Interplay of noncovalent interactions in antiseptic quaternary ammonium surfactant Miramistin

Area of Science:

• Molecular modeling and structural analysis.
• Quantum chemistry and computational physics.
• Crystallography and supramolecular chemistry.

Background:

• Miramistin (MR) is a widely used antiseptic with a known chemical structure.
• Understanding the molecular conformation and intermolecular interactions is crucial for its efficacy.
• Previous studies have not fully elucidated the structural basis of Miramistin's interaction with biological membranes.

Purpose of the Study:

• To determine the molecular and crystal structure of Miramistin (MR).
• To analyze the intermolecular interactions within the crystal lattice using quantum theory of atoms in molecules (QTAIM) and density functional theory (DFT).
• To investigate the conformational preferences of the Miramistin cation and hypothesize their role in biomembrane interactions.

Main Methods:

• Single-crystal X-ray diffraction for determining the crystal structure.
• Quantum Theory of Atoms in Molecules (QTAIM) approach for analyzing electron density distribution.
• Periodic and molecular Density Functional Theory (DFT) calculations for interaction energy quantification.

Main Results:

• The molecular and crystal structure of Miramistin (MR) monohydrate was determined.
• Analysis revealed diverse noncovalent interactions (O-H...Cl, N-H...Cl, C-H...Cl, C-H...O, C-H...π) in hydrophilic regions and van der Waals H...H contacts in hydrophobic regions.
• The Miramistin cation exhibits a bent conformation, stabilized by intramolecular interactions (C-H...π, C-H...N, H...H), in both crystalline and isolated states.
• Interaction energies in hydrophilic and hydrophobic regions were found to be comparable.

Conclusions:

• The bent conformation of the Miramistin cation, stabilized by intramolecular interactions, is a key structural feature.
• This conformation is hypothesized to be critical for Miramistin's interaction with biological membranes.
• The study provides a detailed structural and energetic basis for understanding Miramistin's antiseptic properties.