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

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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.