Comparative DFT Investigation of Electronic Structure and Reactivity Descriptors of Dopamine, Serotonin, and Acetylcholine

Grade XI, Dublin Jerome High School, United States, 43016

Abstract

Neurotransmitters are biologically significant molecules responsible for chemical communication within the nervous system. Understanding their electronic structure is essential for explaining their biochemical reactivity, intermolecular interactions, and functional behavior under physiological conditions. In the present study, Density Functional Theory (DFT) calculations were employed to comparatively investigate the electronic properties of Dopamine, Serotonin, and Acetylcholine in both gas and solvated phases. Geometry optimization and frequency calculations were performed using the B3LYP functional with the 6-31G basis set in Gaussian 09. Solvent effects were modeled using the Conductor-like Polarizable Continuum Model (CPCM). Frontier Molecular Orbital (FMO) analysis was conducted to determine HOMO and LUMO energies, while Koopmans’ approximation was used to calculate global reactivity descriptors, including chemical hardness, softness, chemical potential, electronegativity, and electrophilicity index. The results demonstrate clear structure–property relationships among the neurotransmitters. Serotonin exhibits the highest stability due to its extended π-conjugated indole system, while dopamine displays intermediate reactivity associated with its catechol functionality. Acetylcholine, lacking aromaticity, shows distinct solvent-dependent stabilization attributed to its quaternary ammonium group. Solvation significantly influences orbital energies and global descriptors, particularly in acetylcholine. The study highlights the importance of conjugation length, functional groups, and charge distribution in governing electronic behavior. Overall, the work demonstrates the applicability of conceptual DFT in understanding biologically relevant molecules and provides insight into molecular reactivity relevant to neurochemistry, pharmacology, and biosensor design.