Unveiling the\nPreference for a Carbon Spacer Length\nof Three in Zwitterionic Sulfobetaines: Insights from DFT Calculations

Zwitterionic\nsulfobetaines (SBs) have shown excellent\nperformance\nin biological and chemical applications. The carbon spacer lengths\n(CSLs) between oppositely charged groups are crucial for the properties\nof SBs. However, most reported studies naturally selected the SB molecule\nwith a CSL of three, although the underlying reason for this choice\nremains unclear. In this work, using DFT calculations, we systemically\ninvestigated the effect of CSL on the molecular properties of SB molecules,\nincluding optimized confirmations, electrostatic potentials, atomic\ncharges, dipole moments, and their self-association behaviors in both\nthe gas phase and water solvent. The solvation free energies of SB\nmolecules with various CSLs were calculated to evaluate the hydrophilicity\nof SBs. The results of our calculations demonstrated that a CSL of\nthree is a critical length for optimal molecular properties, offering\nthe strongest charge separation and the best hydrophilicity. While\nall SB molecules can form stable dimers through strong intermolecular\nelectrostatic interactions, the dimers become unstable in water due\nto electrostatic shielding by water molecules. These findings shed\nlight on the preference for a CSL of three in zwitterionic SBs and\nprovide guidance for the rational design of SB-based materials.