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Many pathogenic organisms have developed resistance to many antibiotics, which leads to an increase in the spread of many microbial infections. There is an urgent need to find more effective drugs to curb widespread transmission. Hence, this study synthesized and evaluated the antimicrobial activities of mixed-ligand complexes of Cu(II), Co(II), Ni(II), Mn(II), and Zn(II) ions with barbituric acid and 1,10 phenanthroline ligands in effort to find more effective antibiotics. The complexes were characterized using elemental analysis, metal analysis, melting points, solubility tests, and spectroscopic analyses (IR and UV-visible). The antimicrobial activities of the complexes were evaluated against two gram-positive bacteria (Bacillus subtilis and Staphylococcus aureus), two gram-negative bacteria (Pseudomonas aeruginosa and Clostridium spp.), and four pathogenic fungi (Candida albicans, Aspergillus flavus, Aspergillus niger, and Saccharomyces cerevisiae). The biological activities of the metal complexes were compared to the activities of some conventional antibiotics. The molecular formulas for the complexes in 1:1:1 (L-M-L) were established based on the results of the elemental and metal analyses. The IR spectroscopic data results showed the coordination of 1,10-phenanthroline to the metal ions through the nitrogen donor atom, while barbituric acid coordinated with the metal ions through nitrogen and oxygen atoms. The formation of the complexes was confirmed by UV-visible spectroscopic data. Many of the mixed-ligand metal complexes demonstrated higher biological activities than the standard drugs and also succeeded where the conventional antibiotics failed. Therefore, the metal complexes could be considered as more efficacious antibiotics that could be added to the arsenal of effective antibiotics for the prevention of the intrinsic problems of multidrug resistance. Keywords: Bacteria, Fungi, Ligands, Metal complexes, Multidrug resistance, Barbituric acid

Formations of bimolecular barbituric acid (BA) complexes through hydrogen-bonding (HB) interactions were investigated in this work. BA has been known as a starting compound of pharmaceutical compounds developments, in which the molecular and atomic features of parent BA in homo-paring with another BA molecule were investigated here. The models were optimized to reach the stabilized structures and their properties were evaluated at the molecular and atomic scales. Density functional theory (DFT) calculations were performed to provide required information for achieving the goal of this work. Six dimer models were obtained finally according to examining all possible starting dimers configurations for involving in optimization calculations. N-H . . . O and C-H . . . O interactions were also involved in dimers formations besides participation of the X-center of parent BA in interaction. Molecular and atomic scales features were evaluated for characterizing the dimers formations. As a consequence, several configurations of BA dimers were obtained showing the importance of performing such structural analyses for developing further compounds from BA.

An economic, sustainable, and straightforward environmentally friendly route for synthesis of 3-methyl-4-aryl-1,4-dihydropyrazolo[4ʹ,3ʹ:5,6]pyrano[2,3-d]pyrimidine-5,7(6H,8H)-diones via condensation of ethyl acetoacetate, hydrazine hydrate, barbituric acid, and aromatic aldehydes in the presence of catalytic amount of H3PMo7W5O40·24H2O under solvent-free condition was reported. This environmentally benign protocol offers selective synthesis of pyrazolopyranopyrimidine derivatives without any side product with excellent yield in shorter time.

2-Hydroxy-1-naphthaldehyde based barbiturates were synthesized through an eco-friendly greener approach, by reaction of 2-hydroxynaphthalene-1-carbaldehyde with three different barbituric acid deri...

This study was conducted to assess the acute toxicity of three previously synthesised 5-(3 '-amino-4 '-arylazo-1H-pyrazole-5 '-ylazo) barbituric acid dyes (dyes 1-3) using Gammarus roeseli (Crustacea: Amphipoda) and Chironomus riparius (Insecta: Diptera) and to compare their sensitivities to these dyes. The toxicity of the tested dyes was found to increase with lengthened exposure period in both bioassays. The azo dye toxicity to both species was determined to increase due to the presence of the nitro and chloro groups in the structure. G. roeseli exhibited more tolerance to the nitro group containing azo dye (dye 2) than C. riparius, whereas C. riparius exhibited more tolerance to the chloro group containing azo dye (dye 3) than G. roeseli; however, the sensitivity of two species to the azo dye without these groups (dye 1) did not significantly differ. The results suggest that the sensitivity varies depending on the species and the azo dye structure and that both species are suitable for ecotoxicological tests of the azo dyes. Nevertheless, further studies are recommended to determine all aspects of the toxicity mechanisms of these azo dyes, to investigate their degradation products and to assess their actual risk in the environment based on the results of this study.

In this research, a new heterogeneous catalyst is fabricated through covalent modification of iron-based metal–organic framework with ionic liquid. In more detail, using 2-aminoterephthalic acid and iron (III) chloride hexahydrate, amino-functionalized metal–organic framework has been synthesized and then reacted with 2,4,6-trichloro-1,3,5-triazine and 1,4-diazabicyclo[2.2.2]octane successively to furnish ionic liquid on metal–organic framework. The as-prepared catalyst was characterized by FTIR, TGA, BET, SEM/EDS, XRD and elemental mapping analysis and then employed for catalyzing synthesis of pyrano [2,3‐d]pyrimidines (with yields of 80–100%) from one-pot three-component reaction of aldehydes, barbituric acid and malononitrile in aqueous media. The catalytic test inferred high catalytic activity of the catalyst, superior to that of IL and metal–organic framework. Furthermore, the catalyst could be recovered and recycled for five reaction runs with preserving its morphology.

Barbiturates, which are derived from the medically significant substance barbituric acid also known as malonylurea or 4-hydroxyuracil, are employed as anaesthetics, sedative-hypnotics, anticonvulsants, and depressants of the central nervous system. In recent years, researchers have paid great attention to compounds and derivatives of barbituric acid, although the first barbituric acid was discovered in 1864 by Adolf Von Baeyer. Due to its great medical and biological importance and wide applications in polymerization catalysts, plastics and textiles, aqueous or oil inks, and polymers. The background, reactions, and methods of preparing barbituric acid have been studied over the last ten years.

C8H9N2O4 was prepared via acetylation of 1,3-dimethyl barbituric acid. The atomic and crystalline structures were determined using single crystal analysis (X-ray). It is a member of the monoclinic system P 21/c group of space with a = 8.6056 (3) Å, b = 9.1602 (3) Å, c = 11.9601 (4) Å, β = 109.410 (3)°, Z = 4 and V = 889.22 (5) Å3. π–π interactions between circles of nearby molecules with intercentroid distances of 3.4300 (11) aid in the stability of the structure by keeping the crystals in place. The Hirshfeld surface (HS) analysis of the crystal structure reveals that the H... O/O... H (45.9%) and H... H (32.9%) interactions contribute the most to crystal packing. The most essential interactions in crystal packing are hydrogen bonding and van der Waals interactions. According to the dispersion, electrostatic and overall energy frameworks, the contribution of dispersion energy dominates the stability.

Aim and Objective: In the current study, environmentally benign and cost-effective procedures were suggested for the preparation of carboxy group functionalized imidazolium salts, including [Cmmim]BF4 - or [Cmmim]Br- as a new, reusable Brønsted acidic ionic liquid (BAIL) catalyst. Then, the catalytic performance of [Cmmim]BF4 - or [Cmmim]Br- were successfully inspected towards the three-components one pot preparation of pyrano[2,3-d]pyrimidinone derivatives 4a-4q. The mentioned procedures show short reaction times, easy work-up procedure, green conditions, high yields of the products, high potent of recovering, and reusing capability. The current study is useful and adequate for the application and development of imidazolium salts on the basis of green chemistry principles. Materials and Methods: An aromatic aldehyde (1 mmol), barbituric acid (1 mmol), and malononitrile (1 mmol) were placed in a round-bottomed flask containing ethanol (5 mL). BAILs A and B (0.1 mmol, 10 mol%) were added to the mixture. The suspension was magnetically stirred at room temperature for an appropriate time (Table 2). After completion of the reaction, which was monitored by TLC (n-hexane:ethyl acetate = 3:1), the pure product was filtered off to separate the catalyst, washed with water, and recrystallized from ethanol to afford the pure compound. After separation of the product, the catalyst was recovered by evaporation of water, washed with Et2O, dried under vacuum for 2 h, and reused for the same reaction. Results: The mentioned procedure shows short reaction times, easy work-up procedure, green conditions, high yields of the products, and high potent of recovering and reusing capability. Conclusion: In this study, we unveiled the synthesis of a new acetic acid functionalized ionic liquids [Cmmim]BF4 - BAIL A or [Cmmim]Br- BAIL B and their application for the preparation of pyrano[2,3-d]pyrimidinone derivatives via a three-component reaction among various aromatic aldehydes, barbituric acid, and malononitrile under mild and metal-free conditions. A wide range of pyrano[2,3-d]pyrimidinone derivatives bearing diverse functional groups was obtained in short reaction and excellent yields. Operational simplicity, recoverability, and reusability of catalysts, cheap and chemically stable reagents, high catalytic activity, easy work-up, and the eco-friendly procedure, make this method environmentally benign and cost-effective.

We synthesized two types of donor-acceptor Stenhouse adducts (DASAs), a new type of photochromic molecules showing dual color in two different isomeric forms in solution phase, using Meldrum acid (DASA-Mel) and barbituric acid (DASA-Bar), along with a naphthalimide derivative to obtain interesting fluorescence properties. DASA-Mel was found to have fast photochromic conversion in comparison to DASA-Bar, evident from ultraviolet-visible (UV-vis) and fluorescence spectroscopic studies. The colored form of DASA-Mel was encapsulated inside the water-soluble Stoddart's blue box and became soluble in water much faster than DASA-Bar. Interestingly, the competitive encapsulation experiment showed that DASA-Mel was selectively encapsulated inside the blue box in water whereas DASA-Bar was mostly separated out from the solution after centrifugation, and this phenomenon was confirmed by 1H and DOSY NMR and mass spectroscopies. Moreover, we found through density functional theory (DFT) optimization that the open form of DASA-Mel was more stable during the encapsulation reaction in a water medium in comparison to DASA-Bar. The calculated binding energies of encapsulated DASA-Mel and DASA-Bar are -10.2 and -9.9 kcal/mol, respectively, clearly showing that the former is more stable by 0.3 kcal. Consequently, the organic macrocycle selectively separating one kind of DASA from a mixture by encapsulation in water is reported for the first time with experimental and theoretical support in the literature.

6 pags., 5 figs., 1 tab. -- This work is dedicated to Prof. Rafael Notario (IQFR-CSIC)., The gas phase acidities (GA) of 5,5-alkylbarbituric acids have been experimentally determined by electrospray ionization-triple quadrupole (ESI-TQ) mass spectrometry and by using the extended kinetic Cooks method (EKCM). The GAs of C-H (1330.9 ± 10.0 kJ mol-1) and N-H (1361.5 ± 10.5 kJ mol-1) deprotonated sites of bifunctional barbituric acid were determined from the selective production of their corresponding heterodimers. The GA value in the N-H site was confirmed by measuring the GAs of 5,5-dimethyl- and 5,5-diethyl barbituric acids (∼1368 kJ mol-1). The experimental results have been rationalized and discussed with the support of quantum chemical calculations with Gaussian-n (G3 and G4) composite methods, which confirmed the excellent consistency of the results., A.F.L. acknowledges the support from the Brazilian funding agencies CNPq, FAPESP, and CAPES. J.M.O.-E. acknowledges support from the Spanish MICINN, Grant Number CTQ2018-094644-B-C22.

The protonation of a number of 4,6-dihydroxypyrimidine derivatives is studied, and the features of the electronic spectra of free bases and protonated forms are considered. It is shown that the alkyl substituents in position 2 increase the basicity of the compound, and the nitro group in position 5 leads to its decrease. In an acid medium (0.1-99.5% H2SO4), 4,6-dihydroxypyrimidine, 6-hydroxy-2-methylpyrimidine-4(3H)-one, and 6-hydroxy-2-ethylpyrimidine-4(3H)-one have two protonation stages, barbituric acid is protonated in three stages, and 6-hydroxy-2-methyl-5-nitropyrimidine-4(3H)-one and 6-hydroxy-2-ethyl-5-nitropyrimidine-4(3H)-one form a monocation.

A 2,2′-Bipyridine-based ionic compound named 2,2′-bipyridinium dihydrogen phosphate was synthesized by addition of phosphoric acid to a solution of 2,2′-Bipyridine in dichloromethane. After the characterization using FT-IR, mass, 1H, 13C and 31P NMR techniques, it was used as a Bronsted dicationic acidic catalyst for the promotion of the synthesis of 2-arylidene malononitrile and 5-arylidene barbituric acid derivatives via Knoevenagel condensation reaction in water. Some of the advantages of this method are the utilization of an easy preparable, cost-effective and eco-friendly organic salt as a catalyst within high rates and yields of the reactions, simple and quick work-up and acceptable reusability of the catalyst.

An efficient methodology was developed to generate novel N,N′-dialkyl-2-thiobarbituric acid based sulfonamides S1–S4 in good to excellent yields (84%–95%). The synthesized compounds S1–S4 were docked to screen their in silico activities against two enzymes i.e., SARS-CoV-2 main protease enzyme with unliganded active site (2019-nCoV, coronavirus disease 2019, COVID-19) PDB ID: 6Y84 and SARS-CoV-2 Mpro PDB ID: 6LU7. Furthermore, some in silico physicochemical and physicokinetic properties were evaluated using the OSIRIS Property Explorer, Molinspiration property calculator, ADMET property calculator, and GUSAR to assess these compounds as potential candidates as lead compounds for the quest of SARS-CoV-2 main protease inhibitors. Molecular docking analyses of the synthesized compounds predicted that compound S3 is more potent as SARS-CoV-2 main protease inhibitor with binding energy –11.65 kcal/mol in comparison with reference inhibitor N3 (–10.95 kcal/mol), whereas compounds S1, S2, and S4 recorded comparable binding energies –9.89, –10.84, and –10.94 kcal/mol with reference inhibitor N3, which were much better than remdesivir (–9.85 kcal/mol). In case of SARS-CoV-2 Mpro, all compounds S1–S4 with docking energy values of –7.28, –8.38, –8.31, and –7.34 kcal/mol, respectively, were found to be potent in comparison with reference inhibitor N3 (–6.31 kcal/mol) and remdesivir (–6.33 kcal/mol). Ligand efficiency values against the target SARS-CoV-2 proteins, as well as α-glucosidase and DNA-(apurinic or apyrimidinic site) lyase inhibition results of these newly synthesized compounds, were also found to be promising.

The paper presents the contribution of the cocrystallization method in the physicochemical modification of catechins that exhibit low oral bioavailability. This was done to obtain cocrystals for two naturally occurring polyphenolic diastereoisomers (+)-catechin and (-)-epicatechin with commonly used coformers. Due to distinct crystallization behavior, only the (-)-epicatechin cocrystal with barbituric acid in a 1:1 stoichiometry was obtained. The cocrystal of (-)-epicatechin (EC) with barbituric acid (BTA) was prepared by the slow solvent-evaporation technique. The structure and intermolecular interactions were determined by X-ray crystallographic techniques. The analysis of packing and interactions in the crystal lattice revealed that molecules in the target cocrystal were packed into tapes, formed by the O-H···O type contacts between the (-)-epicatechin and coformer molecules. The EC molecules interact with the carboxyl group in the BTA coformer mainly by -OH groups from the benzene ring A. The cocrystalline phase constituents were also investigated in terms of Hirshfeld surfaces. The application of Raman spectroscopy confirmed the involvement of the C=O group in the formation of hydrogen bonds between the (-)-epicatechin and barbituric acid molecules. Additionally, the solubility studies of pure EC and the EC-BTA cocrystal exhibited minor enhancement of EC solubility in the buffer solution, and pH measurements confirmed a stable level of solubility for EC and its cocrystal.

A simple and efficient method for the synthesis of pyrazolopyranopyrimidines under solvent-free has been developed. The one-pot multicomponent condensation of arylaldehydes with hydrazine hydrate, ethyl acetoacetate and barbituric acid in the vicinity of a mesoporous basic nanomagnetic catalyst, namely DBU immobilized on Fe3O4@nSiO2@mSiO2 was synthesized in remarkably high yields and in short reaction times. Significantly, this catalyst can be easily separated from the reaction media by applying an external magnet, and can be reused for several cycles.

This study aimed at examining atmospheric-pressure chemical ionization of barbituric acid through the corona discharge ion mobility spectrometry (CD-IMS) and the quantum chemical calculations. The results indicated two product ion peaks in the IMS spectrum of barbituric acid. The thermal decomposition of the barbituric acid sample was investigated by scanning the temperature of the injection port and analyzing the temporal evolution of the IMS peaks over elapsed time. It was found that the barbituric acid sample was not thermally decomposed in the injection port of the instrument. Experimental evidences were collected by changing the reactant ions, concentration of barbituric acid sample, and IMS cell temperature. The two observed peaks were then assigned to cationic form and oxygen protonated isomers of barbituric acid. The positions of the product ion peaks were explicated considering the dipole moments of the product ions.

Dihydro [2,3D] pyridine substituted enaminosulfonamide compounds have been synthesized and their effects on carbonic anhydrase II (hCAII) have been evaluated. Pyrido [2,3 d] pyrimidines were synthesized from barbituric acid derivatives, malonanitrile, aldehyde derivatives in basic condition and then hydrolyzed with hydrochloric acid. The targeted compounds were syn-thesized from amino sulfanilamide, dihydro [2,3D] pyridine compounds, and triethylorthoformate. 1H NMR, 13C NMR, FT-IR and elemental analysis were used for the structural analysis of the compounds. The half maximal inhibitory concentration (IC50) values of the compounds were determined to be between 27.03 and 104.39 μM for hCA II and 19.85-76.64 μM for Ki.

A heterogeneous organic–inorganic hybrid durable nanocatalyst γ-Al2O3@Silane-TMG was prepared by covalently functionalization of nano-γ-Al2O3 through anchored 3-chloropropyl- trimethoxysilane with 1,1,3,3-tetramethylguanidine (TMG). The structure of the catalyst was characterized by various techniques including FT-IR, XRD, SEM, EDX and TGA analyses. The synthesized nanocatalyst was successfully used in an efficient and green four-component synthesis of pyrazolopyranopyrimidine derivatives using ethyl acetoacetate, hydrazine hydrate, arylaldehydes and barbituric acid (or thiobarbituric acid) in H2O at 40 oC. This practical method produced the desired products at reduced reaction times (10–25 min) and high to excellent yields (85–98%). The main advantages of this practical method are the use of heterogeneous basic nanocatalyst, simple work-up procedure with no need to chromatographic purification, affording highly selective conversion and recyclability of the catalyst which could be used in 5 cycles with only a small decrease in its activity.

A facile one-pot multicomponent protocol for the synthesis of bio-active Pyrano[2,3-d]pyrimidine derivatives by a one- step condensation reaction of substituted aldehyde, malononitrile/methyl cyanoacetate, barbituric acid has been demonstrated using nano ZnO@PEG as a catalyst at room temperature. The present approach offers several advantages, such as shorter reaction time, higher yields, and environmental friendliness. Easy isolation of products, absence of column chromatographic purification, use of commercially available low-cost starting materials and reusability of the catalyst make the methodology viable in organic synthesis.

A set of C3N4 samples has been prepared by using melamine, cyanuric acid and barbituric acid as the precursors. The materials were subjected both to physical and chemical characterization and were used as photocatalysts for the selective oxidation of aromatic alcohols in water suspension under UV and visible irradiation. The photoactivity of the materials versus the partial oxidation of four substituted benzyl alcohols was investigated. The type and position of the substituents in the aromatic molecule influenced conversion and selectivity to the corresponding aldehyde. The presence of barbituric and cyanuric acids in the preparation method has changed the graphitic-C3N4 structure, and therefore both the characteristics of the material and the ability of light to activate the surface of the photocatalyst. The most active material prepared in the presence of melamine and cyanuric acid showed a remarkable selectivity towards the aldehyde even under visible irradiation.

A series of indolenine and barbituric acid zwitterion scaffolds were synthesized with a maximum yield of 98% via the formation of C–C single bonds. The structures were unambiguously elucidated by various spectroscopic techniques such as 1H, 13C NMR (1D and 2D), FT-IR and high-resolution mass spectrometry (HRMS). Single crystal X-ray crystallography analysis on 22, as the 22.DMF 1 : 1 solvate, confirms the presence of well-separated iminium and enolate centres, and also confirms that the BA ring is highly twisted with respect to the indolenine ring due to steric hindrance. The presence of N–H⋯O− and N–H⋯O− groups favours 1D-supramolecular assembly in the solid-state. The orange or yellow solutions of the zwitterion exhibit an intense molar absorption coefficient, e, ranging between 0.21 × 104 and 2.93 × 104 M−1 cm−1 in the UV-vis region. Furthermore, the Intramolecular Charge Transfer (ICT) peak of the zwitterion displays a hypsochromic shift in the absorption behavior when the polarity of the solvent increases. Moreover, treatment with a small amount of trifluoroacetic acid (TFA) with the DMF solution of 19 resulted in the protonation of the enolate of the BA ring. This fundamental work provides valuable structural design and information for the construction of supramolecular chemistry and synthetic dyes based on indolenine substituted BA derivatives.

The well-resolved terahertz (THz) absorption spectrum of barbituric acid has been investigated using terahertz time-domain spectroscopy. Four distinct THz spectral features and two shoulder peaks were observed in the range of 10–124 cm–1. A complete analysis was performed with density functional theory, which provided an excellent agreement between solid-state simulation and experiment. The solid-state analysis indicates that the six experimental spectral features observed at low temperature consist of nine infrared-active vibrational modes. Further simulations based on hydrogen-bond isotopologues were performed to study the involvement of hydrogen bonds in the collective modes. A feature at 118.0 cm–1 mainly stems from the collective vibration of dimer hydrogen bonds (m) while features at 102.0 and 109.6 cm–1 primarily come from the collective vibrations of linear hydrogen bonds (n). The results may be useful for monitoring molecular reaction in industrial production according to the state of hydrogen bonds.

A green and highly efficient synthesis of some new ?-amido-aroyl carbonyl derivatives has been achieved through a one-pot, three-component reaction of dimedone/barbituric acid derivatives, arylglyoxals, and amides in choline chloride/urea as a deep eutectic solvent (DES). The use of biodegradable materials, short reaction time and high yields of products introduced this protocol as an efficient environmentally friendly method. The DES could be easily recovered and reused about four times with satisfied catalytic activity.

Graphitic carbon nitride quantum dots (CNQDs) with a high quantum yield (up to 43%) were synthesized by incorporating the unique organic functional group of barbituric acid into the framework of the carbon nitride structure by supramolecular pre-organization. The CNQDs were introduced onto the surface of basic zinc carbonate (BZC) by co-precipitation. The resulting CNQDs/BZC composite showed that the degradation efficiency of tetracycline was 2.4 times higher than that of ZnO. The Z-scheme mechanism for the as-prepared sample was proposed for the enhanced photocatalytic degradation rate. The ˙O2− and ˙OH radicals played major roles due to the suitable bandgap. Finally, the formation and possible photocatalytic mechanisms of the CNQDs/BZC composite are proposed.

Two pyran based bipodal D–π–A systems, CAPBA and CAPTBA, have been developed as Hg2+ ion selective colorimetric and fluorescent ratiometric probes. Both probes formed a 1 : 2 complex, with two mercury ions per probe. The stoichiometry of binding, limit of detection and binding constants were determined using absorption and fluorescence spectroscopy. The metal ion complexation proceeds with deprotonation of the NH protons of the barbituric acid or thiobarbituric acid moiety which was characterized using 1H NMR spectroscopy and MALDI-TOF mass spectrometry. Fluorescence lifetime studies ascertained the formation of a static complex. DFT computations at the B3LYP and CAM-B3LYP levels of theory corroborated the experimental findings and further supported the deprotonation process during complex formation. The complexation is found to be reversible on treatment with cysteamine hydrochloride.

A series of mono-, di-, and tri-topic receptors, in which H-bonding sites, complementary to those of barbituric acid (BA), are fused, is used to induce the supramolecular assembly of n x m ladders containing 1, 2, or 3 triphenylenevinylene units appended with BA. The topological constraint enforced by the architectures induces through-space interactions between the electroactive moieties that are reflected in the electronic absorption and emission spectrum. The n =2, m =2 or m =3 architectures undergo two single electron oxidation events indicative of the formation of the corresponding mono- and di-radical cation species with comproportionation constants of 340 and 70, respectively. Comparison of the electrochemical potentials suggests that the charges are delocalized over the electroactive units in the assembly.

In the last two decades, a large number of self-assembled materials were synthesized and they have already found their way into large-scale industry and science. Hydrogen-bond-based supramolecular adducts are found to have unique properties and to be perfect host structures for trapping target molecules or ions. Such chemical systems are believed to resemble living matter and can substitute a living cell in a number of cases. Herein, a report on an organic material based on supramolecular assembly of barbituric acid and melamine is presented. Surprisingly, the structure is found to host and stabilize radicals under mild conditions allowing its use for biological applications. The number of free radicals is found to be easily tuned by changing the pH of the environment and it increases when exposed to light up to a saturation level. We describe a preparation method as well as stability properties of melamine-barbiturate self-assembly, potentiometric titration, and hydrogen ions adsorption data and EPR spectra concerning the composite.

Diabetes mellitus is a metabolic disorder characterized by high blood glucose levels and instability in carbohydrate metabolism. For treating diabetes, one important therapeutic approach is reducing the postprandial hyperglycemia which can be managed by delaying the absorption of glucose through inhibition of the carbohydrate-hydrolyzing enzymes, α-amylase (α-Amy) and α-glucosidase (α-Gls) in the digestive tract. In this work, a new class of curcumin derivatives incorporating pyrano[2,3-d]pyrimidine heterocycles was synthesized using a multicomponent reaction between curcumin, aldehydes, and barbituric acid. Using UV-Vis spectroscopic method, the synthetic compounds were assessed for their inhibitory properties against α-Amy and α-Gls enzymes. Also, the antioxidant potential of these compounds was measured spectroscopically and compared with Trolox which is known as a gold standard to measure antioxidant capacity. The results of present study suggest that the curcumin derivatives were able to efficiently inhibit both yeast and mammalian α-Gls. In comparison with the antidiabetic medicine acarbose, the synthetic curcumin derivatives were also capable to inhibit more effectively the yeast α-Gls. The partial inhibitory effects of these compounds against pancreatic α-Amy were also important in the terms of avoiding development of the possible gastrointestinal side effects. Moreover, some of the curcumin derivatives indicated stronger antioxidant activity than Trolox. Overall, these synthetic curcumin analogues might be considered as novel molecular templates for development of efficient antidiabetic compounds with promising inhibitory activities against α-Amy and α-Gls enzymes. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40200-020-00685-z.

The oxidation of a heterocyclic compound—barbituric acid (BBA) by diperiodatoargentate(III) (DPA) was carried out in the absence and presence of ruthenium(III) catalyst in alkaline medium with a constant ionic strength of 0.20 mol dm–3 at 298 K. The reaction was monitored spectrophotometrically. The reaction was of first order with respect to [DPA] and was less than unity order with respect to [BBA] in both catalyzed and uncatalyzed cases. Positive and negative fractional order in [OH–] for uncatalyzed and Ru(III) catalyzed reaction respectively was observed, whereas perioadate has retarding effect in both the cases. A unity order with respect to [Ru(III)] was observed. The uncatalyzed reaction in alkaline medium has been shown to proceed via a DPA–BBA complex, which decomposes in a rate determining step to give the free radicals, which is followed by other fast steps to give the products. Whereas in catalyzed reaction, it has been shown to proceed via a Ru(III)–BBA complex, and similar other steps as in uncatalyzed reaction to give the products. The reaction constants involved in the various steps involved in the mechanisms were calculated for both the reactions. The catalytic constant (kC) was also calculated for catalyzed reaction at four temperatures. The activation parameters with respect to slow step of the mechanism and also the thermodynamic data for all the equilibrium steps were determined and discussed.

We have developed a SnO2/SiO2 catalyzed efficient and rapid protocol for the synthesis of pyrano[2,3-d]pyrimidinone derivatives by the three-component cyclocondensation of aromatic benzaldehydes, malononitrile, and barbituric acid in ethanol at room temperature. Nanocomposite SnO2/SiO2 catalytic materials were synthesized using the sol–gel method. The synthesized catalytic materials were well characterized by using a transmission electron microscope, X-ray diffraction spectroscopy, scanning electron microscopy, energy dispersive spectroscopy, Fourier transform infrared spectroscopy, temperature-programmed desorption (NH3-TPD), and Brunauer–Emmett–Teller theory. This protocol has several advantages such as high yield, simple workup procedure, non-toxic, clean, and easy recovery and reusability of the catalytic system. An efficient catalytic system has been developed for the synthesis of pyrano[2,3-d]pyrimidinone derivatives from one-pot three-component cyclocondensation of aromatic benzaldehydes, malononitrile, and barbituric acid in ethanol at room temperature using 15 wt% SnO2/SiO2.

Emerald coloured crystal of copper complex of barbituric acid (CuB) (C8H10CuN4O9) is grown by conventional gel method. The crystal structure is orthorhombic with space group Fdd2 and has unit cell dimensions a = 11.6951(7) A, b = 30.1113(19) A, c = 7.1767(7) A and α = β = γ = 90°. Analysis of the crystal by Hall–Williomson plot revealed the strain free nature of the grown crystals. Identification of the functional groups by FTIR and the study of thermal behaviour of the crystal by TGA/DTA were done.The optical band gap is determined as 1.57 eV from UV–visible absorption studies. The photoluminescence study provides information about the structural quality and purity of the crystal. Antibacterial studies of the sample revealed its medicinal applications. The high hardness value of the crystal is identified by Vickers micro hardness test.

The reaction of 1-methylpyrimidine-(1H,3H,5H)-2,4,6-trione (1-MBA 1a’) as an unsymmetrical barbituric acid with cyanogen bromide (BrCN) and various aldehydes in the presence of L-(+)-tartaric acid (L-(+)-TA) as an organocatalyst afforded heterocyclic stable 5-aryl-1,1′-dimethyl- and 5-aryl-3,1′-dimethyl-1H,1′H-spiro[furo[2,3-d]pyrimidine-6,5′-pyrimidine]2,2′,4,4′,6′(3H,3′H,5H)-pentaones which had the dimeric form of 1-methyl barbiturate at the range of 0 °C to room temperature. In this reaction, L-(+)-TA acted as a sieve to reduce the number of diastereomeric products. Knoevenagel condensation and Michael adduct were the main processes involved in this reaction. The structure of compounds was investigated by 1H and 13C-NMR, and FTIR spectroscopy techniques.

In this study, an efficient, rapid and simple plant-mediated green sol-gel auto-combustion procedure was presented to synthesis magnesium-cobalt ferrite (MgCoFe2O4) nanocatalyst using an aqueous extract of apple skins as a chelating/combustion agent. The catalyst was assessed by multiple techniques, including FT-IR, XRD, FE-SEM, EDS, elemental mapping, TGA-DTA and VSM. Then, the catalytic potential of the as-prepared MgCoFe2O4 nanocatalyst was examined in the three-component condensation reaction of 1,3-dimethyl barbituric acid, aldehydes and malononitrile for the one-pot synthesis of pyrano[2,3-d]pyrimidinedione and their bis-derivatives. The obtained results indicated the excellent catalytic activity of the MgCoFe2O4 in the three-component reaction. The high catalytic activity of these nanomaterials could be attributed to the synergistic electronic effect between nanoparticles, which showcased the enormous potential of multi-metallic nanomaterials in the catalysis field. More importantly, MgCoFe2O4 showed excellent magnetic properties, and it could be successfully separated and recovered by applying an external magnetic for further reuses. To the best of our knowledge, green synthesis of MgCoFe2O4 mediated by aqueous plant extract was reported here for the first time, and this work, therefore, can open up a new insight in the course of design, green synthesis and application of excellent green nanocatalyst for the sustainable processes. MgCoFe2O4 as a magnetically recyclable heterogeneous catalyst, has been synthesized through plant-mediated procedure using an aqueous extract of apple skins.

A new method has been proposed for the synthesis of pyranopyrimidinone and xanthene derivatives using zinc oxide–starch nanocomposite as catalyst under microwave irradiation. The ZnO–starch nanocomposite was characterized by X-ray diffraction and scanning electron microscopy data, and the size of the ZnO-starch nanocomposite particles was estimated at 70–90 nm. The catalyst was used in the three-component condensation of aromatic aldehydes with barbituric acid and malononitrile and the 1:2 condensation of aromatic aldehydes with naphthalen-2-ol to obtain pyranopyrimidinone and xanthene derivatives, respectively. The catalyst can be reused several times without loss of catalytic activity. The proposed procedure utilizes affordable and inexpensive materials, provides excellent yields in short reaction time, and is eco-friendly, which makes it more economic than conventional methods. The antibacterial activity of the synthesized compounds was evaluated against M. luteus and P. aeruginosa.

Increased charge transfer and light absorption as well as large specific surface area are effective ways to improve the catalytic efficiency of photocatalysts. In this paper, barbituric acid, urea and thiourea were separately freeze-dried to form a homogeneous precursor with melamine, followed by thermal polymerization at 750 °C, g-C3N4 was doped successfully with C, N and S. Among them, C-doped g-C3N4 revealed well photocatalytic hydrogen production which reached to 2.45 mmol g−1 h−1. N-doped g-C3N4 exhibited enhanced photocatalytic degradation properties for organic dye (RhB) which is completely degraded within 8 min while the performance S-doped sample is not satisfied. The introduction of C resulted in planarized sample which has a larger specific surface area and provides more active sites. N doping makes the valence band position moving in the direction of high energy. Thus, holes have stronger oxidizing ability. Accordingly, the effect of C and N ratios in g-C3N4 photocatalysis was fully discussed for more comprehensive understanding of g-C3N4.

Understanding the transitions between polymorphs is essential in the development of strategies for manufacturing and maximizing the efficiency of pharmaceuticals. However, this can be extremely challenging: crystallization can be influenced by subtle changes in environment, such as temperature and mixing intensity or even imperfections in the crystallizer walls. Here, we highlight the importance of in situ measurements in understanding crystallization mechanisms, where a segmented flow crystallizer was used to study the crystallization of the pharmaceuticals urea: barbituric acid (UBA) and carbamazepine (CBZ). The reactor provides highly reproducible reaction conditions, while in situ synchrotron powder X-ray diffraction (PXRD) enables us to monitor the evolution of this system. UBA has two polymorphs of almost equivalent free-energy and so is typically obtained as a polymorphic mixture. In situ PXRD analysis uncovered a progression of polymorphs from UBA III to the thermodynamic polymorph UBA I, where different positions along the length of the tubular flow crystallizer correspond to different reaction times. Addition of UBA I seed crystals modified this pathway such that only UBA I was observed throughout, while transformation from UBA III into UBA I still occurred in the presence of UBA III seeds. Information regarding the mixing-dependent kinetics of the CBZ form II to III transformation was also uncovered in a series of seeded and unseeded flow crystallization runs, despite atypical habit expression. These results illustrate the importance of coupling controlled reaction environments with in situ XRD to study the phase relationships in polymorphic materials.

In our present work, we emphasized on the potential of barbituric acid (1) derivatives as drugs like anti-bacterial, hypnotic, sedative, anti-microbial and antifungal agents. As naturally occurring, barbituric acid (1) is inactive but in the derivative form, it has a large number of medicinal uses and nowadays, it has a great demand in the pharmaceutical industry. Barbituric acid has a wide range of applications in the synthesis of a diverse class of compounds like heterocyclic, carbocyclic, synthetic alkaloids, and due to its broad-spectrum applications, barbituric acid acquired the position of building blocks in synthetic chemistry. Through the history of humanity, a number of bioactive agents have been applied to cure the disease related to hypnotics and sedatives, while the exact efficacy of these agents was found to be limited. Till now, review articles on barbituric acid only express their specific aspect but in present review article, all aspects are discussed in detail to provide a platform to readers and researchers so that they could obtain all information and background knowledge from a single point.

Purpose: To synthesize some pyrimidine derivatives and investigate their radical scavenging activities. Methods: A series of newly pyranopyrimidines derivatives and dithiopyridopyrimidinediones were synthesized by condensation of barbituric acid, malononitrile and different substituted benzaldehydes reacted with 1,4-Diazabicyclo[2.2.2] octane (DABCO) as a base. Compounds P1-7 (series 1), S1-11 (series 2) Scheme 1 and 6-amino-2-thiouracil with aromatic aldehydes in glacial acetic acid under reflux J1-13 (series 3) Scheme 2. 1H & 13C NMR, CHN, GC-MS and IR were used to characterize the compounds and were also screened for radical scavenging activity using 2,2-diphenyl- 1-picrylhydrazyl (DPPH) radical scavenging activity (IC50 = 50 μg/ml). Results: The potency of radical scavenging activity was ranked as series 1 > series 3 > series 2. Compounds P3, J4, S10, P5, P7 with inhibitory concentration at 50 % level (IC50) of 12, 40, 48, 50, and 54 μg/ml, respectively, showed radical scavenging activity equal or more potent than the standard antioxidant, ascorbic acid (IC50 = 50 μg/ml). Conclusion: Series of newly pyranopyrimidines and dithiopyridopyrimidinediones derivatives have been successfully synthesized, and they demonstrate good radical scavenging activity. Keywords: Pyranopyrimidine, Dipyrimidines, Anti-oxidant, DPPH, Ascorbic acid, Radical scavenging

Intermolecular proton transfer in barbituric acid (BA) both in the gas phase and in the presence of water molecule was investigated using the B3LYP method with aug-cc-pVDZ basis set. The overall process involves keto-enol and lactam-lactim tautomerism that occurs. The most stable form of barbituric acid turns into the intermediates with three-step proton transfer at three different positions of the structure of this compound. Then, these intermediates become to the final products passing through two competing processes. In order to determine the priority of each competitive process, energy changes of all possible tautomeric forms were investigated along with the role of solvent molecules in multiple routes. Also, transposition in the proton transfer process makes changes in the electron transfer energy which was investigated both in the gas phase and in the presence of water molecules. Frequency calculations performed to characterize ground and transition states and calculation of zero point energies. Natural bond orbital analysis and topological property of electron density were investigated using natural bond orbital (NBO) and atoms in molecules (AIM) analysis. From the results, all proton transfer process in the gas phase and in the presence of the solvent molecule (water) is exothermic and non-spontaneous. In the gas phase and in the water assisted condition, the route 1b is kinetically more preferred. Despite the increase of the increase of ring resonance of stronger hydrogen bonds in the product compared to the reactant, the products are more unstable than the reactant. Therefore, the only factor can make the product unstable is the severe decrease of LP (N) →σ* (C-O) electron transfer energy.

We report five new transition-metal complexes that inhibit the urease enzyme. Barbituric acid (BTA), thiobarbituric acid (TBA), isoniazid (INZ), and nicotinamide (NCA) ligands were employed in complexation reactions. The resulting complexes were characterized using a variety of analytical techniques including infra-red and UV–vis spectroscopy, 1H NMR spectroscopy, elemental analysis, and single-crystal X-ray diffraction analysis. We describe two mononuclear complexes with a general formula {[M(NCA)2(H2O)4](BTA)2(H2O)}, where M = Co (1) and Zn (2), a mononuclear complex {[Ni(NCA)2(H2O)4](TBA)2(H2O)} (3), and two polymeric chains of a general formula {[M(INZ) (H2O)3](BTA)2(H2O)3}, where M = Co (4) and Zn (5). These complexes displayed significant urease enzyme inhibition with IC50 values in the range of 3.9–19.9 μM.

The present work describes an efficient and environmentally benign four component synthesis of structurally diverse substituted pyrido-pyrimidines involving the reaction of barbituric acid, 4-hydroxy 6-methyl 2-pyrone, an aromatic aldehyde and ammonium acetate in low transition temperature mixture (LTTM) (glycerol:proline: 1:1). The LTTM serves as green solvent which is an inexpensive, nontoxic and plays a dual function (reusable catalyst and solvent), and is found to be an excellent reaction endorsing medium. The present protocol offers some advantages such as easy work up, shorter reaction time, an excellent yield with higher atom economy, maximum reaction efficiency with an excellent green chemistry metrics. The synthesized compounds have been evaluated for their antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay as well as molecular docking studies performed on myeloperoxidase enzyme. Tested scaffolds exhibits an excellent results of virtual screening and antioxidant activity.

Novel, inexpensive, and relatively expeditious procedure to achieve the synthesis of different 2-aminopyrimidine and barbituric acid derivatives is presented here, starting from readily ava...

A series of pyran based Donor-π-Acceptor (D-π-A) systems have been synthesized and used as sensitizer in Dye-Sensitized Solar Cell (DSSC), in which phenothiazine (PH), triphenylamine (TPA), methoxy phenyl amino styryl (ATPA), diethyl aniline (EA) and carbazole (CA) were used as electron donors and barbituric acid as electron acceptor. The optical, electrochemical, theoretical and photovoltaic studies are carried out. The devise with PHPBA as sensitizer achieved the highest solar energy-to-electricity conversion efficiency (η) of 1.16%.

Two novel multi-hydroxyl N-halamine precursors were successfully synthesized in a green and facile way via Knoevenagel condensation reaction between barbituric acid and an aldehyde (citral or cinnamaldehyde), followed by a hydroxylation reaction with hydrogen peroxide. 1H-NMR and FT-IR spectral analyses confirmed their formation. Through the melt-blending process, the multi-hydroxyl derivatives of barbituric acid were introduced via transesterification into poly(ethylene terephthalate) (PET) at 265 °C in a rheometer. The crystallization behaviors of the modified PET samples were investigated using X-ray diffraction (XRD), differential scanning calorimetry (DSC), and polarized optical microscopy (POM) analyses. The results showed that the crystallization temperature and crystallization rate of PET were significantly improved upon the introduction of the precursor. Meanwhile, the relative crystallinity of the modified PET samples increased with an increase in the dosage of the N-halamine precursor. After the treatment with sodium hypochlorite solution, the PET surfaces modified with N-halamine derivatives would impart powerful antibacterial properties and achieve 100% killing of Staphylococcus aureus (ATCC 6538) and Escherichia coli (CMCC44103) cells within 30 min. Therefore, the multi-hydroxyl N-halamine precursors exhibit great potential as bifunctional additives (nucleating and antibacterial agents) in the manufacturing of functional PET materials.