Stereochemical Origins of Chromophore Extension in O2-Substituted Diazeniumdiolates, Prodrugs of Nitric Oxide

Abstract

Ultraviolet spectral data for nitric oxide prodrugs of structure R2NN(O)=NOR′ tend to fall into two classes: those in which R2N is pyrrolidinyl have λmax near 255 nm when R′ is a simple alkyl substituent, while those in which R2N is not pyrrolidinyl display λmax around 230 nm. To test the hypothesis that this spectral difference might reflect an electronic interaction large enough to affect key bond lengths and the configuration at the R2N nitrogen, we have compared the crystal structures of two compounds in which R′ was β-D-glucopyranosyl tetraacetate and R2N was pyrrolidinyl versus diethylamino. The X-ray studies revealed a pyramidyl R2N nitrogen for the diethylamino derivative while the pyrrolidine derivative’s R2N approached planarity, consistent with substantial electronic interaction between the N(O)=NOR′ chromophore and pyrrolidine’s (but not diethylamine’s) nitrogen atom. Compensatory changes in key bond lengths were also seen. These findings indicate that overlap between the pyrrolidine nitrogen’s p orbital and the N(O)=NOR′ chromophore can be an important determinant of structure and electron distribution in the diazeniumdiolate series.