Synthesis, Properties, and Evaluation of Mn(I) Tetracarbonyl Complexes Designed for Therapeutic Release of Carbon Monoxide

This Thesis comprises an investigation of [Mn(ppy)(CO)4] (ppy = 2-phenylpyridyl), 88, and related Mn(I) tetracarbonyl complexes, for application as carbon monoxide-releasing molecules (CORMs). The photochemical behaviour of [Mn(ppy)(CO)4] was studied using ultrafast time-resolved infrared spectroscopy (TRIR) to probe light-triggered CO-release (Chapter 2). Compared to the isoelectronic complex [Cr(bpy)(CO)4], a striking difference in the balance between CO-release and unreactive excited state formation is observed, providing insight into why photo-CO release is inefficient in some compounds. Novel intermediates in light-triggered CO dissociation were detected on the picosecond timescale including C-H σ-complexes. Over longer (minute) timescales, complementary in situ infrared experiments suggested possible production of multinuclear Mn-hydroxy clusters in wet organic solvents. Thus, new evidence for the light-triggered CO-release mechanism is provided.
Three novel ferrocene-containing [Mn(ppy)(CO)4]-derived CORMs, a family of compounds incorporating two organometallic therapeutic moieties within the same molecule, are described (Chapter 3). Although these CORMs are all redox-active and were all capable of photo-induced CO-release it was not possible to achieve redox-triggered CO-release. To further probe the possibility of redox-triggered CO-release, tetracarbonyl Mn compounds incorporating a cyclometalated azo ligand, a metal-free redox-active moiety, also shown to increase the CO-release wavelength of tricarbonyl Mn(I) complexes, were synthesised (Chapter 4). Although CO-release at a higher wavelength of light can be attributed to the azo, redox-release is not possible and TRIR shows that unreactive excited states dominate over CO photodissociation. Thus, this work demonstrates the need to consider both efficiency and wavelength in designing triggered-CO release and emphasises the value of the mechanistic work described.
Finally, fluorescent labelling of a [Mn(ppy)(CO)4] derivative is reported (Chapter 5). Confocal microscopy of mammalian and bacterial samples proves that viable cells of both types will uptake such CORMs and the methodology for assaying the antibiotic activity of photoCORMs is significantly improved to minimise age effects of the bacteria.