Abstract
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.
- Copyright © 1976 by Academic Press, Inc.
MolPharm articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|
