Determination of the Spatial Structure of Lidocaine in SC-CO2 by the 2D NOESY Method

Belov, Konstantin V.; Dyshin, A. A.; Киселев, М. Г.; Krest’yaninov, М. А.; Sobornova, V.V.; Khodov, Ilya A.

doi:10.1134/s1990793121080145

Cited by 10 publications

(9 citation statements)

References 32 publications

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“…To determine the accuracy of conformer population estimation by a two-position exchange equation (see Equation (5)), we plotted a graph of the dependence of the difference between the calculated (see Table 2 ) and experimental values of the distance to be found on the conformer populations for FFA in DMSO-d 6 and mixed SC-CO 2 +DMSO-d 6 solvent (see Figure 7 and Figure 8 ) [ 37 , 39 , 79 ].…”

Section: Resultsmentioning

confidence: 99%

“…The nuclear Overhauser effect spectroscopy (2D NOESY) technique is a powerful tool for chemical structure elucidation of small drug-like molecules by NMR. In the last few years [ 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 ], this technique has been extensively used to study the structure and conformational preference of small molecules in supercritical media. The value of the cross-relax rate between proton spins in a small molecule of FFA is proportional to the sixth power of the distance between the corresponding protons.…”

Section: Introductionmentioning

confidence: 99%

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Investigation of the Spatial Structure of Flufenamic Acid in Supercritical Carbon Dioxide Media via 2D NOESY

et al. 2023

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The search for new forms of already known drug compounds is an urgent problem of high relevance as more potent drugs with fewer side effects are needed. The trifluoromethyl group in flufenamic acid renders its chemical structure differently from other fenamates. This modification is responsible for a large number of conformational polymorphs. Therefore, flufenamic acid is a promising structural modification of well-known drug molecules. An effective approach in this field is micronization, employing “green” supercritical fluid technologies. This research raises some key questions to be answered on how to control polymorphic forms during the micronization of drug compounds. The results presented in this work demonstrate the ability of two-dimensional nuclear Overhauser effect spectroscopy to determine conformational preferences of small molecular weight drug compounds in solutions and fluids, which can be used to predict the polymorphic form during the micronization. Quantitative analysis was carried out to identify the conformational preferences of flufenamic acid molecules in dimethyl sulfoxide-d6 medium at 25 °C and 0.1 MPa, and in mixed solvent medium containing supercritical carbon dioxide at 45 °C and 9 MPa. The data presented allows predictions of the flufenamic acid conformational preferences of poorly soluble drug compounds to obtain new micronized forms.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Investigation of the Spatial Structure of Flufenamic Acid in Supercritical Carbon Dioxide Media via 2D NOESY

et al. 2023

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“…Assuming that the values of ω (Larmor frequency), τ c (rotational correlation time), and γ (magnetogyric ratio) remain constant for each nuclear pair in a given 2D NMR experiment, the ratio of intensities of a pair of NOE signals, η I (1) S (1) : η I (2) S (2) , can be proportional to the ratio of their internuclear distances (Equation (4)) for isotropic intramolecular motion. As such, by comparing η I (1) S (1) and η I (2) S (2) within the same 2D NOESY experiment [ 75 , 76 ], we only need to know the reference distance of one of the nuclear pairs, depending on the conformer, e.g., r I (1) S (1) , in order to calculate the experimental distance of the other, r I (2) S (2) .

…”

Section: Resultsmentioning

confidence: 99%

Exploring the Conformational Equilibrium of Mefenamic Acid Released from Silica Aerogels via NMR Analysis

Khodov

Sobornova

Mulloyarova

et al. 2023

IJMS

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This study examines the influence of mefenamic acid on the physical and chemical properties of silica aerogels, as well as its effect on the sorption characteristics of the composite material. Solid state magic angle spinning nuclear magnetic resonance (MAS NMR) and high-pressure 13C NMR kinetic studies were conducted to identify the presence of mefenamic acid and measure the kinetic rates of CO2 sorption. Additionally, a high-pressure T1–T2 relaxation-relaxation correlation spectroscopy (RRCOSY) study was conducted to estimate the relative amount of mefenamic acid in the aerogel’s pores, and a high-pressure nuclear Overhauser effect spectoscopy (NOESY) study was conducted to investigate the conformational preference of mefenamic acid released from the aerogel. The results indicate that mefenamic acid is affected by the chemical environment of the aerogel, altering the ratio of mefenamic acid conformers from 75% to 25% in its absence to 22% to 78% in the presence of aerogel.

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“…The experimental interproton distances were computed using both cross-relaxation rates σ 0 and σ ij for the reference and conformation-dependent distances, respectively, as demonstrated in Equation (3). These values were obtained from the analysis of the dependence of the normalized values of the integrated cross-peak intensities on the mixing time in the framework of the initial rate approximation (IRA), as shown in [ 15 , 23 , 68 ].…”

Section: Resultsmentioning

confidence: 99%

Conformational State of Fenamates at the Membrane Interface: A MAS NOESY Study

et al. 2023

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The present work analyzes the 1H NOESY MAS NMR spectra of three fenamates (mefenamic, tolfenamic, and flufenamic acids) localized in the lipid–water interface of phosphatidyloleoylphosphatidylcholine (POPC) membranes. The observed cross-peaks in the two-dimensional NMR spectra characterized intramolecular proximities between the hydrogen atoms of the fenamates as well as intermolecular interactions between the fenamates and POPC molecules. The peak amplitude normalization for an improved cross-relaxation (PANIC) approach, the isolated spin-pair approximation (ISPA) model, and the two-position exchange model were used to calculate the interproton distances indicative of specific conformations of the fenamates. The results showed that the proportions of the A+C and B+D conformer groups of mefenamic and tolfenamic acids in the presence of POPC were comparable within the experimental error and amounted to 47.8%/52.2% and 47.7%/52.3%, respectively. In contrast, these proportions for the flufenamic acid conformers differed and amounted to 56.6%/43.4%. This allowed us to conclude that when they bind to the POPC model lipid membrane, fenamate molecules change their conformational equilibria.

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Determination of the Spatial Structure of Lidocaine in SC-CO2 by the 2D NOESY Method

Cited by 10 publications

References 32 publications

Investigation of the Spatial Structure of Flufenamic Acid in Supercritical Carbon Dioxide Media via 2D NOESY

Investigation of the Spatial Structure of Flufenamic Acid in Supercritical Carbon Dioxide Media via 2D NOESY

Exploring the Conformational Equilibrium of Mefenamic Acid Released from Silica Aerogels via NMR Analysis

Conformational State of Fenamates at the Membrane Interface: A MAS NOESY Study

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