Chiral resolution of copper aspartate under reaction–diffusion: synergy of experiment and simulation

Abstract

Chiral resolution is essential in the pharmaceutical and food industries and in materials science, due to the unique properties of enantiomers. Here, we investigate the coordination polymerization of homochiral (L- and D-) and racemic (DL-) copper aspartate (CuAsp), as well as the spatiotemporal resolution of racemic aspartic acid (DL-Asp) using L- and D-proline (Pro) as tailor-made additives (TMAs), all within the reaction–diffusion framework (RDF) in a quasi-one-dimensional (1D) agar gel system. We combine experimental approaches—leading to spherulitic CuAsp coordination polymers characterized by solid-state circular dichroism (CD), powder X-ray diffraction (PXRD), and thermal analyses—with a newly developed simulation model grounded in classical reaction–diffusion and Cahn–Hilliard equations. These numerical simulations reproduce the experimentally observed Liesegang banding and the chiral inversion phenomenon, where the earliest precipitates adopt the opposite handedness to the proline dopant, consistent with Harada's application of the ‘rule of reversal’. Parameter choices in the model draw on Harada's original insights, capturing both racemic and chiral scenarios. The simulations confirm how slight adjustments to nucleation barriers and stability can account for increased solubility in enantiopure conditions and partial chiral switching in doped systems. Experimentally, CuAsp near the liquid–gel interface crystallizes in the opposite configuration of the TMA, while more distant regions show varied chirality due to concentration gradients. Overall, both experiment and simulation highlight how the RDF, combined with a modest chiral bias, offers a versatile method for effecting chiral resolution in conglomerate crystalline systems, with broad potential for enantioselective separation strategies.