Photochemical and photophysical investigations of dye derivatized iron sulfur nitrosyl compounds: Photochemical production of nitric oxide via single and two photon excitation

Nitric Oxide (NO) is a ubiquitous biological messenger which is involved in a plethora of roles in mammalian biology including vasodilation, immune response, and neurotransmission. NO has also been demonstrated to be a gamma-radiation sensitizer, and as such, maybe used to improve the therapeutic effects of radiation treatment in the fight against certain cancers. These properties have provided attractive promise for the use of NO in the treatment of disease, but the deleterious effects of NO on vascular biology have limited their use as thermal NO delivery systems. One strategy to circumvent the undesired side effects of thermally delivered NO drugs is to develop thermally stable, NO containing precursors that can be photochemically triggered to release nitric oxide. In this regard, our group is concerned with the development of metal-nitrosyl complexes that photochemically produce nitric oxide on demand. A characteristic of particular importance to photochemical delivery drugs is the ability to absorb light at wavelengths between 800--1100 run where light penetration through tissue is maximized. Therefore the current focus is on designing compounds that can absorb light (by single or two photon excitation) in the NIR, undergo energy transfer to the metal center, and then result in the photochemical labilization of NO. A second advantage of using two photon excitation (TPE) for pro-drug activation is the enhanced spatial selectivity gained due to the intensity squared dependence of a two photon process.; In these contexts, the primary focus of this dissertation has been on the development, photochemical and photophysical investigations of dye derivatized iron sulfur nitrosyl compounds (known as the Roussin's red salt esters, RSE) for use as photochemical NO delivery agents via single and two photon excitation. One compound developed for these purposes was Fluor-RSE (Bis-[(mu-S, mu-S')-fluorescein-thioethylester]-tetranitrosyl diiron), which contains two fluorescein moieties as the light absorbing antenna. The photochemistry and photophysics of Fluor-RSE were investigated under single photon excitation (SPE) with UV-vis light and two photon excitation with near infrared (NIR) light, and have demonstrated that Fluor-RSE photochemically produces NO via single and two photon excitation.