Valency driven modulation of SDS-insulin complexation: A physicochemical study with biorelevant electrolytes

Electrolytes are more than passive participants in biological systems; they actively shape molecular interactions critical to drug delivery and protein stability. This study investigates how the valency of physiologically relevant cations (Na⁺, K⁺, Zn²⁺, and Co²⁺) modulates the complexation between sodium dodecyl sulphate (SDS), a model anionic surfactant, and insulin, a key therapeutic protein. Using conductometric, tensiometric, and UV-Visible spectroscopic techniques, we reveal that divalent cations significantly enhance micellization and strengthen SDS insulin binding. Conductivity data show a linear decline in specific conductance without a distinct critical micelle concentration (CMC), indicating ion sequestration and complex formation. Surface tension (ST) measurements confirm a marked reduction in CMC and altered interfacial parameters upon electrolyte addition, reflecting enhanced molecular packing. Thermodynamic analysis yields negative "Gibbs free energy" values for both binding and partitioning, confirming the spontaneous nature of these interactions. Notably, Zn²⁺ and Co²⁺ substantially increase binding and partitioning constants, suggesting stronger electrostatic and hydrophobic stabilization of the protein-surfactant complex compared to monovalent ions. These findings provide mechanistic insights into how electrolyte identity and valency govern micelle formation, interfacial behaviour, and protein stability. The results offer a foundation for designing electrolyte-tuned, surfactant-assisted biotherapeutic systems with improved performance and stability.