Underlying mechanistic insights into the structural properties of melamine and uric acid complexes with compositional variation under ambient conditions

Abstract

The structural properties of melamine-uric acid complexes (which are responsible for kidney stones) with compositional variations are examined using a series of classical molecular dynamics simulations. The preferential interaction parameters imply that melamine interacts more strongly with uric acid than with other melamine molecules present in the system, whereas uric acid preferentially interacts with other uric acid molecules rather than with melamine. The stronger interactions among uric acid molecules produce higher-order uric acid clusters, which “drag” neighboring melamine molecules to be added to a cluster. Determination of orientational preferences between aromatic planes reveals that π–π stacking is responsible for uric acid self-association but less significant for melamine-melamine and melamine-uric acid accumulation. Cluster structure analyses suggest that higher concentrations of melamine, uric acid, or both result in a large insoluble melamine-uric acid complex cluster. Molecular mechanics-Poisson Boltzmann surface area calculations give a negative binding energy, indicating favorable complexation between melamine and uric acid molecules. Moreover, the overall complexation energy [ΔG0(mel-mel)+ ΔG0(uri-uri)+ ΔG0(mel-uri)] is more negative than ΔG0bind(mel-uri). The lifetime of melamine dimers is quite low compared with those of uric acid-uric acid and melamine-uric acid dimers, resulting in a low percentage of larger clusters for melamine-melamine interaction and a significant percentage of higher-order melamine-uric acid and uric acid-uric acid clusters with longer lifetimes. Furthermore, melamine and uric acid form strong hydrogen bonds, and melamine-melamine interactions are dominated by hydrogen bonding, whereas uric acid forms only a small number of hydrogen bonds with other uric acid molecules.