UC Santa Cruz

Photoactive metal nitrosyls (NO complexes of metals) have drawn attention as potential drugs for delivery of nitric oxide (NO) to biological targets under the control of light. Major success in this area has been achieved with designed metal nitrosyls derived from ligands that contain carboxamide group(s). This thesis details the design strategies used to synthesize such carboxamide containing metal nitrosyls. As a first step, DFT and TDDFT calculations were used to elucidate the electronic structures and varying photoactivities of iron, manganese, and ruthenium nitrosyls derived from identical pentadentate ligand frames, as described in Chapter 2.

In Chapter 3, a set of tetradentate dicarboxamide ligand frames with different combinations of phosphine-P, phenolato-O, and/or pyridine-N donors was employed in order to uncover which atom types promote low-energy light absorption in ruthenium nitrosyls. Part one details the reactions of phosphine containing ligands with RuCl₃ and subsequent exposure to NO gas. Such reactions lead to the eventual isolation of diamagnetic Ru(II) complexes with oxidized ligand frames and no bound NO.

The second part of Chapter 3 focuses on a set of {RuNO}⁶ nitrosyls with dicarboxamide ligands with a varying numbers of phenolate-O and pyridine-N donors. The resulting nitrosyls have been characterized by X-ray crystallography. All three complexes are diamagnetic, exhibit νNO in the range 1780-1840 cm^-1 and rapidly release NO in solution upon exposure to low power UV light. Results of theoretical studies on these {RuNO}⁶ nitrosyls indicate considerable contribution from ligand orbitals in the MOs involved in transitions leading to NO photolability.

In Chapter 4, the attachment of resorufin and fluorescein derived dye chromophores was explored as a way to further sensitize ruthenium nitrosyls to visible light. First, the steric effects of the in-plane ligands in these dye-sensitized {RuNO}⁶ nitrosyls on their NO photolability were examined. Next, the direct conjugation of dye chromophores was compared with dye attachment via a linker to understand the mechanism of photoactivation in these dye-bound ruthenium nitrosyls. In addition the fluorescence properties of these dye-conjugated nitrosyls were characterized and found to provide a potential signal showing when and where NO has been delivered.