Synthesis, characterization and redox behaviour of benzoyldiazenido- and oxorhenium complexes bearing N,N- and S,S-type ligands

The reactions of [ReCl2{eta(2)-N2C(O)Ph}(PPh3)(2)](1) with 2-aminopyrimidine (H(2)Npyrm), 2,2'-bipyridine (bpy) and tetraethylthiuram disulfide (tds), in MeOH upon reflux, lead to the new eta(1)-(benzoyldiazenido)-rhenium(III) complexes [ReCl{eta(1)-N2C(O)Ph}(HNpyrm)(PPh3)(2)](2)and [ReCl2{eta(1)-N2C(O)Ph}(bpy)(PPh3)] (3), and the known oxo(diethyldithiocarbamato)dirhenium(v)complex [Re2O2(mu O){Et2NC(S)S}(4)](4), respectively. The Et2NC(S)S ligands in 4 result from S-S bond rupture of tds molecules. The obtained compounds have been characterized by IR, H-1, P-31{H-1} and C-13{H-1} NMR spectroscopies, FAB(+)-MS, elemental and single-crystal X-ray diffraction (for 2 and 4)analyses. Complex 2 represents the first structurally characterized Re compound derived from 2-aminopyrimidine. Besides, the redox behaviour of 2-4 in CH2Cl2 solution has been studied by cyclic voltammetry, and the Lever electrochemical ligand parameter (E-L)has been estimated, for the first time, for HNpyrm. The electrochemical results are discussed in terms of electronic properties of the Re centres and the ligands.

Biochemical and structural characterization of β-lactamases tem-180 and tem-201

With the constant development of new antibiotics, selective pressure is a force to reckon when investigating antibiotic resistance. Although advantageous for medical treatments, it leads to increasing resistance. It is essential to use more potent and toxic antibiotics. Enzymes capable of hydrolyzing antibiotics are among the most common ways of resistance and TEM variants have been detected in several resistant isolates. Due to the rapid evolution of these variants, complex phenotypes have emerged and the need to understand their biological activity becomes crucial. To investigate the biochemical properties of TEM-180 and TEM-201 several computational methodologies have been used, allowing the comprehension of their structure and catalytic activity, which translates into their biological phenotype. In this work we intent to characterize the interface between these proteins and the several antibiotics used as ligands. We performed explicit solvent molecular dynamics (MD) simulations of these complexes and studied a variety of structural and energetic features. The interfacial residues show a distinct behavior when in complex with different antibiotics. Nevertheless, it was possible to identify some common Hot Spots among several complexes – Lys73, Tyr105 and Glu166. The structural changes that occur during the Molecular Dynamic (MD) simulation lead to the conclusion that these variants have an inherent capacity of adapting to the various antibiotics. This capability might be the reason why they can hydrolyze antibiotics that have not been described until now to be degraded by TEM variants. The results obtained with computational and experimental methodologies for the complex with Imipenem have shown that in order to this type of enzymes be able to acylate the antibiotics, they need to be capable to protect the ligand from water molecules.

Chromatographic behaviour of monoclonal antibodies against wild-type amidase from Pseudomonasaeruginosa on immobilized metal chelates

The aim of this work was to devise a one-step purification procedure for monoclonal antibodies (MAbs) of IgG class by immobilized metal affinity chromatography (IMAC). Therefore, several stationary phases were prepared containing immobilized metal chelates in order to study the chromatographic behaviour of MAbs against wild-type amidase from Pseudomonas aeruginosa. Such MAbs adsorbed to Cu(II), Ni(II), Zn(II) and Co(II)-IDA agarose columns. The increase in ligand concentration and the use of longer spacer arms and higher pH values resulted in higher adsorption of MAbs into immobilized metal chelates. The dynamic binding capacity and the maximum binding capacity were 1.33 +/- 0.015 and 3.214 +/- 0.021 mg IgG/mL of sedimented commercial matrix, respectively. A K(D) of 4.53 x 10(-7) M was obtained from batch isotherm measurements. The combination of tailor-made stationary phases of IMAC and the correct selection of adsorption conditions permitted a one-step purification procedure to be devised for MAbs of IgG class. Culture supernatants containing MAbs were purified by IMAC on commercial-Zn(II) and EPI-30-IDA-Zn(II) Sepharose 6B columns and by affinity chromatography on Protein A-Sepharose CL-4B. This MAb preparation revealed on SDS-PAGE two protein bands with M(r) of 50 and 22 kDa corresponding to the heavy and light chains, respectively. Copyright (C) 2011 John Wiley & Sons, Ltd.

Coordination Chemistry of the (eta(6)-p-Cymene)ruthenium(II) Fragment with Bis-, Tris-, andTetrakis(pyrazol-1-yl)borate Ligands: Synthesis, Structural, Electrochemical, and CatalyticDiastereoselective Nitroaldol Reaction Studies

Novel [Ru(eta(6)-p-cymene)(kappa(2)-L)X] and [Ru(eta(6)-p-cymene)(kappa(3)-L)]X center dot nH(2)O complexes (L = bis-, tris-, or tetrakis-pyrazolylborate; X = Cl, N-3, PF6, or CF3SO3) are prepared by treatment of [Ru(eta(6)-p-cymene)Cl-2](2) with poly-(pyrazolyl)borate derivatives [M(L)] (L in general; in detail L = Ph(2)Bp = diphenylbis-(pyrazol-1-yl)borate; L = Tp = hydrotris(pyrazol-1-yl)borate; L = pzTp = tetrakis(pyrazol-1-yl)borate; L = Tp(4Bo) = hydrotris(indazol-1-yl)borate, L = T-p4Bo,T-5Me = (5-methylindazol-1-yl)borate; L = Tp(Bn,4Ph) = hydrotris(3-benzyl-4-phenylpyrazol-1-yl)borate; M = Na, K, or TI) and characterized by analytical and spectral data (IR, ESIMS, H-1 and C-13 NMR). The structures of [Ru(eta(6)-p-cymene)(Ph(2)Bp)Cl] (1) and [Ru(eta(6)-p-cymene)(Tp)Cl] (3) have been established by single-crystal X-ray diffraction analysis. Electrochemical studies allowed comparing the electron-donor characters of Tp and related ligands and estimating the corresponding values of the Lever E-L ligand parameter. The complexes [Ru(eta(6)-p-cymene)-(kappa(2)-L)X] and [Ru(eta(6)-p-cymene)(kappa(3)-L)]X center dot nH(2)O act as catalyst precursors for the diastereoselective nitroaldol reaction of benzaldehyde and nitroethane to the corresponding beta-nitroalkanol (up to 82% yield, at room temperature) with diastereoselectivity toward the formation of the threo isomer.

Copper Bis(oxazoline) Encapsulated in Zeolites and Its Application as Heterogeneous Catalysts for the Cyclopropanation of Styrene

A copper C(2)-symmetric bis(oxazoline), CuBox, was introduced in two forms of commercial Y zeolite: a sodium form (NaY) and an ultrastable form (NaUSY). CuBox was introduced by first partially exchanging the sodium cations of both zeolites for copper and then by refluxing the obtained materials with a solution of bis(oxazoline) (Box). Two different loadings were prepared for each form of zeolite. The materials were characterized by copper ICP-AES, elemental analysis, XPS, FTIR, TG, and nitrogen adsorption isotherms at -196 degrees C. Evidence for Box ligand location in the supercages of NaY and NaUSY zeolites and its coordination to the exchanged copper(II) was obtained by the several techniques used. The materials were all active in the cyclopropanation of styrene with ethyldiazoacetate at room temperature and diastereoselective toward trans cydopropanes. Although the materials containing Box showed low enantioselectivities, their catalytic activities were higher than the parent copper exchanged zeolites, and did not decrease with reuse, at least during three consecutive cycles.

A new cloning system based on the OprI lipoprotein for the production of recombinant bacterial cell wall-derived immunogenic formulations

The conjugation of antigens with ligands of pattern recognition receptors (PRR) is emerging as a promising strategy for the modulation of specific immunity. Here, we describe a new Escherichia coli system for the cloning and expression of heterologous antigens in fusion with the OprI lipoprotein, a TLR ligand from the Pseudomonas aeruginosa outer membrane (OM). Analysis of the OprI expressed by this system reveals a triacylated lipid moiety mainly composed by palmitic acid residues. By offering a tight regulation of expression and allowing for antigen purification by metal affinity chromatography, the new system circumvents the major drawbacks of former versions. In addition, the anchoring of OprI to the OM of the host cell is further explored for the production of novel recombinant bacterial cell wall-derived formulations (OM fragments and OM vesicles) with distinct potential for PRR activation. As an example, the African swine fever virus ORF A104R was cloned and the recombinant antigen was obtained in the three formulations. Overall, our results validate a new system suitable for the production of immunogenic formulations that can be used for the development of experimental vaccines and for studies on the modulation of acquired immunity.

Ruthenium(II) Arene Complexes Bearing Tris(pyrazolyl)methanesulfonate Capping Ligands.Electrochemistry, Spectroscopic, and X-ray Structural Characterization

Novel [Ru(L)(Tpms)]Cl and [Ru(L)(Tpms(Ph))]Cl complexes (L = p-cymene, benzene, or hexamethylbenzene, Tpms = tris(pyrazolyl)-methanesulfonate, Tpms(Ph) = tris(3-phenylpyrazoly)methanesulfonate) have been prepared by reaction of [Ru(L)(mu-Cl)(2)](2) with Li[Tpms] and Li[Tpms(Ph)], respectively. [Ru(p-cymene)(Tpms)]BF4 has been synthesized through a metathetic reaction of [Ru(p-cymene)(Tpms)]Cl with AgBF4. [RuCl(cod)(Tpms)] (cod = 1,5-cyclooctadiene) and [RuCl(cod)(Tpms(Ph))] are also reported, being obtained by reaction of [RuCl2(cod)(MeCN)(2)] with Li[Tpms] and Li[Tpms(Ph)], respectively. The structures of the complexes and the coordination modes of the ligands have been established by IR, NMR, and single-crystal X-ray diffraction (for [RuL(Tpms)]X (L = p-cymene or HMB, X = Cl; L = p-cymene, X = BF4)) studies. Electrochemical studies showed that each complex undergoes a single-electron R-II -> R-III oxidation at a potential measured by cyclic voltammetry, allowing to compare the electron-donor characters of the tris(pyrazolyl)methanesulfonate and arene ligands, and to estimate, for the first time, the values of the Lever E-L ligand parameter for Tmps(Ph), HMB, and cod.

Synthesis, Antimicrobial and Antiproliferative Activity of Novel Silver(I) Tris(pyrazolyl)methanesulfonateand 1,3,5-Triaza-7-phosphadamantane Complexes

Five new silver(I) complexes of formulas [Ag(Tpms)] (1), [Ag(Tpms)-(PPh3)] (2), [Ag(Tpms)(PCy3)] (3), [Ag(PTA)][BF4] (4), and [Ag(Tpms)(PTA)] (5) {Tpms = tris(pyrazol-1-yl)methanesulfonate, PPh3 = triphenylphosphane, PCy3 = tricyclohexylphosphane, PTA = 1,3,5-triaza-7-phosphaadamantane) have been synthesized and fully characterized by elemental analyses, H-1, C-13, and P-31 NMR, electrospray ionization mass spectrometry (ESI-MS), and IR spectroscopic techniques. The single crystal X-ray diffraction study of 3 shows the Tpms ligand acting in the N-3-facially coordinating mode, while in 2 and 5 a N2O-coordination is found, with the SO3 group bonded to silver and a pendant free pyrazolyl ring. Features of the tilting in the coordinated pyrazolyl rings in these cases suggest that this inequivalence is related with the cone angles of the phosphanes. A detailed study of antimycobacterial and antiproliferative properties of all compounds has been carried out. They were screened for their in vitro antimicrobial activities against the standard strains Enterococcus faecalis (ATCC 29922), Staphylococcus aureus (ATCC 25923), Streptococcus pneumoniae (ATCC 49619), Streptococcus pyogenes (SF37), Streptococcus sanguinis (SK36), Streptococcus mutans (UA1S9), Escherichia coli (ATCC 25922), and the fungus Candida albicans (ATCC 24443). Complexes 1-5 have been found to display effective antimicrobial activity against the series of bacteria and fungi, and some of them are potential candidates for antiseptic or disinfectant drugs. Interaction of Ag complexes with deoxyribonucleic acid (DNA) has been studied by fluorescence spectroscopic techniques, using ethidium bromide (EB) as a fluorescence probe of DNA. The decrease in the fluorescence of DNA EB system on addition of Ag complexes shows that the fluorescence quenching of DNA EB complex occurs and compound 3 is particularly active. Complexes 1-5 exhibit pronounced antiproliferative activity against human malignant melanoma (A375) with an activity often higher than that of AgNO3, which has been used as a control, following the same order of activity inhibition on DNA, i.e., 3 > 2 > 1 > 5 > AgNO3 >> 4.

A Hexanuclear Mixed-Valence Oxovanadium(IV,V) Complex as a Highly Efficient Alkane Oxidation Catalyst

The new hexanuclear mixed-valence vanadium complex [V3O3(OEt)(ashz)(2)(mu-OEt)](2) (1) with an N,O-donor ligand is reported. It acts as a highly efficient catalyst toward alkane oxidations by aqueous H2O2. Remarkably, high turnover numbers up to 25000 with product yields of up to 27% (based on alkane) stand for one of the most active systems for such reactions.