The understanding developed here applies broadly, because the chemical interactions among polar SiOH functions, reactive intermediates, metal active sites, and protic solvents are recognized to strongly affect multiple classes of reactions that occur within microporous catalysts including methanol-to-hydrocarbons (MTH), alkene epoxidations, glucose isomerization, alcohol dehydration, transfer hydrogenation, and Baeyer-Villiger oxidation reactions. These data and interpretations clarify how the proximity of hydrogen-bonded solvent structures to reactive metal atoms leads to significant changes in the free energies of reactive intermediates via solvent reorganization. The condensation of protic molecules within zeolite pores may lead to the formation of extended solvent structures even during gas-phase catalysis. As such, similar phenomena should be considered in these circumstances. These concepts should also be considered examine in the context of optimizing rate, selectivities, and yields for catalytic conversions. Our findings demonstrate that the zeolite framework may be viewed as a way to escape the single-factor linear free energy relationships that link the stabilization of the reactant in a solvent to the stability of the transition state. Combinations of solvents (single or multicomponent) and microporous frameworks (zeolite, metal-organic-frameworks, or covalent-organic-frameworks) may be identified that make use of these emergent enthalpy-entropy compensation effects. While previous discoveries in this area often involved some level of serendipity, the comparisons demonstrated here suggest rational approaches for harnessing solvent, zeolite, reactant interactions to improve catalyst performance by significant margins. On-going work within our group seeks to understand how the structure of protic solvents and aqueousorganic solvent mixtures influence catalytic reactions and to exploit the characteristics of these hydrogen bonded solvation shells.