Novel Chiral Separation Based on Mixed Conglomerate Crystallization

该研究的目的是基于Blackmond实验室最近开发的两种不同的对映体富集方法的协同组合，开发一种新的手性分离和手性扩增概念。这项工作有望扩大目前可通过结晶方法分离的手性化合物的比例。大多数手性化合物以两种形式之一结晶：如果类似对映体之间的相互作用是首选的，那么手性分子的每只手将形成单独的晶体（称为聚集体）。如果首选异手性相互作用，则每个晶体将包含手性分子（称为外消旋化合物）的左手和右手的1:1混合物。虽然前一种化合物显然更易于分离，但在自然界中最常见的是后一种化合物，其比例约为10:1。目前研究项目的第一部分寻求改变手性化合物相行为的方法，将外消旋化合物转变为我们所说的“可调聚合体”或“混合聚合体”。该项目的第二部分将研究选定的候选系统如何通过扩展“手性遗忘”过程，从晶体的近外消旋混合物演变为单一的固体对映异构体，该过程之前由该小组在简单的砾岩系统中证明。目的是证明出现的固相对映不纯的每一个不同的手性分子存在于混合物中。这项工作将有助于阐明动力学和热力学之间以及物理和化学速率过程之间的基本相互作用。最重要的是，本研究将扩大这种新型分离方法在制药工业中的应用。分子手性的性质长期以来一直吸引着科学家和外行人。除了它的实用性之外，单手性也是地球上生命起源之谜的一部分。这一领域的研究成为激发科学挑战和乐趣的极好渠道，以吸引正在考虑研究化学、生物或工程的年轻观众。我们将与scrip研究所（TSRI）的多方面学术准备和推广计划合作，支持一名高中生作为我实验室的暑期研究实习生。这提高了人们对生物医学和化学科学的职业机会的认识，并促进了公众对基础研究的兴奋及其与我们物质世界的联系的理解。沿着这条路线，已经开展了一个普遍感兴趣的研讨会，题为“氨基酸如何向左转向：探索生物同手性的起源”。除了参与对高中生的演讲和指导之外，教师咨询讲座系列还与TSRI的女性科学网络一起举办，包括对研究生和博士后的专业和个人指导。

1066608BlackmondThe objective of the proposed research is to develop a novel concept for chiral separations and chiral amplification based on a synergistic combination of two distinct methods for enantioenrichment recently developed in the Blackmond laboratories. This work promises to expand the fraction of chiral compounds currently amenable to separation by crystallization methods. Most chiral compounds crystallize in one of two forms: if the interaction between like enantiomers is preferred, then separate crystals of each hand of the chiral molecule will be formed (known as conglomerates). If heterochiral interactions are preferred, then each crystal will contain a 1:1 mixture of the left and right hands of the chiral molecule (known as racemic compounds). While the former type of compound is clearly more amenable to separation, it is the latter type that is most commonly found in Nature, by about a 10:1 preference. The first part of the current research project seeks ways to alter the phase behavior of chiral compounds to turn racemic compounds into what we term "tunable conglomerates" or "mixed conglomerates". The second part of the project will study how selected candidate systems may evolve from near racemic mixtures of crystals to a single solid enantiomorph through an extension of the "chiral amnesia" process previously demonstrated by this group for simple conglomerate systems. The goal is to demonstrate the emergence of solid phase enantiopurity for each distinct chiral molecule present in the mixture. This work will help to shed light on the fundamental interplay between kinetics and thermodynamics and between physical and chemical rate processes. Most significantly, this research will expand the application of this novel separation method in the pharmaceutical industry. The property of molecular chirality has long fascinated scientists and laymen alike. In addition to its practical aspects, single chirality is part of the mystery of the origin of life on earth. Research in this area becomes a superb conduit for evoking the challenges and joy of science in ways that appeal to young audiences contemplating the study of chemistry, biology, or engineering. We will team with The Scripp Research Institute's (TSRI) multi-faceted Academic Preparation and Outreach Programs by supporting a high school student as a summer research intern in my laboratories. This raises awareness of career opportunities in the biomedical and chemical sciences and fosters an understanding in the general public of the excitement of basic research as well as its connection to our material world. Along these lines a general interest seminar has been developed entitled "How Amino Acids Took a Left-Hand Turn: Probing the Origin of Biological Homochirality". In addition to becoming involved in speaking to and mentoring high school students, faculty advisory lecture series are held with TSRI's Network for Women in Science, involving both professional and personal mentoring to graduate students and postdoctoral fellows.