Abstract
Ab initio calculations at the MP2/6-31G* level have shown that variously substituted di- and trifluorobenzenes form non-covalent complexes with benzene that adopt either aromatic–aromatic or H---F binding, the choice being determined by the pattern of fluorination. The binding energies of these structures are from 3.4 to 4.5 kcal mol−1. This range is large enough to account for observed variations in the binding affinity of a library of fluoroaromatic inhibitors of carbonic anhydrase. This enzyme has an aromatic amino acid at a central position in the active site. The diverse modes of binding of the dimers also suggest that aggregates of fluorobenzenes might adopt specified 3-dimensional shapes in the solid state.
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Acknowledgments
AJ thanks Swarthmore College, the Petroleum Research Fund, DuPont (Young Professor Award) and the Howard Hughes Medical Institute for support. AMS thanks the City University of New York for a PSC-CUNY award.
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Chandra, P.P., Jain, A. & Sapse, AM. An ab initio study of di- and trifluorobenzene–benzene complexes as relevant to carbonic anhydrase II–drug interactions. J Mol Model 10, 1–5 (2004). https://doi.org/10.1007/s00894-003-0146-9
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DOI: https://doi.org/10.1007/s00894-003-0146-9