Carbon monoxide (CO) is notorious for its toxic effects but is also recognized as a gasotransmitter with considerable therapeutic potential. Due to the inherent challenges in its delivery, the utilization of organic CO photoreleasing molecules (photoCORMs) represents an interesting alternative to CO administration characterized by high spatial and temporal precision of release. This paper focused on the design, synthesis, and photophysical and photochemical studies of 20 3-hydroxyflavone (flavonol) and 3-hydroxyflavothione derivatives as photoCORMs. Newly synthesized compounds bearing various electron-donating and electron-withdrawing groups show bathochromically shifted absorption maxima and considerably enhanced CO release yields compared to the parent unsubstituted flavonol, exceeding 0.8 equiv of released CO in derivatives exhibiting excited states with a charge-transfer character. Until now, such outcomes have been limited to flavonol derivatives possessing a π-extended aromatic system. In addition, thione analogs of flavonols, 3-hydroxyflavothiones, show substantial bathochromic shifts of their absorption maxima and enhanced photosensitivity but provide lower yields of CO formation. Our study elucidates in detail the mechanism of CO photorelease from flavonols and flavothiones, utilizing steady-state and time-resolved spectroscopies and photoproduct analyses, with a particular emphasis on unraveling the structure-photoreactivity relationship and understanding competing side processes.

• Publication type
• Journal Article MeSH

We report on porphyrin-flavonol hybrids consisting of a porphyrin antenna and four covalently bound 3-hydroxyflavone (flavonol) groups, which act as highly efficient photoactivatable carbon monoxide (CO)-releasing molecules (photoCORMs). These bichromophoric systems enable activation of the UV-absorbing flavonol chromophore by visible light up to 650 nm and offer precise spatial and temporal control of CO administration. The physicochemical properties of the porphyrin antenna system can also be tuned by inserting a metal cation. Our computational study revealed that the process occurs via endergonic triplet-triplet energy transfer from porphyrin to flavonol and may become feasible thanks to flavonol energy stabilization upon intramolecular proton transfer. This mechanism was also indirectly supported by steady-state and transient absorption spectroscopy techniques. Additionally, the porphyrin-flavonol hybrids were found to be biologically benign. With four flavonol CO donors attached to a single porphyrin chromophore, high CO release yields, excellent uncaging cross sections, low toxicity, and CO therapeutic properties, these photoCORMs offer exceptional potential for their further development and future biological and medical applications.

• Publication type
• Journal Article MeSH

meso-Methyl BODIPY photocages stand out for their absorption properties and easy chromophore derivatization. However, their low uncaging efficiencies often hinder applications requiring release of protected substrates in high amounts. In this study, we demonstrate that the sulfonothioated BODIPY group photocleaves a sulfonylthio group from the meso-methyl position with a 10-fold higher quantum yield than the most efficient leaving groups studied to date. Photocleavage, observed in solution and in cells, is accompanied by the spatiotemporally controlled photorelease of H2Sn. For this reason, sulfonothioated BODIPY may be applied in cell signaling, redox homeostasis, and metabolic regulation studies.

• MeSH
• Signal Transduction * MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene MeSH Browser

Photoremovable protecting groups (PPGs) represent one of the main contemporary implementations of photochemistry in diverse fields of research and practical applications. For the past half century, organic and metal-complex PPGs were considered mutually exclusive classes, each of which provided unique sets of physical and chemical properties thanks to their distinctive structures. Here, we introduce the meso-methylporphyrin group as a prototype hybrid-class PPG that unites traditionally exclusive elements of organic and metal-complex PPGs within a single structure. We show that the porphyrin scaffold allows extensive modularity by functional separation of the metal-binding chromophore and up to four sites of leaving group release. The insertion of metal ions can be used to tune their spectroscopic, photochemical, and biological properties. We provide a detailed description of the photoreaction mechanism studied by steady-state and transient absorption spectroscopies and quantum-chemical calculations. Our approach applied herein could facilitate access to a hitherto untapped chemical space of potential PPG scaffolds.

• MeSH
• Photochemistry MeSH
• Ions MeSH
• Metals MeSH
• Porphyrins * MeSH
• Light MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Ions MeSH
• Metals MeSH
• Porphyrins * MeSH