Water structure and dynamics under distinct microheterogeneity in DMSO–water and acetone–water mixtures

Dimethyl sulfoxide (DMSO) and acetone are water miscible structural analogs with sharply contrasting cryoprotective properties. These cosolvents perturb water structure and dynamics in different ways, leading to distinct molecular associations, hydration patterns, and solute-specific microheterogeneous environments. To explore these divergences, this work presents a comparative study of DMSO–water and acetone–water mixtures over a cosolvent mole-fraction range of 0.05–0.5, using classical molecular dynamics simulations combined with graph theoretical analysis, quantification of spatial inhomogeneity via the h-value, and analysis of water dynamics. DMSO integrates into the water network, locally disrupting tetrahedral order while minimizing DMSO–DMSO self-association and preserving connectivity through the formation of DMSO–water complex. In contrast, acetone promotes cohesive self-aggregation of acetone molecules and enhanced clustering of water molecules, creating a microheterogeneous environment. Correspondingly, water in acetone mixtures exhibits faster translational diffusion and rotational dynamics with shorter H-bond lifetimes, whereas DMSO mixtures slow water dynamics and lengthen H-bond lifetimes. Notably, the study on these differences in structural and dynamical properties in both aqueous mixtures could help rationalize DMSO’s established effectiveness in cryopreservation, owing to its relatively low microinhomogeneity, in contrast to the tendency of acetone to promote microinhomogeneity, thereby limiting its utility as a cryoprotectant.