Intramolecular Hydrogen Bond Reverting the Solvent Effect on Phosphorus Hyperfine Coupling Constants of β‐Phosphorylated Nitroxides

Abstract

Recently, we reported a dramatic solvent effect on the phosphorus hyperfine coupling constant a of β-phosphorylated six-membered ring nitroxides, that is, approximately 25 G of difference in a from n-hexane to water (Org. Biomol. Chem. 2016, 14, -1228-1292). In this article, we report on the effect of intramolecular hydrogen bonding (IHB) in three nitroxides exhibiting IHB between the hydroxyl and diethylphosphoryl groups and one exhibiting IHB between the hydroxyl group and the nitroxyl moiety. It is observed that for the first three nitroxides, a increases with increasing polarity/polarizability and hydrogen bond donor (HBD) properties of the solvent (π* and α, respectively)-in sharp contrast to the data reported in the literature-and for the last nitroxide, a decreases with π* and α. In fact, the occurrence of IHB induces a large strain, its suppression by hydrogen bond acceptor (HBA) solvents affords an increase in a .

Probing the Solute-Solvent Interaction of an Azo-Bonded Prodrug in Neat and Binary Media: Combined Experimental and Computational Study

“…Thus, further investigations concerning the solute-solvent interactions of pharmaceuticals are still necessary in this regard. To this end, the solute-solvent interactions and their corresponding effects have been investigated utilizing various experimental and computational methods 34–41 . Indeed, combination of experimental and computational represents an inimitable opportunity for observing such kind of interactions, where the experimental results can be molecularly interpreted using various computational approaches 36 .…”