Influence of Structurally Related Impurities on the Crystal Nucleation of Curcumin

In this work, the influence of the structurally related impurities, demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC) on the primary nucleation of curcumin (CUR) has been investigated in propan-2-ol. The induction time for nucleation was measured at different CUR driving forces and impurity concentrations 0.10 mmol·dm^–3, 0.30 mmol·dm^–3, and 0.60 mmol·dm^–3 and the results are analyzed by the classical nucleation theory (CNT). The nucleation rate for the impure systems was noticeably lower than the nucleation rate of the pure system, and the times of growth to visibility were much longer for the impure systems. The pre-exponential factors are clearly lower for the impure system compared to the pure CUR system, while the increase in the solid–liquid interfacial energy is small. Density functional theory and metadynamic molecular modeling reveal that the 1:1 bonding between CUR and an impurity molecule is stronger than to another CUR molecule, thus suggesting that the developing CUR nucleus has to overcome a certain energy barrier in order to remove the impurity molecules from their surface, which may explain why nucleation of CUR is more difficult in the presence of the structurally related impurities, DMC and BDMC.