Polymorphism, Intermolecular Interactions, and Spectroscopic Properties in Crystal Structures of Sulfonamides.

The antibiotics family of sulfonamides has been used worldwide intensively in human therapeutics and farm livestock during decades. Intermolecular interactions of these sulfamides are important to understand their bioactivity and biodegradation. These interactions are also responsible for their supramolecular structures. The intermolecular interactions in the crystal polymorphs of the sulfonamides, sulfamethoxypyridazine, and sulfamethoxydiazine, as models of sulfonamides, have been studied by using quantum mechanical calculations. Different conformations in the sulphonamide molecules have been detected in the crystal polymorphs. Several intermolecular patterns have been studied to understand the molecular packing behavior in these antibiotics. Strong intermolecular hydrogen bonds and π-π interactions are the main driving forces for crystal packing in these sulfonamides. Different stability between polymorphs can explain the experimental behavior of these crystal forms. The calculated infrared spectroscopy frequencies explain the main intermolecular interactions in these crystals.

Density functional theory study of direct and indirect photodegradation mechanisms of sulfameter.

Sulfonamide antibiotics (SAs) have been observed to undergo direct and indirect photodegradation in natural water environments. In this study, the density functional theory (DFT) method was employed for the study of direct and indirect photodegradation mechanisms of sulfameter (SME) with excited triplet states of dissolved organic matter ((3)DOM(*)) and metal ions. SME was adopted as a representative of SAs, and SO2 extrusion product was obtained with different energy paths in the triplet-sensitized photodegradation of the neutral (SME(0)) and the anionic (SME(-)) form of SME. The selected divalent metal ions (Ca(2+), Mg(2+), and Zn(2+)) promoted the triplet-sensitized photodegradation of SME(0) but showed an inhibitory effect in triplet-sensitized photodegradation of SME(-). The triplet-sensitized indirect photodegradation mechanism of SME was investigated with the three DOM analogues, i.e., 2-acetonaphthone (2-AN), fluorenone (FN), and thioxanthone (TN). Results indicated that the selected DOM analogues are highly responsible for the photodegradation via attacking on amine moiety of SME. According to the natural bond orbital (NBO) analysis, the triplet-sensitized photodegradation mechanism of SME(0) with 2-AN, FN, and TN was H-transfer, and the SME(-) was proton plus electron transfer with these DOM analogues.

Hirshfeld surface analysis of sulfameter (polymorph III), sulfameter dioxane monosolvate and sulfameter tetrahydrofuran monosolvate, all at 296†K.

The ability of the antibacterial agent sulfameter (SMT) to form solvates is investigated. The X-ray crystal structures of sulfameter solvates have been determined to be conformational polymorphs. Both 1,4-dioxane and tetrahydrofuran form solvates with sulfameter in a 1:1 molar ratio. 4-Amino-N-(5-methoxypyrimidin-2-yl)benzenesulfonamide (polymorph III), C11H12N4O3S, (1), has two molecules of sulfameter in the asymmetric unit cell. 4-Amino-N-(5-methoxypyrimidin-2-yl)benzenesulfonamide 1,4-dioxane monosolvate, C11H12N4O3S·C4H8O2, (2), and 4-amino-N-(5-methoxypyrimidin-2-yl)benzenesulfonamide tetrahydrofuran monosolvate, C11H12N4O3S·C4H8O, (3), crystallize in the imide form. Hirshfeld surface analyses and fingerprint analyses were performed to study the nature of the interactions and their quantitative contributions towards the crystal packing. Finally, Hirshfeld surfaces, fingerprint plots and structural overlays were employed for a comparison of the two independent molecules in the asymmetric unit of (1), and also for a comparison of (2) and (3) in the monoclinic crystal system. A three-dimensional hydrogen-bonding network exists in all three structures, involving one of the sulfone O atoms and the aniline N atom. All three structures are stabilized by strong intermolecular N-H···N interactions. The tetrahydrofuran solvent molecule also takes part in forming significant intermolecular C-H···O interactions in the crystal structure of (3), contributing to the stability of the crystal packing.

Porous molecularly imprinted monolithic capillary column for on-line extraction coupled to high-performance liquid chromatography for trace analysis of antimicrobials in food samples.

A novel porous molecularly imprinted monolithic capillary column (MIMCC) based on ternary porogen was synthesized by in situ technique with sulfaquinoxaline as the template molecule. The characteristics of the MIMCC were investigated by scanning electron microscopy, infrared spectrum, thermogravimetric analysis and solvent resistance test. The saturated adsorption amount of sulfaquinoxaline on MIMCC was 2.7 times over that on the non-imprinted monolithic capillary column (NIMCC). The MIMCC also exhibited good enrichment ability to its analogs and the enrichment factors were 46-211 for five antimicrobials. High permeability and imprinting factors as well as good stability, reproducibility and long lifetime were obtained. An on-line method based on MIMCC solid-phase microextraction coupled with high-performance liquid chromatography was developed for the determination of trace antimicrobials in complex samples. The good linearity for sulfametoxydiazine, sulamethoxazole and sulfaquinoxaline was 0.05-10 µg/L, the limits of detection (LODs) were 10.0-14.0 ng/L. The linear range for mequindox and quinocetone were 0.10-10.0 µg/L, the LODs were 20.0-27.0 ng/L respectively. The recoveries were 71.0-108.2% with relative standard deviation of 1.6-8.5%, correspondingly. The results showed that MIMCC could effectively enrich antimicrobials from complex matrices. The on-line method based on MIMCC and HPLC was selective, sensitive and convenient for trace determination of antimicrobials in complex samples.

Desolvation kinetics of sulfameter solvates.

Solvates are often encountered in pharmaceutical solids and knowledge of their physical stability is necessary for their effective formulation. This work investigates the solid-state stability of five structurally related solvates of sulfameter (5-methoxysulfadiazine) by studying the kinetics of their desolvation reaction with thermogravimetric analysis, both isothermally and nonisothermally. Desolvation kinetic analysis was done isothermally by conventional model-fitting and nonisothermally by the complementary method. Calculated kinetic parameters (model, A and E(a)) were compared and related to the crystal structure of these solvates. A relationship was established between desolvation activation energy from isothermal results and solvent size; the larger the solvent molecule, the higher its solvate's desolvation activation energy. The best fitting solid-state reaction model correlated to single crystal structural features of sulfameter-solvates where solvent molecules occupied cavities in the unit cell. Finally, it was found that kinetic parameters obtained isothermally and nonisothermally were at variance. Therefore, kinetic results obtained from one method may not be extended to results form the other.

[Qualification and quantification of 10 sulfonamides in animal feedstuff by high performance liquid chromatography-electrospray tandem mass spectrometry].

The presence of sulfonamide (SA) residues in foods is largely due to the raising of animals with sulfonamide antibiotics added or polluted feedstuff. Because of interference from the matrices, the commonly used immunoassay or chromatographic method is not suitable for the analysis of multi-SAs in feedstuff. A high performance liquid chromatographic-electrospray tandem mass spectrometric (HPLC/ESI-MS-MS) method has been established for the simultaneous determination of multi-SAs including sulfadiazine (SD), sulfapyridine (SPD), sulfamerazine (SM1), sulfameter (SM), sulfamethazine (SM2), sulfamethoxypyridazine (SMP), sulfamethoxazole (SMZ), sulfamonomethoxine (SMM), sulfadimethoxine (SDM) and sulfaquinoxaline (SQX). After solvent extraction, solid phase extraction, dilution and reversed-phase HPLC separation, SAs were detected by ESI-MS-MS under multi-reaction monitoring mode. The qualification analysis was done by using retention time and distribution of diagnostic ion pairs, and the quantification was based on the peak intensity of common fragment ion m/z 156. The limits of quantification for 10 SAs were 0.5 - 2.0 microg/kg (S/N = 10). The correlation coefficient of linear calibration curve was over 0.9995 within the SAs concentration range 2.0 - 200 microg/L except for SDM and SQX. At the spiked level of 1.0 mg/kg, the average recoveries for the 10 SAs were between 70% and 92%, the relative standard deviations were under 10% for intra-day and under 15% for inter-day. Routine tests showed the method was fast, sensitive, specific, and practical for the SAs determination in feedstuff.

[The physicochemical characterization and therapeutic evaluation of Cicatrol]. / Caracterizarea fizico-chimica si evaluarea terapeutica a produsului Cicatrol.

Cicatrol ointment with the formula: argentic sulphamethoxydiasine 1 g, bentonite hydrogel 12.5% for 100 g is manufactured at the Microproduction Laboratory of the Faculty of Pharmacy of Iasi. The one-year physicochemical determinations of the aspect, colour, homogeneity, pH, rheological behaviour and relative viscosity, content in argentic sulphamethoxydiasine as well as "in vitro" antimicrobial activity of Cicatrol showed a good stability and gel properties enabling an uniform and long-term contact with the wound. The clinical investigations carried out until now in patients with burns, varicose ulcers, trophic shank ulcers, superficial phlebitis with atonic ulcerations or wounds with multiple sites revealed its remarkable therapeutic value. As compared to other similar products, Cicatrol by its aseptic properties favours the scarring of any type of wound, a normal skin, without keloid scars being obtained, it also being well tolerated.