Computational investigation on the chiral differentiation of D- and L-penicillamine by β-cyclodextrin.

The identification of chiral penicillamine (Pen) is of great significance for clinical medication safety. The host-guest systems formed by enantiomers and macromolecule can be applied to differentiate the chiral drugs and enable the drug delayed release. We hereby performed the dispersion corrected density functional theory (DFT-D) calculation on the complex formed by β-cyclodextrin(β-CD) and D/L-penicillamine (D/L-Pen). The diverse encapsulation configurations with different interaction energy show that both D-Pen and L-Pen tend to longitudinally embedded into the narrow aperture of β-CD with the front part of the sulfur group and the methyl group, and the interaction energy between L-Pen and β-CD is 5.47 kJ/mol(M062XD3) lower than that between D-Pen and β-CD. Based on the computed vibration frequency of host, guest, and the most stable complex, it is found that the featured peaks attributed to the vibration of the carboxyl group of guest and the skeleton vibration of complex are the most significant spectral standard to distinguish the β-CD-D/L-Pen and β-CD. Moreover, the peaks resulted from the skeleton vibration in terahertz spectra can be also used to distinguish the complex of β-CD with chiral Pen. Through the topological analysis and the Independent Gradient Model (IGM) analysis, the O-H…O hydrogen bond in β-CD-D-Pen is stronger than that in β-CD-L-Pen, and the van der Waals interactions such as C-H…O,C-H…N,C-H…S, O…S and C-H…C-H have the most contributions to the intermolecular interaction in β-CD-D/L-Pen. It is also noted that the H(-OH) in D-Pen and S in L-Pen contribute the most to the intermolecular interaction with β-CD in comparison with other atoms in Pen.