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.

• Publikační typ
• časopisecké články 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.

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• časopisecké články MeSH

Spin-orbit coupling between electronic states of different multiplicity can be strongly coupled to molecular vibrations, and this interaction is becoming recognized as an important mechanism for controlling the course of photochemical reactions. Here, we show that the involvement of spin-vibronic coupling is essential for understanding the photophysics and photochemistry of heptamethine cyanines (Cy7), bearing iodine as a heavy atom in the C3' position of the chain and/or a 3H-indolium core, as potential triplet sensitizers and singlet oxygen producers in methanol and aqueous solutions. The sensitization efficiency was found to be an order of magnitude higher for the chain-substituted than the 3H-indolium core-substituted derivatives. Our ab initio calculations demonstrate that while all optimal structures of Cy7 are characterized by negligible spin-orbit coupling (tenths of cm-1) with no dependence on the position of the substituent, molecular vibrations lead to its significant increase (tens of cm-1 for the chain-substituted cyanines), which allowed us to interpret the observed position dependence.

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• časopisecké články MeSH

Photoactivatable (alternatively, photoremovable, photoreleasable, or photocleavable) protecting groups (PPGs), also known as caged or photocaged compounds, are used to enable non-invasive spatiotemporal photochemical control over the release of species of interest. Recent years have seen the development of PPGs activatable by biologically and chemically benign visible and near-infrared (NIR) light. These long-wavelength-absorbing moieties expand the applicability of this powerful method and its accessibility to non-specialist users. This review comprehensively covers organic and transition metal-containing photoactivatable compounds (complexes) that absorb in the visible- and NIR-range to release various leaving groups and gasotransmitters (carbon monoxide, nitric oxide, and hydrogen sulfide). The text also covers visible- and NIR-light-induced photosensitized release using molecular sensitizers, quantum dots, and upconversion and second-harmonic nanoparticles, as well as release via photodynamic (photooxygenation by singlet oxygen) and photothermal effects. Release from photoactivatable polymers, micelles, vesicles, and photoswitches, along with the related emerging field of photopharmacology, is discussed at the end of the review.

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• časopisecké články MeSH
• práce podpořená grantem MeSH