Effect of zwitterionic monomer polymerization on water dynamics: a molecular dynamics simulation study supported by differential scanning calorimetry and terahertz spectroscopy

The behavior of water molecules significantly influences the effectiveness of protein stabilizers and biomaterials. Although the polymerization of low-molecular-weight molecules enhances their functionality, the hydration states and water dynamics around polymers and small molecules are typically examined separately. Therefore, the effect of polymerization on water dynamics at the molecular level remains unclear. By density functional tight-binding molecular dynamics (DFTB-MD) simulations of five zwitterionic solute solutions, (trimethylamine N-oxide) (TMAO), the N-[3-(dimethylamino)propyl]acrylamide N-oxide (DMAO) monomer, poly(N-[3-(dimethylamino)propyl]acrylamide N-oxide) (PDMAO), the 2-methacryloyloxyethyl phosphorylcholine (MPC) monomer, and poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC), the effects of polymerization on water dynamics were investigated. DMAO and MPC polymerization (to PDMAO and PMPC, respectively) promote the slow and rapid rotation of water molecules, respectively. In PDMAO, water molecules are trapped between side chains due to the formation of hydrogen bonds between water and PDMAO, resulting in slow water dynamics, whereas in PMPC, a reduction in the solvent-accessible surface area due to polymerization disrupts the hydrogen-bond network among the water molecules, resulting in acceleration of the rotational dynamics of water molecules. The hydration amount determined using differential scanning calorimetry (DSC) and terahertz time-domain spectroscopy (THz-TDS) is consistent with the MD simulation results, which provide molecular-level insights that advance the current understanding of water dynamics in small-molecule polymerization for potential functional enhancement. Caption: A different effect of polymerization on water dynamics: water molecules trapped by the side chains exhibit slow dynamics, whereas water dynamics is accelerated without the trap.