Aggregation-Modulated Excited-State Intramolecular Proton Transfer and Antifungal Potential of Selected 1,3,4-Thiadiazole Derivatives
TL;DR
Spectroscopic results support the occurrence of excited-state intramolecular proton transfer (ESIPT) in both derivatives and indicate that this process is facilitated by molecular aggregation, which identifies PhTD-ClB and FTD-EtB as environmentally responsive ESIPT fluorophores.
Abstract
The spectroscopic and biological properties of two 1,3,4-thiadiazole derivatives, 4-chloro-6-{5-[(3-chlorophenyl)amino]-1,3,4-thiadiazol-2-yl}benzene-1,3-diol (PhTD-ClB) and 4-ethyl-6-[5-(furan-2-yl)-1,3,4-thiadiazol-2-yl]benzene-1,3-diol (FTD-EtB), were investigated using electronic absorption, steady-state fluorescence, resonance light scattering (RLS), and time-correlated single-photon counting (TCSPC) measurements. The experimental analysis was complemented by fluorescence quantum-yield determination, calculation of radiative and non-radiative rate constants, solvatochromic estimation of dipole-moment changes, and evaluation of intermolecular distances using Kasha’s exciton-splitting model. The spectroscopic results support the occurrence of excited-state intramolecular proton transfer (ESIPT) in both derivatives and indicate that this process is facilitated by molecular aggregation. Spectroscopic studies performed in solvents of different polarity, aqueous media, solvent mixtures, and micellar systems were complemented by an assessment of the antifungal activity of both compounds against selected cereal pathogens. Pronounced changes in fluorescence behavior were observed in micellar systems formed by Triton X-100 and sodium deoxycholate. Depending on the medium, the compounds exhibited either a single short-wavelength emission band or dual emission comprising a second, strongly red-shifted band. Dual emission was particularly evident in selected aqueous, low-polarity, and micellar environments. The combined fluorescence and RLS results indicate that molecular aggregation modifies the balance between the enol- and keto-related emission pathways and promotes an AIE-like enhancement of the ESIPT-associated long-wavelength emission. These findings identify PhTD-ClB and FTD-EtB as environmentally responsive ESIPT fluorophores, while the pronounced antifungal activity observed exclusively for FTD-EtB supports its further investigation as a potential antifungal agent.