Chiral differentiation of l- and d-penicillamine by β-cyclodextrin: Investigated by IRMPD spectroscopy and theoretical simulations.

The chirality of penicillamine (Peni) results in different clinic applications. Host-guest complex based drug delivery system that differentiates the two enantiomers and provides delayed release is of significance in medication. We hereby used β-CD to encapsulate d- and l-Peni. IRMPD spectra show different characteristic vibrations to distinguish the two enantiomers. Besides common peaks found at 3000-3100 cm-1 and 3520 cm-1, featured peaks are found around 2900 cm-1 and 3400 cm-1. It is found that the featured vibrations of [β-CD + l-Peni + H]+ are more red-shifted than those of [β-CD + d-Peni + H]+. Through DFT calculations on the complex configurations sampled from molecular dynamics simulations, d-Peni is found embedded inside β-CD with a lower free energy of 11.5 kJ mol-1 in the lowest configuration than that of the lowest [β-CD + l-Peni + H]+ configuration, in which l-Peni is found lying upon the β-CD. The featured vibrational peaks are attributed to the specific NH⋯O, OH⋯O intermolecular hydrogen bonds. The red-shifted characteristic peaks of [β-CD + l-Peni + H]+ in IRMPD spectra owe to the stronger NH⋯O hydrogen bonds.