Electron density topography based model to explore N-methyl-d-aspartate receptor channel blockers

Highlights: • Ring critical point (ρ_rcp), emerges as a signature to correlate with the dwell time of a channel blocker molecule. • Steric nature of molecules yields directional approach to the reactive site of the molecule. • Symmetric distribution of electron density obtained with the protonation of Amantadine based methyl derivatives. • Electrophilic nature of molecules can be identified using global reactivity descriptors. The dwell time of a molecule in a voltage dependent NMDA receptor channel is an important factor in defining its activity as channel blocker. A model has been designed, based on quantum chemical descriptors like geometrical parameters, charge distribution, electron density topography and global reactivity descriptors, to shed lights on the dwell time of a channel blocker. Structure and charge distribution studies indicate polarization of molecules with the electron density located at the core of the molecule. Electron density topography reveals ring critical point (ρ_rcp), emerging as a signature parameter to understand the dwell time of a channel blocker molecule.