Solvent-structuring at the interface between crystals and mixed organic-aqueous solvents

非技术摘要：溶液结晶是广泛的工业、实验室和生理过程的基础。近年来，有机和有机混合水溶液作为制备结晶材料和结晶分离(或提纯)的替代溶剂引起了人们越来越大的兴趣，特别是在医药和精细化学品等高价值材料中。与从水溶液中结晶相比，从有机溶剂中生长晶体的基本过程的理解水平受到严重限制。缺乏对相关基本机制和途径的了解，已成为对有机和混合有机-水介质中结晶的优化和控制的合理方法的主要障碍。这个项目的目的是提供对包括从混合溶剂中结晶的分子过程的理解，重点关注潜在的溶剂结构的热力学和动力学结果。技术摘要：有机和混合溶剂在结晶过程中所起的作用是本项目所要解决的开放问题。用先进的原子力显微镜成像表征了晶体-溶液界面的溶剂结构，并与它们对结晶热力学的影响进行了关联。通过确定溶质分子在到达晶体生长位置的过程中所采取的步骤，阐明了溶剂的化学性质如何影响结晶机理。阐明了将分子结合到晶体中的活化势垒的性质，以确定溶剂的结构和与溶剂分子的相互作用是否是存在该活化势垒的主要机制。确定分子机理中的步骤及其各自的调控参数，为优化和控制有机和混合溶剂的结晶和抑制缺陷诱导的不稳定性提供了工具。比较了几个卟啉-溶剂对的数据，阐明了溶剂中化学部分的作用以及它们在形成溶剂结构中形成氢键和范德华键的能力。解开包括结晶在内的相互交错的化学和物理过程，并确定相关的控制参数，代表了有机晶体合理设计的新范式。

Non-technical Abstract:Solution crystallization underlies a broad range of industrial, laboratory, and physiological processes. In recent years, organic and mixed organic-aqueous liquids have garnered increased interest as an alternative solvent for the preparation of crystalline materials and separation (or purification) by crystallization, in particular for high-value materials such as pharmaceuticals and fine chemicals. In contrast to crystallization from aqueous solvents, the level of understanding of the fundamental processes of crystal growth from organic solvents is severely limited. The lack of insight into the relevant fundamental mechanisms and pathways has emerged as the main obstacle to a rational approach to the optimization and control of crystallization in organic and mixed organic-aqueous media. The objective of this project is to provide understanding of the molecular processes comprising crystallization from mixed solvents focusing on the thermodynamic and kinetic consequences of potential solvent structuring.Technical Abstract:The roles that organic and mixed solvents play in crystallization are the open question addressed in this project. The solvent structures at the crystal-solution interface are characterized by advanced atomic force microscopy imaging and correlated with their effects on the thermodynamics of crystallization. How the chemical properties of the solvent affect the crystallization mechanism is elucidated by determining the steps that a solute molecule takes en route to a crystal growth site. The nature of the activation barrier for incorporation of molecules into the crystal is elucidated to establish whether solvent structuring and interactions with solvent molecules are the primary mechanisms underlying the existence of this barrier. Determining the steps in the molecular mechanism and their respective governing parameters provides tools to optimize and control crystallization from organic and mixed solvents and suppress defect-inducing instabilities. Comparing data for several porphyrin-solvent pairs elucidates the roles of the chemical moieties in the solvents and their abilities to form hydrogen and van der Waals bonds in the formation of solvent structures. Untangling the interlaced chemical and physical processes comprising crystallization and identifying the relevant governing parameters represents a new paradigm in the rational design of organic crystals.