Anion-Dependent Modulation of Cytochrome c Structural Dynamics in Bmim-Based Ionic Liquid–Water Systems

The stability and functionality of biomolecules in ionic liquid (IL) environments have garnered significant interest due to their potential applications in biocatalysis, pharmaceutical formulations, and, particularly, protein preservation. In this study, we systematically investigated the effect of three Bmim-based IL–water systems, [BmimAcO–water], [BmimDCA–water], and [BmimPF 6 –water], on the stability of cytochrome c (Cyt-C) using molecular simulation tools. Our study reveals a significant impact on the structural stability of cytochrome c in different ionic liquids. We show that [BmimAcO–water] is the most suitable solvent for Cyt-C, and it preserves its structural topology better than the other two ionic liquid complexes. In contrast, the [BmimPF 6 –water] system showed the highest destabilization, particularly near the heme cofactor. The [BmimDCA–water] system exhibited intermediate behavior, with structural stability metrics intermediate between those of the AcO – and PF 6 – systems. Taken together, these findings highlight the pivotal influence of IL composition on the protein structure and dynamics.