Unveiling the Preference for a Carbon Spacer Length of Three in Zwitterionic Sulfobetaines: Insights from DFT Calculations

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