Theoretical ab initio study of lone pair and anion-π interactions in fluorinated tropolones

Complexes between several anions (or lone pair donor molecules) and fluorinated tropolones have been optimized at the RI-MP2/aug-cc-pVDZ level of theory. It has been recently demonstrated [J. Med. Chem. 54 (2011) 4462] that alpha-hydroxytropolone and manicol (5,7-dihydroxy-2-isopropenyl-9-methyl-1,2,3,4-tetrahydro-benzocyclohepten-6-one) are potent and specific inhibitors of the ribonuclease H activity of human immunodeficiency virus reverse transcriptase in vitro. In the active site a lone pair-pi interaction between a nitrogen atom of His539 amino acid and the tropolone ring is established. In this study we demonstrate that both lone pair-pi and anion-pi complexes are energetically favorable in two tropolone derivatives. The interaction has been characterized by means of the Bader's theory of "atoms-in-molecules". (c) 2012 Elsevier B.V. All rights reserved.