Extended Hückel theory and the method of perturbative configuration interaction using localized orbitals (PCILO) predict strikingly different results for the conformation of histamine cations. Extend Hückel theory predicts that both mono- and dications should exist as mixtures of trans and gauche forms, as observed with NMR studies in solution, whereas PCILO predicts a strong preference of the monocation for the gauche form and of the dication for the trans form, as shown by X-ray crystallography. In order to resolve this dilemma, nonempirical ab initio computations have been performed for the two species. They confirm the results of the PCILO calculations and indicate that the intrinsic conformational preferences of the isolated molecule correspond closely to the crystal structure data. In order to elucidate the situation prevailing in solution, the principal hydration sites of the histamine cations have been determined by calculations ab initio, and new conformational energy maps have been constructed for the hydrated species by the "supermolecule" approach within the PCILO method. The results indicate that hydrated cations should have a much weaker tendency than free ones for an exclusive conformation and should exist in solution as a mixture of gauche and trans forms, in close agreement with NMR results. Similar computations are reported for the rare N1—H tautomer of histamine. Conformational and electronic differences appear between the two monocationic tautomers, which may be of significance for their activity at different receptors.
ACKNOWLEDGMENT The collaboration of P. Courrière in the construction of the PCILO conformational energy maps of the N1—H monocation, the dication, and N-trimethylhistamine is gratefully acknowledged.
- Copyright ©, 1974, by Academic Press, Inc.