国际上脂肪酸酐水解及脂肪酸囊泡组装的研究均未考虑大分子拥挤效应。本研究的意义在于揭示系列大分子拥挤环境对不同结构脂肪酸酐自催化水解反应中调控规律的物理化学机制；同时也将大分子拥挤效应研究领域拓展向大分子调控小分子自催化反应及自组装研究；或许也对于理解人体肠道内大分子存在下脂肪的消化吸收有着重要的科学意义。

An unusual chain-length-dependent autocatalytic hydrolysis of fatty acid anhydrides induced by polyethylene glycol was found by our group recently. Therefore, further disclosing the thermodynamic mechanism behind the autocatalytic hydrolysis of fatty acid anhydrides in macromolecular crowding becomes an important scientific problem. In this proposal, the research starts with preparation of different kinds of macromolecular crowded solutions with varied structure and concentration. Systematical research will focus on the physiochemical properties of crowded media as well as the energy both in vesicles formation and in the hydrolysis of fatty acid anhydrides catalyzed by vesicles in the presence of macromolecular crowding. The driving force involved in the change of the enthalpy, the entropy and the Gibbs energy will be analyzed to find how the macromolecular crowding agents influence and control the autocatalytic hydrolysis of fatty acid anhydrides, which results in the unusual chain-length-dependent effect. Current research mainly focuses on the effect of macromolecular crowding agents on the structural change of proteins or nuclear acid as well as the kinetics of enzyme-catalyzed reactions. On the other hand, autocatalytic hydrolysis of fatty acid anhydrides catalyzed by the spontaneously formed vesicles in macromolecular crowded solutions remains unknown. Therefore, it is of great importance to discover the thermodynamic basis for this unusual chain-length-dependent autocatalytic hydrolysis of fatty acid anhydrides in macromolecular crowded conditions. Meantime, this research will open up an area to study how macromolecules control the reaction and self-assembly of small molecules. Moreover, it will provide useful information for understanding the hydrolysis of fats in small intestine where it is crowded and occupied by many macromolecular species.