SBIR Phase I: Molecular Modeling as a Screening Tool to Separate Enantiomers of Chiral Compounds Using Polysaccharide-based Chiral Stationary Phases for Orphan Drugs

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The broader impact/commercial potential of this Small Business Innovation Research Phase I project is to develop an effective cost saving screening technology based on molecular modeling for separating molecules that are identical except for geometric differences, that are present in the development of pure orphan drugs. The separation of these molecules from one another is both important and challenging, since while one molecular form can have beneficial therapeutic value, the other molecular form can at best be benign but often can also be toxic. The implementation of this proposed strategy should have a significant impact on the rapid development of new medicines especially those being formulated by drug manufacturers with limited R&D resources. Ultimately, a successful outcome from this project will accelerate drug discovery in pharmaceutical companies and allow for unique drug formulations to be available in the market to consumers that are relying on them for treatment and to extend their life. The technical objectives in this Phase I research project are to develop a predictive molecular model which can guide experimentation in purifying chiral molecules for pharmaceutical companies to use in drug formulations. Over the past decade, the efforts in the pharmaceutical community have shifted to studying pure chiral drugs rather than racemic mixtures due to the discovery that certain enantiomers may have negative implications on the human body by causing toxicity or certain defects. Owed to the possibility of harmful side effects from racemic mixtures, the commercial focus has turned to purifying pharmaceutical drugs to create an enantio-pure chiral product. The modeling tools to be built will take advantage of significant proprietary data Orochem has developed in the past few years as part of their R&D activities in developing new and innovative methods for the separation of racemic mixtures of enantiomers. The initial molecular model will demonstrate interaction between a Chiral Stationary Phase, mobile phase, and enantiomers known to be resolved by the particular system. The dynamic model will allow examination of conformations of the enantiomer within the chiral separation system in a more detailed fashion since molecular modeling input parameters include detail on the bond, angle, and dihedral energies present in molecules of the racemate. Overall, molecular simulations of chromatographic separations will lessen the time of discovery of systems for separating these chiral isomers by leading experimental investigation and aiding research scientists at pharmaceutical companies to identify suitable chiral stationary phases apriori. This will reduce both the cost and time of bringing new drugs to market.