UC Santa Cruz

Recent investigations on the protective aspects of carbon monoxide (CO) have renewed interest in the design and syntheses of a new generation of metal carbonyl complexes as tunable CO-delivery systems. The inherent photosensitivity of transition metal carbonyls has made photochemical metal—CO bond labilization the most promising approach towards controlled CO-delivery to biological targets. This thesis details the design strategies employed in the preparation of photoactive carbon monoxide releasing molecules (photoCORMs) for use as CO donors in physiologically relevant settings. The Introduction (Chapter 1) examines the origins of CO photodissociation in metal carbonyl complexes and describes some photoCORMs known to date.

As an initial step detailed in Chapter 2, we explored whether the design principles we established in the isolation of photolabile metal nitrosyls can be extended to the generation of photoCORMs. We utilized structurally related pentadentate ligand frames in the syntheses of Fe(II)-based carbon monoxide releasing molecules that undergo solvent-assisted CO release under physiologically-relevant conditions.

Chapter 3 covers our research on photoCORMs bearing tridentate ligand frames. The first section focuses on the effects of increasing conjugation and/or number of pyridine donors on a series of fac-Mn(I) carbonyl complexes bearing tripodal polypyridine ligands. The resulting UV-active photoCORMs have demonstrated a capacity to function as light-activated vasorelaxing agents. The second section of chapter 3 discusses the synthetic routes towards the preparation of Ru(II) carbonyl complexes of a conjugated ligand frame featuring an NNS donor set. The effect of both σ-donating and π-accepting groups on the photosensitivity of the corresponding Ru(II) compounds are highlighted.

Chapter 4 is centered on the use of density functional theory (DFT) and time-dependent DFT as tools in identifying the ligand design parameters that lead to the observed CO photorelease by some d⁶ metal carbonyl complexes. The contributions of auxiliary groups and conjugated moieties to CO photolability are rationalized in terms of their capacity to promote metal to ligand charge transfer processes.