Porphyrin-Flavonol Hybrid Molecules for Efficient Delivery of CO

Andrea Ramundo,^1, 2 Jiří Janoš,^3 Lucie Muchová,^4 Mária Šranková,^4 Libor Vítek,^4 Petr
Slavíček,^3 Petr Klán^1, 2 ,*


^1Department of Chemistry, Faculty of Science, Masaryk University, Kamenice 5, 62500, Brno, Czech
Republic. ^2RECETOX, Faculty of Science, Masaryk University, Kamenice 5, 62500, Brno, Czech
Republic. ^3Department of Physical Chemistry, University of Chemistry and Technology, Technická 5,
16628 Prague 6, Czech Republic. ^4Institute of Medical Biochemistry and Laboratory Diagnostics, and
4th Department of Internal Medicine, General University Hospital in Prague and 1st Faculty of
Medicine, Charles University, Na Bojišti 3, 12108 Prague 2, Czech Republic.  E-mail:
andre.ramundo@gmail.com

^

Since carbon monoxide (CO) has been recognized as a gas signaling molecule with attractive
properties and considerable potential as a therapeutic agent, light-activated CO-releasing
molecules (photoCORMs) soon emerged as the keystone for controlled, targeted delivery.^1,2 Although
many photoCORMs have been proposed, the need for full water solubility, harmless red to near
infrared light activation, and high quantum efficiency is still preventing their widespread
adoption. In this study, we present a novel class of photoCORMs based on a central light harvesting
porphyrin covalently combined with four flavonol-based, CO releasing appendices.^3 Multiple CO
molecules are released upon irradiation with red light (up to 670 nm) in both methanol and water
solution. A facile metal insertion is used to modulate the photoproperties to the extent that
uncaging cross sections (Φ[CO]ε[max]) exceeding 10^4 M^–1cm^–1 became accessible. The system
biocompatibility has been tested in vitro, and a proton-coupled energy transfer (PCEnT)^4 mechanism
has been proposed, supported both experimentally and thorough quantum-chemical calculations.

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References

1.       Verma, A.; Hirsch, D.; Glatt, C.; Ronnett, G. Science 1993, 259, 381-384.

2.       Motterlini, R.; Otterbein, L. E. Nat. Rev. Drug Discov. 2010, 9, 728-743.

3.       Studer, L. S.; Brewer W. E.; Martinez, M. L.; Chou, P. J. Am. Chem. Soc. 1989, 111,
7643-7644.

4.       Rimgard, B. P; Tao, Z.; Parada, G. A.; Cotter L. F.; Hammes-Schiffer, S.; Mayer J. M.;
Hammarström, L. Science 2022, 377, 742-747.