The structures of certain compounds are known to spontaneously interchange between two different forms called tautomers. In pharmaceutical applications of these compounds, only one tautomer form acts as the active drug while the other may be more likely to cause unwanted side effects or be entirely inactive. The interchange process makes it impossible to physically separate the two tautomers, so studying the tautomer ratio requires analyzing the mixture using spectroscopy and advanced data analysis techniques. We propose using UV-visible spectroscopy and chemometrics to find the ratio of tautomers for 2-aminobenzimidazole in solution as an alternative to time-consuming and costly techniques like 15N-NMR. We collected spectra of 2-aminobenzamidozole (a model compound for imine-amine tautomerization) in various solvents and at various temperatures. These data sets were analyzed in the Matlab programing environment using the SIMPLISMA algorithm (simple to use interactive self-modeling mixture analysis) and an alternating least squares algorithm to determine the ratio of tautomers in different solutions, and to identify which tautomer is the major form under different conditions. Solvent based calculations are also being performed to add theoretical support to experimental findings.

Tautomerization in drug design: Study of an imine-amine pair using spectroscopy, chemometrics, and quantum theory

254th National Meeting (2017)

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