Understanding Strong Hydration, Salt-Resistance, and Antibiofouling of Zwitterionic Materials from Ab Initio Simulations*

Zwitterions are emerging affordable antibiofouling candidates due to their strong hydration and resistance against salt molecules. The robust hydration introduces physical and energetical barriers, preventing biomolecules from attaching to the surfaces.  Experimentally, their antifouling efficacies increase as the separation between the two oppositely charged head groups decreases. However, how zwitterionic separation controls the hydration is not known to date. We employ ab initio molecular dynamics (AIMD) and symmetry-adapted perturbation theory (SAPT) to investigate hydration of different zwitterions with varied separation. Our results reveal that zwitterionic hydrations are primarily governed by the hydrogen bonds between zwitterionic oxygens and water hydrogens, the strengths of which vary with the zwitterionic gaps. The bond strength is the strongest when the zwitterionic gap vanishes, as quantified by the quantum theory of atoms in molecules (QTAIM) analysis. Our SAPT analysis further demonstrates that the electrostatic interaction is the dominating attractive component in the hydrogen-bond makeup and   highest for the shortest zwitterionic gap material. Our results explain why TMAO exhibits strong salt-resistance and antibiofouling efficacy against proteins.