Letter Cite This: Org. Lett. XXXX, XXX, XXX−XXX
pubs.acs.org/OrgLett
Visible to NIR Light Photoactivation of Hydrogen Sulfide for Biological Targeting Peter Š tacko,*,† Lucie Muchova,́ ‡ Libor Vítek,‡ and Petr Klań *,† †
Department of Chemistry and RECETOX, Faculty of Science, Masaryk University, Kamenice 5, 625 00, Brno, Czech Republic Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University, Na Bojišti 3, 121 08 Praha 2, Czech Republic
‡
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S Supporting Information *
ABSTRACT: The synthesis and photochemical properties of H2S-releasing BODIPY thiocarbamate photocage scaffolds activatable by visible-to-NIR (up to 700 nm) light to release carbonyl sulfide (COS), which is transformed to H2S using either isolated or natural carbonic anhydrase, is reported. The excellent uncaging cross section and high H2S release yields in in vitro experiments, including live-cell imaging, suggest that these photocages can serve as a platform for the bio-orthogonal phototriggered release within the tissue-transparent window.
H
light (470 nm), reported by Chakrapani and co-workers, took advantage of photorelease of thiocarbamate from the boron atom of a BODIPY scaffold to trigger H2S formation.27 Photoactivation within a so-called tissue-transparent or phototherapeutic window, limited by the absorption of hemoglobin below 600 nm and absorption of water over 900 nm,28,29 is crucial for biological and medical applications. The current absence of H2S-photoreleasing systems activatable with these wavelengths still remains a serious obstacle in H2S therapeutic applications in living organisms. The teams of Winter and Weinstein as well as our group have recently demonstrated the advantages of a BODIPY scaffold acting as a photoremovable protecting group (PPG, Scheme 1) from its meso-position via a photosolvolysis step.30−33 Subsequently, this concept was used by Szymanski and co-workers to photorelease amines via a carbamate linker.34
ydrogen sulfide (H2S), along with carbon monoxide (CO) and nitric oxide (NO), is a gasotransmitter produced endogenously from cysteine and homocysteine,1 which acts as a signaling agent and mediator of important cellular processes resulting in numerous beneficiary antioxidative, anti-inflammatory, vasorelaxant, and generally cytoprotective effects.2−4 For example, relaxation of blood vessels by KATP channels activation5 and protection of cardiomyocytes from reactive oxygen species (ROS)6,7 have been attributed to both endogenous H2S presence and its exogenous administration. These effects are likely to provide important clinical benefits, such as protection from atherosclerosis8 and cardiovascular diseases,3 obesity, metabolic syndrome and possibly diabetes,9 and aging and neurodegenerative diseases.10 Controlled modulation of the biological levels of H2S has received considerable attention in recent years. A number of H2S-releasing molecules have been developed utilizing various triggers, such as pH,11 reaction with glutathione (GSH),12 esterase-activated release,13 redox-controlled release,14 or light,15,16 which offers unparalleled advantages in terms of availability, adjustability, very high spatial and temporal precision, high release orthogonality toward biochemical systems, and reducing side-product formations. The absorption of the reported photoactivatable H2Sreleasing systems, such as an o-nitrobenzyl photocage17 or ketoprofenate18 and xanthone19 photocages, require biologically adverse20 UV or near-UV (
