Proton-Coupled Triplet-Triplet Energy Transfer: Carbon Monoxide Photorelease from Porphyrin-Flavonol Hybrids

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Abstract

A new photochemical mechanism, termed proton-coupled energy transfer (PCEnT), was recently discovered in anthracene-phenol-pyridine triads (Pettersson Rimgard et al., Science 2022, 377, 742). It couples an electronic transition to nuclear motions allowing Förster (dipole-dipole) energy transfer even though there is no overlap of the donor emission and acceptor absorption spectra. Here, we extend this concept to triplet-triplet energy transfer (TEnT) from light-harvesting porphyrin to a covalently bound flavonol group. While direct TEnT to the flavonol acceptor would be highly endergonic, it becomes feasible thanks to the flavonol energy stabilization upon intramolecular proton transfer in the triplet state. We describe the overall mechanism as proton-coupled TEnT (PCTEnT) – a one-photon process that enables the activation of a UV-absorbing chromophore by visible light. Several porphyrin-flavonol hybrids containing 4 flavonol units attached to the porphyrin meso positions were designed as photoactivatable carbon monoxide (CO)-releasing molecules (photoCORMs). The photoreaction mechanism was studied by steady-state and transient absorption spectroscopy techniques and complementary quantum-chemical calculations. While intrinsically toxic, CO is an endogenous signaling molecule with therapeutic potential that regulates various physiological processes, and photoCORMs offer precise spatial and temporal control of CO administration. We evaluated the viability of the human hepatoblastoma HepG2 cells in the presence of the studied hybrids and tested the effects associated with the intracellular release of CO and the production of singlet oxygen. We demonstrate that the PCTEnT process could be used to devise new photoactivatable molecular devices with potential biological applications.

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Supplementary material

Proton-Coupled Triplet-Triplet Energy Transfer: Supplementary Materials
Methods, quantum-chemical calculations, synthesis, photochemistry, spectroscopy, in vitro biological studies, NMR and HRMS data.