Counterion Structure Tunes Cetyltrimethylammonium Association in Water: Thermodynamics and Weak-Contact Networks

Abstract The role of counterion structure in the stability and interaction mechanisms of cetyltrimethylammonium ion pairs was investigated by employing isothermal titration calorimetry (ITC), molecular dynamics simulations, and quantum-chemical calculations. Alkyl sulfate anions with increasing chain length and tetraphenylborate were used to distinguish between the effects of electrostatic and hydrophobic interactions as well as static anion polarizability. The ITC measurements showed stronger binding for longer alkyl sulfate chains. Namely, the corresponding Gibbs free energy spanned from −6.78 kcal/mol for octyl sulfate to −8.82 kcal/mol for dodecyl sulfate. Tetraphenylborate showed similar binding strength with ΔG equal to −8.75 kcal/mol. Molecular dynamics simulations were applied to study the conformational space of CTA+/anion associates in water. Afterward, the representative structures were selected for quantum-chemical characterization. The energy decomposition analysis showed that although electrostatic interaction dominates, dispersion becomes more important for both longer alkyl sulfates and tetraphenylborate-based systems. Quantum theory of atoms in molecules (QTAIM) analysis showed that stabilization is not determined by a single strong contact. Instead, longer alkyl chains form more weak hydrophobic contacts. The results explain how the structure of the studied counterions affects the CTA+ association through a balance of electrostatic interactions and multiple hydrophobic contacts.