Search Results (10)

Polyphenolic compounds are considered one as the most important plant-originated species with antioxidant properties. This paper focuses on exploring the structure and antiradical properties of supramolecular complexes derived from the selected polyphenolic (caffeic and protocatechuic) acids and isomers of pyridinecarboxamide. The chemical interactions between polyphenolic acids and carboxamides were analyzed using FT–IR spectroscopy. The thermal behavior of the solid phases was tested with the help of thermal analysis via thermogravimetry (TG) coupled with differential scanning calorimetry (DSC). The antiradical activity was determined by using the ABTS method (2,2′-azino-bis(3-ehylbenzothiazoline-6-sulfonic acid). The obtained results indicate that the solutions prepared by dissolving the solid materials exhibited better antiradical activity than the binary mixtures prepared by mixing the stock reagents’ solutions. These studies confirmed that supramolecular complexes derived from polyphenolic compounds and N-heterocyclic entities may constitute a quite interesting material for future research. Full article

A binuclear dioxomolybdenum catalyst [(MoO₂Cl₂)₂(L)] (1) (with L (1S,2S)-N,N′-bis(2-pyridinecarboxamide)-1,2-cyclohexane) was prepared and used as catalyst for the desulfurization of a multicomponent model fuel containing the most refractory sulfur compounds in real fuels. This complex was shown to have a high efficiency to oxidize the aromatic benzothiophene derivative compounds present in fuels, mainly using a biphasic 1:1 model fuel/MeOH system. This process conciliates catalytic oxidative and extractive desulfurization, resulting in the oxidation of the sulfur compounds in the polar organic solvent. The oxidative catalytic performance of (1) was shown to be influenced by the presence of water in the system. Using 50% aq. H₂O₂, it was possible to reuse the catalyst and the extraction solvent, MeOH, during ten consecutive cycles without loss of desulfurization efficiency. Full article

The main aims of the study were to disclose the influence of the structure on the solubility, distribution and permeability of the parent substances, iproniazid (IPN), isoniazid (INZ) and isonicotinamide (iNCT), at 310.2 K and to evaluate how the presence of cyclodextrins (2-hydroxypropyl-β-cyclodextrin (HP-β-CD) and methylated β-cyclodextrin (M-β-CD)) affects the distribution behavior and diffusion properties of a model pyridinecarboxamide derivative, iproniazid (IPN). The following order of decreasing the distribution and permeability coefficients was estimated: IPN > INZ > iNAM. A slight reduction of the distribution coefficients in the 1-octanol/buffer pH 7.4 and n-hexane/buffer pH 7.4 systems (more pronounced in the first system) was revealed. The extremely weak IPN/cyclodextrins complexes were estimated from the distribution experiments: K_C(IPN/HP-β-CD) > K_C(IPN/M-β-CD). The permeability coefficients of IPN through the lipophilic membrane—the PermeaPad barrier—were also measured with and without cyclodextrins in buffer solution. Permeability of iproniazid was increased in the presence of M-β-CD and reduced by HP-β-CD. Full article

The extent to which insecticides harm non-target beneficial insects is controversial. The effects of long-term exposure on honey bees to sublethal concentrations of flonicamid, a pyridinecarboxamide compound used as a systemic insecticide against sucking insects, were examined in a field study and two cage studies. The field study involved the continuous weight, temperature, and CO₂ monitoring of 18 honey bee colonies, 6 of which were exposed over six weeks to 50 ppb flonicamid in sugar syrup, 6 exposed to 250 ppb flonicamid in syrup, and 6 exposed to unadulterated syrup (control). Treatments were derived from concentrations observed in honey samples in a published study. No effects were observed on foraging activity, hive weight gain, thermoregulation, or average CO₂ concentrations. However, Varroa mite infestations may have also contributed to experimental variability. The two cage studies, in which cages (200 newly-emerged bees in each) were exposed to the same flonicamid concentrations as the field study and kept in a variable-temperature incubator, likewise did not show any experiment-wide effects on survivorship, thermoregulation, or syrup consumption. These results suggest that field applications of flonicamid that result in concentrations as high as 250 ppb in honey may be largely safe for honey bees. Full article

We prepared cocrystals of DL-2-Hydroxy-2-phenylacetic acid (D, L-H₂ma) with the pyridinecarboxamide isomers, picolinamide (pic) and isonicotinamide (inam). They were characterized by elemental analysis, single crystal and powder X-ray, IR spectroscopy and ¹H and ¹³C NMR. The crystal and molecular structures of (pic)-(D-H₂ma) (1), (nam)-(L-H₂ma) (2) and (inam)-(L-H₂ma) (3) were studied. The crystal packing is stabilized primarily by hydrogen bonding and in some cases through π-π stacking interactions. The analysis of crystal structures reveals the existence of the characteristic heterosynthons with the binding motif $R_2^2$(8) (primary amide–carboxilic acid) between pyridinecarboxamide molecules and the acid. Other synthons involve hydrogen bonds such as O-H_(carboxyl)···N_(pyridine) and O-H_(hydroxyl)···N_(pyridine) depending on the isomer. The packing of 1 and 3 is formed by tetramers, for whose formation a crystallization mechanism based on two stages is proposed, involving an amide–acid (1) or amide–amide (3) molecular recognition in the first stage and the formation of others, and interdimeric hydrogen bonding interactions in the second. The thermal stability of the cocrystals was studied by differential scanning calorimetry and thermogravimetry. Further studies were conducted to evaluate other physicochemical properties of the cocrystals in comparison to the pure coformers. Density-functional theory (DFT) calculations (including NCIplot and QTAIM analyses) were performed to further characterize and rationalize the noncovalent interactions. Full article

We have prepared co-crystals of racemic DL-2-Hydroxy-2-phenylacetic acid (DL-Mandelic acid, DL-H₂ma) with achiral 2-Pyridinecarboxamide (picolinamide, pic), 3-Pyridinecarboxamide (nicotinamide, nam), and 4-Pyridinecarboxamide (isonicotinamide, inam); they have been characterized by elemental analysis, single crystal and powder X-ray, IR spectroscopy and ¹H and ¹³C NMR. The crystal packing is stabilized primarily by hydrogen bonding and, in some cases, through π–π stacking interactions. The analysis of crystal structures reveals the existence of the characteristic heterosynthons with the binding motif $R_2^2\left(8\right)$ (primary amide-carboxilic acid) between pyridinecarboxamide molecules and the acid. Other synthons involve hydrogen bonds such as (carboxyl)O-H···N(pyridine) and (hydroxyl)O-H···N(pyridine). Full article

In this work, co-crystal screening was carried out for two important dihydrofolate reductase (DHFR) inhibitors, trimethoprim (TMP) and pyrimethamine (PMA), and for 2,4-diaminopyrimidine (DAP), which is the pharmacophore of these active pharmaceutical ingredients (API). The isomeric pyridinecarboxamides and two xanthines, theophylline (THEO) and caffeine (CAF), were used as co-formers in the same experimental conditions, in order to evaluate the potential for the pharmacophore to be used as a guide in the screening process. In silico co-crystal screening was carried out using BIOVIA COSMOquick and experimental screening was performed by mechanochemistry and supported by (solid + liquid) binary phase diagrams, infrared spectroscopy (FTIR) and X-ray powder diffraction (XRPD). The in silico prediction of low propensities for DAP, TMP and PMA to co-crystallize with pyridinecarboxamides was confirmed: a successful outcome was only observed for DAP + nicotinamide. Successful synthesis of multicomponent solid forms was achieved for all three target molecules with theophylline, with DAP co-crystals revealing a greater variety of stoichiometries. The crystalline structures of a (1:2) TMP:THEO co-crystal and of a (1:2:1) DAP:THEO:ethyl acetate solvate were solved. This work demonstrated the possible use of the pharmacophore of DHFR inhibitors as a guide for co-crystal screening, recognizing some similar trends in the outcome of association in the solid state and in the molecular aggregation in the co-crystals, characterized by the same supramolecular synthons. Full article

Improving dissolution properties of active pharmaceutical ingredients (APIs) is a critical step in drug development with the increasing occurrence of sparingly soluble APIs. Cocrystal formation is one of the methods to alter the physicochemical properties of APIs, but its dissolution behavior in biorelevant media has been scrutinized only in recent years. We investigated the combined strategy of cocrystallization and eutectic formation in this regard and utilized the cocrystal model system of naproxen and three pyridinecarboxamide isomers. Binary melting diagrams were constructed to discover the eutectic compositions of the three cocrystals with excess amounts of pyridinecarboxamides. The melt–crystallized eutectics and cocrystals were compared in their dissolution behaviors with respect to neat naproxen. The eutectics enhanced the early dissolution rates of the cocrystals in both the absence and presence of biologically relevant bile salt and phospholipid components, whereas the cocrystal dissolution was expedited and delayed, respectively. The combined strategy in the present study will be advantageous in maximizing the utility of the pharmaceutical cocrystals. Full article

Isothiazolopyridines, pyridothiazines and pyridothiazepines are important compounds that possess valuable biological activities. This paper reports on the synthesis of these compounds using both conventional chemical methods and modern microwave techniques. 3-Bromo-6-hydroxy-4-methyl-2-thioxo-2,3-dihydropyridine-3-carboxamide, 5-arylazo-6-hydroxy-4-methyl-2-thioxo-1,2-dihydropyridine-3-carboxamides, 3,5-bis-arylazo-6-hydroxy-4-methyl-2-thioxo-2,3-dihydropyridine-3-caboxamide, 4-methyl-2,3,6,7-tetra-hydroisothiazolo[5,4-b]-pyridine-3,6-dione, 2,2'-(methylene-bis-(sulfanediyl))bis(4-methyl-6-oxo-1,6-dihydropyridine-3-carboxamide), 2-hydroxy-5-methyl-4H-pyrido[3,2-e][1,3]-thiazine-4,7(8H)-dione and 2-arylmethylene-8-hydroxy-6-methyl-2,3,4,5-tetrahydropyrido-[3,2-f][1,4]thiazepine-3,5-diones have been prepared from 6-hydroxy-4-methyl-2-thioxo-2,3-dihydropyridine-3-carboxamide. Some of these compounds were prepared using microwave-assisted reaction conditions, that provided higher yields in shorter times than the conventional methods. Full article

3-Amino-3-thioxopropanamide (1) reacted with ethyl acetoacetate to form 6-hydroxy-4-methyl-2-thioxo-2,3-dihydropyridine-3-carboxamide (2), which reacted with α-haloketones 3 to produce 2,3-disubstituted-8-hydroxy-6-methyl-2H,5H-pyrido[3,2-f]-[1,4]thiazepin-5-ones 4a-c. Benzoylation of 4c led to the formation of the dibenzoate derivative 9. Compounds 4a-c could be prepared stepwise through the formation of S-alkylated derivatives 10a-c. Compounds 2, 4a-c, 9 and 10a-c were prepared using microwave as a source of heat, and gave better yields in shorter times than those achieved by traditional methods. Coupling of 4a-c with arenediazonium chlorides proceeded unusually to give the 6-hydroxy-4-methyl-2-(arylazo)thieno[2,3-b]pyridin-3(2H)-one ring contraction products 14. Structures of the newly synthesized compounds were proven by spectral and chemical methods. Full article