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

该奖项是根据2009年美国复苏和再投资法案（公法111-5）资助的。这项由美国国家科学基金会化学与生物分离项目颁发的奖项支持了普渡大学Nien-Hwa (Linda) L.Wang教授和Elias I. Franses教授对手性对映体对或外消旋混合物吸附分离的研究。这些分离是制药和精细化学品的关键问题。这是一个综合研究和教育项目。一种新的方法被用来了解一类主要的衍生直链淀粉和纤维素手性吸附剂的吸附剂-溶质-溶剂相互作用。这些吸附剂用于50%以上的分析性和制备性吸附性手性分离，涉及右手性或左手性手性分子，但在物理和化学上完全相同。仅使用一种对映体时，沙利度胺、许多他汀类药物、抑郁症和呼吸系统药物等药物更有效。事实上，效果较差的对映体可能有毒或致畸，就像20世纪50年代发生的沙利度胺一样。由于这些原因，FDA要求对每一对对映体进行分离和测试。利用洗脱色谱法研究了一系列具有一个或两个氢键官能团和疏水官能团的简单非手性溶质，以确定在各种溶剂中影响溶质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，给予了特别的注意。选择良性溶剂和尽量减少溶剂的使用对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（核磁共振波谱）和x射线衍射，被用来帮助识别关键的分子相互作用和聚合物吸附剂膜的结构变化，由溶质和溶剂的吸附引起。分子模拟用于可视化、阐明、教育学生和预测对映体分子在有溶剂和无溶剂情况下的结合能。将预测结果与高对映体分辨率溶质的色谱分离结果和光谱结果进行了比较（该吸附剂-溶剂组合分离效果好）。了解单个官能团的特定相互作用用于解释溶质在不同溶剂和不同温度下具有两个或两个以上官能团的保留行为和对映选择性（分离质量）。色谱研究与直接探测技术和分子模拟的结合在科学上是独特的，并且对这一研究领域具有变革性。这些结果为选择溶剂、吸附剂和温度提供了新的规则、见解和一般指导方针，用于优化生产单对映体的工艺设计。这种理解是理解大分子与表面或其他分子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。手性分离对于生产安全和负担得起的对映体药物至关重要。本研究旨在帮助降低分析和生产规模手性分离的成本。本项目应改善手性色谱的研究基础，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训，他们将在一个重要的技术领域接受培训并专攻，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民族和女性学生群体中招募。这项研究将有助于提高研究生和本科生在分离、界面工程、热力学和质量输运等领域的教学水平。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.