Carbon monoxide (CO) is an endogenous signaling molecule that controls a number of physiological processes. To circumvent the inherent toxicity of CO, light-activated CO-releasing molecules (photoCORMs) have emerged as an alternative for its administration. However, their wider application requires photoactivation using biologically benign visible and near-infrared (NIR) light. In this work, a strategy to access such photoCORMs by fusing two CO-releasing flavonol moieties with a NIR-absorbing cyanine dye is presented. These hybrids liberate two molecules of CO in high chemical yields upon activation with NIR light up to 820 nm and exhibit excellent uncaging cross-sections, which surpass the state-of-the-art by two orders of magnitude. Furthermore, the biocompatibility and applicability of the system in vitro and in vivo are demonstrated, and a mechanism of CO release is proposed. It is hoped that this strategy will stimulate the discovery of new classes of photoCORMs and accelerate the translation of CO-based phototherapy into practice.

Department of Chemistry and RECETOX Faculty of Science Masaryk University Kamenice 5 62500 Brno Czech Republic

Institute of Medical Biochemistry and Laboratory Diagnostics General Faculty Hospital and 1st Faculty of Medicine Charles University Na Bojišti 3 12108 Praha 2 Czech Republic

Zobrazit více v PubMed

Phan T. G., Bullen A., Immunol. Cell Biol. 2010, 88, 438–444. PubMed

Lim Y. T., Kim S., Nakayama A., Stott N. E., Bawendi M. G., Frangioni J. V., Mol. Imaging 2003, 2, 50–64. PubMed

Allison R. R., Sibata C. H., Photodiagn. Photodyn. Ther. 2010, 7, 61–75. PubMed

Romão C. C., Blättler W. A., Seixas J. D., Bernardes G. J. L., Chem. Soc. Rev. 2012, 41, 3571–3583. PubMed

Motterlini R., Otterbein L. E., Nat. Rev. Drug Discovery 2010, 9, 728–743. PubMed

Ling K., Men F., Wang W. C., Zhou Y. Q., Zhang H. W., Ye D. W., J. Med. Chem. 2018, 61, 2611–2635. PubMed

Szabo C., Nat. Rev. Drug Discovery 2016, 15, 185–203. PubMed PMC

Levitt D. G., Levitt M. D., Clin. Pharmacol. Adv. Appl. 2015, 7, 37–56. PubMed PMC

Vander Heiden M. G., Cantley L. C., Thompson C. B., Science 2009, 324, 1029–1033. PubMed PMC

Wegiel B., Gallo D., Csizmadia E., Harris C., Belcher J., Vercellotti G. M., Penacho N., Seth P., Sukhatme V., Ahmed A., Pandolfi P. P., Helczynski L., Bjartell A., Persson J. L., Otterbein L. E., Cancer Res. 2013, 73, 7009–7021. PubMed PMC

Vítek L., Gbelcová H., Muchová L., Váňová K., Zelenka J., Koníčková R., Šuk J., Zadinova M., Knejzlík Z., Ahmad S., Fujisawa T., Ahmed A., Ruml T., Dig. Liver Dis. 2014, 46, 369–375. PubMed

Ahmad S., Hewett P. W., Fujisawa T., Sissaoui S., Cai M., Gueron G., Al-Ani B., Cudmore M., Faraz Ahmed S., Wong M. K. K., Wegiel B., Otterbein L. E., Vítek L., Ramma W., Wang K., Ahmed A., Thromb. Haemostasis 2015, 113, 329–337. PubMed

Heinemann S. H., Hoshi T., Westerhausen M., Schiller A., Chem. Commun. 2014, 50, 3644–3660. PubMed PMC

García-Gallego S., Bernardes G. J. L., Angew. Chem. Int. Ed. 2014, 53, 9712–9721; PubMed

Angew. Chem. 2014, 126, 9868–9877.

Romanski S., Kraus B., Guttentag M., Schlundt W., Rücker H., Adler A., Neudörfl J. M., Alberto R., Amslinger S., Schmalz H. G., Dalt. Trans. 2012, 41, 13862–13875. PubMed

Sitnikov N. S., Li Y., Zhang D., Yard B., Schmalz H. G., Angew. Chem. Int. Ed. 2015, 54, 12314–12318; PubMed

Angew. Chem. 2015, 127, 12489–12493.

Martínek M., Filipová L., Galeta J., Ludvíková L., Klán P., Org. Lett. 2016, 18, 4892–4895. PubMed

Poloukhtine A. A., Mbua N. E., Wolfert M. A., Boons G. J., Popik V. V., J. Am. Chem. Soc. 2009, 131, 15769–15776. PubMed PMC

Kuzmanich G., Gard M. N., Garcia-Garibay M. A., J. Am. Chem. Soc. 2009, 131, 11606–11614. PubMed

Kuzmanich G., Garcia-Garibay M. A., J. Phys. Org. Chem. 2011, 24, 883–888.

Chapman O. L., Wojtkowski P. W., Adam W., Rodriguez O., Rucktaeschel R., J. Am. Chem. Soc. 1972, 94, 1365–1367.

Peng P., Wang C., Shi Z., Johns V. K., Ma L., Oyer J., Copik A., Igarashi R., Liao Y., Org. Biomol. Chem. 2013, 11, 6671–6674. PubMed

Antony L. A. P., Slanina T., Šebej P., Šolomek T., Klán P., Org. Lett. 2013, 15, 4552–4555. PubMed

Soboleva T., Esquer H. J., Benninghoff A. D., Berreau L. M., J. Am. Chem. Soc. 2017, 139, 9435–9438. PubMed

Popova M., Soboleva T., Arif A. M., Berreau L. M., RSC Adv. 2017, 7, 21997–22007.

Anderson S. N., Richards J. M., Esquer H. J., Benninghoff A. D., Arif A. M., Berreau L. M., ChemistryOpen 2015, 4, 590–594. PubMed PMC

Feng W., Feng S., Feng G., Chem. Commun. 2019, 55, 8987–8990. PubMed

Popova M., Soboleva T., Ayad S., Benninghoff A. D., Berreau L. M., J. Am. Chem. Soc. 2018, 140, 9721–9729. PubMed PMC

Russo M., Štacko P., Nachtigallová D., Klán P., J. Org. Chem. 2020, 85, 3527–3537. PubMed

Palao E., Slanina T., Muchová L., Šolomek T., Vítek L., Klán P., J. Am. Chem. Soc. 2016, 138, 126–133. PubMed

Gorka A. P., Nani R. R., Schnermann M. J., Acc. Chem. Res. 2018, 51, 3226–3235. PubMed

Sun W., Guo S., Hu C., Fan J., Peng X., Chem. Rev. 2016, 116, 7768–7817. PubMed

Estrada L. A., Neckers D. C., J. Org. Chem. 2009, 74, 8484–8487. PubMed

Rosenthal E. L., Warram J. M., De Boer E., Chung T. K., Korb M. L., Brandwein-Gensler M., Strong T. V., Schmalbach C. E., Morlandt A. B., Agarwal G., Hartman Y. E., Carroll W. R., Richman J. S., Clemons L. K., Nabell L. M., Zinn K. R., Clin. Cancer Res. 2015, 21, 3658–3666. PubMed PMC

From https://ClinicalTrials.gov, Search Term: ICG, last accessed on July 30, 2020.

Usama S. M., Lin C. M., Burgess K., Bioconjugate Chem. 2018, 29, 3886–3895. PubMed

Štacková L., Štacko P., Klán P., J. Am. Chem. Soc. 2019, 141, 7155–7162. PubMed

Samanta A., Vendrell M., Das R., Chang Y. T., Chem. Commun. 2010, 46, 7406–7408. PubMed

König S. G., Krämer R., Chem. Eur. J. 2017, 23, 9306–9312. PubMed

Štacková L., Muchová E., Russo M., Slavíček P., Štacko P., Klán P., J. Org. Chem. 2020, 85, 9776–9790. PubMed

Nani R. R., Kelley J. A., Ivanic J., Schnermann M. J., Chem. Sci. 2015, 6, 6556–6563. PubMed PMC

Gorka A. P., Nani R. R., Zhu J., Mackem S., Schnermann M. J., J. Am. Chem. Soc. 2014, 136, 14153–14159. PubMed PMC

Nani R. R., Gorka A. P., Nagaya T., Yamamoto T., Ivanic J., Kobayashi H., Schnermann M. J., ACS Cent. Sci. 2017, 3, 329–337. PubMed PMC

Levitt D. G., Levitt M. D., Clin. Pharm. Adv. Appl. 2015, 7, 37–56. PubMed PMC

Zhu T. C., Kim M. M., Liang X., Finlay J. C., Busch T. M., Photon. Lasers Med. 2015, 4, 59–71. PubMed PMC

James N. S., Chen Y., Joshi P., Ohulchanskyy T. Y., Ethirajan M., Henary M., Strekowski L., Pandey R. K., Theranostics 2013, 3, 692–702. PubMed PMC

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

Byers G. W., Gross S., Henrichs P. M., Photochem. Photobiol. 1976, 23, 37–43. PubMed

Structure-Photoreactivity Relationship Study of Substituted 3-Hydroxyflavones and 3-Hydroxyflavothiones for Improving Carbon Monoxide Photorelease

Visible-Light-Activated Carbon Monoxide Release from Porphyrin-Flavonol Hybrids

Spin-Vibronic Control of Intersystem Crossing in Iodine-Substituted Heptamethine Cyanines

Visible-to-NIR-Light Activated Release: From Small Molecules to Nanomaterials