Design, synthesis, crystal structure, photophysical behavior and aggregation-induced emission of a novel pyrene scaffold multifunctional Schiff base ligand: inhibition of digestive enzymes and docking studies†
Abstract
A novel pyrene-imidazole based Schiff base condensate, 2-(2-(pyren-1-ylmethylene)hydrazineyl)-4,5-dihydro 1H-imidazole hydrobromide monohydrate (PI), has been synthesized. PI has been comprehensively characterised on the basis of elemental analysis, electrical conductivity measurement and different spectroscopic techniques like FT-IR, 1H, 13C NMR and ESI mass spectrometry and TGA. The single crystal X-ray structure of PI has been determined. The solution and solid state electronic spectra of PI confirm its invariant identity in terms of peak position and phase purity, both in the solid state and in solution phase. The geometry of PI has been optimised through Density Functional Theory (DFT) calculations. Computations at the level of Time-Dependent Density Functional Theory (TD-DFT) predict an absorption band at 357.20 017 nm in methanol for PI against an observed absorption at 360 nm. UV-visible absorption, steady-state and time-resolved fluorescence, field emission scanning electron microscopy (FESEM) and dynamic light scattering (DLS) techniques have been employed to establish the photophysical aspect of PI. The photophysical behaviour of PI has been thoroughly studied in its methanolic solution. The emission intensity of PI gradually increases on progressive addition of water and becomes maximum on addition of 20% water. The fluorescence quantum yield (ΦF) and radiative and non-radiative constants have been determined in pure methanol and in a methanol/water mixture. Fluorescence lifetime studies on PI also reveal the change in lifetime with concomitant addition of water. Expounded results demonstrate that PI manifests aggregation-induced emission (AIE) through suppression of the photo-induced electron transfer (PET) process. PXRD patterns of PI in different fractions of methanol/water mixtures also substantiate the aggregation-induced emission behaviour of it. Moreover, the inhibitory activity of PI against digestive enzymes like trypsin, amylase, lipase, pepsin, and cathepsin B has been studied. PI effectively inhibits the proteases (trypsin, pepsin and cathepsin B) and fat hydrolysing enzyme (lipase); whereas it is moderately effective against starch hydrolysing enzyme (amylase) at lower concentrations. We attempted to determine the mechanism of the observed inhibitory activity of PI. Molecular docking studies also reveal the conformational changes in enzymes during interaction with PI and reference compounds (curcumin and orlistat). PI shows remarkable inhibition towards the said enzymes in a concentration dependent manner.