Interplay of noncovalent interactions in antiseptic quaternary ammonium surfactant Miramistin

Abstract

The molecular and crystal structure of the widely used antiseptic benzyldimethyl-{3-[(1-oxotetradecyl)amino]propyl}ammonium chloride monohydrate (Miramistin, MR), C 26 H 47 N 2 O + ÁCl À ÁH 2 O, 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-HÁ Á ÁCl, N-HÁ Á ÁCl, C-HÁ Á ÁCl, C-HÁ Á ÁO and C-HÁ Á Á). The hydrophobic parts are built up exclusively by van der Waals HÁ Á ÁH 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-HÁ Á Á, C-HÁ Á ÁN and HÁ Á ÁH interactions. This conformation preference is hypothesized to play an important role in the interaction of MR with biomembranes. research papers Acta Cryst. (2019). C75, 402-411 Dolgushin et al. Interplay of noncovalent interactions 403 research papers Acta Cryst. (2019). C75, 402-411 Dolgushin et al. Interplay of noncovalent interactions 411

Cationic Antiseptics Facilitate Pore Formation in Model Bacterial Membranes

“…Also, its terminal aliphatic groups penetrated deeper into the hydrophobic core of the bilayer (Figure D). In contrast to other CA species, miramistin (MIR) exhibits a “hook”-shaped conformation anchored by a single long hydrophobic tail inside the membrane with its charged moiety located near the head groups of lipids (Figure C), as proposed earlier …”

“…In contrast to other CA species, miramistin (MIR) exhibits a "hook"-shaped conformation anchored by a single long hydrophobic tail inside the membrane with its charged moiety located near the head groups of lipids (Figure 1C), as proposed earlier. 25 Remarkably, all of the studied antiseptics neither disintegrated the membrane nor solubilized individual lipids or pulled them from the bilayer plane even in the simulations with the highest concentration of CA (1:4 antiseptic/lipid ratio). We neither observed the formation of transient transmembrane pores nor membrane protrusions at the investigated timescale up to 30 μs.…”

Noncovalent Sulfoxide–Nitrile Coupling Involving Four-Center Heteroleptic Dipole–Dipole Interactions between the Sulfinyl and Nitrile Groups

“…The second approach, the most consistent, typically includes “true” periodic calculations taking into account the crystalline structure of studied systems. It is perfectly correct for highly symmetrical crystals (see reviews − and recent works − ) but has certain limitations for less symmetric, disordered molecular crystals, and crystallosolvates. Notably, this approach is time-consuming, and this is a certain limitation especially for the crystals with low point symmetry …”

Structural Significance of Hydrophobic and Hydrogen Bonding Interaction for Nanoscale Hybridization of Antiseptic Miramistin Molecules with Molybdenum Disulfide Monolayers

“…For modeling the organic layers, their thicknesses were set equal to those determined from the PXRD data for each compound. The initial conformation of MR molecules within these layers was taken as identical to the bent conformation, with the head group inclined to the long-chain alkyl tail, revealed previously by single-crystal XRD study [ 27 ] ( Figure S2 ). Importantly, the DFT calculations have showed that this conformation of the MR cation, stabilized by intramolecular interactions, is a preferable one also in the water surrounding [ 27 ].…”

“…The distinctive feature of MR molecular skeleton is the presence of amidopropyl linker, which is capable of playing the role of a hinge between the ammonium head and aliphatic tail ( Figure 1 ). The conformation preference of this molecule and peculiarities of the packing geometry of its hydrophilic and hydrophobic parts have recently been determined by single-crystal X-ray diffraction [ 27 ]. Considering the potential usage of MR–MoS 2 hybrid composites as combined photothermal and antiseptic materials, it was of utmost interest to study the mutual affinity of the components, in particular, to reveal the conditions for filling the MoS 2 interlayer gaps with MR molecules, which have never been reported before.…”