Connection between the structure and the antibacterial activity of the N-oxides of quinoxalines. Molecular structure of dioxidine and quinoxidine

Dvoryantseva, G. G.; Lindeman, Sergey V.; Aleksanyan, M. S.; Struchkov, Yu. T.; Tetenchuk, K. P.; Khabarova, L. S.; Elina, A. S.

doi:10.1007/bf00767037

Cited by 9 publications

(11 citation statements)

References 4 publications

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“…In three of these compounds, [36][37][38] the crystallographic packing leads to hydrogen bonds involving the oxygen atom of the N-O group, which may contribute to the elongation of this bond. This is the case for 2-(N-(2-hydroxyethyl)carboxamide)-3-methylquinoxaline 1,4-dioxide, 36 very similar to 2, that displays N-O distances of 1.286 and 1.304 Å .…”

Section: Resultsmentioning

confidence: 99%

Energetic and structural characterization of 2‐R‐3‐methylquinoxaline‐1,4‐dioxides (R = benzoyl or tert‐butoxycarbonyl): experimental and computational studies

Gomes

Sousa

Gonçalves

et al. 2007

J of Physical Organic Chem

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The gaseous standard molar enthalpies of formation of two 2-R-3-methylquinoxaline-1,4-dioxides (R ¼ benzoyl or tert-butoxycarbonyl), at T ¼ 298.15 K, were derived using the values for the enthalpies of formation of the compounds in the condensed phase, measured by static bomb combustion calorimetry, and for the enthalpies of sublimation, measured by Knudsen effusion, using a quartz crystal oscillator. The three dimensional structure of 2-tert-butoxycarbonyl-3-methylquinoxaline-1,4-dioxide has been obtained by X-ray crystallography showing that the two N-O bond lengths in this compound are identical. The experimentally determined geometry in the crystal is similar to that obtained in the gas-phase after computations performed at the B3LYP/6-311 þ G(2d,2p) level of theory. The experimental and computational results reported allow to extend the discussion about the influence of the molecular structure on the dissociation enthalpy of the N-O bonds for quinoxaline 1,4-dioxide derivatives. As found previously, similar N-O bond lengths in quinoxaline-1,4-dioxide compounds are not linked with N-O bonds having the same strength.

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Section: Resultsmentioning

confidence: 99%

Energetic and structural characterization of 2‐R‐3‐methylquinoxaline‐1,4‐dioxides (R = benzoyl or tert‐butoxycarbonyl): experimental and computational studies

Gomes

Sousa

Gonçalves

et al. 2007

J of Physical Organic Chem

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“…The examples of the experimentally recorded X-ray diffraction of cryochemically converted dioxidine patterns, obtained using different carrier gas (CO 2 ) flow rates are presented in Figure 3 , Figure 4 and Figure 5 . The crystallographic parameters of previously obtained anhydrous polymorphic modifications of dioxidine (Triclinic (T-phase) and monoclinic (M-phase) [ 40 ]) and its crystal hydrates (monohydrate (1:1) [ 41 ] and hydrate (1:3) (H-phase) [ 40 ]) and the molecular packing (3D-fragments) in these crystal structures, as well as the calculated powder diffraction patterns for these phases, are shown in Supplementary Materials, Figures S2–S9 . Data on the phase composition and on the average particle sizes of cryomodified dioxidine nanoforms obtained by the proposed cryochemical method are presented in Table 1 .…”

Section: Resultsmentioning

confidence: 99%

“…The sample obtained by the sublimation-condensation of dioxidine in the absence of a carrier gas flow contains an almost pure Triclinic (T) phase with small additions of the H-phase (1/3 crystalline hydrate of dioxidine) [ 41 ]. Previously, to obtain the T-phase, it was required to heat the dioxidine crystal hydrate obtained by freeze-drying at 120 °C over 8 h [ 41 ]. During such temperature exposure, the sample loses the properties of nanoforms because the particles of the drug are enlarged.…”

Section: Resultsmentioning

confidence: 99%

“…The effect of the carrier gas (CO 2 ) flow on the crystal phase state of cryochemically modified dioxidine can be explained by several considerations. Anhydrous modifications of dioxidine—monoclinic or M-phase and triclinic or T-phase—are characterized by different organization of the system of intermolecular hydrogen bonds [ 41 ]. The triclinic or T-phase of dioxidine is characterized by the presence of infinite chains of molecules connected by intermolecular hydrogen bonds, with two N-oxide and two hydroxyl groups forming cross-linked hydrogen bonds (N→O....H-O) with two neighboring dioxidine molecules.…”

Section: Resultsmentioning

confidence: 99%

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Cryochemical Production of Drug Nanoforms: Particle Size and Crystal Phase Control of the Antibacterial Medication 2,3-Quinoxalinedimethanol-1,4-dioxide (Dioxidine)

et al. 2021

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Increasing the effectiveness of known, well-tested drugs is a promising low-cost alternative to the search for new drug molecular forms. Powerful approaches to solve this problem are (a) an active drug particle size reduction down to the nanoscale and (b) thermodynamically metastable but kinetically stable crystal modifications of drug acquisition. The combined cryochemical method has been used for size and structural modifications of the antibacterial drug 2,3-quinoxalinedimethanol-1,4-dioxide (dioxidine). The main stage of the proposed technique includes the formation of a molecular vapor of the drug substance, combined with a carrier gas (CO2) flow, followed by a fast condensation of the drug substance and CO2 molecules on a cooled-by-liquid nitrogen surface of preparative cryostate. It was established that the molecular chemical structure of the drug substance remained unchanged during cryochemical modification; however, it led to a significant decrease of the drug particles’ size down to nanosizes and changes in the crystal structures of the solid drug nanoforms obtained. Varying carrier gas (CO2) flow led to changes in their solid phase composition. A higher dissolution rate and changes in antibacterial activity were demonstrated for cryomodified dioxidine samples in comparison to the properties of the initial pharmacopeia dioxidine.

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“…For T and H, the low-angle part of powder pattern was used in simulated annealing runs, while for M, the search for the solution was based on the set of 150 low-angle Xobs values [38] extracted from three-phase powder pattern after a Pawley fit with the program MRIA [39]. The model of dioxidine molecule used in a direct space search without H atoms was taken from the literature [40].…”

Section: Structure Determinationmentioning

confidence: 99%

Cryochemically Obtained Nanoforms of Antimicrobial Drug Substance Dioxidine and Their Physico-chemical and Structural Properties

et al. 2018

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Nanoforms of the antimicrobial drug substance 2,3-bis-(hydroxymethyl) quinoxaline-N,N′-dioxide with particles sizes between 50 and 300 nm were obtained by cryochemical modification of the initial pharmaceutical substance using a freeze-drying technique and were characterized by different physicochemical methods (FTIR, UV-Vis, 1H-NMR, DSC, TG and X-ray diffraction) and transmission electron microscopy (TEM). The data obtained from FTIR- and UV–Vis-spectroscopy confirmed the unaltered chemical structure of dioxidine molecules due to the cryochemical modification method. At the same time, X-ray diffraction and thermal analysis data show the change of the crystal structure compared to the parameters of the initial pharmaceutical dioxidine substance. A higher dissolution rate was revealed for cryomodified dioxidine nanoforms. The existence of three polymorphic crystal phases was established for cryomodified dioxidine samples possessed by some thermal activation processes: two anhydrous polymorphic phases, triclinic (T) and monoclinic (M), and one hydrated form (H).

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Connection between the structure and the antibacterial activity of the N-oxides of quinoxalines. Molecular structure of dioxidine and quinoxidine

Cited by 9 publications

References 4 publications

Energetic and structural characterization of 2‐R‐3‐methylquinoxaline‐1,4‐dioxides (R = benzoyl or tert‐butoxycarbonyl): experimental and computational studies

Energetic and structural characterization of 2‐R‐3‐methylquinoxaline‐1,4‐dioxides (R = benzoyl or tert‐butoxycarbonyl): experimental and computational studies

Cryochemical Production of Drug Nanoforms: Particle Size and Crystal Phase Control of the Antibacterial Medication 2,3-Quinoxalinedimethanol-1,4-dioxide (Dioxidine)

Cryochemically Obtained Nanoforms of Antimicrobial Drug Substance Dioxidine and Their Physico-chemical and Structural Properties

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