Fr Francium

Glycosyltransferases (GTs) are a large family of enzymes that are essential in all domains of life for the biosynthesis of complex carbohydrates and glycoconjugates. GTs catalyse the transfer of a sugar from a glycosyl donor to a variety of acceptor molecules, for example, oligosaccharides, peptides, lipids or small molecules. Such glycosylation reactions are central to many fundamental biological processes, including cellular adhesion, cell signalling and bacterial- and plant-cell-wall biosynthesis. GTs are therefore of significant interest as molecular targets in chemical biology and drug discovery. In addition, GTs have found wide application as synthetic tools for the preparation of complex carbohydrates and glycoconjugates. In order to exploit the potential of GTs both as molecular targets and synthetic tools, robust and operationally simple bioassays are essential, especially as more and more protein sequences with putative GT activity but unknown biochemical function are being identified. In this minireview, we give a brief introduction to GT biochemistry and biology. We outline the relevance of GTs for medicinal chemistry and chemical biology, and describe selected examples for recently developed GT bioassays, with a particular emphasis on fluorescence-based formats.

Breaking the cycle: A series of N-(2-arylindol-7-yl)benzenesulfonamide derivatives were prepared. Among them, compound 2 showed promising antiproliferative activity against hormone-resistant prostate cancer PC-3 cells, induced G2/M-phase arrest, and induced apoptosis through a caspase-dependent pathway.

Base-catalysed condensation of Ph2P-C5H5 (1) with an excess of acetone leads to a fulvene-like diphenyl(4,4,6-trimethyl-4,5-dihydropentalen-2-yl)phosphane Ph2P-C11H13 (3) as a product of double condensation. Carbometallation of 3 with MeLi, followed by aqueous work-up, results in formation of a new cyclopentadienylphosphane bearing a highly sterically demanding, anellated 1,1,3,3-tetramethylcyclopentane moiety (4, Ph2P-CpTMH). It reacts with chalcogene oxidants (H2O2, S8, Se) to form the corresponding phosphane chalcogenides Ph2P(=X)CpTMH, X = O (5), S (6), Se (7) in high yields. Quaternization of 4 with MeI gives the phosphonium salt 8 as a single isomer in high yield. Dehydrohalogenation of 8 by reaction with nBuLi gives CpTM-phosphonium ylide Ph2P(CpTM)Me (9). An alternative protocol towards 9 that includes deprotonation of 8 with benzylpotassium followed by P-alkylation is superior and gives 9 in more than 95 % yield. Staudinger reaction of 4 with tBuN3 gives onlyP-amino-cyclopentadienylidenephosphorane Ph2P(CpTM)NHtBu (10), whereas with Me3SiN3 only the tautomeric P-imino-cyclopentadienylphosphane Ph2P(NSiMe3)CpTMH (11) was isolated. Hydrolysis of 11 with wet MeCN leads to the new parent P-amino-cyclopentadienylidenephosphorane Ph2P-(CpTM)NH2 (12). Treatment of 4 with benzylpotassium followed by transmetallation with FeCl2 leads to the sterically most crowded ferrocenyl-bisphosphane [{Ph2P-CpTM}2Fe] (13, dppfTM) in high yield. Its X-ray diffraction analysis reveals an anti-orientation of phosphane functionalities at both cyclopentadienyl rings. However, upon reaction of dppfTM with [PdCl2(MeCN)2], a constrained syn-orientation is achieved in the product [{dppfTM}PdCl2] (14). Halogen exchange by reaction of 14 with NaI leads to the corresponding [{dppfTM}PdI2] (15). Molecular structures of 4, 9, 13 and 15 have been confirmed by XRD studies.

Sr2Fe1.33Mo0.66O6 (alternately written as Sr3Fe2MoO9) perovskite has been prepared in polycrystalline form by thermal treatment, in air, of previously decomposed citrate precursors. This material has been studied by X-ray and neutron powder diffraction (XRPD and NPD), magnetic and transport measurements. At room temperature, the crystal structure is cubic with a = 7.8585(2) Å and V = 485.30(2) Å3, defined in the space group Fmm. Magnetic measurements indicate a ferromagnetic ordering below TC = 246 K. As prepared, the sample is an electrical insulator. A topotactic reduction of the stoichiometric sample performed at 600, 700, and 800 °C, in H2/N2 flows, leads to the oxygen-deficient double perovskites, Sr2Fe1.33Mo0.66O6-[delta] with increasing [delta] values. The evolution of the crystal structure upon reduction has been studied from XRPD and NPD data. For the sample obtained at 800 °C, exhibiting the largest [delta] value, the low-temperature evolution from NPD data was investigated between 2 K and 500 K: in all the temperature range the crystal structure is cubic with space group Fmm; at room temperature a = 7.87060(6) Å and V = 487.555(6) Å3. The magnetic behavior of this reduced sample suggests the presence of ferromagnetic domains characterized by Curie temperatures with TC > 400 K. The conductivity dramatically increases upon H2 reduction. Moreover, this reduced sample exhibits magnetoresistance, as high as 2.5 % at room temp. for H = 5 T. Magnetic and magnetotransport results are consistent with a large component of itinerancy for down-spin Mo t2g electrons, injected through hydrogen reduction.

The reactions of [{([eta]6-C6H6)RuCl([mu]-Cl)}2] and [{([eta]6-p-cymene)RuCl([mu]-Cl)}2] with N-[2-(arylchalcogeno)ethyl]morpholines (L) (aryl = Ph/2-pyridyl for S, Ph for Se, 4-MeOC6H4 for Te) and NH4PF6 result in "piano-stool" complexes of RuII of composition [RuCl([eta]6-C6H6)(L)][PF6]/[RuCl([eta]6-p-cymene)(L)][PF6], which give characteristic 1H, 13C{1H}, 77Se{1H}, and 125Te{1H} NMR spectra. Some of them have also been characterized by X-ray crystallography [Ru-S, Ru-Se, and Ru-Te bond lengths: 2.3815(12)/2.3742(14), 2.4837(14), and 2.6143(7) Å, respectively]. The cyclic voltammograms show that all the complexes undergo irreversible oxidation (E = 0.290-0.586 V). All the ruthenium complexes have been explored for their catalytic activity in the oxidation of primary and secondary alcohols with N-methylmorpholine N-oxide (NMO), tBuOOH, NaOCl, and NaIO4 (TON values upto 9.8 × 104). The efficiency of the catalytic oxidation reaction decreases in the order Te > Se > S. The intermediate species involved in the oxidation reactions appear to incorporate the RuIV=O group.

The compound CaAgGe and its Mn-substituted derivative CaMn0.07Ag0.93Ge were synthesized by reaction of the element mixtures at high temperature. Their structures were refined from single-crystal X-ray diffraction data. CaAgGe crystallizes in the isomorphic (i3) superstructure of the TiNiSi type (CaCuGe type). The LMTO band structure calculations predicted the CaAgGe phase to be metallic. In addition, it appeared that the valence electron concentration is critical for the atomic ordering and the resulting superstructure. Thus, CaAgGe is one electron short per asymmetric unit, but a drastic narrowing of the electron shortage is achieved through the more complex atomic ordering in the supercell, relative to the simple TiNiSi type subcell. This results in the formation of {Ge2} dumbbells in the supercell, which ascribe greater electronic flexibility to the structure. Despite the fact that CaAgGe is not a Zintl phase in the strict definition as valence balanced intrinsic semiconductor, its structural aspects and transport properties can still be understood within the Zintl concept. The formal Zintl phase Ca3MnAg2Ge3 could be predicted from the theoretical calculations, but no significant phase width was observed experimentally in the substituted derivative Ca3Mn0.21Ag2.79Ge3.

Hooking up! Hsp90 is a molecular chaperone involved in the stabilisation of numerous client proteins including those involved in oncogenic transformations. Through a high-throughput biochemical fragment screen, we have identified novel fragment inhibitors of Hsp90. Two fragment hits were combined to give a dual-fragment Hsp90 complex, and the following successful fragment-linking resulted in a 1000-fold improvement in activity.

Have I got noose for you! Lasso peptides are a growing class of bioactive peptides of microbial origin. The first crystal structure of a member of this family, the glucagon receptor antagonist BI-32169, shows that the fold is built predominantly by regular secondary structural elements and a tight network of hydrogen bonds that are partially shielded from solvent by hydrophobic amino acid side chains. This results in an extraordinarily stable structure that is resistant to thermal unfolding or proteolytic digestion, which facilitates its biological function.

A series of pseudo-tetrahedral copper(I) complexes carrying bis(imino)acenaphthene (BIAN) ligands as acceptor subunits and various phosphane derivatives was prepared and characterized by elemental analysis, X-ray crystallography and spectroscopic techniques. The electronic spectra of the compounds are dominated by low-lying metal-to-ligand charge transfer (MLCT) transitions which could be systematically modified by different substituent patterns at the diimine acceptor subunit and by variations of the electron donating properties and bite angles of the phosphane moiety. A qualitative model based on frontier-orbital overlap arguments is introduced to describe the observed variations in optical spectra, excited state energies, solvatochromic behaviour, charge transfer character, and extent of electronic coupling following moderate changes in orbital mixing. Due to their readily tuneable properties and the potential of the BIAN ligands to reversibly store up to four redox equivalents, these systems are of considerable interest for the development of novel multi-electron transfer photosensitizers which are based on the abundant and environmentally benign transition metal copper.

We present the magneto-structural correlations for two novel discrete cyano-bridged assemblies based on cationic complexes of manganese(II) with diimine ligands and octacyanotungstate(V) ions. The crystal structure of [MnII(terpy)(dmf)(H2O)2][MnII(terpy)(H2O)(dmf)([mu]-NC)WV(CN)7]2·6H2O (1) (terpy = 2,2[prime];6[prime],2[Prime]-terpyridine, dmf = dimethylformamide) contains dinuclear {MnIIWV}- cyano-bridged anions, while the crystal structure of [MnII(phen)3]2[MnII(phen)2([mu]-NC)2WV(CN)6]2(ClO4)2·9H2O (2) (phen = 1,10-phenanthroline) is built of tetranuclear {MnII2WV2}2- square anions. Intramolecular Mn-W magnetic interactions through the cyano bridges are represented by magnetic coupling constants J = -39 cm-1 for the {MnIIWV}- unit in 1 and J1 = -25.7 and J2 = -16.7 cm-1 for the {MnII2WV2}2- unit in 2. J and J1 represent relatively strong W-CN-Mn interactions and are ascribed to the bridges in b positions of TPRS-8 (trigonal prism square-face bicapped) of [W(CN)8]3- polyhedra, favoring the strongest electronic interactions between the dz2-dx2-y2 orbital of W and the [pi]* orbitals of CN-, whereas J2 is related to the m vertex of [W(CN)8]3-. The magnetic properties of 1 and 2 are compared with reference compounds and discussed in the context of the type of coordination polyhedra of [W(CN)8]3- as well as the metric parameters of cyano-bridged W-CN-Mn linkages. We found the type of coordination polyhedra and bridging mode of [W(CN)8]3- to be the most important factors influencing the magnitude of the Mn-W magnetic interaction.