Theoretical investigations of free energy of binding and chiral recognition studies of (R)- and (S)-Noradrenaline towards β-cyclodextrin

Abstract

Noradrenaline (NA), one of the important excitatory catecholamine neurotransmitters, is used as a medication for Parkinson's Disease (PD). The β-cyclodextrin (β-CD) is one of the most effective drug carrier & also used in chiral separation. So, in this theoretical investigation, the R/S-Noradrenaline (R/S-NA) forms binding & chiral recognition mechanisms and energies with β-CD were explored. Using the AutoDock, R/S forms were first docked into the cavity of β-CD giving host-guest complexes with the free energy of binding for S-NA (−4.81 kcal/mol) larger than R-NA (−4.53 kcal/mol). The host-guest inclusion 1:1 complexes between R/S-NA and β-CD have been also modeled and optimized with ONIOM2 (B3LYP/6-31g++DP: PM6) method by using the Gaussian software. Further, frequency calculations were carried out to obtain the free energies. In comparison to the R-NA (−54.59 kcal/mol), it was observed that the S-NA (−56.48 kcal/mol) with β-CD is more stable. Furthermore, the H-bond results from molecular dynamics simulation revealed that S-NA/β-CD was more stable than R-NA/β-CD. In addition, the thermodynamic properties, vibrational analysis (IR), HOMO-LUMO band gap energy, inter molecular hydrogen bond interactions, and conformational analysis were investigated for both the R/S forms to support & compare the stability of the inclusion complex. These inclusion & high stability of S-NA/β-CD and in turn its theoretical chiral recognition behavior observed agreeing well with the reported NMR experimental data have implications in drug delivery and chiral separation research.