A facile and rapid approach to synthesize uric acid-capped Ti3C2 MXene quantum dots for the sensitive determination of 2,4,6-trinitrophenol both on surfaces and in solution.

Herein, uric acid@Ti3C2 quantum dots (UA@Ti3C2 QDs) were synthesized via a microwave-assisted strategy on the basis of acid etching and stripping. The UA@Ti3C2 QDs have bright blue emission. Intriguingly, the fluorescence emission of the UA@Ti3C2 QDs was significantly quenched after the addition of 2,4,6-trinitrophenol (TNP), due to inner-filter effect (IFE). Based on these findings, a novel environmentally friendly and water-soluble fluorescence probe based on UA@Ti3C2 QDs was demonstrated for the sensitive and selective detection of TNP. The method presented a wide linear range for TNP detection in the 0.01-40 µM range, with a low detection limit of 9.58 nM. Furthermore, the probe was successfully used for the sensitive detection of TNP in real water and smartphone-based colorimetric (SPBC) detection of TNP on surfaces with the linear range from 10.0 to 100.0 ng. On the whole, this work provides an effective strategy for the synthesis of UA@Ti3C2 QDs and an alternative fluorescence probe for detecting TNP both on surface and in solution.

Evaluation of Turmeric Nanoparticles as Anti-Gout Agent: Modernization of a Traditional Drug.

Background and objectives: Turmeric has assisted in the control of inflammation and pain for decades and has been used in combination with other nutraceuticals to treat acute and chronic osteoarthritis pain. Recently, the effect of turmeric, turmeric extract, or curcuminoids on musculoskeletal pain, either by themselves or in conjunction with other substances, has been reported. The aim of this study was to develop and characterize turmeric nanoparticles (T-NPs) for various parameters, both in vitro and in vivo. Materials and Methods: The T-NPs were successfully synthesized and characterized using particle size analysis, solubility improvement, SEM, EDX, X-ray diffraction, and in vivo antigout activity in mice model. Results: The T-NPs were of about 46 nm in size with a positive zeta potential +29.55 ± 3.44 and low polydispersity index (PDI) (0.264). Furthermore, the diseased mice, with induced gout via monosodium urate crystals, were treated with 5, 10, and 20 ppm T-NPs, administered orally, and the anti-gout potential was observed through measurement of joint diameter and changes in biochemical parameters, including lipid profile, renal function test, and liver function tests which significantly reduced the levels of these biochemical parameters. Conclusions: Uric acid levels were significantly reduced after the treatment with T-NPs. indicating that T-NPs show superior potential against gout management. Thus, T-NPs can be developed as an efficient antigout agent with minimum toxicities.

Facile Preparation of 4-Substituted Quinazoline Derivatives.

Reported in this paper is a very simple method for direct preparation of 4-substituted quinazoline derivatives from a reaction between substituted 2-aminobenzophenones and thiourea in the presence of dimethyl sulfoxide (DMSO). This is a unique complementary reaction system in which thiourea undergoes thermal decomposition to form carbodiimide and hydrogen sulfide, where the former reacts with 2-aminobenzophenone to form 4-phenylquinazolin-2(1H)-imine intermediate, whilst hydrogen sulfide reacts with DMSO to give methanethiol or other sulfur-containing molecule which then functions as a complementary reducing agent to reduce 4-phenylquinazolin-2(1H)-imine intermediate into 4-phenyl-1,2-dihydroquinazolin-2-amine. Subsequently, the elimination of ammonia from 4-phenyl-1,2-dihydroquinazolin-2-amine affords substituted quinazoline derivative. This reaction usually gives quinazoline derivative as a single product arising from 2-aminobenzophenone as monitored by GC/MS analysis, along with small amount of sulfur-containing molecules such as dimethyl disulfide, dimethyl trisulfide, etc. The reaction usually completes in 4-6 hr at 160 ºC in small scale but may last over 24 hr when carried out in large scale. The reaction product can be easily purified by means of washing off DMSO with water followed by column chromatography or thin layer chromatography.

Synthesis of uranyl(II), vanadyl(II) and zirconyl urate complexes, spectral, thermal and biological studies.

Three urate chelations were obtained when uric acid was reacted with UO2(CH3COO)2H2O, VOSO4·XH2O and ZrOCl2·XH2O salts with neutralized with 0.1 M NaOH aqueous media. The 1:2 metal-to-ligand complexes [(UO2)2(C5H2N4O3)2](H2O), [(ZrO)2(H2O)2(C5H2N4O3)2] and [VO((C5H3N4O3)2] were characterized by elemental analyses, molar conductivity, (infrared, Raman and UV-vis) spectra, effective magnetic moment in Bohr magnetons, and thermal analysis (TG/DTG). The urate ligand coordinates as mononegative bidentate donor towards the mononuclear central vanadium atom and coordinated as binegative tetradentate mode towards the binuclear dioxouranium and zirconyl centers. The antibacterial activity of the metal complexes were tested against some kind of bacteria and fungi strains and compared with uric acid. The ligand, ZrO(II) and UO2(II) complex showed a week potential degradation on calf thymus DNA, whereas VO(II) complex slightly degraded the DNA.

Hydroxyl radical induced oxidation of theophylline in water: a kinetic and mechanistic study.

Oxidative destruction and mineralization of emerging organic pollutants by hydroxyl radicals (˙OH) is a well established area of research. The possibility of generating hazardous by-products in the case of ˙OH reaction demands extensive investigations on the degradation mechanism. A combination of pulse radiolysis and steady state photolysis (H2O2/UV photolysis) followed by high resolution mass spectrometric (HRMS) analysis have been employed to explicate the kinetic and mechanistic features of the destruction of theophylline, a model pharmaceutical compound and an identified pollutant, by ˙OH in the present study. The oxidative destruction of this molecule, for intermediate product studies, was initially achieved by H2O2/UV photolysis. The transient absorption spectrum corresponding to the reaction of ˙OH with theophylline at pH 6, primarily caused by the generation of (T8-OH)˙, was characterised by an absorption band at 330 nm (k2 = (8.22 ± 0.03) × 10(9) dm(3) mol(-1) s(-1)). A significantly different spectrum (λmax: 340 nm) was observed at highly alkaline pH (10.2) due to the deprotonation of this radical (pKa∼ 10.0). Specific one electron oxidants such as sulphate radical anions (SO4˙(-)) and azide radicals (N3˙) produce the deprotonated form (T(-H)˙) of the radical cation (T˙(+)) of theophylline (pKa 3.1) with k2 values of (7.51 ± 0.04) × 10(9) dm(3) mol(-1) s(-1) and (7.61 ± 0.02) × 10(9) dm(3) mol(-1) s(-1) respectively. Conversely, oxide radicals (O˙(-)) react with theophylline via a hydrogen abstraction protocol with a rather slow k2 value of (1.95 ± 0.02) × 10(9) dm(3) mol(-1) s(-1). The transient spectral studies were complemented by the end product profile acquired by HRMS analysis. Various transformation products of theophylline induced by ˙OH were identified by this technique which include derivatives of uric acids (i, iv & v) and xanthines (ii, iii & vi). Further breakdown of the early formed product due to ˙OH attack leads to ring opened compounds (ix-xiv). The kinetic and mechanistic data furnished in the present study serve as a basic frame work for the construction of ˙OH induced water treatment systems as well as to understand the biological implications of compounds of this kind.

A new route for the prebiotic synthesis of nucleobases and hydantoins in water/ice solutions involving the photochemistry of acetylene.

The origin of nucleobases and other heterocycles is a classic question in the chemistry of the origins of life. The construction of laboratory models for the abiotic synthesis of nitrogen heterocycles in plausible natural conditions also aids the understanding and prediction of chemical species in the Solar System. Here, we report a new explanation for the origin of hydantoins, purines, and pyrimidines in eutectic water/ice/urea solutions driven by ultraviolet irradiation (in the 185-254 nm range, UVC) of acetylene under anoxic conditions. An analysis of the products indicates the synthesis of hydantoin and 5-hydroxyhydantoin, the purines uric acid, xanthine, and guanine, and the pyrimidines uracil and cytosine. The synthesis occurred together with the photo-oxidation of bases in a complex process for which possible pathways are proposed. In conclusion, an acetylene-containing atmosphere could contribute to the origin of nucleobases in the presence of a urea/water system by an HCN-independent mechanism. The presence of ice has a dual role as a favorable medium for the synthesis of nucleobases and protection against degradation and as a source of free radicals for the synthesis of highly oxidized heterocycles. A mechanism for the origin of hydantoins and uracil from urea in plausible conditions for prebiotic chemistry is also proposed.

Preparation and characterization of uniform particles of uric acid and its salts.

Uric acid, the major component in many kinds of kidney stones, as well as its sodium, ammonium, calcium, and barium salts were successfully prepared as uniform dispersions by precipitation in basic aqueous solutions. The effects of the reactant concentrations, pH, and the stabilizers were evaluated in detail. Except for the platelets of the pure acid, all prepared compounds appeared as needles or their aggregates. The electron micrographs showed that kidney stones consisted of such aggregates although less regular in size and morphology. All prepared urate salts had a 1:1 cation/uric acid ratio, regardless of the valence of the cation. The electrokinetic measurements showed all these particles to have negative ζ-potentials over the pH range 3-9. The precipitated salt particles were chemically and morphologically unstable at low pH values by decomposing into ill-defined aggregates of the pure uric acid.

A new concept for glycosyltransferase inhibitors: nonionic mimics of the nucleotide donor of the human blood group B galactosyltransferase.

Glycosyltransferases play an important role in the formation of oligosaccharides and glycoconjugates. To find suitable and selective inhibitors for this class of enzymes is still challenging. Here, we describe a novel concept that allows the design of inhibitors based on the structure of the donor substrate binding pocket. As a first step we describe the design, synthesis and analysis of inhibitors of the human blood group B galactosyltransferase (GTB). This enzyme served as a model system to study the concept, which can be used for easy access of glycosyltransferase inhibitors in general. In silico docking of bicyclic heteroaromatic ligands to GTB and experimental verification of binding affinities by saturation transfer difference NMR (STD NMR) spectroscopy gave 9-N-pentityl uric acid derivatives as non-ionic mimics of UDP. Two derivatives were synthesized and showed inhibitory activity for GTB as determined by competitive STD NMR experiments and by a radiolabeled enzyme assay.

Estudio del metabolismo proteico en una población de jóvenes sanos: factores asociados / Results from the application of a quality management system in the community pharmacy

INTRODUCCIÓN: La ingesta de proteína en la población andaluza presenta valores cercanos al 200% de la IR1, pudiendo afectar a la función hepática y renal. En esta situación, los niveles de biomarcadores específicos de la función de dichos órganos se verán alterados pudiendo causar daños a veces irreversibles. OBJETIVOS: En el presente estudio se analizan la frecuencia de ingesta proteica y parámetros relacionados con el metabolismo proteico en una muestra de jóvenes procedentes de la provincia de Granada. METODOLOGÍA: El estudio se ha llevado a cabo con 71 estudiantes sanos (15 hombres y 56 mujeres) de la Universidad de Granada con edades comprendidas entre 18 y 31 años. Se procedió a la extracción de muestras de sangre para la obtención de suero y la posterior determinación de los parámetros bioquímicos de estado nutricional proteico. Se determinaron parámetros antropométricos, como talla, peso e índice de masa corporal. Se efectuó una encuesta de frecuencia de consumo de alimentos de origen proteico. RESULTADOS: los resultados obtenidos muestran una frecuencia de consumo superior a la recomendada en aves del 20,3% para la ternera el 1% y para el cerdo el 6%. Curiosamente se encontró una correlación significativa positiva entre el pulso y la ingesta de ternera. Con respecto a los resultados obtenidos en los niveles de creatinina, urea y ácido úrico se observó que un 13% de la población mostraba niveles de urea superiores a los de referencia. Las determinaciones realizadas en orina mantienen la normalidad en el 100% de los casos. Igualmente se obtuvo correlación significativa negativa entre los niveles de creatinina y ácido úrico con la talla y positiva entre los niveles de urea y la edad(AU)

CONCLUSIÓN: nuestros resultados confirman los datos esperados y referidos por otros autores 2, ya que las ingestas proteicas altas encontradas pueden alterar los valores de referencia en los biomarcadores de daño renal tales como la urea, el ácido úrico y la creatinina. Por tanto seria aconsejable mejorar la formación preventiva de la población sobre las recomendaciones de la ingesta de alimentos proteicos, intentando cambiar hábitos de consumo clásicos frecuentes en la población española(AU)

INTRODUCTION: Protein intake in andalusian population presents values near 200% recommended intake 1, can affect kidney and liver function. In this situation, levels of specific biomarkers of the function of these organs will be altered and can cause irreversible damage sometimes. OBJECTIVES: This study analyzed the frequency of protein intake and parameters related to protein metabolism in a sample of young people from the province of Granada. METHODOLOGY: The study was conducted with 71 healthy students (15 men and 56 women) from the University of Granada, aged between 18 and 31 years. We proceeded to the extraction of blood samples to obtain serum and the subsequent determination of biochemical parameters of protein nutritional status. We determined anthropometric parameters, such as size, weight and body mass index. We made a survey of frequency of consumption of high protein foods. RESULTST: he results show a frequency of consumption higher than recommended in birds of 20.3%, for1% beef and pork in 6%. Interestingly we found a significant positive correlation between pulse and intake of beef. With respect to the results in levels of creatinine, urea and uric acid was observed that 13% of the population showed urea levels higher than reference. Determinations made on urine remains normal in 100% of cases. Equally significant negative correlation was obtained between the levels of creatinine and uric acid with positive size and between the levels of urea and age. CONCLUSIONS: Our results confirm the expected data and reported by other authors 2, since high protein intake can alter the values found for reference in the renal damage biomarkers such as urea, uricacid and creatinine. It would therefore be advisable to improve preventive training the population on the recommendations of the intake of protein foods, trying to change traditional habits common in Spanish population(AU)

Inhibition of CTP synthase from Escherichia coli by xanthines and uric acids.

CTP synthase (CTPS) catalyzes the conversion of UTP to CTP and is a recognized target for the development of anticancer, antiviral, and antiprotozoal agents. Xanthine and related compounds inhibit CTPS activity (IC(50)=0.16-0.58mM). The presence of an 8-oxo function (i.e., uric acids) enhances inhibition (IC(50)=0.060-0.121mM). An intact purine ring with anionic character favors inhibition. In general, methylation of the purine does not significantly affect inhibition.

Method for the synthesis of uric acid derivatives.

A general procedure to obtain tetra-substituted uric acid by stepwise N-alkylation is described. 2,6-Dichloropurine (1) was condensed with 1-propanol by Mitsunobu reaction to give 9-propyl congener (2). Treatment of 2 with ammonia gave adenine derivative (4a), which was converted to the 8-oxoadenine (5b) in 3 steps. Methylation of 5b proceeded site-specifically to give 6-amino-2-chloro-7,8-dihydro-7-methyl-9-propylpurin-8-one (6) as a sole product. Compound 6 was successively treated with NaNO2 and iodomethane to give 2-chloro-1,6,7,8-tetrahydro-1,7-dimethyl-9-propylpurin-6,8-dione (9) accompanied by the O6-methyl product (8) in 75% and 6.9%, respectively. After nucleophilic substitution of 9 with NaOAc, the product (11) was reacted with iodomethane to give the uric acid (12) and the 2-methoxy product (13) in 46% and 15.5%, respectively. However, the reaction of 11 with the benzylating agents gave only O-benzyl products (14a,b).

Uric acid synthesis by rat liver supernatants from purine bases, nucleosides and nucleotides. Effect of allopurinol.

The synthesis of uric acid from purine bases, nucleosides and nucleotides has been measured in reaction mixtures containing rat liver supernatant and each one of the following compounds at 1 mM concentration (except xanthine, 0.5 mM and guanosine and guanine, 0.1 mM). The rates of the reaction, expressed as nanomoles of uric acid synthesized g-1 of wet liver min-1 were: ATP, 10; ADP, 37; AMP, 62; adenosine, 108; adenine 6; adenylosuccinate, 9; IMP 32; inosine, 112; hypoxanthine, 50; GTP, 19; GDP, 19; GMP, 27; guanosine, 34; guanine, 72; XMP, 10; xanthosine, 24; xanthine, 144. These figures divided by 55 correspond to nanomoles of uric acid synthesized min-1 per mg-1 of protein. The rate of synthesis of uric acid obtained with each one of those compounds at 0.1 and 0.05 mM concentrations was also determined. ATP (1 mM) strongly inhibited uric acid synthesis from 0.05 mM AMP (91 per cent) and from 0.05 mM ADP (88 per cent), but not from adenosine. CTP or UTP (1 mM) also inhibited (by more than 90 per cent) the synthesis of uric acid from 0.05 mM AMP. Xanthine oxidase was inhibited by concentrations of hypoxanthine higher than 0.012 mM. The results favour the view that the level of uric acid in plasma may be an index of the energetic state of the organism. Allopurinol, besides inhibiting uric acid synthesis, reduced the rate of degradation of AMP. The ability of crude extracts to catabolize purine nucleotides to uric acid is an important factor to be considered when some enzymes related to purine nucleotide metabolism, particularly CTP synthase, are measured in crude liver extracts.

Tophus-derived monosodium urate monohydrate crystals are biologically much more active than synthetic counterpart.

Monosodium urate monohydrate (MSUM) crystals derived from a tophus surgically removed from patients suffering from gout and MSUM prepared from a supersaturated solution of sodium urate were studied and compared with respect to their ability to: (1) stimulate chemiluminescence (CL) production by human polymorphonuclear (PMN) cells, (2) induce hemolysis of the human red blood cells and (3) induce inflammation when injected in the rat paw and knee joint. Human MSUM crystals were considerably more active in stimulating CL production by PMN cells and in inducing synovial inflammation. Both serum and papain pretreatment of human MSUM crystals caused inhibition of their enhancing effect on CL production by PMN cells. Papain pretreatment only reduced their phlogogenic activity. Uncoated and, to a much lesser extent, serum-coated human MSUM crystals induced secretion by mononuclear cells (MNC) of the factor(s) that considerably enhanced CL production by PMN cells. Both tophus-derived and synthetic crystals appeared to be weak hemolytic agents. Serum pretreatment of synthetic MSUM crystals reduced their hemolytic activity. These results suggest that surface coating, destroyed by papain treatment, was probably responsible for cell activation induced by human MSUM crystals.

Chemiluminescent determination of adenosine, inosine, and hypoxanthine/xanthine.

A fully automatic method for analysis of adenosine, inosine, and hypoxanthine/xanthine which combines the specificity of enzymatic catalysis and sensitivity of chemiluminescence is presented. The hydrogen peroxide formed by sequential catabolism of purines to uric acid is detected by the oxidation of luminol in the presence of peroxidase. The method takes advantage of the fact that light output in the H2O2/luminol system is transient. By adopting a two-step procedure this feature enables selective determination of adenosine, inosine, and hypoxanthine/xanthine. In step 1 any purines lower in the catabolic sequence than the analyte under study are converted to uric acid. Light emission is allowed to decay to baseline levels. During step 2 the analyte is selectively degraded. The H2O2 formed leads to a new light emission which is proportional to the square of analyte concentration. The method can be performed with commercially available reagents and enzymes and requires minimal processing of biological samples. Excellent agreement has been obtained with HPLC analysis. Sensitivity is in the range of 5-10 nmol/liter in as little as 0.1 ml. More than 200 samples per day can be analyzed by a single operator.

A new synthesis of 9-beta-D-ribofuranosyluric acid and its 5'-monophosphate.

Syntheses for 9-beta-D-ribofuranosyluric acid (16) and its 5'-monophosphate (14) starting from guanosine and by applying the p-nitrophenylethyl blocking group are described.

Morphological characteristics of monosodium urate: a transmission electron microscopic study of intact natural and synthetic crystals.

Transmission electron microscopic studies of synthetic and natural monosodium urate crystals dried on formvar coated grids showed identical internal structures in all crystals. At higher magnification the crystals' surface showed angular or wavy irregularities, and more rarely some crystals appeared to have other tiny crystals on the surface. Protein-like surface coating was not observed except in crystals from one asymptomatic patient in whom synovial fluid was loaded with monosodium urate crystals, but no inflammatory cells were present. Heated synthetic monosodium urate crystals retained the ultrastructural characteristics in their interior but they lost their needle or rod-like shape. Transmission electron microscopic study of monosodium urate crystals dried on formvar coated grids provides a quick method of investigating crystal ultrastructure.