| Abstract
| - Here, we explore the chemistry of the previously undocumented E form of diazeniumdiolateshaving the structure R1R2NN(O)NOR3. 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 Me2NN(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 R1= Me = R3 and R2 = 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 theE 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)NOCH2CH2Br 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.
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