Elucidating the influence of urea and creatinine concentrations on their hydration structure and transport properties in water: a molecular dynamics study

In this work, molecular dynamics simulations were utilised to investigate the effect of urea and creatinine concentrations on solvation and their diffusion coefficients at 310.15 K. The simulations were performed for urea concentrations ranging from 3.31 to 14,000 mg/dL, representing normal blood, uremic blood, and urine conditions, and creatinine concentrations ranging from 73.8 to 11,200 mg/dL, representing uremic blood and urine conditions. The results show that increasing solute concentrations progressively reduce hydration around urea and creatinine and promote solute self-association. Radial distribution function, coordination number, potential of mean force, and hydrogen bond lifetime analyses indicate weakened solute-water interactions and favorable solute-solute interactions at elevated concentrations. Concurrently, water-water associations become stronger, suggesting reinforcement of hydrogen-bond network among water molecules. These structural changes are reflected in the transport properties of solutions, where diffusion coefficients decrease at high concentrations as intermolecular association becomes pronounced. At the highest concentrations investigated, the diffusion coefficients of urea and creatinine decrease to 2.10 × 10−⁵ and 0.47 × 10−⁵ cm²/s, respectively. The effect is evident for creatinine, which exhibits stronger self-association and greater reduction in mobility than urea. The results demonstrate that concentration-dependent intermolecular interactions play key role in governing the solvation and transport behavior of uremic solutes in aqueous environments.