Molecular crowding effect in Hantzch pyridine synthesis in polyethylene glycol aqueous solution

Abstract

In a molecular crowding environment, the kinetics and thermodynamics differ from those in a diluted solution. Although the molecular crowding effect has been extensively investigated, its fundamental kinetics and thermodynamics remain unclear. In this study, we investigated the change in the rate constant (k) of the Hantzch pyridine reaction in a molecular crowding environment using polyethylene glycol (PEG). While the k value increased to a PEG concentration (C_PEG) of 10 vol%, a decreasing trend was observed for C_PEG > 20 vol%. This intriguing behavior was analyzed based on the increase in reactant activity due to volume exclusion and the decrease in water activity due to osmotic pressure. Volume exclusion and osmotic pressure had opposing effects on the reaction, which were positive for volume exclusion and negative for osmotic pressure. We found that k decreased when the negative effect of the osmotic pressure surpassed the volume exclusion effect.