Novel Chiral Separation Based on Mixed Conglomerate Crystallization

基于混合团聚物结晶的新型手性分离

• 批准号: 1066608
• 负责人: Donna Blackmond
• 金额: $ 33.44万
• 依托单位: The Scripps Research Institute
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2015-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1066608&HistoricalAwards=false
• 关键词: Novel; Chiral; Separation; Based; Mixed

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.

1066608 Blackmond拟议研究的目的是开发一种新的概念，用于手性分离和手性扩增，该概念基于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。这项工作有望扩大目前适用于结晶方法分离的手性化合物的馏分。 大多数手性化合物以两种形式之一结晶：如果相似的对映异构体之间的相互作用是优选的，则手性分子的每一个手性分子的单独晶体将形成（称为聚集体）。如果优选异手性相互作用，则每个晶体将含有手性分子的左手和右手的1：1混合物（称为外消旋化合物）。虽然前一种类型的化合物显然更容易分离，但后一种类型在自然界中最常见，约为10：1的偏好。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，将外消旋化合物转化为我们所说的“可调聚集体”或“混合聚集体”。该项目的第二部分将研究选定的候选系统如何从晶体的近外消旋混合物演变为单一的固体对映体，这是通过该小组先前为简单的砾岩系统证明的“手性遗忘”过程的延伸。目的是证明混合物中存在的每个不同手性分子的固相对映体纯度的出现。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，这项研究将扩大这种新的分离方法在制药工业中的应用。分子手性的特性长期以来一直吸引着科学家和外行人。除了它的实用方面，单手性是地球上生命起源之谜的一部分。这一领域的研究成为一个极好的渠道，以吸引年轻观众考虑化学，生物学或工程学研究的方式唤起科学的挑战和乐趣。我们将与斯克里普研究所（TSRI）的多方面的学术准备和推广计划，通过支持高中生作为我的实验室暑期研究实习生。这提高了人们对生物医学和化学科学职业机会的认识，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。沿着这些思路，一个题为“氨基酸如何左转：探索生物同手性的起源”的一般兴趣研讨会已经开发出来。 除了参与演讲和指导高中学生，教师咨询讲座系列与TSRI的网络为妇女在科学，涉及专业和个人指导研究生和博士后研究员举行。