A desolvation-based molecular crowding mechanism revealed through α,β,γ,δ-tetrakis(1-methylpyridinium-4-yl)porphyrin p-toluenesulfonate–Zn complexation in alcohols

Abstract

Molecular crowding can substantially alter chemical reactivity, yet its mechanistic influence in organic solvents remains largely unexplored. Here, we quantitatively and mechanistically extend this concept to non-aqueous media by evaluating the elementary-step kinetics of TMPyP–Zn²⁺ complexation in methanol (MeOH), ethanol (EtOH), and 1-propanol (PrOH). Rate constants for ion-pair formation, ion-pair dissociation, and metal insertion were extracted from time-resolved absorbance changes and analyzed as a function of polyethylene glycol concentration (C_PEG). Our analysis reveals that across all solvents and concentrations, crowding enhances reaction rates primarily through osmotic-pressure-driven desolvation. Notably, ion-pair formation is influenced by both volume exclusion and osmotic pressure effects, for which the excluded-volume contribution becomes negligible (Γ ≈ 1). These findings demonstrate that molecular crowding can effectively accelerate reactions in organic media and provide a unified physico-chemical interpretation of crowding effects beyond aqueous systems, establishing solvent activity engineering as a generalizable framework for controlling reaction kinetics in non-aqueous environments.