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 α-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–π interaction between a nitrogen atom of His539 amino acid and the tropolone ring is established. In this study we demonstrate that both lone pair–π and anion–π complexes are energetically favorable in two tropolone derivatives. The interaction has been characterized by means of the Bader’s theory of “atoms-in-molecules”.