Thio and Seleno‐Psoralens as Efficient Triplet Harvesting Photosensitizers for Photodynamic Therapy

• Published in: Chemistry : a European journal 2024-07, Vol.30 (39), p.e202400733-n/a
• Main Authors: Jena, Subhrakant, Mohanty, Pranay, Rout Rout, Saiprakash, Kumar Pati, Saswat, Biswal, Himansu S.
• Format: Article
• Language: English
• Subjects: Absorption; Absorption spectra; Apoptosis; Atomic energy levels; Carbonyl compounds; Carbonyls; Chemotherapy; Chromophores; Electron transfer; Energy gap; Ficusin - chemistry; Ficusin - pharmacology; Humans; Intersystem Crossing; Oxygen; Photochemotherapy - methods; Photodynamic Therapy; Photon absorption; Photosensitizers; Photosensitizing Agents - chemistry; Photosensitizing Agents - pharmacology; Psoralen; Reactive Oxygen Species; Selenium; Selenium - chemistry; Sulfur; Sulfur - chemistry; Triplet Harvesting; Triplet state; Two-photon Absorption
• ISSN: 0947-6539; 1521-3765; 1521-3765
• DOI: 10.1002/chem.202400733

The Psoralen (Pso) molecule finds extensive applications in photo‐chemotherapy, courtesy of its triplet state forming ability. Sulfur and selenium replacement of exocyclic carbonyl oxygen of organic chromophores foster efficient triplet harvesting with near unity triplet quantum yield. These triplet‐forming photosensitizers are useful in Photodynamic Therapy (PDT) applications for selective apoptosis of cancer cells. In this work, we have critically assessed the effect of the sulfur and selenium substitution at the exocyclic carbonyl (TPso and SePso, respectively) and endocyclic oxygen positions of Psoralen. It resulted in a significant redshifted absorption spectrum to access the PDT therapeutic window with increased oscillator strength. The reduction in singlet‐triplet energy gap and enhancement in the spin‐orbit coupling values increase the number of intersystem crossing (ISC) pathways to the triplet manifold, which shortens the ISC lifetime from 10−5 s for Pso to 10−8 s for TPso and 10−9 s for SePso. The intramolecular photo‐induced electron transfer process, a competitive pathway to ISC, is also considerably curbed by exocyclic functionalizations. In addition, a maximum of 115 GM of two‐photon absorption (2PA) with IR absorption (660–1050 nm) confirms that the Psoralen skeleton can be effectively tweaked via single chalcogen atom replacement to design a suitable PDT photosensitizer. This work demonstrates the role of exocyclic replacement of carbonyl oxygen of psoralen with sulfur and selenium. DFT and TD‐DFT studies revealed a significant red‐shifted absorption, increased oscillator strength, and spin‐orbit coupling values, along with reduced singlet‐triplet energy gaps in thio and seleno derivatives of psoralen. These factors led to efficient triplet harvesting, enabling them as promising photosensitizers for photodynamic therapy.