Experimental Probing and Molecular Modeling of Key Sorbent-Solute-Solvent Interactions in Chiral Separations

该奖项由2009年美国复苏和再投资法案(公法111-5)资助。0854247王化学和生物分离计划授予的这一NSF奖项支持普渡大学的王念华(Linda)L.Wang教授和Elias I.Franses教授研究手性对映体对或外消旋混合物的吸附分离。这些分离是制药和精细化学品的一个关键问题。这是一个综合性的研究和教育项目。一种新的方法被用来理解一类主要的衍生直链淀粉和纤维素的手性吸附剂中的吸附剂-溶质-溶剂的相互作用。这些吸附剂用于超过50%的分析性和制备性吸附分离，涉及手性分子，手性分子要么是右手的，要么是左手的，但在其他方面物理和化学上是完全相同的。当只使用一种对映体时，沙利度胺等药物和许多他汀类药物、抑郁症和呼吸系统药物更有效。事实上，效果较差的对映体可能是有毒的或致畸的，就像20世纪50年代的S时代的沙利度胺一样。出于这些原因，FDA要求每对对映体都要进行分离和测试。用洗脱色谱研究了一系列具有一个或两个氢键(H键)官能团和疏水官能团的简单非手性溶质，以确定影响溶质在不同溶剂中保留因子的关键分子基团。在研究溶剂对吸附剂-溶质相互作用的影响时给予了特别的关注。选择无害的溶剂和最大限度地减少溶剂的使用对于环境和工人安全都很重要。各种先进的实验物理化学方法，包括红外光谱、固体核磁共振光谱和X射线衍射，被用来帮助识别由于吸附溶质和溶剂而引起的关键分子相互作用和聚合物吸附膜的结构变化。分子模拟被用来可视化、阐明、教育学生和预测有无溶剂的对映体分子的结合能。将预测结果与高对映体分辨率的溶质的色谱分离结果和光谱结果进行了比较(该吸附剂-溶剂组合具有良好的分离效果)。了解单个官能团的特定相互作用被用来解释溶质与两个或更多官能团在不同溶剂和不同温度下的保留行为和对映体选择性(分离质量)。将层析研究与直接探测技术和分子模拟相结合，在科学上是独一无二的，对这一研究领域具有变革性。这些结果为选择溶剂、吸附剂和温度、优化单一对映体生产的工艺设计提供了新的规则、见解和一般指导方针。这种理解是理解大分子与表面或其他分子之间更复杂的相互作用的基础。在分子水平上提高对特定手性识别机制相互作用的科学理解可能会导致其他领域的创新，如传感器、生物材料、药物设计和纳米技术。手性拆分是生产安全和廉价的对映体药物的关键。这项研究旨在帮助降低分析和生产规模手性分离的成本。该项目将改进手性层析的研究基础设施，以及表征吸附剂和薄膜及其与各种溶质相互作用的技术。这项研究将影响两名研究生和两名本科生的培养，他们将接受一个重要技术领域的培训和专业，并可能导致进一步的基础研究和创新材料和工艺。其中一些学生将从代表性不足的少数族裔和女性学生群体中招募。这项研究将导致分离、界面工程、热力学和质量传输领域的几个研究生和本科生课程的教育改进。该项目旨在帮助提高美国工业和美国大学在一个重要的先进技术领域的竞争力。

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).0854247WangThis NSF award by the Chemical and Biological Separations program supports work by Professors Nien-Hwa (Linda) L.Wang and Elias I. Franses of Purdue University to study adsorptive separations of chiral enantiomer pairs, or racemic mixtures. These separations are a critical problem of the pharmaceutical and fine chemicals. This is an integrated research and education project. A new approach is used to understand the sorbent-solute-solvent interactions in a major class of chiral sorbents of derivatized amylose and cellulose. These sorbents are used in over 50% of all analytical and preparative adsorptive chiral separations, involving chiral molecules, which are either right-handed or left-handed, but otherwise exactly the same physically and chemically. Drugs such as thalidomide, and many statins, depression, and respiratory drugs are more effective when only one enantiomer is used. In fact, the less effective enantiomer may be toxic or teratogenic, as it happened with thalidomide in the 1950's. For these reasons the FDA has mandated that each enantiomer pair should be separated and tested. A series of simple non-chiral solutes with one or two hydrogen bonding (H-bonding) functional groups and hydrophobic functional groups are studied using elution chromatography, to identify the key molecular groups which contribute to solute retention factors in various solvents. Particular attention is given in the study of the effect of the solvent on sorbent-solute interactions. Choice of benign solvents and minimization of solvent use are important for the environment and for worker safety. Various advanced experimental physicochemical methods, including infrared spectroscopy, solid-state NMR (Nuclear Magnetic Resonance spectroscopy), and X-ray diffraction, are used to help identify the key molecular interactions and the structural changes of the polymer sorbent films, caused by adsorption of solutes and solvents. Molecular simulations are used to visualize, elucidate, educate the students, and predict the binding energies of the enantiomer molecules with and without solvent. The predictions are compared with chromatographic separation results and spectroscopic results for solutes of high enantioresolution (good separation with that sorbent-solvent combination). Understanding the specific interactions of the individual functional groups is used to interpret the retention behavior and enantioselectivities (quality of separation) of solutes with two or more functional groups in different solvents and at different temperatures. The combination of chromatography studies with direct probing techniques and molecular simulations is scientifically unique and transformative for this area of research. The results lead to new rules, insights, and general guidelines for selecting solvents, sorbents, and temperatures, for optimizing process design for production of single enantiomers. Such understanding is the foundation for understanding more complex interactions of large molecules with surfaces or other molecules. Improved scientific understanding of the interactions of the specific chiral recognition mechanisms at the molecular level could lead to innovation in other areas, such as sensors, biomaterials, drug design, and nanotechnology. Chiral separations are crucial for producing safe and affordable enantiomer drugs. This research aims at helping reduce costs of analytical and production scale chiral separations. The project should improve the research infrastructure in chiral chromatography and techniques for characterizing sorbents and thin films, and their interactions with various solutes. The research will impact the training of two graduate and two undergraduate students, who will be trained and specialize in an important technology area, and may lead to further fundamental research and innovative materials and processes. Some of these students will be recruited from under-represented minority and female student groups. The research will lead to educational improvements of several graduate and undergraduate courses, in the areas of Separations, Interfacial Engineering, Thermodynamics, and Mass Transport. The project aims to help enhance the competitiveness of the US industry and of the US universities in an important area of advanced technology.