Theoretical Chemistry Facilitated Understanding of Supramolecular Chirality Regulation by Metal Ions

Supramolecular chirality regulation by metal ions remains a fundamental challenge, yet the underlying molecular origins have been poorly understood. Herein, we report a combined experimental and theoretical study to unveil how metal ions dictate supramolecular chirality inversion in folate-based hydrogels. Folate-Cu2+ and Folate-Zn2+ are observed to display M- and P-form Cotton splitting, respectively. DFT calculations reveal that the coordination of Cu2+ and Zn2+ at the α-carboxylate headgroups of folate induces inversed folate conformation. Energy calculations demonstrate that the helical handedness of tetramer stacks is governed by interlayer coordination, as the P-form Folate-Zn2+ and the M-form Folate-Cu2+ tetramer stacks exhibit lower energy than their counterparts, respectively. This mechanism can be generalized to other metal ions (Ca2+, Pb2+, Mn2+, and Cd2+), where the supramolecular chirality of Folate-M2+ systems can be accurately predicted by DFT calculation. This work establishes a molecular-level picture for metal-ion-mediated chirality control, providing a predictive tool for rational design of chiral supramolecular materials.