Solute partitioning across a variety of alkane/aqueous interfaces was examined as a function of solute and alkane solvent structure. Solutes include p-nitrophenol (PNP), 3,5-dimethyl-p-nitrophenol (3,5-DMPNP), and 2,6-dimethyl-p-nitrophenol (2,6-DMPNP), the latter two being isomers distinguished solely by the location of methyl substituents on the aromatic ring. The alkane solvents included cylohexane, methylcyclohexane, octane, and iso-octane (2,2,4-trimethylpentane). PNP partitioned preferentially into the water by factors as high as 160:1. The dimethyl isomers partitioned more equally between water and the different alkanes. 2,6-DMPNP showed a 3-fold greater affinity for the alkane phase than 3,5-DMPNP. Ab initio calculations were used to characterize the molecular and electronic structure of the three solutes and to quantify individual contributions to each solute's solvation energy in model aqueous and alkane phases. Differences between 2,6-DMPNP and 3,5-DMPNP partitioning are interpreted based on the ability of the methyl groups in 2,6-DMPNP to weaken hydrogen bonding between the phenol group and adjacent water molecules. This diminished solvation interaction reduces the barrier to solute migration into the nonpolar organic phase despite the fact that 2,6-DMPNP has a larger (calculated) permanent, ground-state dipole than 3,5-DMPNP.