Development of Photoactivatable Carbon Monoxide-Releasing Molecules (photoCORMs)

            Qiuyun Yang,^1 Jiří Váňa,^2 Peter Štacko,^1 Lenka Štackova,^1 Petr Klán*^,1

 ^1Department of Chemistry and RECETOX, Masaryk University, Kamenice 5, 62500 Brno, Czech Republic

  ^2Institute of Organic Chemistry and Technology, Faculty of Chemical Technology, University of
                    Pardubice, Studentská 573, 53210 Pardubice, Czech Republic

Carbon monoxide (CO) is a colorless and odorless gas, which is considered to be a “silent killer”
because of its strong affinity for hemoglobin over molecular oxygen.^1 However, despite its
toxicity, CO is increasingly appreciated as a potential therapeutic agent, thanks to its
anti-inflammatory, anti-microbial, anti-cancer, and other therapeutic effects at low
concentration.^2 When directly inhaled, CO rapidly reacts with hemoglobin, which forms
carbonylhemoglobin, and thus inhibiting the oxygen transport by red blood cells, and subsequently
leads to tissue hypoxia. Hence, the control of the concentration of CO released in biological
systems is of great significance.

To date, numerous carbon monoxide-releasing molecules (CORMs) based on metal complexes or organic
compounds have been developed;^3 however, their medical applications are still challenged by the
capacity to effectively deliver and liberate CO in a biological system. Hence, the development of
metal-free CORMs is a promising alternative strategy for intracellular CO delivery. The
light-triggered CO release as one of the most promising ways provides a precise temporal and
spatial control of this process. The light-triggered CO releasing molecule is then called photoCORM
and can be used as a prodrug when it is stable in the dark.

This presentation includes two parts. The first part, we studied the photophysical and
photochemical properties of coumarin-3-carboxylic acid. Meanwhile, the mechanism of CO release was
investigated by using HPLC, HRMS, and spectroscopy techniques. The second part was designed based
on the study of flavonol^ and cyanines^4 from our group in very recent years. Fusing those two
chromophores can lead to a novel CO-releasable hybrid system that could serve as a general strategy
for designing new classes of photoCORMs. The major target of this project is to develop better
water solubility photoCORMs. The comprehensive mechanistic studies of these two projects will be
presented in detail in the presentation.




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    (b) Heinemann, S. H., et al. Chem. Commun. (Camb) 2014, 50 (28), 3644-3660.

2. (a)Ling, K., et al. J. Med. Chem. 2018, 61 (7), 2611-2635.

3. Kottelat, E., et al. Inorganics 2017, 5 (2), 1-19.

4. (a) Štacková L., et al. Chem. Eur. J. 2020, 26, 13184-13190.

    (b) Russo M., et al. J. Org. Chem. 2020, 85, 3527-3537.