Synthesis of Triazole-Containing Furanosyl Nucleoside Analogues and Their Phosphate, Phosphoramidate or Phoshonate Derivatives as Potential Sugar Diphosphate or Nucleotide Mimetics.

The synthesis of stable and potentially bioactive xylofuranosyl nucleoside analogues and potential sugar diphosphate or nucleotide mimetics comprising a 1,2,3-triazole moiety is reported. 3'-O-Methyl-branched N-benzyltriazole isonucleosides were accessed in 5-7 steps and 42-54 % overall yields using a Cu(I)-catalyzed cycloaddition of 3-O-propargyl-1,2-O-isopropylidene-α-D-xylofuranose with benzyl azide as key step. Related isonucleotides were obtained by 5-O-phosphorylation of acetonide-protected 3-O-propargyl xylofuranose and further "click" cycloaddition or by Staudinger-phosphite reaction of a 5-azido N-benzyltriazole isonucleoside. Hydroxy-, amino- or bromomethyl triazole 5'-isonucleosides were synthesized by thermal cycloaddition of 5-azido 3-O-benzyl/dodecyl xylofuranoses with propargyl alcohol, propargylamine or propargyl bromide. Better yields (82-85 %) were obtained when using propargyl alcohol and a high 1,4-regioselectivity was attained with propargyl bromide. Further O/N-phosphorylation or Arbuzov reaction led to (triazolyl)methyl phosphates, phosphoramidates or phosphonates. The latter were converted into uracil nucleoside 5'-(triazolyl)methyl phosphonates as prospective nucleoside diphosphate mimetics.

A comparative study on emergent pollutants photo-assisted degradation using ruthenium modified titanate nanotubes and nanowires as catalysts.

Several methods have been used to tailor nanomaterials structure and properties. Sometimes, slight changes in the structure outcomes expressive improvements in the optical and photocatalytic properties of semiconductor nanoparticles. In this context, the influence of the metal doping and the morphology on a catalyst performance was studied in this work. Here, ruthenium doped titanate nanotubes (RuTNT) were synthesised for the first time using an amorphous Ru-containing precursor. Afterwards, the photocatalytic performance of this sample was compared to the one obtained for ruthenium titanate nanowires (RuTNW), recently reported. Two samples, RuTNW and RuTNT, were produced using the same Ru-containing precursor but distinct hydrothermal methodologies. The powders were structural, morphological and optical characterized by X-ray diffraction and fluorescence, transmission electron microscopy, Raman, X-ray photoelectron and photoluminescence spectroscopies. Distinct variations on the structural and optical properties of the RuTNT and RuTNW nanoparticles, due to ruthenium incorporation were observed. Their potential use as photocatalysts was evaluated on the hydroxyl radical photo-assisted production. Both samples were catalytic for this reaction, presenting better performances than the pristine counterparts, being RuTNT the best photocatalyst. Subsequently, the degradation of two emergent pollutants, caffeine and sulfamethazine, was studied. RuTNT demonstrated to be better photocatalyst than RuTNW for caffeine but identical performances were obtained for sulfamethazine. For both catalysts, the degradation mechanism of the pollutants was explored through the identification and quantification of the intermediate compounds produced and several differences were found. This indicates the importance of the structural and morphological aspects of a material on its catalytic performance.

Impact of Fe, Mn co-doping in titanate nanowires photocatalytic performance for emergent organic pollutants removal.

The unexpected incorporation of ionic Mn and Fe in the crystalline structure of titanate nanowires was accomplished when a contaminated a titanium source was used. The presence of Mn (8.1 mg L-1) and Fe (4.3 mg L-1) result in the production of a novel co-doped (Fe,Mn) titanate nanowires (TNW) material with improved optical and photocatalytic properties. After structural characterization, the results indicate that both Mn and Fe were incorporated in the TNW structure by replacement of Na+ in the interlayers, together with Ti4+ substitution in the TiO6 octahedra. The potential of this new material to be used for pollutants photocatalytic degradation was further investigated. The terephthalic acid was used as probe molecule to first evaluate the catalytic ability of the pristine and FeMnTNW modified powders for the photo-assisted hydroxyl radical formation. Afterwards, the degradation process of a model emergent pollutant, caffeine, was studied. The results showed that FeMnTNW was the best photocatalyst, with the complete caffeine removal (20 mg L-1) within 60 min of radiation (13 mg catalyst/L solution). The action of several oxidant species, including h+, OH• and O2•-, during caffeine removal was carefully analyzed using specific radical scavengers. A mechanism for the charge-transfer in irradiated FeMnTNW particles, including the possibility of a photo-Fenton and photodegradation combination process, is proposed and discussed.

Bioactive Silver-Organic Networks Assembled from 1,3,5-Triaza-7-phosphaadamantane and Flexible Cyclohexanecarboxylate Blocks.

Three novel bioactive silver-organic networks, namely, the 2D polymer [Ag(µ3-PTA)(chc)]n·n(Hchc)·2nH2O (1), the 3D bioMOF [Ag2(µ3-PTA)2(µ2-chdc)]n·5nH2O (2), and the 2D polymer [Ag2(µ2-PTA)2(µ4-H2chtc)]n·6nH2O (3), were constructed from 1,3,5-triaza-7-phosphaadamantane (PTA) and various flexible cyclohexanecarboxylic acids as building blocks {cyclohexanecarboxylic (Hchc), 1,4-cyclohexanedicarboxylic (H2chdc), and 1,2,4,5-cyclohexanetetracarboxylic (H4chtc) acid, respectively}. The obtained products 1-3 were fully characterized by IR and NMR spectroscopy, ESI-MS(±) spectrometry, elemental and thermogravimetric (TGA) analyses, and single-crystal and powder X-ray diffraction. Their structural diversity originates from distinct coordination modes of cyclohexanecarboxylate moieties as well as from the presence of unconventional N,N,P-tridentate or N,P-bidentate PTA spacers. Topological classification of underlying metal-organic networks was performed, disclosing the hcb, 4,4L28, and a rare fsc-3,4-Pbcn-3 topology in 1, 2, and 3, respectively. Moreover, combination of aqueous solubility (S25°C ≈ 4-6 mg mL(-1)), air stability, and appropriate coordination environments around silver centers favors a release of bioactive Ag(+) ions by 1-3, which thus act as potent antibacterial and antifungal agents against Gram-positive (S. aureus) and Gram-negative (E. coli and P. aeruginosa) bacteria as well as a yeast (C. albicans). The best normalized minimum inhibitory concentrations (normalized MIC) of 10-18 (for bacterial strains) or 57 nmol mL(-1) (for a yeast strain) were achieved. Detailed ESI-MS studies were performed, confirming the relative stability of 1-3 in solution and giving additional insight on the self-assembly formation of polycarboxylate Ag-PTA derivatives and their crystal growth process.

Synthesis and hydrolysis of gas-phase lanthanide and actinide oxide nitrate complexes: a correspondence to trivalent metal ion redox potentials and ionization energies.

Several lanthanide and actinide tetranitrate ions, M(III)(NO3)4(-), were produced by electrospray ionization and subjected to collision induced dissociation in quadrupole ion trap mass spectrometers. The nature of the MO(NO3)3(-) products that result from NO2 elimination was evaluated by measuring the relative hydrolysis rates under thermalized conditions. Based on the experimental results it is inferred that the hydrolysis rates relate to the intrinsic stability of the M(IV) oxidation states, which correlate with both the solution IV/III reduction potentials and the fourth ionization energies. Density functional theory computations of the energetics of hydrolysis and atoms-in-molecules bonding analysis of representative oxide and hydroxide nitrates substantiate the interpretations. The results allow differentiation between those MO(NO3)3(-) that comprise an O(2-) ligand with oxidation to M(IV) and those that comprise a radical O(-) ligand with retention of the M(III) oxidation state. In the particular cases of MO(NO3)3(-) for M = Pr, Nd and Tb it is proposed that the oxidation states are intermediate between M(III) and M(IV).

Monitoring abacavir bioactivation in humans: screening for an aldehyde metabolite.

The anti-HIV drug abacavir is associated with idiosyncratic hypersensitivity reactions and cardiotoxicity. Although the mechanism underlying abacavir-toxicity is not fully understood, drug bioactivation to reactive metabolites may be involved. This work was aimed at identifying abacavir-protein adducts in the hemoglobin of HIV patients as biomarkers of abacavir bioactivation and protein modification. The protocol received prior approval from the Hospital Ethics Committee, patients gave their written informed consent and adherence was controlled through a questionnaire. Abacavir-derived Edman adducts with the N-terminal valine of hemoglobin were analyzed by an established liquid chromatography-electrospray ionization-tandem mass spectrometry method. Abacavir-valine adducts were detected in three out of ten patients. This work represents the first evidence of abacavir-protein adduct formation in humans. The data confirm the ability of abacavir to modify self-proteins and suggest that the molecular mechanism(s) of some abacavir-induced adverse reactions may require bioactivation.

Titanium(III) trisamidotriazacyclononane: reactions with C60 and radicals.

The reaction of titanium trisamidotriazacyclononane, [Ti{N(Ph)SiMe2}3tacn] (1), with C60 led to the synthesis of [Ti{N(Ph)SiMe2}3tacn]C60 (2) in high yield. Treatment of 2 with PhCH2Br led to the formation of [Ti{N(Ph)SiMe2}3tacn]Br and the radical PhCH2C60 (3). The reaction of CH3I with 1 gives two products. One is [Ti{N(Ph)SiMe2}3tacn]I (4), which results from the oxidation of 1 by an I radical. The other product, 5, resulting from a multistep reaction scheme that involves redox and nucleophilic reactions, presents an imido ligand formed by ligand rearrangement upon C-N bond cleavage. In solution, an exchange process that corresponds to a reversible 1,3-silyl shift between two Ti-bonded N atoms leads to isomers 5a and 5b. This equilibrium transforms an imido (TiNPh) into an amido ligand (Ti{NPh}SiMe2CH2Ph) with concomitant generation of an anionic moiety in the originally neutral triazacyclononane ring. In solution, either 5a or 5b displays additional fluxional processes that consist of its corresponding racemization processes.