Exploring the binding mode of ester-based cationic gemini surfactants with calf thymus DNA: A detailed physicochemical, spectroscopic and theoretical study

Abstract

Gene therapy is a transfectant method for the treatment of hereditary disease, which transfers the gene mutation into the cells. In the view of the high prospects of utilization of cationic gemini surfactants as a non-viral vector for the gene transfection, we have made a comprehensive study on the interactions between a recently synthesized series of ester-functionalized cationic C_m-E2O-C_m gemini surfactants (m = 12, 14 and 16) with calf thymus deoxyribonucleic acid (ctDNA) utilizing various techniques. The micellization behavior of gemini surfactants has been altered in the presence of ctDNA. A series of measurements (fluorescence, UV-vis and time-resolved fluorescence) show that the quenching of ctDNA proceeds by a static mechanism. The competitive displacement studies (EB, AO and HO), KI quenching analysis, CD studies and viscosity measurements suggested intercalative binding mode in a stoichiometry ratio of 1:1 with the K_b (binding constant) order being: C₁₆-E2O-C₁₆ > C₁₄-E2O-C₁₄ > C₁₂-E2O-C₁₂. The thermodynamic parameters show that the geminis interacted with ctDNA spontaneously through ionic/electrostatic interactions. Furthermore, the theoretical approaches offer accurate insights about the binding of gemini surfactants with DNA, and are in consistence with the experimental results.

Keywords: C(m)-E2O-C(m) gemini surfactants; Surface tension measurements; Theoretical techniques; Time-resolved fluorescence (TRF); ctDNA.