Enzymatic glycosylation involving fluorinated carbohydrates.

Fluorinated carbohydrates, where one (or more) fluorine atom(s) have been introduced into a carbohydrate structure, typically through deoxyfluorination chemistry, have a wide range of applications in the glycosciences. Fluorinated derivatives of galactose, glucose, N-acetylgalactosamine, N-acetylglucosamine, talose, fucose and sialic acid have been employed as either donor or acceptor substrates in glycosylation reactions. Fluorinated donors can be synthesised by synthetic methods or produced enzymatically from chemically fluorinated sugars. The latter process is mediated by enzymes such as kinases, phosphorylases and nucleotidyltransferases. Fluorinated donors produced by either method can subsequently be used in glycosylation reactions mediated by glycosyltransferases, or phosphorylases yielding fluorinated oligosaccharide or glycoconjugate products. Fluorinated acceptor substrates are typically synthesised chemically. Glycosyltransferases are most commonly used in conjunction with natural donors to further elaborate fluorinated acceptor substrates. Glycoside hydrolases are used with either fluorinated donors or acceptors. The activity of enzymes towards fluorinated sugars is often lower than towards the natural sugar substrates irrespective of donor or acceptor. This may be in part attributed to elimination of the contribution of the hydroxyl group to the binding of the substrate to enzymes. However, in many cases, enzymes still maintain a significant activity, and reactions may be optimised where necessary, enabling enzymes to be used more successfully in the production of fluorinated carbohydrates. This review describes the current state of the art regarding chemoenzymatic production of fluorinated carbohydrates, focusing specifically on examples of the enzymatic production of activated fluorinated donors and enzymatic glycosylation involving fluorinated sugars as either glycosyl donors or acceptors.

Toward the self-assembly of metal-organic nanotubes using metal-metal and π-stacking interactions: bis(pyridylethynyl) silver(I) metallo-macrocycles and coordination polymers.

Shape-persistent macrocycles and planar organometallic complexes are beginning to show considerable promise as building blocks for the self-assembly of a variety of supramolecular materials including nanofibers, nanowires, and liquid crystals. Here we report the synthesis and characterization of a family of planar di- and tri-silver(I) containing metallo-macrocycles designed to self-assemble into novel metal-organic nanotubes through a combination of π-stacking and metal-metal interactions. The silver(I) complexes have been fully characterized by elemental analysis, high resolution electrospray ionization mass spectrometry (HR-ESI-MS), IR, (1)H and (13)C NMR spectroscopy, and the solution data are consistent with the formation of the metallo-macrocycles. Four of the complexes have been structurally characterized using X-ray crystallography. However, only the di-silver(I) complex formed with 1,3-bis(pyridin-3-ylethynyl)benzene is found to maintain its macrocyclic structure in the solid state. The di-silver(I) shape-persistent macrocycle assembles into a nanoporous chicken-wire like structure, and ClO(4)(-) anions and disordered H(2)O molecules fill the pores. The silver(I) complexes of 2,6-bis(pyridin-3-ylethynyl)pyridine and 1,4-di(3-pyridyl)buta-1,3-diyne ring-open and crystallize as non-porous coordination polymers.

Palladium(II) complexes of readily functionalized bidentate 2-pyridyl-1,2,3-triazole "click" ligands: a synthetic, structural, spectroscopic, and computational study.

The Cu(I)-catalyzed 1,3-cycloaddition of organic azides with terminal alkynes, the CuAAC "click" reaction is currently receiving considerable attention as a mild, modular method for the generation of functionalized ligand scaffolds. Herein we show that mild one-pot "click" methods can be used to readily and rapidly synthesize a family of functionalized bidentate 2-pyridyl-1,2,3-triazole ligands, containing electrochemically, photochemically, and biologically active functional groups in good to excellent yields (47-94%). The new ligands have been fully characterized by elemental analysis, HR-ESI-MS, IR, (1)H and (13)C NMR and in three cases by X-ray crystallography. Furthermore we have demonstrated that this family of functionalized "click" ligands readily form bis-bidentate Pd(II) complexes. Solution studies, X-ray crystallography, and density functional theory (DFT) calculations indicate that the Pd(II) complexes formed with the 2-(1-R-1H-1,2,3-triazol-4-yl)pyridine series of ligands are more stable than those formed with the [4-R-1H-1,2,3-triazol-1-yl)methyl]pyridine "click" ligands.

Ruthenium(II) and osmium(II) 1,2,3-triazolylidene organometallics: a preliminary investigation into the biological activity of 'click' carbene complexes.

Taking advantage of the facile and versatile synthetic properties of 'click' 1,2,3-triazolylidene N-heterocyclic carbenes (tzNHC's), a range of new organometallic Ru(II) and Os(II) arene complexes containing functionalised tzNHC ligands, [M(η(6)-p-cymene)(tzNHC)Cl2] [M = Ru(II), Os(II)], have been synthesised and fully characterised, including the X-ray crystal structure of one of the Os(II) complexes. The tzNHC ligands remain coordinated to the metal centres under relevant physiological conditions, and following binding to the model protein, ubiquitin. The in vitro cytotoxicity of the compounds towards human ovarian cancer cells is dependent on the substituent on the tzNHC ligand but is generally <50 µM and in some cases <1 µM, whilst still retaining a high degree of selectivity towards cancer cells over healthy cells (1.85 µM in A2780 ovarian cancer cells versus 435 µM in human embryonic kidney cells in one case).

Ruthenium(II) arene PTA (RAPTA) complexes: impact of enantiomerically pure chiral ligands.

Organometallic ruthenium(II) arene complexes containing the PTA ligand ([Ru(η(6)-arene)Cl(2)(PTA)], PTA = 1,3,5-triaza-7-phosphatricyclo-[3.3.1.1]decane, termed RAPTA) show pharmacologically relevant anti-tumour properties in vitro. Two new enantiomeric pairs of RAPTA compounds, containing the chiral arene (R)- or (S)-2-phenyl-N-(1-phenylethylene)acetamide and either dichlorido or oxalato ligands were synthesised and fully characterised. The stability of the complexes towards hydrolysis was assessed and the dichlorido complexes were found to be more stable towards hydrolysis than the prototype complex RAPTA-C, ([Ru(η(6)-p-cymene)Cl(2)(PTA)]). The cytotoxicity of the compounds towards human ovarian cancer cells is moderate to good with a degree of selectivity towards the cancer cells over healthy cells. More significantly, for the first time we were able to establish the influence of a bulky, chiral group attached to the arene on the cytotoxicity of this class of compound, with the S-enantiomer being more cytotoxic than the R-enantiomer.

Gold(I) "click" 1,2,3-triazolylidenes: synthesis, self-assembly and catalysis.

Novel gold(I) "click" carbene(1,2,3-triazolylidene) complexes have been synthesised, characterised and exploited for the self-assembly of a metallomacrocycle and as precatalysts for gold(I)-catalysed reactions.

Cycloaurated triphenylphosphine-sulfide and -selenide.

The first examples of cycloaurated phosphine sulfides and triphenylphosphine selenide have been synthesised; these complexes are fairly rare examples of gold(iii) complexes with potentially reducing sulfur- and selenium-donor ligands. The cycloaurated complex (AuCl(2)(2-C(6)H(4)P(S)Ph(2)) was synthesised in good yield by transmetallation of the organomercury precursor Hg(2-C(6)H(4)P(S)Ph(2))(2) with Me(4)N[AuCl(4)]. A route to the chloro-mercury analogue ClHg(2-C(6)H(4)P(S)Ph(2)) was developed by reaction of the cyclomanganated triphenylphosphine sulfide (CO)(4)Mn(2-C(6)H(4)P(S)Ph(2)) with HgCl(2); this mercury substrate was also used in the synthesis of AuCl(2)(2-C(6)H(4)P(S)Ph(2)). The cycloaurated triphenylphosphine selenide complex AuCl(2)(2-C(6)H(4)P(Se)Ph(2)) was synthesised by an analogous methodology using the new phosphine selenide Hg(2-C(6)H(4)P(Se)Ph(2))(2) [prepared from Hg(2-C(6)H(4)PPh(2))(2) and elemental Se under sonication]. The phosphonamidic analogue AuCl(2)(2-C(6)H(4)P(S)(NEt(2))(2)) has also been synthesised from PhP(S)(NEt(2))(2)via lithiation and mercuration. X-Ray crystal structures of several compounds are reported, and show the presence of puckered ring systems.

Cycloauration of pyridyl sulfonamides.

The pyridyl-2-alkylsulfonamides C(5)H(4)N(CH(2))(n)NHSO(2)R (n = 1,2; R = Me, Ph or p-C(6)H(4)Me) and 8-(p-tosylamino)quinoline undergo facile cycloauration reactions with H[AuCl(4)] in water, giving metallacyclic complexes coordinated through the pyridyl (or quinolyl) nitrogen atom and the deprotonated nitrogen of the sulfonamide group. The complexes have been fully characterised by NMR spectroscopy, ESI mass spectrometry and elemental analysis. The X-ray crystal structures of two derivatives reveal the presence of non-planar sulfonamide nitrogen atoms. The complexes show low activity against P388 murine leukaemia cells, possibly as a result of their ease of reduction with mild reducing agents.