Synthesis and hydrolysis of substituted tetrahydropyrimidinium salts. Behaviour of the degradation products on varying pH

Reaction of 1,2-diaryl-3-methyl-1,4,5,6-tetrahydropyrimidinium iodides 1a-i with alkaline solutions afforded N-aroyl-N-aryl-N'-methyltrimethylenediamines 2a-i . Compounds 2 are stable under acid conditions but in neutral or alkaline media spontaneously rearrange giving N-aroyl-N'-aryl-N-methyltrimethylenediamines 3a-i . Treating compounds 3 with concentrated acids reverse reaction takes place. Kinetic studies were performed on this intramolecular N → N' aroyl transfer over the H_o-pH range -0.9 to 2.30. Compounds 3 undergo acyl transfer to give 2 by a mechanism which involves a change in the rate determining step from formation to acid-catalysed decomposition of a six-membered heterocyclic intermediate on going from H_o to pH values. The existence of maxima in the pH rate profile allow to determine apparent pKa values of the hexahydropyrimidine intermediates which gave good correlation with the Swain F substituent constants. Stability of these heterocycles was also predicted by determination of thermodinamic parameters. Comparisons are made with the behaviour of five-membered heterocyclic intermediates (imidazolidine derivatives) which were studied in an earlier paper.     

Potent "clicked" MMP2 inhibitors: synthesis, molecular modeling and biological exploration

A new series of MMP2 inhibitors is described, following a fragment-based drug design approach. One fragment containing an azide group and a well known hydroxamate Zinc Binding Group in a α-sulfone, α-tetrahydropyrane scaffold, has been synthesized. Water-LOGSY, STD and competition-STD experiments indicate that this fragment binds to the active site of the enzyme. A click chemistry reaction was used to connect the azide to lipophilic alkynes selected to interact selectively with the S1' subunit of MMP2, as shown by docking and molecular dynamic experiments of the designed compounds. The most potent compounds 18 and 19 displayed an IC(50) of 1.4 and 0.3 nM against MMP2 respectively, and showed negligible activity towards MMP1 and MMP7, two metalloproteinases which have a shallow S1' subsite. Compound 18 also showed a promising selectivity profile against some antitarget metalloproteinases, such as MMP8, and considerably less activity against MMP14 (IC(50) = 65 nM), and MMP9 (IC(50) = 98 nM), other MMPs characterized by having a deep S1' pocket and, therefore, more similar to MMP2.     

Iron,copper and zinc ammonium-1-hydroxyalkylidene-diphosphonates with zero-, one- and two-dimensional covalent metal–ligand structures extended into three-dimensional supramolecular networks by charge-assisted hydrogen-bonding

Hydrothermal synthesis with MCl₂ (M = Fe, Cu, and Zn) and disodium 5-ammonium-1-hydroxypentylidene-1,1-bisphosphonate, (Na⁺)₂[⁺H₃N(CH₂)₄C(OH)(PO₃²⁻)(PO₃H⁻)] (Na₂HAC₅OHP₂) or sodium 3-ammonium-1-hydroxypropylidene-1,1-bisphosphonate hydrate, Na⁺[⁺H₃N(CH₂)₂C(OH)(PO₃H^–)(PO₃H^–)]·H₂O (NaH₂PAM·H₂O) the sodium salt of pamidronic acid, H₃PAM) yielded the one-dimensional (1D) iron, molecular copper and two-dimensional (2D) zinc compounds 1D-{[Fe(μ₃-η⁵-HAC₅OHP₂)]·H₂O}, 1, [Cu(η²-H₂AC₅OHP₂)₂], 2, 2D-{[Zn₂(μ₅-η⁷-AC₅OHP₂)Cl], 3, and 2D-{[Zn(μ₂-η³-H₂PAM)₂], 4, respectively. The bisphosphonate ligand bridges (μ_n) between 2–5 metal atoms and uses 2–7 oxygen donor atoms towards metal coordination (ηⁿ). The zwitterionic nature of the now bis- or tetrakis-deprotonated ammonium–bisphosphonate is retained in the metal complexes. From the reaction of NiCl₂ and Na₂HAC₅OHP₂ the zwitterionic 5-ammonium-1-hydroxypentylidene-1-phosphonic acid, ⁺H₃N(CH₂)₄CH(OH)PO₃H⁻, 5 was obtained as a product of the ligand P–C bond hydrolysis. Adjacent strands, molecules or layers in 1–4, respectively are organized through the Coulomb attraction between the positive ammonium group and the negative phosphonate groups, supported by hydrogen-bonding. Each protic H atom on the C–OH, NH₃⁺ and –PO₃H⁻ group is involved in charge-assisted hydrogen-bonding. The ammonium-pentylidene groups act as hydrophobic separators between the hydrophilic units with the polar M{C(OH)(PO₃)₂} and {NH₃} units. Bond valence sum calculations support the Fe(II) oxidation state in 1, which was experimentally determined from a quantitative polarographic Fe(II)/Fe(III) speciation analysis as well as a temperature variable magnetic study.     

Fixed-bed adsorption of carbon dioxide/methane mixtures on silicalite pellets

The adsorption of carbon dioxide and methane on silicalite pellets packed on a fixed bed has been studied. Equilibrium and kinetic measurements of the adsorption of carbon dioxide and methane have been performed, and a binary adsorption isotherm for carbon dioxide/methane mixtures has been obtained. A model based on the LDF approximation for the mass transfer has been used to describe the breakthrough curves obtained experimentally. A PSA cycle has been proposed for obtaining methane with purity higher than 98% from carbon dioxide/methane mixtures containing 38% and 50% methane, and its performance has been simulated using the proposed model. The simulation results show that silicalite can be a suitable adsorbent for employment in a PSA separation process for carbon dioxide removal from coalseam and landfill gases.     

Determination of degree of conversion as a function of depth of a photo-initiated dental restoration composite—III application to commercial Prodigy Condensable™

In this third work, we evaluated the degree of conversion (DC) versus depth of dental filling composite named Prodigy Condensable™ using infrared spectroscopy. Confirming previous results, there was a gradual reduction of DC with increasing depth but the composite exhibited extreme values of DC, an upper value (45.9%) on the surface and a lower one (6.1%) at a depth of 5 mm. The composite presented the worst performance among materials studied. The composite formulation was 80% of inorganic fillers and BisfenolA/dimethacrylate (BisGMA) (18%)/triethyleneglycoldimethacrylate (TEGDMA) (2.0%) as monomers. As stated before, type/ratio/viscosity of monomers and type, amount, size and size distribution of fillers all together had an important role in the cure reaction contributing to the final performance of the composite.     

Determination of the amino acid tryptophan and the biogenic amine tryptamine in foods by the heavy atom induced-room temperature phosphorescence methodology

Very simple and selective methods are presented to determine the amino acid tryptophan (Trp) and the biogenic amine tryptamine (Tryp), both compounds with an indole-type molecular structure by the methodology named Heavy Atom Induced-Room Temperature Phosphorescence (HAI-RTP) which constitutes the first time that HAI-RTP has been used to detect compounds with non-naphthalenic structures in their molecules. Different variables affecting the phosphorescence signal (heavy atom perturber and sodium sulfite concentration) were carefully studied. The analytical curves give a linear dynamic range of 15-100 ng ml(-1) and a detection limit of 4 ng ml(-1) for Trp and 94-400 ng ml(-1) and 28 ng ml(-1) for Tryp. The methods have been successfully applied to the analysis of complex food matrices such as the presence of tryptophan in yoghurt and tryptamine in bottled beer. A single alkaline hydrolysis to release Trp from yoghurt proteins and two methods for extracting Tryp from beer samples are proposed and optimised. A total Trp content of 374 mg of Trp per kg of yoghurt was quantified by the standard addition method of calibration and a recovery of 90% was obtained for 250 ng ml(-1) of Tryp in spiked non-alcoholic beer samples.     

Solvent and stereoelectronic effects on the solvolysis rates of oxaspirocyclopropanated 1-norbornyl triflates and related bridgehead derivatives

The study of the stereochemical outcome of the solvolysis of oxaspirocyclopropanated 1-norbornyl triflates is highly interesting since these reactions do not lead to the usual retention or fragmentation products but only synthetically interesting rearranged products are enantiospecifically formed. There is no correlation between the experimental solvolysis rates (ln k) and the B3LYP/6-31G(d)-computed ionization energies (Delta E) of the corresponding bridgehead hydrocarbons in gas phase. However, this work demonstrates the existence of a fair linear correlation between the experimental reaction rates and the PCM//B3LYP/6-31G(d)-computed free ionization energies in solution (Delta G). This theoretically relevant result reveals that the reason for the lack of linearity in gas phase is not the rearrangement of the intermediate carbocations but unspecific solvent effects on the solvolysis rates, accounted for by the PCM model.     

Synthetic nanocrystalline diamond as a third-generation biosensor support

Horseradish peroxidase (HRP) has been immobilized on the surface of functionalized nanocrystalline diamond (NCD) thin films. The structure of the modified NCD surface as well as the electrochemical behavior of the whole system was characterized by impedance spectroscopy and cyclic voltammetry. The proximity of HRP heme groups to the NCD surface allowed direct electron transfer between them, resulting in two separated one-electron-transfer peaks at 0.05 V and 0.29 V vs Ag/AgCl, corresponding to the cathodic and anodic process, respectively. The heterogeneous electron-transfer constant for both processes was calculated to be 0.066 s(-1), the charge-transfer coefficient alpha = 0.49, and the immobilized enzymatic layer about 2.10(-10) mol/cm2. The modified NCD electrode was used as a third-generation biosensor for hydrogen peroxide determination showing a linear response in the 0.1-45 mM H2O2 range, at +0.05 V vs Ag/AgCl.     

Quantitative determination of alpha(s2)- and alpha(s1)-casein in goat's milk with different genotypes by capillary electrophoresis

A capillary electrophoresis (CE) method has been applied for the quantitative determination of alpha(s1)- and alpha(s2)-CN in goat's milk. Several analytical parameters were evaluated showing the reliability of this CE method. Coefficients of determination (R2) greater than 99% were obtained and determination limits of 1.23 and 0.98 mg/ml were achieved for alpha(s1)- and alpha(s2)-CN, respectively. The analytical parameters studied in terms of accuracy, precision and recovery were within acceptable limits. Among 18 samples of 4 different genotypes (BB, EE, BF and FF) for alpha(s1)-CN were analysed, different amounts were obtained from the genotypes.     

Determination of polycyclic aromatic hydrocarbons in honey by matrix solid-phase dispersion and gas chromatography/mass spectrometry

A multiresidue method was developed for the de termination of 16 polycyclic aromatic hydrocarbons (PAHs) in unifloral and multifloral honeys. The analytical procedure is based on the matrix solid-phase dispersion of honey on a mixture of Florisil and anhydrous sodium sulfate in small glass columns and extraction with hexane-ethyl acetate (90 + 10, v/v) with assisted sonication. The PAH residues are determined by gas chromatography with mass spectrometric detection using selected-ion monitoring. Average recoveries for all the PAHs studied were in the range of almost 80 to 101%, with relative standard deviations of 6 to 15%. The limits of detection ranged from 0.04 to 2.9 microg/kg. The simultaneous extraction and cleanup of samples makes this method simple and rapid, with low consumption of organic solvents