Inclusion of Theobromine Modifies Uric Acid Aggregation with Possible Changes in Melamine Uric Acid Clusters Responsible for Kidney Stones

Theobromine, a naturally occurring substance, can be conceived as a prospective inhibitor for uric acid clustering. In aqueous solution, aggregates of pi-stacked uric acid molecules with the larger size of clusters are modified into lower-order clusters with a substantial percentage of monomer by the incorporation of theobromine. The composite made of theobromine-uric acid is expected to have enhanced water solubility, allowing stable kidney stones to be excreted through urine. Interestingly, the strategy for the decomposition with feasible modifications in melamine-uric acid composites (that are hydrogen-bonded) is developed (by implementing the cluster structure analysis technique and binding free energies). The all-atom molecular dynamics (MD) data provides new insights into the structure and dynamics of uric acid along with melamine molecules in the context of aggregation. The simulation in the present study is supported further by structural and dynamical property calculations. The calculations of hydrogen bond dynamics, the average number of hydrogen bonds, dimer existence autocorrelation functions, umbrella sampling, and coordination number theorize that the incorporation of theobromine significantly modifies the aggregated structure of uric acid. The overall complexation energy, along with the quantum chemical calculations, further explains the alternation of aggregated structure. Furthermore, the preferential interaction parameter describes at which concentration theobromine-uric acid interaction (which is pi-stacked) predominates over uric acid-uric acid interactions. Interestingly, the interactions between theobromine-melamine and melamine-melamine (which are hydrogen-bonded) are not relevant here. Thus, melamine-uric acid cluster size is reduced owing to the disintegration of self-aggregated uric acid clusters by the involvement of theobromine. Moreover, an excellent agreement is observed between present MD results and experimentally obtained data.