Time-resolved spectroscopy of the metal-to-metal charge transfer excited state in dinuclear cyano-bridged mixed-valence complexes

Visible pump-probe spectroscopy has been used to identify and characterize short-lived metal-to-metal charge transfer (MMCT) excited states in a group of cyano-bridged mixed-valence complexes of the formula [(LCoNCMII)-N-III(CN)(5)](-), where L is a pentadentate macrocyclic pentaamine (L-14) or triamine-dithiaether (L-14S) and M is Fe or Ru. Nanosecond pump-probe spectroscopy on frozen solutions of [(LCoNCFeII)-Co-14-N-III(CN)(5)](-) and [(LCoNCFeII)-Co-14S-N-III(CN)(5)](-) at 11 K enabled the construction of difference transient absorption spectra that featured a rise in absorbance in the region of 350-400 nm consistent with the generation of the ferricyanide chromophore of the photoexcited complex. The MMCT excited state of the Ru analogue [(LCoNCRuII)-Co-14-N-III(CN)(5)](-) was too short-lived to allow its detection. Femtosecond pump-probe spectroscopy on aqueous solutions of [(LCoNCFeII)-Co-14-N-III(CN)(5)](-) and [(LCoNCFeII)-Co-14S-N-III(CN)(5)](-) at room temperature enabled the lifetimes of their Co-II-Fe-III MMCT excited states to be determined as 0.8 and 1.3 ps, respectively.

Diphenyltin(IV) complexes of the 2-quinolinecarboxaldehyde Schiff bases of S-methyl- and S-benzyldithiocarbazate (Hqaldsme and Hqaldsbz): X-ray crystal structures of Hqaldsme and two conformers of its diphenyltin(IV) complex

New organometallic tin(IV) complexes of the empirical formula Sn(NNS)Ph2Cl (NNS = anionic forms of the 2-quinolinecarboxaldehyde Schiff bases of S-methyl- and S-benzyldithiocarbazate) have been prepared and characterized by IR, electronic, I H NMR and ES mass spectroscopic techniques. The molecular structures of the 2-quinolinecarboxaldehyde Schiff base of S-methyldithiocarbazate (Hqaldsme) and its diphenyltin(IV) complex, Sn(qaldsme)Ph2Cl, have been determined by X-ray diffraction. In the solid state, the ligand remains as the thione tautomer in which the dithiocarbazate chain adopts an E,E configuration and is almost coplanar with the quinoline ring. The Sn(qaldsme)Ph2Cl complex crystallizes in two distinctly different conformationally isomeric forms, each having the same space group but different lattice parameters. X-ray analysis shows that in each polymorph, the tin atom adopts a distorted octahedral geometry with the Schiff base coordinated to it as a uninegatively charged tridentate chelating agent via the quinoline nitrogen atom, the azomethine nitrogen atom and the thiolate sulfur atom. The two phenyl groups occupy axial positions and the chloride ligand occupies the sixth coordination position of the tin atom. The deprotonated ligand adopts an E,E,Z configuration in the complex. (C) 2004 Elsevier Ltd. All rights reserved.

Complexes of cytotoxic chelators from the dipyridyl ketone isonicotinoyl hydrazone (HPKIH) analogues

In an effort to better understand the antiproliferative effects of the tridentate hydrazone chelators di-2-pyridyl ketone isonicotinoyl hydrazone (HPKIH) and di-2-pyridyl ketone benzoyl hydrazone (HPKBH), we report the coordination chemistry of these ligands with the divalent metal ions, Mn, Co, Ni, Cu, and Zn. These complexes are compared with their Fe-II analogues which were reported previously. The crystal structures of Co(PKIH)(2), Ni(PKIH)(2), Cu(PKIH)(2), Mn(PKBH)(2), Ni(PKBH)(2), Cu(PKBH)(2), and Zn(PKBH)(2) are reported where similar bis-tridenate coordination modes of the ligands are defined. In pure DMF, all complexes except the Zn-II compounds exhibit metal-centered M-III/II (Mn, Fe, Co, Ni) or M-II/I (Cu) redox processes. All complexes show ligand-centered reductions at low potential. Electrochemistry in a mixed water/DMF solvent only elicited metal-centered responses from the Co and Fe complexes. Remarkably, all complexes show antiproliferative activity against the SK-N-MC neuroepithelioma cell line similar to (HPKIH) or significantly greater than that of the (HPKBH) ligand which suggests a mechanism that does not only involve the redox activity of these complexes. In fact, we suggest that the complexes act as lipophilic transport shuttles that allow entrance to the cell and enable the delivery of both the ligand and metal which act in concert to inhibit proliferation.

Prediction of HLA-DQ3.2 beta ligands: evidence of multiple registers in class II binding peptides

Motivation: While processing of MHC class II antigens for presentation to helper T-cells is essential for normal immune response, it is also implicated in the pathogenesis of autoimmune disorders and hypersensitivity reactions. Sequence-based computational techniques for predicting HLA-DQ binding peptides have encountered limited success, with few prediction techniques developed using three-dimensional models. Methods: We describe a structure-based prediction model for modeling peptide-DQ3.2 beta complexes. We have developed a rapid and accurate protocol for docking candidate peptides into the DQ3.2 beta receptor and a scoring function to discriminate binders from the background. The scoring function was rigorously trained, tested and validated using experimentally verified DQ3.2 beta binding and non-binding peptides obtained from biochemical and functional studies. Results: Our model predicts DQ3.2 beta binding peptides with high accuracy [area under the receiver operating characteristic (ROC) curve A(ROC) > 0.90], compared with experimental data. We investigated the binding patterns of DQ3.2 beta peptides and illustrate that several registers exist within a candidate binding peptide. Further analysis reveals that peptides with multiple registers occur predominantly for high-affinity binders.

Spectroscopic characterization of copper(II) binding to the immunosuppressive drug mycophenolic acid

Mycophenolic acid (MPA) is a drug that has found widespread use as an immunosuppressive agent which limits rejection of transplanted organs. Optimal use of this drug is hampered by gastrointestinal side effects which can range in severity. One mechanism by which MPA causes gastropathy may involve a direct interaction between the drug and gastric phospholipids. To combat this interaction we have investigated the potential of MPA to coordinate Cu(II), a metal which has been used to inhibit gastropathy associated with use of the NSAID indomethacin. Using a range of spectroscopic techniques we show that Cu(II) is coordinated to two MPA molecules via carboxylates and, at low pH, water ligands. The copper complex formed is stable in solution as assessed by mass spectrometry and H-1 NMR diffusion experiments. Competition studies with glycine and albumin indicate that the copper-MPA complex will release Cu(II) to amino acids and proteins thereby allowing free MPA to be transported to its site of action. Transfer to serum albumin proceeds via a Cu(MPA)(albumin) ternary complex. These results raise the possibility that copper complexes of MPA may be useful in a therapeutic situation.

Transition metal complexes as mediator-titrants in protein redox potentiometry

A selection of nine macrocyclic Fe-III/II and Co-III/II transition metal complexes has been chosen to serve as a universal set of mediator-titrants in redox potentiometry of protein samples. The potential range spanned by these mediators is approximately from +300 to -700 mV vs the normal hydrogen electrode, which covers the range of most protein redox potentials accessible in aqueous solution. The complexes employed exhibit stability in both their oxidized and their reduced forms as well as pH-independent redox potentials within the range 6 < pH < 9. The mediators were also chosen on the basis of their very weak visible absorption maxima in both oxidation states, which will enable (for the first time) optical redox potentiometric titrations of proteins with relatively low extinction coefficients. This has previously been impractical with organic mediators, such as indoles, viologens and quinones, whose optical spectra interfere strongly with those of the protein.

Cobalt complexes of tripodal hexadentate ligands: Electrochemically driven rearrangements

The Co-III complexes of the hexadentate tripodal ligands HOsen (3-(2'-aminoethylamino)-2,2-bis((2 ''-aminoethylamino) methyl) propan-1-ol) and HOten (3-(2'-aminoethylthia)-2,2-bis((2 ''-aminoethylthia) methyl) propan-1-ol) have been synthesized and fully characterized. The crystal structures of [Co(HOsen)]Cl-3 center dot H2O and [Co(HOten)](ClO4)Cl-2 are reported and in both cases the ligands coordinate as tripodal hexadentate N-6 and N3S3 donors, respectively. Cyclic voltammetry of the N3S3 coordinated complex [Co(HOten)](3+) is complicated and electrode dependent. On a Pt working electrode an irreversible Co-III/II couple ( formal potential - 157 mV versus Ag-AgCl) is seen, which is indicative of dissociation of the divalent complex formed at the electrode. The free HOten released by the dissociation of [Co(HOten)](2+) can be recaptured by Hg as shown by cyclic voltammetry experiments on a static Hg drop electrode ( or in the presence of Hg2+ ions), which leads to the formation of an electroactive Hg-II complex of the N3S3 ligand (formal potential + 60 mV versus Ag-AgCl). This behaviour is in contrast to the facile and totally reversible voltammetry of the hexaamine complex [Co(HOsen)](3+) ( formal potential (Co-III/II) - 519 mV versus Ag-AgCl), which is uncomplicated by any coupled chemical reactions. Akinetic and thermodynamic analysis of the [Co(HOten)](2+)/[Hg(HOten)](2+) system is presented on the basis of digital simulation of the experimental voltammetric data.

Arthritic disease suppression and cartilage protection with glycosaminoglycan polypeptide complexes (Peptacans) derived from the cartilage extracellular matrix: A novel approach to therapy

Molecular fragments of cartilage are antigenic and can stimulate an autoimmune response. Oral administration of type II collagen prevents disease onset in animal models of arthritis but the effects of other matrix components have not been reported. We evaluated glycosaminoglycan polypeptides (GAG-P) and matrix proteins (CaP) from cartilage for a) mitigating disease activity in rats with collagen-induced arthritis (CIA) and adjuvant-induced arthritis (AIA) and b) stimulating proteoglycan (PG) synthesis by chondrocytes in-vitro. CIA and AIA were established in Wistar rats using standard methods. Agents were administered orally (10–200 mg/kg), either for seven days prior to disease induction (toleragenic protocol), or continuously for 15 days after injecting the arthritigen (prophylactic protocol). Joint swelling and arthritis scores were determined on day 15. Histological sections of joint tissues were assessed post-necropsy. In chondrocyte cultures, CaP + / − interleukin-1 stimulated PG biosynthesis. CaP was also active in preventing arthritis onset at 3.3, 10 or 20 mg/kg in the rat CIA model using the toleragenic protocol. It was only active at 20 and 200 mg/kg in the CIA prophylactic protocol. GAG-P was active in the CIA toleragenic protocol at 20 mg/kg but chondroitin sulfate and glucosamine hydrochloride or glucosamine sulfate were all inactive. The efficacy of CaP in the rat AIA model was less than in the CIA model. These findings lead us to suggest that oral CaP could be used as a disease-modifying anti-arthritic drug.

Peptide binding prediction for the human class II MHC allele HLA-DP2:a molecular docking approach

MHC class II proteins bind oligopeptide fragments derived from proteolysis of pathogen antigens, presenting them at the cell surface for recognition by CD4+ T cells. Human MHC class II alleles are grouped into three loci: HLA-DP, HLA-DQ and HLA-DR. In contrast to HLA-DR and HLA-DQ, HLA-DP proteins have not been studied extensively, as they have been viewed as less important in immune responses than DRs and DQs. However, it is now known that HLA-DP alleles are associated with many autoimmune diseases. Quite recently, the X-ray structure of the HLA-DP2 molecule (DPA*0103, DPB1*0201) in complex with a self-peptide derived from the HLA-DR a-chain has been determined. In the present study, we applied a validated molecular docking protocol to a library of 247 modelled peptide-DP2 complexes, seeking to assess the contribution made by each of the 20 naturally occurred amino acids at each of the nine binding core peptide positions and the four flanking residues (two on both sides).

Organotellurium compounds for metal organic vapour phase epitaxy

The infra-red detector material cadmium mercury telluride can be grown by the technique of Metal Organic Vapour Phase Epitaxy using simple alkyl telluride compounds as the source of tellurium. New tellurium precursors are required in order to overcome handling and toxicity problems and to reduce the growth temperature in preparing the material. A range of diaryltellurium(IV) dicarboxylates and some 2-(2'-pyridyl)phenyl-tellurium(II) and tellurium(IV) monocarboxylates have been synthesised and characterised by infra-red, 13C N.M.R. and mass spectroscopy. Infra-red spectroscopy has been used to determine the mode of bonding of the carboxylate ligand to tellurium. Synthetic methods have been devised for the preparation of diorganotritellurides (R2Te3) and mixed diorganotetrachalcogenides (RTeSeSeTeR). A mechanism for the formation of the tritellurides based on aerobic conditions is proposed. The reaction of ArTe- with (ClCH2CH2)3N leads to tripod-like multidentate ligands (ArTeCH2CH2)3N which form complexes with the ions Hg(II), Cd(II), Cu(I), Pt(II) and Pd(II). Synthetic routes to aryltelluroalkylamines and arylselenoalkylamines are also reported. The crystal structure of 2-(2'-pyridyl)phenyltellurium(II) bromide has been solved in which there are six molecules present within the unit cell. There are no close intermolecular Te---Te interactions and the molecules are stabilised by short Te---N intramolecular contacts. The crystal structure of 2-(2'-pyridyl)phenylselenium(II)-tribromomercurate(II) is also presented. A study of the Raman vibrational spectra of some tellurated azobenzenes and 2-phenylpyridines shows spectra of remarkably far superior quality to those obtained using infra-red spectroscopy.

Gold mineralisation in the Caledonides of the British Isles with special reference to the Dolgellau Gold-belt, North Wales and the Southern Uplands, Scotland. Available in 2 volumes.

Two aspects of gold mineralisation in the Caledonides of the British Isles have been investigated: gold-telluride mineralisation at Clogau Mine, North Wales; and placer gold mineralisation in the Southern Uplands, Scotland. The primary ore assemblage at Clogau Mine is pyrite, arsenopyrite, cobaltite, pyrrhotine, chalcopyrite, galena, tellurbismuth, tetradymite, altaite, hessite, native gold, wehrlite, hedleyite, native bismuth, bismuthunite and various sulphosalts. The generalised paragenesis is early Fe, Co, Cu, As and S species, and later minerals of Pb, Bi, Ag, Au, Te, Sb. Electron probe micro-analysis (EPMA) of complex telluride-sulphide intergrowths suggests that these intergrowths formed by co-crystallisation/replacement processes and not exsolution. Minor element chemical variation, in the sulphides and tellurides, indicates that antimony and cadmium are preferentially partitioned into telluride minerals. Mineral stability diagrams suggest that during gold deposition log bf aTe2 was between -7.9 and -9.7 and log bf aS2 between -12.4 and -13.8. Co-existing mineral assemblages indicate that the final stages of telluride mineralisation were between c. 250 - 275oC. It is suggested that the high-grade telluride ore shoot was the result of remobilisation of Au, Bi, Ag and Te from low grade mineralisation elsewhere within the vein system, and that gold deposition was brought about by destabilisation of gold chloride complexes by interaction with graphite, sulphides and tellurbismuth. Scanning electron microscopy of planer gold grains from the Southern Uplands, Scotland, indicates that detailed studies on the morphology of placer gold can be used to elucidate the history of gold in the placer environment. In total 18 different morphological characteristics were identified. These were divided on an empirical basis, using the relative degree of mechanical attrition, into proximal and distal characteristics. One morphological characteristic (a porous/spongy surface at high magnification) is considered to be chemical in origin and represent the growth of `new' gold in the placer environment. The geographical distribution of morphological characteristics has been examined and suggests that proximal placer gold is spatially associated with the Loch Doon, Cairsphairn and Fleet granitoids. Quantitative EPMA of the placer gold reveals two compositional populations of placer gold. Examination of the geographical distribution of fineness suggests a loose spatial association between granitoids and low fineness placer gold. Also identified was chemically heterogeneous placer gold. EPMA studies of these heterogeneities allowed estimation of annealing history limits, which suggest that the heterogeneities formed between 150 and 235oC. It is concluded, on the basis of relationships between morphology and composition, that there are two types of placer gold in the Southern Uplands: (i) placer gold which is directly inherited from a hypogene source probably spatially associated with granitoids; and (ii) placer gold that has formed during supergene processes.

Synthesis and magnetic properties of Fe-Mn-Cr multinuclear complexes with 4-amino-1,2,4-triazole and oxalate ligands

A multinuclear Fe-Mn-Cr complex with 4-amino-1,2,4-triazole (NH2trz) and oxalate (ox) ligands has been synthesized successfully. The formula of the [Fe(NH2trz)3][ClO4][MnCr(ox)3].4H2O complex has been obtained based on the metal and C, H, N contents. The presence of water molecules, metal-ligand bonding and bridge ligand in the multinuclear complex has been confirmed by its infrared spectrum. The compound crystallizes in the hexagonal system with cell parameters of a = b = 18.695 Å and c = 57.351 Å. The compound shows a gradual spin crossover for iron(II) in the [Fe(NH2trz)3]2+ with transition temperature (T1/2) of 205 K. The antiferromagnetic interaction between Cr(III) and Mn(II) ions in the [MnCr(ox)3]n n- network is observed from the Weiss constant (θ) of –2.3 K.

Covalent attachment of chiral manganese(III) salen complexes onto functionalised hexagonal mesoporous silica and application to the asymmetric epoxidation of alkenes

Two modified Jacobsen-type catalysts were anchored onto an amine functionalised hexagonal mesoporous silica (HMS) using two distinct anchoring procedures: (i) one was anchored directly through the carboxylic acid functionalised diimine bridge fragment of the complex (CAT1) and (ii) the other through the hydroxyl group on the aldehyde fragment of the complex (CAT2), mediated by cyanuric chloride. The new heterogeneous catalyst, as well as the precedent materials, were characterised by elemental analyses, DRIFT, UV-vis, porosimetry and XPS which showed that the complexes were successfully anchored onto the hexagonal mesoporous silica. These materials acted as active heterogeneous catalysts in the epoxidation of styrene, using m-CPBA as oxidant, and α-methylstyrene, using NaOCl as oxidant. Under the latter conditions they acted also as enantioselective heterogeneous catalysts. Furthermore, when compared to the reaction run in homogeneous phase under similar experimental conditions, an increase in asymmetric induction was observed for the heterogenised CAT1, while the opposite effect was observed for the heterogenised CAT2, despite of CAT2 being more enantioselective than CAT1 in homogeneous phase. These results indicate that the covalent attachment of the Jacobsen catalyst through the diimine bridge leads to improved enantiomeric excess (%ee), whereas covalent attachment through one of the aldehyde fragments results in a negative effect in the %ee. Using α-methylstyrene and NaOCl as oxidant, heterogeneous catalyst reuse led to no significant loss of catalytic activity and enantioselectivity. © 2005 Elsevier Inc. All rights reserved.

The antioxidant potential of modified quercetins and quercetin-metal complexes

Quercetin is a naturally occurring polyphenol compound present in grapes, red wine, tea, apples and some vegetables. Like other flavonoids, it has been found to have antioxidant activity in studies in vitro, although there is still much debate about the bioavailability of flavonoids in the diet and their in vivo antioxidant activity. In general, it is thought that the antioxidant efficiency of polyphenols increases with increasing hydroxylation of the rings, but there have been few studies of other substitutions. We have prepared several derivatives of quercetin, to test the effect of modification on their antioxidant potential. Sodium salts of quercetin-5-sulfonate and quercetin-5,8-sulfonate, and transition metal complexes of quercetin-5-sulfonate were analysed for their total antioxidant potential using the FRAP assay, and compared to unmodified quercetin. It was found that quercetin-5-sulfonate complexes with Zn, Cu(II), Fe(II) and Mg were all significantly better antioxidants than quercetin, quercetin-5-sulfonate was comparable to quercetin, whereas the sodium salt of quercetin-5,8-sulfonate had a decreased total antioxidant potential. Kinetic studies of the FRAP reaction showed no significant differences between quercitin and any of the derivatives. The reaction of all the quercetins in the FRAP assay was found to be slower to reach completion than ascorbate, and appeared to have biphasic characteristics. These results suggest that transition metal ions may facilitate the transfer of electrons from the polyphenol ring system to the oxidant, while substitution with S03 is electron-withdrawing and destabilizes the ring system. This is important both for understanding the antioxidant ability of flavonoids, and for the design of novel antioxidant compounds. Further work is being carried out to assess the ability of the quercetin complexes to protect cultured cells from oxidative stress.

Alquilação de tolueno com propeno, através de complexo ferro (II) ᵦ- diimina homogêneo e heterogeneizado em MCM-41, Al-MCM-41 e SBA-15

This work describes the synthesis and aplication of homogeneous and heterogenized iron catalysts in the alkylation reaction of toluene with propene, empolying experimental design. The homogenous complex was obtained trough the synthesis of the organic ligand folowed by the complexation of the iron(II) chloride. As to the heterogenized complexes, first were synthetized the inorganic supports (SBA-15, MCM-41 and Al-MCM-41). Then, it was synthetized the ligand again, that through funcionalization with chloropropyltrimethoxysilane (CPTMS), was anchored on the support previously calcinated. To these anchored ligands, was complexed the iron(II) chloride, previously solubilizated in tetrahydrofuran (THF). The organic ligand characterization was accomplished trough nuclear magnetic resonance (NMR) and Infrared spectroscopy (IV). The supports were characterized with x-ray diffraction (DRX), texture analysis with nitrogen adsorption/desorption (before and after the anchoring), termogravimetric analysis (TG) and infrared (IV). The metalic content was quantified trough the atomic absorption spectrophotometry (AAS). The complexes were tested in catalytic reactions emolying ethylaluminium sesquichloride (EASC) as co-catalyst in steel reactor, under mecanic stirring. The reaction conditions ranged from 4 to 36 ◦C, with many aluminum/iron ratios. The catalysts were actives in homogeneous and heterogenized ways. The homogenous catalytic complex showed a maximum turnover frequency (TOF) of 8.63 ×103 · h −1 , while, in some conditions, the anchored complexes showed better results, with TOF of until 8.08 ×103 · h −1 . Aditionally, it was possible to determine an equation, to the homogenous catalyst, that describes the product quantity in function of reacional temperature and aluminum/iron ratio.