Exploration of the ESIPT process in a newly designed potential bioactive thiosemicarbazone Schiff base: Spectroscopic analysis accompanied by molecular optimization and crystallographic study

Abstract

The DNA targeting nature of thiosemicarbazone based Schiff bases has provided a great platform for synthesis of its novel derivatives and their progressive exploitation as therapeutic agents. The present work embodies the synthesis of a potential bioactive pharmacophore thiosemicarbazone Schiff base derivative viz. (E)-1-(4-(diethylamino)-2-hydroxybenzylidene)-4,4-dimethyl-thiosemicarbazide (DAHTS) along with its structural characterisation by 1H NMR, FT-IR, mass spectrometry and single crystal X-ray diffraction analysis. Identification of ground and excited state geometries of the synthesized DAHTS molecule, with possibility of solvent dependent excited state intramolecular proton transfer (ESIPT) reaction have also been unveiled using electronic absorption, steady state and time resolve fluorescence spectroscopic techniques. The ESIPT process has further been validated by Density functional theory (DFT) and Time-dependent density functional theory (TD-DFT) based quantum chemical calculations. Spectral and single crystal XRD analysis indicate existence of intramolecular H-bonding between phenolic hydrogen and azomethine nitrogen in DAHTS molecule that stabilises the normal enol-imine (E) form in the ground state of DAHTS molecule. The synthesised molecule exhibits dual emission in non-polar hexane. On photoexcitation, DAHTS possibly undergoes excited state intramolecular proton transfer (ESIPT) reaction to produce keto-amine species (K) in nonpolar solvents. Frontier molecular orbital (FMO) analysis indicates that although intramolecular proton transfer reaction possibly might not occur in ground state of DAHTS but it may become feasible in the lowest singlet excited state of enol-imine form (E*) to produce its excited tautomer (K*). The lower energy difference (1.17 kcal/mol) between excited enol-imine (E*) and keto-amine (K*)form, obtained from Potential energy curve (PEC) corroborates the observed dual emission of the synthesised fluorophore. DFT and TD-DFT studies also aid in visualization of electronic charge displacement inside the molecular framework of DAHTS; which in turn suggests partial increase of Mulliken charge of azomethine nitrogen that further makes way for intramolecular proton transfer in the excited state. The amalgamated spectroscopic and theoretical research described herein, delivers enormous information about comprehensive synthetic and photophysical aspects of potential bioactive thiosemicarbazone derivatives for further utilization in medicinal chemistry research.