The nanosecond-order EFP-MD method succeeded in reproducing the experimental diffusion coefficients. Our simulation results indicated that in dilute aqueous solutions, the dipole moment of the water molecules near the hydrophilic group of TMAO and TBA increased by an average of 12% and 5%, respectively. The dipole moment of the CH 3 -group decreased by an average of 1% and 3% for TMAO and TBA, respectively. Surprisingly, when the chemical structures of the solutes were similar, the solute-solvent interaction characteristics changed depending on the local structure and polarity of the site. That is, TMAO allowed stable polarization and chargetransfer interactions with water molecules near the hydrophilic group, and the large solute polarization affected water molecules near the CH 3 -group. However, the polarization of TBA was negligible and did not affect water molecules near the CH 3 -group; the interaction was hydrophobic. The effect of small amphiphilic molecules on the change in the electronic state in aqueous solutions is significant, and it is important to investigate the mechanism by which osmolytes and denaturants control the stability of or denature proteins in biological environments.