The time-resolved infrared spectroscopic study of an iminooxirane, a nitronic anhydride, and acylnitroso species: The development of novel N-hydroxysulfonamides as physiological nitroxyl donors

Time-resolved infrared (TRIR) spectroscopy is a powerful tool for studying photochemically-generated organic reactive intermediates in solution. We have applied this laser flash photolytic technique to the study of three different systems. Chapter 2 describes the first direct detection by TRIR spectroscopy of an elusive iminooxirane intermediate, derived from the reaction of phenylchlorocarbene and phenyl isocyanate. The iminooxirane/alpha-lactam rearrangement was also experimentally observed, and studied computationally. Chapter 3 describes the elucidation of the mechanism of the photochemical acylation of amines by N-acyl-5,7-dintiroindoline using both TRIR spectroscopy and computational techniques. The potent acylating species was found to be a mixed nitronic anhydride. Chapter 4 describes the first direct detection by TRIR spectroscopy of acylnitroso species (C-nitrosocarbonyls) and an examination of their reactivity with primary amines, secondary amines, and thiols.; Nitroxyl (HNO), the one-electron reduced congener of nitric oxide, has recently been implicated in a variety of physiological processes. Most notably, HNO has been shown to increase both contractility and relaxation in animal models of the failing heart, making HNO-donors ideal candidates for drug development. Chapter 5 describes the preparation of novel N-hydroxyarenesulfonamides, and an examination of their HNO-releasing properties at physiological pH and temperature.