RT Journal Article
SR Electronic
T1 Tautomerism and the Receptor Action of Histamine: a Mechanistic Model
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 738
OP 745
VO 12
IS 5
A1 HAREL WEINSTEIN
A1 DAVID CHOU
A1 CARL L. JOHNSON
A1 SUNGZONG KANG
A1 JACK PETER GREEN
YR 1976
UL http://molpharm.aspetjournals.org/content/12/5/738.abstract
AB The effect of deprotonation of histamine monocation on the dominant tautomeric forms of the molecule was analyzed theoretically from molecular orbital calculations ab initio. The electron charge redistribution caused by the interaction of the monocation with a negatively charged group. In both cases the result is a shift in the dominant tautomeric form caused by a change in the reactivity of the ring nitrogens, as demonstrated by the molecular electrostatic potentials and total molecular energies. A model for the role of this induced tautomerism in the activation of the histamine H2 receptor is proposed on the basis of these findings. ACKNOWLEDGMENTS The computations were supported in part by a grant of computer time from the Central Computer Facility of the City University of New York. The authors are grateful to Dr. W. F. Raub and the Chemical/Biological Information-Handling Program, Division of Research, National Institutes of Health, for providing access to the PROPHET system computer.