ERI: Solubility-Boosting Effect of Lattice Impurities in Anisotropic Crystals

了解颗粒溶解度对于工业结晶器、半导体制造操作和分离过程（如反渗透海水淡化）的设计至关重要，在这些过程中，不必要的结垢是一个操作挑战。这是一个重要的设计考虑，在药物的合成，溶解度的控制是最佳的药物输送要求。缺乏溶解度控制也可能是食品和膳食补充剂配方中的一个限制因素。以往对晶体材料溶解度的研究主要集中在晶格结构和液体组成对溶解度的影响上。这些研究在很大程度上忽略了单个晶体中组成变化在溶解度中的作用，可能是由于测量这些变化的困难。该项目将研究晶体内的成分变化是否会导致晶体面之间的不同溶解度，从而导致单个晶体内的不均匀生长或溶解。这项研究将挑战目前晶体生长和溶解过程的模型，并将对晶体材料中杂质的释放方式产生新的见解，为从药品中提取潜在有毒杂质创造新的途径。该项目将为10至20名本科生和1名博士生提供教育，他们将获得结晶过程和结晶材料分析的实践经验，这些技能在制药行业很受重视，但在美国的毕业生中却很少找到。本项目为研究晶格掺杂杂质对晶体溶解度的影响提供了一种新的方法。该提议是基于这样一个前提，即晶体可以表现出不同程度的组成各向异性，某些区域完全负责承载杂质。这促使研究计划调查晶格杂质对晶体形式稳定性和溶解度的影响，这些特性应该从单个晶体方面进行研究，而不是从整体上研究粉末（晶体）。该项目旨在证明单晶可能在其晶格中呈现多个溶解度值的假设，并且这些差异可以在设计新的杂质分离策略时加以利用。这个研究项目分为两个研究目的。在目标1中，研究将集中在表征单晶中杂质的各向异性，并研究杂质梯度如何影响溶解和生长。目标2将扩展到晶体悬浮时效动力学的研究，研究共存的纯晶格和不纯晶格如何影响悬浮时效过程中的溶解和生长行为。本研究将利用具有透明溶质和不透明杂质的模型各向异性体系，可以很容易地研究各向异性的存在和程度。拟议的研究与一项教育计划相结合，该计划将为本科生和研究生提供分离过程和材料科学的专业技能，以及在多学科团队中工作的经验。根据研究计划的两个目标，本科生将被分为两个小组，从而形成一个有效的机制，将PI的研究和教育工作结合起来。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Understanding particle solubility is critical for the design of industrial crystallizers, semiconductor manufacturing operations, and separation processes such as reverse osmosis desalination, where unwanted scaling is an operational challenge. It is an important design consideration in the synthesis of pharmaceuticals where control of solubility is required for optimal drug delivery. The lack of solubility control also can be a limiting factor in the formulation of food products and diet supplements. Past studies of the solubility of crystalline materials have focused on the effects of crystal lattice structure and liquid composition on solubility. These studies have largely ignored the role composition variations within individual crystals play in solubility, likely due to the difficulty of measuring these variations. This project will investigate whether compositional variations within a crystal can result in different solubilities among the crystal facets, resulting in uneven growth or dissolution within individual crystals. The research will challenge current models of crystal growth and dissolution processes and will produce new insights into how impurities are released from crystalline materials, creating new routes to extracting potentially toxic impurities from pharmaceutical products. The project will contribute to the education of ten to twenty undergraduate students and one Ph.D. student, who will gain hands-on experience with crystallization processes and analysis of crystalline materials, a skillset valued in the pharmaceutical industry but rarely found in graduates joining the U.S. workforce.This project presents a new approach to studying the effect of lattice-incorporated impurities on crystal solubility. The proposal is based on the premise that crystals can exhibit differing degrees of composition anisotropy, with certain regions being entirely responsible for hosting impurities. This motivates the research plan to investigate the effect that lattice impurities have on crystal form stability and solubility, that these properties should be studied with respect to individual crystal facets and not on powders (of crystals) as a whole. This project sets out to prove the hypothesis that a single crystal may present multiple solubility values across its lattice, and that those differences can be leveraged in the design of novel impurity separation strategies. This research project is divided in two research aims. In Aim 1, research will concentrate on characterizing anisotropy of impurities within single crystals and investigating how impurity gradients affect dissolution and growth. Aim 2 will then expand to the study of crystal suspension aging dynamics by investigating how coexisting pure and impure lattices affect the dissolution and growth behaviors during suspension aging. The research will make use of model anisotropic systems with transparent solutes and opaque impurities, where the presence and extent of anisotropy can be easily studied. The proposed research is integrated with an education plan that will provide undergraduate and graduate students with specialized skills in separation processes and materials science, as well as with experience working in multidisciplinary teams. The undergraduate students will be divided into two groups, aligned with the two Aims of the research proposal, resulting in an effective mechanism for integrating the PI’s research and education efforts.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.