Conformations and intermolecular interactions pattern in solid chloroxylenol and triclosan (API of anti‐infective agents and drugs). A ³⁵Cl NQR, ¹H‐¹⁴ N NQDR, X‐ray and DFT/QTAIM study

Abstract

Two antibacterial and antifungal agents, chloroxylenol (4-chloro-3,5-dimethyl-phenol) and triclosan (5-chloro-2-(2',4'-dichlorophenoxy)-phenol), were studied experimentally in solid state with an X-ray, (35)Cl-nuclear quadrupole resonance (NQR) and (17)O-nuclear quadrupole double resonance (NQDR) spectroscopies and, theoretically, with the density functional theory/quantum theory of atoms in molecules (DFT/QTAIM). The crystallographic structure of triclosan, which crystallises in space group P31 with one molecule in the asymmetric unit [a = 12.64100(10), b = 12.64100(10), c = 6.71630(10) Å], was solved with an X-ray and refined to a final R-factor of 2.81% at room temperature. The NQR frequencies of (35)Cl and (17)O were detected with the help of the density functional theory (DFT) assigned to particular chlorine and oxygen sites in the molecules of both compounds. The NQR frequencies at (35)Cl sites in chloroxylenol and triclosan were found to be more differentiated than frequencies at the (17)O site. The former better describes the substituent withdrawing effects connected to π-electron delocalization within the benzene rings and the influence of temperature; whereas, those at the (17)O site provide more information on O-H bond and intermolecular interactions pattern. The conformation adopted by diphenyl ether of triclosan in solid state was found to be typical of diphenyl ethers, but the opposite to those adopted when it was bound to different inhibitors. According to an X-ray study, temperature had no effect on the conformation of the diphenyl ring of triclosan, which was the same at 90 K and at room temperature (RT). The scattering of NQR frequencies reproduced by the DFT under assumption of the X-ray data at 90 K and RT is found to be a good indicator of the quality of resolution of the crystallographic structure.

Structure, energy, vibrational spectrum, and Bader's analysis of π⋯H hydrogen bonds and H−δ⋯H+δdihydrogen bonds

“…[796][797][798][799][800][801][802][803][804] Specifically in the context of the chemical bond and intermolecular interactions, 55,[805][806][807][808][809][810][811][812][813][814][815] a traditional task is to use a series of basis sets in order to reproduce accurately the available experimental data, [816][817] in general those derived from structural and vibrational analysis. 203 Regarding the QTAIM characterization of intermolecular interactions, 212,[818][819][820][821][822][823][824][825][826][827][828][829] in particular the hydrogen bonds, it has been demonstrated that Pople's split-valence double-z incremented by polarization functions 830,831 with higher angular momentum are not appropriate for basis sets to describe the electronic density computed through the QTAIM protocols. 832 Otherwise, valence and diffuse functions fairly do it well.…”

Hydrothermal Conversion of Triclosan—The Role of Activated Carbon as Sorbent and Reactant

“…Adsorption of TCS might occur in one of the preferred conformations, which have prior been determined by quantum chemical calculations. 23,24 In this optimized geometry, TCS has a twisted conformation in the solid state with a dihedral angle of 62°between the dichlorobenzene and phenolic ring due to the steric effect between the ortho-chlorine and ortho-hydroxyl substituents. Sorption of TCS could occur in a geometry that minimizes steric hindrance.…”

“…One reason for the inhibition of DCDD formation could be that the necessary conformation for the nucleophilic substitution could not be adopted in the sorbed state and that the transition state for an intramolecular substitution was less favorable in the sorbed state as compared to freely dissolved TCS. Adsorption of TCS might occur in one of the preferred conformations, which have prior been determined by quantum chemical calculations. , In this optimized geometry, TCS has a twisted conformation in the solid state with a dihedral angle of 62° between the dichlorobenzene and phenolic ring due to the steric effect between the ortho-chlorine and ortho-hydroxyl substituents. Sorption of TCS could occur in a geometry that minimizes steric hindrance.…”

Polymorphism and Thermal Stability of Natural Active Ingredients. 3,3′-Diindolylmethane (Chemopreventive and Chemotherapeutic) Studied by a Combined X-ray, 1H–14N NMR-NQR, Differential Scanning Calorimetry, and Solid-State DFT/3D HS/QTAIM/RDS Computational Approach

“…In both polymorphs, common structural motifs are molecules linked by NH•••π interactions with the locking ability of the rings conformation, 70 indicate a significant thermal hysteresis, defined here as the difference between the melting and freezing points.…”

“…In both polymorphs, common structural motifs are molecules linked by NH···π interactions with the locking ability of the rings conformation, but, in form I two neighboring molecules are mutually linked and form hydrogen-bonded dimeric synthons, while in form II chains of molecules are formed, Figure S2 (Supporting Information). These packing motifs are kept unchanged upon cooling/heating in each form.…”