Internlay of noncovalent interactions in antiseptic quaternary ammonium surfactant Miramistin

Acta Crystallographica. Section C, Structural chemistry. 2019. Vol. 75. P. 402–411.

Долгушин Ф., Головешкин А., Ananyev I., Осинцева С., Торубаев Ю., Крылов С., Голубь А.

The molecular and crystal structure of the widely used antiseptic benzyldimethyl-{3-[(1-oxo tetradecyl) amino] propyl} ammonium chloride monohydrate (Miramistin, MR), C26H47N2O+center dot Cl-center dot H2O, was determined by a single-crystal X-ray diffraction study and analyzed in the framework of the QTAIM (quantum theory of atoms in molecules) approach using both periodic and molecular DFT (density functional theory) calculations. The various noncovalent intermolecular interactions of different strengths were found to be realized in the hydrophilic parts of the crystal packing (i.e. O-H center dot center dot center dot Cl, N-H center dot center dot center dot Cl, C-H center dot center dot center dot Cl, C-H center dot center dot center dot O and C-H center dot center dot center dot pi). The hydrophobic parts are built up exclusively by van der Waals H center dot center dot center dot H contacts. Quantification of the interaction energies using calculated electron-density distribution revealed that the total energy of the contacts within the hydrophilic and hydrophobic regions are comparable in value. The organic MR cation adopts the bent conformation with the head group tilted back to the long-chain alkyl tail in both the crystalline and the isolated state due to stabilization of this geometry by several intramolecular C-H center dot center dot center dot pi, C-H center dot center dot center dot N and H center dot center dot center dot H interactions. This conformation preference is hypothesized to play an important role in the interaction of MR with biomembranes.

Keywords: hydrogen bonding, crystal structure, quaternary ammonium surfactant, amphiphilic molecule, antiseptic, QTAIM, periodic DFT calculation, hydrophobic interaction