Molecular Aggregation and Percolation Behavior in Aqueous Binary Liquid Mixtures

Abstract

Understanding how small organic molecules aggregate and influence solvent structure is fundamental to explaining phenomena ranging from phase separation to protein destabilization. In complex biological environments, such solutes can subtly or drastically alter the hydrogen bonding network of water, affect solvation layers, and promote conformational changes in biomolecules. Our study provides a systematic framework for probing this relationship, offering insights that can guide further exploration into solute mediated protein unfolding, solvent dependent phase transitions, and the design of solute in aqueous environments. We investigate the molecular aggregation and percolation behavior of ethanol (ETH), tetramethylurea (TMU), and tetrahydrofuran (THF) in aqueous binary mixtures employing molecular dynamics simulations using graph-theoretical analysis, and percolation analysis at temperature, 350 K. Our results show that percolation behavior is governed not simply by solute concentration but by how molecules interact and spatially organize. ETH remains well-solvated with weak self-association, showing delayed percolation transition with low spanning probability even at higher concentration. THF undergoes early and sharp percolation due to strong self-aggregation and phase separation tendencies, forming compact clusters giving high fractal dimension values greater then critical value of 2.53 with minimal impact on water structure. TMU exhibits a unique dual behavior, forming spatially dispersed with low h-value, but internally dense clusters with high spanning probability and large fractal dimension value, that percolate without macroscopic phase separation, while simultaneously causing significant disruption to the hydrogen-bond network of water. Our findings demonstrate that the balance between solute-solute aggregation and solute-water interactions plays a critical role in network connectivity and percolation thresholds. Further the results offer into how solutes modulate aqueous environments and highlight TMU’s distinct capacity to perturb water structure, providing a molecular basis for its known effects on protein conformation and stability.