Here, we explore the chemistry of the previously undocumented
E form of diazeniumdiolateshaving the structure R
1R
2NN(O)=NOR
3. Reported crystallographic studies have uniformly revealed the
Zconfiguration, and our attempts to observe a
Z
E conversion through thermal equilibration or photochemicalmeans have, until now, consistently failed to reveal a significant amount of a second conformer. As atypical example, the NMR spectrum of trimethyl derivative Me
2NN(O)=NOMe revealed no evidence for asecond configuration. Electronic structure calculations attribute this finding to a prohibitively highinterconversion 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 bydissociating 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 isolableif a
Z anion were formed and given sufficient time to assume the
E configuration, then quenched by reactionwith 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-memberedheterocycle that was crystallographically characterized as containing the -N(O)=NO- functional group inthe
E configuration. The results suggest an approach for generating pairs of
Z and
E diazeniumdiolates forsystematic comparison of the rates at which the individual isomers release bioactive NO and of otherphysicochemical determinants of their biomedical utility.