The proton acceptor orbital of TMAO has a significant overlap integral with the H 2 O orbital around the hydrophilic group and facilitates the charge-transfer (0.04 e). However, the orbital overlap between the OH groups of TBA and H 2 O is small; thus, the charge-transfer is small (0.01 e). Therefore, we can conclude that the factors that cause the N + O -group to strongly supplement water in an aqueous TMAO solution are the polarization and charge-transfer interactions derived from the large polarization of TMAO.