Observation of quantum signature in rivastigmine chemical bond break-up and quantum energetics, spectral studies of anti-Alzheimer inhibitors

Abstract

Semi-empirical calculations on the torsion potential for dihedral angle of rivastigmine linking NAP and Carbamyle moieties consistently show regions of several discontinuities and a cusp indicating molecular instability and eventual break-up of rivastigmine observed in the X-ray structure. The phenomena can be explained both by definition of large classical force or quantum nature of chemical bond break-up. Also, to better understand the molecular properties and quantum energetics of the inhibitor molecules, we have performed several ab initio based calculations on all four inhibitors at equilibrium geometry, in ground state and gas phase using the density functional theory level wB97X/6-31G* and HF/6-31G*. A number of properties like computational vibrational (IR), Raman and nuclear magnetic resonance (NMR) spectra as well as HOMO and LUMO orbital energies at optimized geometries have been computed by SPARTAN16 and Gaussian16 utilities. Also, the thermodynamic and QSAR properties of the inhibitors have been assessed and compared by a number of different semi-quantum, Hartree-Fock and density functional methods. The theoretical NMR and IR spectra have been benchmarked against experimental spectrum to compare and assess suitability of the computational methodologies and basis set levels for the calculations.

Communicated by Ramaswamy H. Sarma

Keywords:

• Density functional theory (DFT)
• Hartree-Fock methods (HF)
• equilibrium and transition states geometries
• quantum signature
• torsional potential energy

Acknowledgements

We acknowledge XSEDE Super Computer Research Resources (Allocation # TG-MCB140084) in Texas Advanced Computing Center in Stampede2 Facilities and Scientific Computation and Resources in Icahn School of Medicine at Mount Sinai. Also we acknowledge Drs. Paul Smith and Stephen Holler of Fordham University for co-operations with NMR and IR experiments. MRA thanks St. John’s University (SJU) for the chemicals used in NMR and IR experiments and also former SJU chemistry undergraduate major Alexander Ng for plotting a few graphs.

Disclosure statement

No potential conflict of interest was reported by the authors.