# Electronic Structure and Redox of the Antidepressants Venlafaxine and Desvenlafaxine

## TL;DR

This paper studies the electronic structure and redox behavior of venlafaxine and desvenlafaxine to better understand their electrochemical properties.

## Contribution

The study combines electroanalytical and computational methods to reveal pH-dependent redox behaviors and molecular energetics of these antidepressants.

## Key findings

- Desvenlafaxine shows higher anodic peak intensities at neutral pH compared to venlafaxine.
- Venlafaxine exhibits peak activity at alkaline pH.
- DFT calculations reveal molecular charge distribution and energetics in different protonation states.

## Abstract

Venlafaxine and its
primary metabolite desvenlafaxine are antidepressants
that block presynaptic reuptake of serotonin and norepinephrine in
the brain. Electroanalytical and computational analyses were performed
to evaluate the electrochemical characterization of these drugs through
measurements using a carbon paste electrode alongside quantum calculations
(DFT and TD–DFT) to support the electrochemical data and propose
potential oxidation pathways. The results showed that both venlafaxine
and desvenlafaxine exhibit different pH-dependent electrochemical
behaviors, with desvenlafaxine showing higher anodic peak intensities
at neutral pH, while venlafaxine peaks at alkaline pH. Computational
insights from DFT calculations provided a deeper understanding of
the molecular charge distribution, orbital profiles, and energetics
of both drugs in neutral and protonated states. The Gibbs free energy
variations in different medium environments revealed the critical
role of the medium in modulating the thermodynamic stability. These
findings presented here improve our understanding of the electrochemical
and electronic properties of these antidepressants and may pave the
way for the development of more effective therapeutic agents.