The interactions between chiral analytes and chitosan-based chiral stationary phases during enantioseparation.

The goal of the present study was to disclose the interactions between chitosan-type chiral selectors (CSs) and chiral analytes during enantioseparation. Hence, six chitosan 3,6-bis(phenylcarbamate)-2-(cyclohexylmethylurea)s were synthesized and characterized. These chitosan derivatives were employed as CSs with which the corresponding coated-type chiral stationary phases (CSPs) were prepared. According to the nature and position of the substituents on the phenyl group, the CSs and CSPs were divided into three sets. The counterparts of the three sets were 3,5-diMe versus 3,5-diCl, 4-Me versus 4-Cl and 3-Me versus 3-Cl. The enantioseparation capability of the CSPs was evaluated with high-performance liquid chromatography. The CSPs demonstrated a good enantioseparation capability to the tested chiral analytes. In enantioselectivity, the CSs with 3,5-diCl and with 4-Me roughly were better than the counterparts with 3,5-diMe and with 4-Cl respectively. The CS with 3-Me enantiomerically recognized more analytes than the one with 3-Cl, but showed lower separation factors in more enantioseparations. The acidity of the amide hydrogen in the phenylcarbamates was investigated with density functional theory calculations and 1H NMR measurements. The trend of the acidity variation with different substituents on the phenyl group was confirmed by the retention factors of acetone on the CSPs. Compared the retention factors of analytes on every set of the counterparts, the formation of hydrogen bond (HB) in enantioseparation could be outlined as follows: when the CSs interacted with chiral analytes without reactive hydrogen but with lone paired electrons, the carbamate N‒Hs in the CSs were HB donors and the analytes were HB acceptors; if the CSs interacted with analytes with a reactive hydrogen, the role of the CSs in HB formation was related to the acidity of the reactive hydrogen; the patterns of HB formation between the CSs and analytes were also impacted by compositions of mobile phases, in addition to the nature, number and position of substituents on the phenyl group. Based on the discussion, chiral recognition mechanism could be understood in more detail. Besides, the strategy to improve enantioseparation capability of a CSP by introducing a substituent onto phenyl group was clarified and further comprehended.

Antitumour properties based on the self-assembly of camptothecin and carbamoylmannose conjugates.

Camptothecin (CPT) and its analogues show potent antitumour activity. However, poor water solubility and severe side effects have restricted their applications in clinical practice. In this paper, a novel self-assembly based on camptothecin and carbamoylmannose conjugates (CPT-Man) was constructed. The self-assembly increased the water solubility of camptothecin to 0.64 mg/ml and antitumour activity. Moreover, CPT-Man could induce obvious cancer cell apoptosis. This work provides a new approach for exploring carbohydrate-modified antitumour properties by self-assembled CPT drugs.

Guiding Lead Optimization for Solubility Improvement with Physics-Based Modeling.

Although there are a number of computational approaches available for the aqueous solubility prediction, a majority of those models rely on the existence of a training set of thermodynamic solubility measurements or/and fail to accurately account for the lattice packing contribution to the solubility. The main focus of this study is the validation of the application of a physics-based aqueous solubility approach, which does not rely on any prior knowledge and explicitly describes the solid-state contribution, in order to guide the improvement of poor solubility during the lead optimization. A superior performance of a quantum mechanical (QM)-based thermodynamic cycle approach relative to a molecular mechanical (MM)-based one in application to the optimization of two pharmaceutical series was demonstrated. The QM-based model also provided insights into the source of poor solubility of the lead compounds, allowing the selection of the optimal strategies for chemical modification and formulation. It is concluded that the application of that approach to guide solubility improvement at the late discovery and/or early development stages of the drug design proves to be highly attractive.

Dimethylolurea as a Novel Slow-Release Nitrogen Source for Nitrogen Leaching Mitigation and Crop Production.

Rapid hydrolysis of urea results in further fertilization frequency and excessive nitrogen (N) input. A modified urea, dimethylolurea (DMU), was synthesized in this study. The structure of the sample was characterized by Fourier transform infrared and nuclear magnetic resonance analysis, manifesting the formation of DMU. N release investigation confirmed that DMU enabling provided a gradual N supply. The N leaching experiment indicated that increasing the applied DMU significantly reduced the NH4+-N, NO3--N, and total N leaching, compared with urea application alone. The application effect on maize and wheat was evaluated. The results revealed that singly applied DMU with 100% or 80% N input, irrespective of the amount, promoted crop yield and agronomic characteristic and N use efficiency (NUE) of maize and wheat, beyond urea with two split applications at the recommended rate. Thus, the potential availability of DMU was proven; this could be widely used in agricultural fields as a slow-release fertilizer.

Enzyme-Functionalized Piezoresistive Hydrogel Biosensors for the Detection of Urea.

Urea is used in a wide variety of industrial applications such as the production of fertilizers. Furthermore, urea as a metabolic product is an important indicator in biomedical diagnostics. For these applications, reliable urea sensors are essential. In this work, we present a novel hydrogel-based biosensor for the detection of urea. The hydrolysis of urea by the enzyme urease leads to an alkaline pH change, which is detected with a pH-sensitive poly(acrylic acid-co-dimethylaminoethyl methacrylate) hydrogel. For this purpose, the enzyme is physically entrapped during polymerization. This enzyme-hydrogel system shows a large sensitivity in the range from 1 mmol/L up to 20 mmol/L urea with a high long-term stability over at least eight weeks. Furthermore, this urea-sensitive hydrogel is highly selective to urea in comparison to similar species like thiourea or N-methylurea. For sensory applications, the swelling pressure of this hydrogel system is transformed via a piezoresistive pressure sensor into a measurable output voltage. In this way, the basic principle of hydrogel-based piezoresistive urea biosensors was demonstrated.

Quantifying Interactions of Nucleobase Atoms with Model Compounds for the Peptide Backbone and Glutamine and Asparagine Side Chains in Water.

Alkylureas display hydrocarbon and amide groups, the primary functional groups of proteins. To obtain the thermodynamic information that is needed to analyze interactions of amides and proteins with nucleobases and nucleic acids, we quantify preferential interactions of alkylureas with nucleobases differing in the amount and composition of water-accessible surface area (ASA) by solubility assays. Using an established additive ASA-based analysis, we interpret these thermodynamic results to determine interactions of each alkylurea with five types of nucleobase unified atoms (carbonyl sp2O, amino sp3N, ring sp2N, methyl sp3C, and ring sp2C). All alkylureas interact favorably with nucleobase sp2C and sp3C atoms; these interactions become more favorable with an increasing level of alkylation of urea. Interactions with nucleobase sp2O are most favorable for urea, less favorable for methylurea and ethylurea, and unfavorable for dialkylated ureas. Contributions to overall alkylurea-nucleobase interactions from interactions with each nucleobase atom type are proportional to the ASA of that atom type with proportionality constant (interaction strength) α, as observed previously for urea. Trends in α-values for interactions of alkylureas with nucleobase atom types parallel those for corresponding amide compound atom types, offset because nucleobase α-values are more favorable. Comparisons between ethylated and methylated ureas show interactions of amide compound sp3C with nucleobase sp2C, sp3C, sp2N, and sp3N atoms are favorable while amide sp3C-nucleobase sp2O interactions are unfavorable. Strongly favorable interactions of urea with nucleobase sp2O but weakly favorable interactions with nucleobase sp3N indicate that amide sp2N-nucleobase sp2O and nucleobase sp3N-amide sp2O hydrogen bonding (NH···O═C) interactions are favorable while amide sp2N-nucleobase sp3N interactions are unfavorable. These favorable amide-nucleobase hydrogen bonding interactions are prevalent in specific protein-nucleotide complexes.

Influence of chelation on the Fenton-based electrochemical degradation of herbicide tebuthiuron.

This study describes the performance of electro-Fenton (EF) and photoelectro-Fenton (PEF) processes to degrade the herbicide tebuthiuron (TBH) in 0.050 M Na2SO4 at pH = 3.0. Experiments were performed in an undivided cell equipped with a boron-doped diamond (BDD) or Pt anode and an air-diffusion cathode that produces H2O2. Physisorbed hydroxyl radicals (M(OH)) generated from water oxidation at the anode and/or free OH formed from Fenton's reaction acted as main oxidants. All processes became much more effective using a BDD anode because of the higher oxidation power of BDD(OH). Sulfate and nitrate were the predominant ions released during TBH destruction. In both, EF and PEF treatments, two distinct kinetic regimes were observed, the first one corresponding to the oxidation of free TBH by OH and the second one to that of the Fe(III)-TBH complex by M(OH). The effect of Fe2+ and TBH concentrations on the kinetics of both regions has been examined. Moreover, a poor mineralization was reached with Pt anode, whereas almost total mineralization was attained by EF and PEF with BDD. Both processes showed analogous mineralization rates because the intermediates produced could not be photodegraded by UVA light. Gas chromatography-mass spectrometry analysis of electrolyzed solutions revealed the generation of eight heteroaromatics along with 1,3-dimethylurea, which have been included in a reaction pathway proposed for the initial degradation of TBH.

The herbicides trifluralin and tebuthiuron have no genotoxic or mutagenic potential as evidenced by genetic tests.

Brazil has been the largest world consumer of pesticides since 2008, followed by the USA. The herbicides trifluralin and tebuthiuron have been widely applied in agriculture. These herbicides are selective for some plant species, and their use brings various benefits. However, the genotoxic and mutagenic effects of tebuthiuron on non-target organisms are poorly known, and in addition, the effects of trifluralin must be better investigated. Therefore, this study employed genetic tests including the comet assay and micronucleus test to evaluate the genotoxic effects of trifluralin and tebuthiuron on HepG2 cells. In addition, we have used the Ames test to assess the mutagenic effects of the herbicides on the TA97a, TA98, TA100, and TA1535 strains of Salmonella typhimurium. On the basis of the comet assay and the micronucleus test, trifluralin did not cause genetic damage to HepG2 cells. In addition, trifluralin did not impact the tested S. typhimurium strains. Regarding tebuthiuron, literature has shown that this herbicide damaged DNA in Oreochromis niloticus. Nevertheless, we have found that tebuthiuron was not genotoxic to either HepG2 cells or the S. typhimurium strains. Therefore, neither trifluralin nor tebuthiuron exerted genotoxic or mutagenic potential at the tested conditions.

Pseudomonas aeruginosa cytochrome c551 denaturation by five systematic urea derivatives that differ in the alkyl chain length.

Reversible denaturation of Pseudomonas aeruginosa cytochrome c551 (PAc551) could be followed using five systematic urea derivatives that differ in the alkyl chain length, i.e. urea, N-methylurea (MU), N-ethylurea (EU), N-propylurea (PU), and N-butylurea (BU). The BU concentration was the lowest required for the PAc551 denaturation, those of PU, EU, MU, and urea being gradually higher. Furthermore, the accessible surface area difference upon PAc551 denaturation caused by BU was found to be the highest, those by PU, EU, MU, and urea being gradually lower. These findings indicate that urea derivatives with longer alkyl chains are stronger denaturants. In this study, as many as five systematic urea derivatives could be applied for the reversible denaturation of a single protein, PAc551, for the first time, and the effects of the alkyl chain length on protein denaturation were systematically verified by means of thermodynamic parameters.

O-Methylisourea Can React with the α-Amino Group of Lysine: Implications for the Analysis of Reactive Lysine.

The specificity of O-methylisourea (OMIU) to bind to the ε-amino group of Lys, an important supposition for the OMIU-reactive Lys analysis of foods, feeds, ingredients, and digesta, was investigated. Crystalline l-Lys incubated under standard conditions with OMIU resulted in low homoarginine recoveries. The reaction of OMIU with the α-amino group of Lys was confirmed by MS analysis, with double derivatized Lys being identified. None of the changes in reaction conditions (OMIU pH, OMIU to Lys ratio, and reaction time) with crystalline l-Lys resulted in 100% recovery of homoarginine. The average free Lys content in ileal digesta of growing pigs and broilers was found to be 13% of total Lys, which could result in a significant underestimation of the reactive Lys content. The reaction of OMIU with α-amino groups may necessitate analysis of free Lys to accurately quantify reactive lysine in samples containing a large proportion of Lys with a free α-amino group.

Functional foldamers that target bacterial membranes: The effect of charge, amphiphilicity and conformation.

By varying the molecular charge, shape and amphiphilicity of a series of conformationally distinct diarylureas it is possible to control the levels of phospholipid membrane lysis using membranes composed of bacterial lipid extracts. From the data obtained, it appears as though the lysis activity observed is not due to charge, conformation or amphiphilicity in isolation, but that surface aggregation, H-bonding and other factors may also play a part. The work provides evidence that this class of foldamer possesses potential for optimisation into new antibacterial agents.

Tebuthiuron Movement via Leaching and Runoff from Grazed Vertisol and Alfisol Soils in the Brigalow Belt Bioregion of Central Queensland, Australia.

Tebuthiuron is one of five priority herbicides identified as a water pollutant entering the Great Barrier Reef. A review of tebuthiuron research in Australia found 13 papers, 6 of which focused on water quality at the basin scale (>10,000 km(2)) with little focus on process understanding. This study examined the movement of tebuthiuron in soil and runoff at the plot (1.7 m(2)) and small catchment (12.7 ha) scales. The greatest concentration and mass in soil occurred from 0 to 0.05 m depth 30-57 days after application. Concentrations at all depths tended to decrease after 55-104 days. Runoff at the small catchment scale contained high concentrations of tebuthiuron (average = 103 µg/L) 100 days after application, being 0.05% of the amount applied. Tebuthiuron concentrations in runoff declined over time with the majority of the chemical in the dissolved phase.

Fate of Tebuthiuron and Hexazinone in Green-Cane Harvesting System.

In Brazil, fire prior to sugar cane harvesting has to be phased out by 2017, but it has already been phased out in up to 85-90% of the cropped area. The new system is called green cane and has entirely changed weed management practices. The main goal of this study was to evaluate the effects of the straw presence as well as humic acid (HA), formulation, soil type, and aging on the sorption and leaching of (14)C-tebuthiuron and hexazinone. Both herbicides presented low sorption for all treatments (Kd,app ≤ 3.25 L kg(-1)), but it was higher for tebuthiuron in the clayer soil (LVd). Straw and aging only slightly enhanced sorption. The HA effects were not clear. Sorption was mostly affected by herbicide and soil type. Straw may promote physical trapping (∼40% of applied amount), which cannot be accessed by "batch" sorption (∼15% of the applied amount is sorbed), attenuating leaching of highly mobile herbicides in green-cane systems. To properly assess leaching through straw residues under laboratory condition, rainfall distribution is very important.

Comparison of various advanced oxidation processes for the degradation of phenylurea herbicides.

Various types of advanced oxidation processes (AOPs), such as UV photolysis, ozonation, heterogeneous photocatalysis and their combinations were comparatively examined at the same energy input in a home-made reactor. The oxidative transformations of the phenylurea herbicides fenuron, monuron and diuron were investigated. The initial rates of transformation demonstrated that UV photolysis was highly efficient in the cases of diuron and monuron. Ozonation proved to be much more effective in the transformation of fenuron than in those of the chlorine containing monuron and diuron. In heterogeneous photocatalysis, the rate of decomposition decreased with increase of the number of chlorine atoms in the target molecule. Addition of ozone to UV-irradiated solutions and/or TiO2-containing suspensions markedly increased the initial rates of degradation. Dehalogenation of monuron and diuron showed that each of these procedures is suitable for the simultaneous removal of chlorinated pesticides and their chlorinated intermediates. Heterogeneous photocatalysis was found to be effective in the mineralization.

Synthesis and antiviral activity of 1-(1,3-disubstitutedimidazolidyn-2-ylidene)-3-ethoxycarbonylmethylurea derivatives.

Novel 1-(1,3-disubstituted-imidazolidyn-2-ylidene)-3-ethoxycarbonylmethylurea derivatives (3a-3j) were obtained from appropriate 1-aryl-3-arylsulfonyl-1H-imidazolidine-2-imines (1a-1j) and ethyl isocyanatoacetate (2), which were subjected to condensation. Seven compounds were tested for their antiviral activity against HSV-1 and CVB3 viruses. Among the tested compounds, 3c was found to be active against HSV-1, proving that 4-methoxy substituent as R and 4-methyl substituent as R1 are most beneficial for activity against this virus. Furthermore, 3e and 3g were active against CVB3, which demonstrated that both 4-methyl and 4-chloro substitution is tolerated as R1, whereas 4-chloro and 2-methoxy substituents are best as R. It was also shown that the active compounds are characterized by relatively big surface area, small ovality, and greatest HOMO and LUMO energies in comparison to the rest of the compounds.

[Investigation of the Interaction between 1,3-Dimethylurea and Solvent by Raman Methods].

Urea family plays significant role in the bio-science area. Because of the unique frame, they can form Hydrogen bond with water as well as other substance. Hydrogen bonds are normal weak interactions in the system of bio-molecules. A Raman spectrum is the most powerful method to obscure the Hydrogen bond interaction between molecules. Initially, we measure the Raman spectra of DMU crystal, and then use density function theory with a B3LYP/6-311G* * basis set to optimize the geometry structure and calculate the vibrational frequency of gas phase DMU, which assigns the Raman pecks. Then, measure the solvent. When dissolving DMU in water, the interaction between DMU-DMU will replaced by the interaction between water-DMU. The orbital hybridization of nitrogen atoms changes from the solid-state the sp' orbital hybridization to sp3. So, the frame of this molecule goes from in-planet to out of plant during this process.

Phenylurea herbicide sorption to biochars and agricultural soil.

Biochar is increasingly been used as a soil amendment to improve water-holding capacity, reduce nutrient leaching, increase soil pH, and also as a means to reduce contamination through sorption of heavy metals or organic pollutants. The sorption behavior of three phenylurea herbicides (monuron, diuron and linuron) on five biochars (Enhanced Biochar, Hog Waste, Turkey Litter, Walnut Shell and Wood Feedstock) and an agricultural soil (Yolo silt loam) was investigated using a batch equilibration method. Sorption isotherms of herbicides to biochars were well described by the Freundlich model (R(2) = 0.93-0.97). The adsorption KF values ranged from 6.94 to 1306.95 mg kg(-1) and indicated the sorption of herbicides in the biochars and Yolo soil was in the sequence of linuron > diuron > monuron and walnut shell biochar > wood feedstock biochar > turkey litter biochar > enhanced biochar > hog waste biochar > Yolo soil. These data show that sorption of herbicides to biochar can have both positive (reduced off-site transport) and negative (reduced herbicide efficacy) implications and specific biochar properties, such as H/C ratio and surface area, should be considered together with soil type, agriculture chemical and climate condition in biochar application to agricultural soil to optimize the system for both agricultural and environmental benefits.

Transnitrosation of non-mutagenic N-nitrosoproline forms mutagenic N-nitroso-N-methylurea.

N-Nitroso-N-methylurea (NMU) is a potent carcinogen and suspected as a cause of human cancer. In this study, mutagenic NMU was detected by HPLC after the transnitrosation of non-mutagenic N-nitrosoproline (NP) to N-methylurea in the presence of thiourea (TU) under acidic conditions. The structure of NMU was confirmed by comparing (1)H NMR and IR spectra with that of authentic NMU after fractionation by column chromatography. Furthermore, a fraction containing NMU formed by transnitrosation was mutagenic in Salmonella typhimurium TA1535. NMU was formed in the reaction of NP and N-methylurea in the presence of 1,1,3,3-tetramethylthiourea (TTU) or 1,3-dimethylthiourea in place of TU as an accelerator. The reaction rate constants (k) for NMU formation were correlated with their nucleophilicity of sulfur atom in thioureas. The N-methylurea concentration did not affect the NMU formation, whereas the rate of NMU formation correlated linearly with concentrations of NP, TTU and oxonium ion. The observed kinetics suggests a mechanism by which the nitroso group was transferred directly from the protonated NP to the thiourea then to N-methylurea to form NMU. The rate-determining step was the formation of the complex with the protonated NP and thiourea.

Liquid anti-solvent recrystallization to enhance dissolution of CRS 74, a new antiretroviral drug.

This study concerns a new compound named CRS 74 which has the property of inhibiting Human Immunodeficiency Virus (HIV) protease, an essential enzyme involved in HIV replication process. It is proved in this study that the original CRS 74 exhibits poor aqueous solubility and a very low dissolution rate, which can influence its bioavailability and clinical response. In an attempt to improve the dissolution rate, CRS 74 was recrystallized by liquid anti-solvent (LAS) crystallization. Ethanol was chosen as solvent and water as the anti-solvent. Recrystallized solids were compared with the original drug crystals in terms of physical and dissolution properties. Recrystallization without additives did not modify the CRS 74 dissolution profile compared to the original drug. CRS 74 was then recrystallized using different additives to optimize the process and formulate physicochemical properties. Steric stabilizer in organic phase ensured size-controlling effect, whereas electrostatic stabilizer in aqueous phase decreased particle agglomeration. Cationic additives avoided drug adsorption onto stainless steel T-mixer. In general, additive improved drug dissolution rate due to improvement of wetting properties by specific interactions between the drug and the additives, and ensured continuous production of CRS 74 by electrostatic repulsion.

Effects of soil attributes and straw accumulation on the sorption of hexazinone and tebuthiuron in tropical soils cultivated with sugarcane.

Brazil is the largest sugarcane producer in the world in which hexazinone (3-cyclohexyl-6-dimethylamino-1-methyl-1,3,5-triazine-2,4-dione) and tebuthiuron (1-(5-tert-butyl-1,3,4-thiadiazol-2-yl)-1,3-dimethylurea) are heavily used. Sugarcane harvesting is changing from the manual system with previous straw burning to the mechanized system without straw burning. The lack of burning results in soil organic carbon accumulation mainly in clayey soils, which should affect herbicides availability and fate. Therefore, we evaluated sorption of these herbicides in soil samples with and without straw burning. Both herbicides presented low apparent sorption coefficients (mean K(d,app)= 0.6 and 2.4 L kg(-1) for hexazinone and tebuthiuron, respectively), suggesting that they may leach to groundwater. Moreover, their sorption correlated primarily with soil organic carbon (SOC), but iron oxide contents extracted with ammonium oxalate (Fe2O3(AOX)) also affected it (K(d,app) = -0.228 + 0.0397 SOC + 0.117 Fe2O3(AOX) for hexazinone and K(d,app) = -1.407 + 0.201 SOC + 0.348 Fe2O3(AOX) for tebuthiuron). Soil organic carbon accumulation due to straw maintenance in the field positively affected sorption of both herbicides, but its effects were not enough to classify them as "non-leachers."