Stability and molecular dynamics of chloroxylenol (API of antiseptics and drugs) in solid state studied by 35Cl-NQR spectroscopy and DFT calculations

Latosińska, J.N.; Tomczak, Marzena Agnieszka; Kasprzak, J.

doi:10.1016/j.cplett.2008.12.076

Cited by 4 publications

(13 citation statements)

References 16 publications

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“…The angle of this motion is in a good agreement with those estimated from 35 Cl NQR data. 27 Moreover, analysis of anisotropic displacement parameters (ADPs) per each atom, 25 especially for both oxygen atoms participating in the O−H•••O bond, linking the neighboring molecules, and chlorine atoms (at para to both oxygens), shows that the rings linked by this hydrogen bond perform skewed motion about their mean positions.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…26 The relaxation mechanism revealed by 35 Cl NQR involves two types of motions, classical librations and fast molecular motion, responsible for frequency averaging and narrowing of the NQR line. 27 We interpreted this motion as modulation of the EFG tensor related to methyl rotation; however, the temperature of the minimum and activation energy seemed high. To verify the nature of this motion, we decided to use another spectroscopic method, 1 H NMR, a technique sensitive to global molecular motions and able to describe the dynamics below the liquid nitrogen temperature and resolve doubts concerning the peculiarities in averaging the EFG tensor at 35 Cl observed in NQR spectra.…”

Section: ■ Introductionmentioning

confidence: 83%

“…Results of combined 1 H NMR and DFT studies presented in this paper considerably expand and, on the other hand, clarify the details of relaxation mechanism derived from our earlier 35 Cl NQR study. 27 They also highlight the importance of the use of different experimental and theoretical techniques to get a comprehensive description of both structural features and molecular dynamics of solid formulations. PCMX is not only a drug and excipient (preservative) but also a contaminant.…”

Section: ■ Introductionmentioning

confidence: 99%

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Complex Mechanism of Relaxation in Solid Chloroxylenol (Antibacterial/Antifungal Agent) Studied by ¹H NMR Spectroscopy and Density Functional Theory Calculations

Latosińska

Tomczak

et al. 2014

J. Phys. Chem. A

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Molecular relaxation in antibacterial/antifungal agent: chloroxylenol (4-chloro-3,5-dimethylphenol, PCMX) in the solid state was studied by the (1)H NMR and quantum chemistry calculations. The temperature dependencies of the proton spin-lattice relaxation time (T1) in the ranges 15-273 K (at 24.667 MHz), 77-295 K (at 15 MHz), and 112-291 K at 90 MHz and the second moment (M2) of (1)H NMR resonant line in the range 106-380 K were measured. The two minima in the temperature dependence of T1 revealed two activation processes, whereas the M2 dependence in the studied range was quite flat and revealed the only significant reduction at 380 K. The low temperature part of T1(T) dependence indicated the occurrence of two processes characteristic of methyl bearing solids; the quantum mechanics governed incoherent tunneling (responsible for the low temperature flattening of T1) and the classical Arrhenius dependence governed hindered rotation (related to the wide low temperature minimum of 0.066 s at 57 K, 24.667 MHz). The 2D potential energy surface obtained using DFT/B3LYP/6-311++G(2d,p) calculations revealed the inequivalence of methyl groups and the lack of their interplay/coupling. The activation energies of classical hindered rotation are 3.35 and 2.5 kJ/mol, whereas temperatures at which the proton tunneling T(tun) finally ceases are 52 and 63 K, for inequivalent methyl groups. C(p)(T) required for the estimation of T(tun) was calculated purely theoretically on the basis of the Einstein and Debye models of specific heat and 51 modes of atomic vibrations, 4 internal rotations, and 3 torsions calculated by DFT. The -CH3 motion (tunneling and classical) results in the reduction in the (1)H NMR line second moment from 17.3 G(2) (rigid) to approximately 11.05 G(2). The pointed high temperature minimum T1(T) of 0.109 s at 89 K, 24.667 MHz, which shifts with frequency, was assigned to small-angle libration jumps, by the Θ2 = ±15° between two positions of equilibrium. The activation energy of this motion estimated on the basis of the fit of the theoretical model to the experimental points is 10.5 kJ/mol. The reduction in the (1)H NMR line second moment assigned to this motion is much lower (due to order parameter s = 0.64) and equal to 1.6 G(2). The high temperature reduction from 9.6 G(2) to 0.9 G(2) at 380 K is a result of the phase transition connected with melting (385-389 K).

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Section: ■ Results and Discussionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 83%

Section: ■ Introductionmentioning

confidence: 99%

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Complex Mechanism of Relaxation in Solid Chloroxylenol (Antibacterial/Antifungal Agent) Studied by ¹H NMR Spectroscopy and Density Functional Theory Calculations

Latosińska

Tomczak

et al. 2014

J. Phys. Chem. A

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“…The importance of this finding is the suggestion of the presence of two enantiomers of triclosan, which would nicely explain a wide spectrum of its activity. The smooth changes in NQR frequency with temperature increasing from 77 K to 300 K [101] and similar parameters of the unit cells at RT and at 90 K (a=12.5225 Å, b=12.5225 Å and c=6.6809 Å [100] versus a=12.6410 Å, b=12.6410 Å and c=6.7163 Å [99]) confirmed no phase transformation from RT to 90 K during the data collection. The differences in RT and 90K structures seem relatively small but the NQR spectrum of triclosan was much better reproduced at the B3LYP/6-311++G(d,p) level of theory assuming the room temperature structure than 90K one.…”

Section: Predicted Structurementioning

confidence: 89%

“…A combination of experimental and theoretical techniques has certainly much to offer for the studies of drugs or potential drugs in early phases of drug research. Their capabilities in particular when applied to the known drugs, have been well documented in literature [92,99,101,104,105,148,[156][157][158][159][160][161][184][185][186][187][188][189]. Although in some fields the NMR or NQR are not competitive to IR, UV or XRD the examples of combined studies given above show that both techniques have a potential to elicit structural and physico-chemical information about a molecule of dug, target or the interaction drug-target.…”

Section: Discussionmentioning

confidence: 99%

Towards Understanding Drugs on the Molecular Level to Design Drugs of Desired Profiles

Latosińska¹,

Latosińska²

2011

Drug Discovery and Development - Present and Future

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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

Latosińska

Tomczak

et al. 2012

Magnetic Reson in Chemistry

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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.

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Stability and molecular dynamics of chloroxylenol (API of antiseptics and drugs) in solid state studied by 35Cl-NQR spectroscopy and DFT calculations

Cited by 4 publications

References 16 publications

Complex Mechanism of Relaxation in Solid Chloroxylenol (Antibacterial/Antifungal Agent) Studied by ¹H NMR Spectroscopy and Density Functional Theory Calculations

Complex Mechanism of Relaxation in Solid Chloroxylenol (Antibacterial/Antifungal Agent) Studied by ¹H NMR Spectroscopy and Density Functional Theory Calculations

Towards Understanding Drugs on the Molecular Level to Design Drugs of Desired Profiles

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

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Stability and molecular dynamics of chloroxylenol (API of antiseptics and drugs) in solid state studied by 35Cl-NQR spectroscopy and DFT calculations

Cited by 4 publications

References 16 publications

Complex Mechanism of Relaxation in Solid Chloroxylenol (Antibacterial/Antifungal Agent) Studied by 1H NMR Spectroscopy and Density Functional Theory Calculations

Complex Mechanism of Relaxation in Solid Chloroxylenol (Antibacterial/Antifungal Agent) Studied by 1H NMR Spectroscopy and Density Functional Theory Calculations

Towards Understanding Drugs on the Molecular Level to Design Drugs of Desired Profiles

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

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Complex Mechanism of Relaxation in Solid Chloroxylenol (Antibacterial/Antifungal Agent) Studied by ¹H NMR Spectroscopy and Density Functional Theory Calculations

Complex Mechanism of Relaxation in Solid Chloroxylenol (Antibacterial/Antifungal Agent) Studied by ¹H NMR Spectroscopy and Density Functional Theory Calculations

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