Chromium(III) cyclam-type complexes with pendant chromophores: New nitric oxide delivery systems.

摘要

The goal of this research involved the design of new chromium(III) dinitrito systems with pendant chromophores that will generate nitric oxide (NO) upon irradiation with light. It has been shown that trans-[Cr(cyclam)(ONO) ₂]BF₄ releases NO photochemically with a high quantum yield (Φ_NO = 0.27). While this is quite encouraging, this system lacks a large absorption cross-section and the ability to absorb light at long wavelengths (>600 nm) suitable for photodynamic therapeutic (PDT) applications.; The synthesis and photochemistry of new chromium(III) dinitrito complexes are described in this dissertation. Two types of modified cyclam ligands have been synthesized bearing pendant chromophores. Substitution at the 1 and 8 positions of the macrocycle resulted in the exclusive formation of the cis dichloro isomer when reacted with CrCl₃•3THF. This is very unique in that when coordinated to the chromium(III) metal center, exclusive folding along the tertiary amine axis causes the normal base-catalyzed cis-trans isomerization to be ineffective.; The second type of ligand involved appending a chromophore at the 6 position, leaving the protons on the nitrogens unaffected for the base-catalyzed isomerization to take place. Coordination of the carbon-substituted macrocycle to a chromium(III) metal center resulted in the formation of the trans dichloro isomer (>80%).; Several new chromium(III) dinitrito complexes with pendant chromophores such as a benzyl, anthracene and pyrene group were synthesized. All were demonstrated in this dissertation to release NO upon irradiation with light. Dilute solutions of the anthracene and pyrene analogues demonstrated NO release via energy transfer. Chromophorehr>- LxCrIIIONO→hnChr omophore*hr>-LxCrIII ONO→CrIV=O+NO ; This was only observed within the range of excitation from 325–560 Mn. Preliminary two-photon absorption (TPA) experiments performed on the pyrene analogue resulted in no observable NO released upon irradiation with a femtosecond laser (λ_irr = 730 nm, 800 nm).; These results described in this dissertation are extremely encouraging to the future of these systems in their applications towards photodynamic therapy. While all of the chromium(III) dinitrito produce NO photochemically, all but the pyrene analogue do not absorb low energy light. These systems maintain the ability to attached new and better chromophores to facilitate the release of NO upon irradiation with low-energy light.