A Unified Thermodynamic and Kinetic Benchmark for the Catalytic Glucose–Fructose–Mannose Interconversion in Water

Catalytic interconversion of glucose–fructose–mannose (GFM) in water is a fundamental reaction network central to carbohydrate chemistry and biomass valorization. Herein, using enzyme-catalyzed equilibrium data, we identified deviations in the standard molar Gibbs free energy of formation (ΔfGθ) and the standard molar entropy (Sθ) of aqueous mannose and refined these values from −910.99 to −912.77 kJ mol–1 and from 266.90 to 272.89 J mol–1 K–1, respectively. An equilibrium composition model accounting for sugar degradation was developed to quantify the GFM network, yielding temperature-dependent normalized concentrations under varying sugar mass balances. This enables quantitative determination of how far any GFM system deviates from its thermodynamic equilibrium. Kinetic modeling shows that irreversible degradation pathways convert the GFM network into a mass-loss system, while byproduct-driven autocatalysis promotes both sugar interconversion and degradation, thereby preventing the GFM system from reaching equilibrium. For chemo-catalytic systems, catalyst-accelerated degradation and catalyst self-deactivation cause irreversible sugar loss to kinetically outcompete GFM interconversion, pulling the system from equilibrium. The near-equilibrium hexose concentrations observed in pairwise interconversion represent a kinetically controlled pseudosteady state rather than true global thermodynamic equilibrium. Notably, the established benchmark applies to dilute aqueous systems, whereas concentrated and nonaqueous systems require activity coefficient correction, reparameterization, and kinetic validation.