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

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.

Critical assessment of selenourea as an efficient small molecule fluorescence quenching probe to monitor protein dynamics.

Organoselenium compounds have recently been the experimentalists' delight due to their broad applications in organic synthesis, medicinal chemistry, and materials science. Selenium atom replacement of the carbonyl oxygen of the urea moiety dramatically reduces the HOMO-LUMO gap and oxidation potential, which completely changes the physicochemical properties of selenocarbonyl compounds. To our surprise, the photophysics and utility of a simple molecule such as selenourea (SeU) have not been explored in detail, which persuaded us to investigate its role in excited state processes. The steady-state emission, temperature-dependent time-correlated single photon counting, and femtosecond fluorescence upconversion experimental results confirmed that SeU significantly enhances the fluorescence quenching through a photoinduced electron transfer (PET) mechanism with an ∼10 ps ultrafast intrinsic PET lifetime component which is mostly absent in thiourea (TU). A wide range of fluorophores, based on their different redox abilities and fluorescence lifetimes covering a broad spectral window (λex: 390-590 nm and λem: 490-690 nm), were chosen to validate the proof of the concept. It was extended to tetramethylrhodamine (TMR)-5-maleimide labeled lysozyme protein, where we observed significant fluorescence quenching in the presence of SeU. The present work emphasizes that the high quenching efficiency with an ultrafast PET process, reduced orbital energy gap, and higher negative free energy change of the electron transfer reaction are the representative characteristics of selenourea or selenoamides to enable them as potential surrogates of thioamides or oxoamides quenching probes to monitor protein conformational changes and dynamics.