This talk will provide an overview of past and ongoing studies that aim to develop effective mechanisms for the delivery of bioactive small molecules, e.g., carbon monoxide or nitric oxide, to physiological targets. One such method is photo-uncaging, since the use of light as a trigger allows one to control the location and timing of such delivery. However, while numerous compounds can serve as photo-activated CO or NO releasing molecules ("photoCORMs and photoNORMs"), most are not photoactive in the near-infrared (NIR) wavelength range capable of deep tissue penetration. Thus, one focus of this talk is on developing conjugate systems designed to utilize tissue-penetrating NIR light as the excitation source. Another focus is on strategies for delivery of the appropriate caged compound to the locations where photochemical activation has the potential to be most effective. We have also developed an interest in elucidating the mechanisms by which CORMs may be thermally activated to release CO under physiological conditions. One such pathway may be metal carbonyl oxidation by reactive oxygen species, in this case H<sub>2</sub>O<sub>2</sub>; a new quantitative study of this topic will be briefly discussed.

Strategies for uncaging bioactive small molecules

ACS Spring 2022

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