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CO Releasing Complexes Using Two Photon Excitation for Therapy

Sydney Hallenbeck
Sydney Hallenbeck
Department of Chemistry
University of Georgia
Inorganic Seminar

Throughout history carbon monoxide (CO) has been thought of as a toxic gas.1 However, over the past 60 years CO was found to be endogenous with distinct physiological functions and a large therapeutic potential.2, 3 4 As a therapeutic, CO modulates the immune system, exerts redox control in the mitochondria, acts as a cytoprotective, and is a vasodilator. Unfortunately, delivering CO via inhalation of the diluted gas affords high concentration of carboxyhemoglobin (COHb), leading to CO poisoning, as well as lack of tissue specificity.5, 6 This limitation has led to the development of CO releasing molecules (CORMs) for targeted release of CO. One common CORM is organometallic in nature, as they allow for tunable release of CO and increased specificity of targeting. Incorporating photoactive functionalities imparts spatiotemporal control on the release of CO (referred to as photoCORMs) allowing for increased tissue specificity and dose regulation. Earlier photoCORM platforms use near UV light to trigger CO release. Unfortunately, UV light does not penetrate deeply into skin and can lead to uncontrolled cell death in normal cells. In order to combat this, more recent photoCORM constructs employ near IR light (NIR), to minimize cell photodamage. This use of NIR light requires two-photon excitation to trigger the same release observed with UV light. This talk discusses a series of NIR-excitable photoCORMS for potential therapeutic CO release.

1.Penney, D. G., Carbon monoxide toxicity. CRC Press: 2000.

2.Tenhunen, R.; Marver, H. S.; Schmid, R., The enzymatic conversion of heme to bilirubin by microsomal heme oxygenase. Proc. Natl. Acad. Sci. USA 1968, 61, 748-755.

3.Marks, G. S.; Brien, J. F.; Nakatsu, K.; McLaughlin, B. E., Does carbon monoxide have a physiological function? Trends Pharmacol. Sci. 1991, 12, 185-188.

4.Verma, A.; Hirsch, D.; Glatt, C.; Ronnett, G.; Snyder, S., Carbon monoxide: a putative neural messenger. Science 1993, 259, 381-384.

5.Motterlini, R.; Otterbein, L. E., The therapeutic potential of carbon monoxide. Nat. Rev. Drug Discovery 2010, 9, 728-743.

6.Romão, C. C.; Blättler, W. A.; Seixas, J. D.; Bernardes, G. J. L., Developing drug molecules for therapy with carbon monoxide. Chem. Soc. Rev. 2012, 41, 3571-3583.

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