Difference in hydration between carboxybetaine and sulfobetaine

In this work, we report a study on the differential hydration of carboxybetaine and sulfobetaine using molecular simulations. The coordination number, spatial distribution, dipole orientation distribution, and residence time of water molecules around the positively charged group (N(CH ₃)₃⁺) and negatively charged group (COO ^- for carboxybetaine and SO₃^- for sulfobetaine) were investigated to compare the hydration of these two betaines. The results show that the negatively charged group of sulfobetaine has more water molecules around it than that of carboxybetaine, while the water molecules around the negatively charged group of the carboxybetaine have a sharper spatial distribution, more preferential dipole orientation, and longer residence time. The behavior of water molecules around the positively charged group of sulfobetaine is similar to those around the positively charged group of carboxybetaine. For both sulfobetaine and carboxybetaine, the positively charged groups are surrounded by more water molecules than the negatively charged groups, whereas the water molecules around the negatively charged groups are more ordered than those around the positively charged ones. We also investigated the hydration free energy of these two molecules with the free energy perturbation method and found that their values are all considerably lower than that of oligo(ethylene glycol).