Revolutionizing molecular-crowding concepts: investigation of oxine complexation in methanol solutions

Abstract Molecular crowding is an intriguing environment in which both the equilibrium and rate constants differ markedly from those in dilute solutions. Although crowding effects such as volume exclusion and osmotic pressure are considered solvent-independent, most discussions have focused on aqueous systems because of their biological relevance. In this study, we examined the effects of molecular crowding on the complexation of Zn, Co, and Cd ions with oxine in methanol by using polyethylene glycol 200 (PEG200) as the crowding reagent. The complexation constants for the 1:1, 1:2, and total complexes increased substantially with the PEG200 concentration, with the maximum enhancement reaching approximately 20-fold. The experimental results were analyzed by using a theoretical model incorporating volume-exclusion and osmotic-pressure effects. The analysis revealed that the 1:1 complexation was facilitated exclusively by osmotic pressure, whereas the 1:2 complexation was driven primarily by volume exclusion. These findings provide clear evidence that molecular-crowding effects can occur even in nonaqueous (methanol) environments. The present work extends the concept of molecular crowding beyond biological systems and suggests that controlling crowding in organic solvents could offer transformative opportunities across diverse areas of chemistry, including coordination chemistry, catalysis, and solvent extraction.