Spectroscopic and molecular docking investigation on the interaction of novel radical scavengers N-acyl monomeric and gemini 3, 4-dihydroxy-L-phenylalanine (L-DOPA) surfactants with bovine serum albumin

Abstract

L-DOPA (3,4-dihydroxyphenyl-L-alanine) is a drug of choice for Parkinson’s disease (PD). However, its clinical application is often hindered by limitations such as poor solubility and bioavailability. Four single-chained N-acyl L-DOPA with varying chain lengths (C10-C16) and three dissymmetric gemini surfactants have been synthesized with a view of overcoming these associated problems. Selected physicochemical properties which included critical micelle concentration (CMC), surface tension, aggregation number, and biochemical properties such as radical scavenging and bovine serum albumin (BSA) binding, have been evaluated. The effect of the hydrophobic chain length as well as unsaturation on the physicochemical, radical scavenging abilities, and binding properties were explored. Contrarily to the monomeric compounds, the CMC of the gemini surfactants increased with the increasing number of carbon atoms, and the presence of unsaturation in the alkyl chain, which contributed to the steric hindrance, led to the perturbation of micelle formation. The aggregation number was found to increase with increasing chain length for the monomeric surfactants, while it decreased with an increase in chain length and unsaturation within the gemini series. The monomeric C12 displayed enhanced radical scavenging abilities, the optimum binding properties with BSA among all the N-acyl L-DOPA derivatives, and also showed better interfacial properties. The radical scavenging abilities and binding affinity of the gemini surfactants were lower compared to the monomeric analogues, while the presence of the double bond in the alkyl chain was found to promote the radical scavenging abilities and binding properties. BSA binding interaction studies showed that N-acyl L-DOPA surfactants quenched the BSA intrinsic fluorescence by a combined static and dynamic mechanism and tended to bind to sub-domains IIA (site I) and IIIA (site II) of BSA. The molecular docking showed similar results, whereby the monomeric surfactants had more affinity towards site I while the gemini surfactants preferred site II. The findings from UV–vis absorption, synchronous, and FT-IR studies corroborated and confirmed the structural conformation changes of BSA resulting from its binding with N-acyl L-DOPA derivatives. This study showed that steric hindrance and rigidity alter aggregation formation and reduce binding ability.