Systematic Molecularity-Dependent Entropy Errors in Continuum/RRHO Solution Thermochemistry: Origin and Correction

Continuum solvation models often reproduce standard solvation free energies accurately, but this does not ensure that solution-phase reaction free energies are thermodynamically consistent. In common workflows, continuum solvation terms are combined with gas-phase RRHO thermochemical corrections. For molecularity-changing processes such as association, clustering, and transition-state formation, the ideal-gas translational and rotational entropy terms do not cancel and can impose an artificial penalty against associated species. Here, we analyze this effect by decomposing solution-phase association free energies into electronic, differential solvation, and RRHO contributions. Carbon tetrachloride self-association in liquid CCl₄ provides a simple diagnostic case: the electronic association is favorable, and the differential continuum solvation term is small, yet the final 1 M association free energy remains positive and essentially gas-phase-like. Water and chloroform clusters further show how this molecularity-dependent RRHO penalty accumulates with increasing association. Confinement-based corrections, including Martin-Pratt density scaling and Benson's free-volume formulation, reduce this artificial destabilization without modifying electronic energies or continuum solvation terms. The main limitation identified here is therefore not the absolute continuum solvation free energy of isolated species but the use of gas-phase RRHO thermochemical corrections to construct reaction free energies in solution. This distinction provides a physical basis for applying condensed-phase translational entropy corrections in association and activation thermochemistry.