Synthesis of dimeric indoles from Friedel–Crafts reaction of indoles with ketones catalysed by a Brønsted acid ionic liquid and their interactions with BSA and DNA

Abstract

The present work involves an improved, pseudo-three-component synthetic approach for the synthesis of dimeric indoles using 4 mol% [BCMIM][Cl] ionic liquid via metal-free synthesis in aqueous ethanol under reflux conditions. A series of 35 derivatives were furnished in up to 95% yields in 0.5 h to 1.5 h. These derivatives were then analyzed using various spectroscopic techniques. The salient features of this methodology are mild reaction conditions, metal-free synthesis, simple work-up procedure, short reaction time, reusability for up to 4 cycles, good to excellent yields and low catalyst loading. The UV-visible and fluorescence spectroscopy techniques were used to investigate the photophysical characteristics of selected derivatives. The absorption and emission spectra reveal a peak wavelength (λ_max) in the ranges of 216–228 nm (π–π*), 262–294 nm (n–π*), and 389–407 nm, respectively. A similar trend to the experimental data can be observed in density functional theory (DFT) calculations. The binding affinities of the synthesised derivatives with bovine serum albumin (BSA) and deoxyribonucleic acid (DNA) were computed using AutoDock Vina. Furthermore, 7af, 7ai, 7aj and 7gk were investigated for BSA and DNA binding studies. The ligands exhibited a binding strength of 10⁵ and 10³ M⁻¹ with BSA and DNA, respectively. The ethidium bromide (EtBr) displacement assay discloses intercalation as the mode of binding with K_sv values in the order of 10²–10³ M⁻¹.