Investigating the binding of organic charge transfer co-crystals to human serum albumin by experimental and theoretical methods: spectroscopy, molecular docking and DFT/TD-DFT studies

Abstract

A new complex was formed by the transfer of charge between 2-ethylimidazole (2-EIM) as an electron donor and 1,2,4,5-benzenetetracarboxylic acid (BTC) as a π acceptor and studied using various physical and chemical methods. The experiment used UV-vis spectroscopy to determine the formation of the complex in solvents such as methanol (MeOH), ethanol (EtOH), dimethylsulfoxide (DMSO), and dimethylformamide (DMF) through the presence of a new broad absorption band with a maximum wavelength in the 200–400 nm range. The thermodynamic analysis showed that van der Waals (vdW) and hydrogen bonding (H-bonding) interactions exist between 2-EIM and BTC in MeOH. The CT complex was evaluated for stability by measuring its formation constant (K_CT), molar extinction coefficient (ε_CT), and various spectrophysical and thermodynamic properties. The results showed that the complex was highly stable in the tested solvents. The shape and particle size of the complex were analyzed using X-ray powder diffraction. The molecular ratio of the complex was recognized as 1 : 1 through Job's continuous variation method. Additionally, the formation constants and some spectroscopic properties were determined. Fluorescence spectroscopy was used to show the interaction of the CT complex with human serum albumin (HSA) and the binding constant was calculated to be 1.058 × 10³ M⁻¹. It was observed that the CT complex binds with aromatic residues of HSA, mainly tryptophan (Trp). Molecular docking was used to further explore the interaction between HSA and the CT complex.