Accurate Determination of Molecular Sizes of a Solute in Water From its Translational Self‐Diffusion Coefficient

Abstract Determining accurate molecular dimensions in water, from measured translational self‐diffusion coefficients ( D t ), is extremely important in biochemistry, supramolecular chemistry, organometallic chemistry and beyond, but it still represents a big challenge especially for small and medium‐sized molecules. Indeed, current semiempirical adaptations of the Stokes‐Einstein equation, which allow accurate determination of molecular size of solutes in organic solvents, proved inadequate for aqueous systems. To overcome such a major limitation, herein, we introduce a novel approach that unlocks the quantitative interpretation of D t in water. By analyzing ~70 diverse molecules with volumes ranging from 10 1 Å 3 to 10 3 Å 3 , and selecting the partial molar radius ( r M ) as a reliable proxy for the hydrodynamic radius ( r H ), we derived a semiempirical equation that enables accurate determination of hydrodynamic volume ( V H ) of solutes in aqueous solutions, effectively accounting for the distinctive hydrogen‐bonding properties of water. This approach fills a crucial gap, enhancing precise molecular characterization of polar and non‐polar solutes in water.