Chemistry of the diazeniumdiolates: Z ⇌ E isomerism

Yan Ni Wang, D. Scott Bohle, Challice L. Bonifant, Gwendolyn N. Chmurny, Jack R. Collins, Keith M. Davies, Jeffrey Deschamps, Judith L. Flippen-Anderson, Larry K. Keefer, John R. Klose, Joseph E. Saavedra, David J. Waterhouse, Joseph Ivanic

Research output: Contribution to journalArticle

Abstract

Here, we explore the chemistry of the previously undocumented E form of diazeniumdiolates having the structure R 1R 2NN(O)=NOR 3. Reported crystallographic studies have uniformly revealed the Z configuration, and our attempts to observe a Z → E conversion through thermal equilibration or photochemical means have, until now, consistently failed to reveal a significant amount of a second conformer. As a typical example, the NMR spectrum of trimethyl derivative Me 2NN(O)=NOMe revealed no evidence for a second configuration. Electronic structure calculations attribute this finding to a prohibitively high interconversion barrier of ∼40 kcal/mol. A similar result was obtained when we considered the case of R 1 = Me = R 3 and R 2 = H at the same levels of theory. However, when MeHNN(O)=NOMe was ionized by dissociating the N-H bond, the barrier was calculated to be lower by approximately 20 kcal/mol, with the E form of the anion being favored over Z. This circumstance suggested that an E isomer might be isolable if a Z anion were formed and given sufficient time to assume the E configuration, then quenched by reaction with an electrophile to trap and neutralize the E form and restore the putatively high interconversion barrier. Consistent with this prediction, basifying iPrHNN(O)=NOCH 2CH 2Br rapidly led to a six-membered heterocycle that was crystallographically characterized as containing the -N(O)=NO- functional group in the E configuration. The results suggest an approach for generating pairs of Z and E diazeniumdiolates for systematic comparison of the rates at which the individual isomers release bioactive NO and of other physicochemical determinants of their biomedical utility.

Original languageEnglish (US)
Pages (from-to)5388-5395
Number of pages8
JournalJournal of the American Chemical Society
Volume127
Issue number15
DOIs
StatePublished - Apr 20 2005
Externally publishedYes

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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    Wang, Y. N., Bohle, D. S., Bonifant, C. L., Chmurny, G. N., Collins, J. R., Davies, K. M., Deschamps, J., Flippen-Anderson, J. L., Keefer, L. K., Klose, J. R., Saavedra, J. E., Waterhouse, D. J., & Ivanic, J. (2005). Chemistry of the diazeniumdiolates: Z ⇌ E isomerism. Journal of the American Chemical Society, 127(15), 5388-5395. https://doi.org/10.1021/ja042258l