The Illusion of Simplicity: The Dramatic Failure of Koopmans Theorem for Antioxidants in Solvents -- The Ascorbic Acid Paradigm

TL;DR

This study reveals that Koopmans' theorem is unreliable for predicting antioxidant reactivity in solvents, emphasizing the importance of explicit solvent modeling for accurate quantum-chemical analysis of compounds like ascorbic acid.

Contribution

The paper demonstrates the failure of Koopmans' theorem in solution and advocates for adiabatic solvent-included calculations in antioxidant research.

Findings

Solvent effects significantly alter reactivity indices.

Koopmans' theorem fails catastrophically in solution.

Explicit solvent modeling is essential for accurate predictions.

Abstract

Antioxidants operate in biological environments where solvent effects dramatically alter their redox properties. Using ascorbic acid (vitamin C) as a paradigmatic example, we present a comprehensive quantum-chemical investigation of its global chemical reactivity indices -- ionization potential, electron affinity, HOMO-LUMO gap, hardness, softness, electronegativity, electrophilicity, and electrodonating/accepting powers -- computed at the compound chemistry CBS-QB3 and various DFT levels in vacuo and across six solvents. The results demonstrate that solvation stabilizes charged species so strongly that reactivity indices shift by several electronvolts, following a roughly Born-like dependence on dielectric constant. Most importantly, we show unequivocally that Koopmans' theorem, often used to estimate these indices from orbital energies, fails catastrophically in solution: it predicts solvent-independent values that are qualitatively and quantitatively wrong, missing the essential physics of dielectric screening and geometric relaxation. We therefore conclude that Koopmans' theorem must be abandoned for antioxidant studies in condensed phases; adiabatic calculations with solvent are mandatory for meaningful predictions.