Investigation on the Mechanisms of Synchronous Interaction of K3Cit with Melamine and Uric Acid That Avoids the Formation of Large Clusters

Uric acid (UA) has an enormous competence to aggregate over melamine (Mel), producing large UA clusters that "drag" Mel to it. Such a combination of donor-acceptor pairs provides a robust Mel-UA composite, thereby denoting a high complexity. Thus, a straightforward but pragmatic methodology might indeed require either destroying the aggregation of UA or impeding a hydrogen-bonded cluster of Mel and UA. Here, potassium citrate (K3Cit) is used as a potent inhibitor for the significant decrease of large UA-Mel clusters. The underlying mechanisms of synchronous interaction between K3Cit and Mel-UA pair are examined by the classical molecular dynamics simulation coupled with the enhanced sampling method. K3Cit binds to Mel-UA pair profoundly to produce Mel-UA-K3Cit complex with favorable complexation energy (as indicated by the reckoning of pairwise ∆G0bind employing MM-PBSA method). The strength of interaction goes according to the order: UA-K3Cit > Mel-K3Cit > Mel-UA, thus clearly demonstrating the instability by upsetting π-stacking of UA and hydrogen bonding of Mel-UA simultaneously. A comprehensive, strategically designed "direct approach" and "indirect approach" cluster structure analysis shows that K3Cit reduces the "direct approach" Mel-UA cluster size significantly irrespective of ensemble variation. Furthermore, the estimation of the potential of mean forces (PMFs) reveals that (UA)decamer-Mel interaction prevails over (UA)tetramer-Mel. The dynamic property (Dimer existence autocorrelation functions) proves the essence of dimerization between Mel and UA in the absence and presence of K3Cit. Moreover, the calculation of the preferential interaction parameter provides the concentration in which interactions between Mel-K3Cit and UA-K3Cit over the interaction of Mel and UA are predominant.