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Selected AbstractsNew N6 -substituted 8-alkyl-2-phenylmethylsulfanyl-adenines.JOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 4 2004Title compounds bearing substituents on C(2), C(6) and C(8) were prepared from a newly synthesized pyrimidine derivative 11. The new pyrimidine 11 was generated from compound 2 through two different synthetic schemes. In one pathway, compound 2 was nitrosated, reduced and alkylated to produce com pounds 9, 10 and 11 respectively (Scheme). In an alternate route using compound 2 as the starting material, a coupling reaction using the diazonium salt derived from p -methylaniline afforded the azo derivative 7, which was subsequently alkylated and reductively cleaved to form compounds 8 and 11 respectively (See Scheme). Compound 11 was annulated to the corresponding hypoxanthine derivatives 12,14; compounds 12 and 13 were chlorinated with phosphorus oxychloride, then reacted with amines to yield compound 17 and 20 respectively. Compounds 21, 22 and 23 were obtained by oxidation of the corresponding sulfide as depicted in Scheme. Alkylation of the thiol function of 1 gave a mixture of 3 and 4. Compound 3 was chlo rinated to 5. Nitration of 5 resulted in electrophilic aromatic substitution of the aryl ring and concomitant oxidation of the sulfide to the sulfoxide, producing 6. [source] Synthesis and Photochemical Evaluation of Iodinated Squarylium Cyanine DyesHELVETICA CHIMICA ACTA, Issue 5 2005Paulo Several (multiply) iodinated squarylium cyanine dyes of type 1 and 8 (see Scheme and Table), derived from 1,3-benzothiazole and 6-iodo-1,3-benzothiazole, were synthesized as potential new photosensitizers, with absorptions in the 700-nm region. Their ability to generate singlet oxygen (1O2) was assessed by luminescence-decay measurement in the near-IR. Some of these new dyes show interesting photophysical properties, and may be potentially used in photodynamic therapy (PDT). [source] Using 1,3-butadiene and 1,3,5-hexatriene to model the cis-trans isomerization of retinal, the chromophore in the visual pigment rhodopsinINTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY, Issue 4-5 2002Fredrik Blomgren Abstract The short polyenes 1,3-butadiene and 1,3,5-hexatriene are used to model the cis-trans isomerization of the protonated Schiff base of retinal (PSBR) in rhodopsin (Rh). We employed the complete active space self-consistent field (CASSCF) method for calculation of the potential energy surfaces (PESs) in C2 symmetry. In the calculations, the central bond was twisted from 0 to 180° in the first singly excited singlet state (Sse), i.e., the state dominated by a configuration with one electron excited from HOMO to LUMO. It was found that the PES of 1,3-butadiene has a maximum whereas the PES of 1,3,5-hexatriene has a minimum for a twist angle of 90°. This is explained by a shift in border of single and double bonds in the Sse state. The first step in the cis-trans isomerization of PSBR, which is the formation of the C6C7 (see Scheme 1 for numbering) twisted PSBR in the first excited singlet state (S1), inside the protein binding pocket of the visual pigment Rh is modeled using crystal coordinates and the calculations performed on 1,3-butadiene and 1,3,5-hexatriene. More specifically, a plausible approximate structure is calculated in a geometric way for the C6C7 90° twisted PSBR, which fits into the protein binding pocket in the best possible way. It has been shown earlier that PSBR has an energy minimum for this angle in S1. The CASSCF method was used to investigate the wave function of the calculated structure of PSBR. © 2002 Wiley Periodicals, Inc. Int J Quantum Chem, 2002 [source] Polysulfurated Pyrene-Cored Dendrimers: Luminescent and Electrochromic PropertiesCHEMISTRY - A EUROPEAN JOURNAL, Issue 33 2008Marc Gingras Prof. Abstract We have synthesized a novel class of dendrimers, consisting of a polysulfurated pyrene core with appended poly(thiophenylene) dendrons (PyG0, PyG1, and PyG2, see Scheme,1), which exhibit remarkable photophysical and redox properties. In dichloromethane or cyclohexane solution they show a strong, dendron-localized absorption band with a maximum at around 260,nm and a band in the visible region with a maximum at 435,nm, which can be assigned to the pyrene core strongly perturbed by the four sulfur substituents. The dendrimers exhibit a strong (,=0.6), short-lived (,=2.5,ns) core-localized fluorescence band with maximum at approximately 460,nm in cyclohexane solution at 293,K. A strong fluorescence is also observed in dichloromethane solution at 293,K, in dichloromethane/chloroform rigid matrix at 77,K, and in the solid state (powder) at room temperature. The dendrimers undergo reversible chemical and electrochemical one-electron oxidation with formation of a strongly colored deep blue radical cation. A second, reversible one-electron oxidation is observed at more positive potential values. The photophysical and redox properties of the three dendrimers are finely tuned by the length of their branches. The strong blue fluorescence and the yellow to deep blue color change upon reversible one-electron oxidation can be exploited for optoelectronic devices. [source] Steric Modulation of Coordination Number and Reactivity in the Synthesis of Lanthanoid(III) FormamidinatesCHEMISTRY - A EUROPEAN JOURNAL, Issue 29 2007Marcus Abstract Reactions of a range of the readily prepared and sterically tunable N,N,-bis(aryl)formamidines with lanthanoid metals and bis(pentafluorophenyl)mercury (Hg(C6F5)2) in THF have given an extensive series of tris(formamidinato)lanthanoid(III) complexes, [Ln(Form)3(thf)n], namely [La(o -TolForm)3(thf)2], [Er(o -TolForm)3(thf)], [La(XylForm)3(thf)], [Sm(XylForm)3], [Ln(MesForm)3] (Ln=La, Nd, Sm and Yb), [Ln(EtForm)3] (Ln=La, Nd, Sm, Ho and Yb), and [Ln(o -PhPhForm)3] (Ln=La, Nd, Sm and Er). [For an explanation of the N,N, - bis(aryl)formamidinate abbreviations used see Scheme,1.] Analogous attempts to prepare [Yb(o -TolForm)3] by this method invariably yielded [{Yb(o -TolForm)2(,-OH)(thf)}2], but [Yb(o -TolForm)3] was isolated from a metathesis synthesis. X-ray crystal structures show exclusively N,N, - chelation of the Form ligands and a gradation in coordination number with Ln3+ size and with Form ligand bulk. The largest ligands, MesForm, EtForm and o -PhPhForm give solely homoleptic complexes, the first two being six-coordinate, the last having an ,1 -,-ArLn interaction. Reaction of lanthanoid elements and Hg(C6F5)2 with the still bulkier DippFormH in THF resulted in CF activation and formation of [Ln(DippForm)2F(thf)] (Ln=La, Ce, Nd, Sm and Tm) complexes, and o -HC6F4O(CH2)4DippForm in which the formamidine is functionalised by a ring-opened THF that has trapped tetrafluorobenzyne. Analogous reactions between Ln metals, Hg(o -HC6F4)2 and DippFormH yielded [Ln(DippForm)2F(thf)] (Ln=La, Sm and Nd) and 3,4,5-F3C6H2O(CH2)4DippForm. X-ray crystal structures of the heteroleptic fluorides show six-coordinate monomers with two chelating DippForm ligands and cisoid fluoride and THF ligands in a trigonal prismatic array. The organometallic species [Ln(DippForm)2(CCPh)(thf)] (Ln=Nd or Sm) are obtained from reaction of Nd metal, bis(phenylethynyl)mercury (Hg(CCPh)2) and DippFormH, and the oxidation of [Sm(DippForm)2(thf)2] with Hg(CCPh)2, respectively. The monomeric, six-coordinate, cisoid [Ln(DippForm)2(CCPh)(thf)] complexes have trigonal prismatic geometries and rare (for Ln) terminal CCPh groups with contrasting LnCC angles (Ln=Nd, 170.9(4)°; Ln=Sm, 142.9(7)°). Their formation lends support to the view that [Ln(DippForm)2F(thf)] complexes arise from oxidative formation and CF activation of [Ln(DippForm)2(C6F5)] intermediates. [source] Internal Nucleophilic Termination in Acid-Mediated Polyene Cyclizations Part 4,HELVETICA CHIMICA ACTA, Issue 12 2005Synthetic Access to Tetracyclic Didehydro, Tetradehydro Analogues of (±)- Ambrox® Treatment of the unsaturated bicyclic homoallylic alcohols (E)- and (Z)- 5 and (Z)- and (E)- 10 and allenic alcohol 16 with an excess of ClSO3H in 2-nitropropane or CH2Cl2 at ,,80° afforded, in moderate yields (ca. 30,70%), diastereoisomer mixtures of racemic tetracyclic ethers 12a,c (Table,1) and 17a,b (Table,2), respectively. These kinetically controlled stereospecific transformations are believed to proceed via concerted or nonconcerted pathways (see Schemes,4 and 6) and the results are fully consistent with our earlier work. Representing novel didehydro bridged analogues of known, olfactively active labdane tricyclic ethers, the organoleptic properties of 12a,c and 17a,b are briefly described, especially those of 12c which, in the context of structure,activity studies, is a racemic didehydro analogue of the known ambergris odorant Ambrox®. [source] On the Scope of a Prins -Type Cyclization of Oxonium IonsHELVETICA CHIMICA ACTA, Issue 11 2004Georg Fráter The Prins cyclization of an aldehyde 1 with a homoallylic alcohol 2, affording tetrahydro-2H -pyrans 4via the oxonium ion 3 as central intermediate, was conceptually transferred to (alk-3-enyloxy)acrylates 6, which form a related oxonium ion 7 upon treatment with acids (Scheme,1). The scope and utility of this modification of the Prins -type cyclization of oxonium ions is discussed exemplarily by means of the syntheses of ten tetrahydro-2H -pyran and tetrahydrofuran derivatives, featuring diverse substitution patterns as well as different degrees of molecular complexity. These target structures include (±)-ethyl (2RS)-2-[(2RS,4SR,6RS)- and (2SR,4RS,6SR)-2-tetahydro-4-hydroxy-6-methylpyran-2-yl]propanoate (23), (±)-ethyl [(2RS, 3RS)-tetrahydro-3-isopropenylfuran-2-yl]acetate (32), (±)-ethyl (2Z)-3-(tetrahydro-2,2-dimethylfuran-3-yl)acrylate (37), (±)-(3aRS,6RS, 7aRS)-octahydro-7a-methylbenzofuran-6-yl formate (42), (±)-ethyl (2RS,3RS,4aRS,8SR,8aRS)-hexahydro-2,5,5,8-tetramethyl-7-oxo-2H,5H -pyrano[4,3- b]pyran-3-carboxylate (48), and (±)-ethyl (2RS,3RS,6SR)-tetrahydro-6-(2-methoxy-2-oxoethyl)-3-methyl-2H -pyran-2-carboxylate (53) (see Schemes,3 and 5,8). Besides the stereochemistry and mechanistic details of this versatile oxonium-ion cyclization, the synthesis of suitable starting materials is also described. [source] Layer-By-Layer Assembly of ,-Estradiol Loaded Mesoporous Silica Nanoparticles on Titanium Substrates and Its Implication for Bone HomeostasisADVANCED MATERIALS, Issue 37 2010Yan Hu Drug-loadingmesoporous silica nanoparticles that serve as a nanoreservoir-type drug-delivery system are successfully attached to titanium substrates via the layer-by-layer assembly technique (see scheme). The obtained structure demonstrates great potential for regulating the biological behaviors of osteoblasts/ steoclasts in order to maintain bone homeostasis. The approach we present here may have wide applications in implant technology, tissue engineering, and regenerative medicine. [source] Novel One-Step Synthesis of Porous-Supported Catalysts by Activated-Carbon Templating,ADVANCED MATERIALS, Issue 9 2006J. Blanco A new, simple, versatile, and easily scaleable one-step preparation method , an impregnated carbon procedure (ICP) , is proposed to produce highly dispersed active phases on supports of tailored porosity (see scheme; AC: activated carbon). This one-step synthesis unites simplicity of preparation with outstanding properties of the final catalysts and offers an interesting pathway towards industrial-catalyst manufacture. [source] Rapid Matrix-Assisted Refolding of Histidine-Tagged ProteinsCHEMBIOCHEM, Issue 5 2009Tetyana Dashivets Abstract Matrix refolded: The formation of inclusion bodies, which are amorphous aggregates of misfolded insoluble protein, during recombinant protein expression, is one of the biggest bottlenecks in protein science. We report a stepwise, rational optimization procedure for refolding of insoluble proteins (see scheme). In comparison to refolding in-solution, this parallelized, matrix-assisted approach allows the refolding of various proteins in a fast and efficient manner. The formation of inclusion bodies (IBs),amorphous aggregates of misfolded insoluble protein,during recombinant protein expression, is still one of the biggest bottlenecks in protein science. We have developed and analyzed a rapid parallel approach for matrix-assisted refolding of recombinant His6 -tagged proteins. Efficiencies of matrix-assisted refolding were screened in a 96-well format. The developed methodology allowed the efficient refolding of five different test proteins, including monomeric and oligomeric proteins. Compared to refolding in-solution, the matrix-assisted refolding strategy proved equal or better for all five proteins tested. Interestingly, specifically oligomeric proteins displayed significantly higher levels of refolding compared to refolding in-solution. Mechanistically, matrix-assisted folding seems to differ from folding in-solution, as the reaction proceeds more rapidly and shows a remarkably different concentration dependence,it allows refolding at up to 1000-fold higher protein concentration than folding in-solution. [source] Cooperative Effects on Radical Recombination in CYP3A4-Catalyzed Oxidation of the Radical Clock ,-ThujoneCHEMBIOCHEM, Issue 4 2009Yongying Jiang Dr. Abstract Tick tock: The timing of the ,-thujone radical clock (see scheme) can be specifically altered by an allosteric effector. Progesterone, a well-documented CYP3A4 allosteric effector, was found to increase the yield of the unrearranged, C4-derived product of ,-thujone oxidation at the expense of the combined yields of all the rearranged C4-oxidized metabolites. The results demonstrate that the apparent radical recombination rate in the CYP3A4 hydroxylation of ,-thujone is accelerated by the progesterone hetereotropic cooperativity. [source] Reinvestigation of a Cyclic Dipeptide N -Prenyltransferase Reveals Rearrangement of N-1 Prenylated Indole DerivativesCHEMBIOCHEM, Issue 7 2008Han-Li Ruan Prof. Dr. Converting revere to regular: Reinvestigation of cyclic dipeptide N -prenyltransferase (CdpNPT) revealed that the enzymatic products are derivatives that carry 3,-(3,,3,)-dimethylallyl moieties at the N-1 position of the indole ring, and they undergo rearrangement in the presence of acids, such as trichloroacetic acid, used for termination of enzymatic reactions and protein precipitation (see scheme). The rearrangement can be avoided by using MeOH instead of acid for termination and protein precipitation. [source] Metal-Free Triazole Formation as a Tool for BioconjugationCHEMBIOCHEM, Issue 13 2007Sander S. van Berkel Who needs copper? There is a strong demand for ligation reactions that proceed spontaneously, selectively, and under physiological conditions. To meet these criteria, we used trifluoromethyl-substituted oxanorbornadienes in reactions with various azides, and achieved an elegant tandem [3+2] cycloaddition,retro-Diels,Alder reaction that forms stable 1,2,3-triazole-linked bioconjugates (see scheme). [source] Characterization of the ,-Methylaspartate-,-decarboxylase (CrpG) from the Cryptophycin Biosynthetic PathwayCHEMBIOCHEM, Issue 12 2007Zachary Q. Beck Dr. More pieces for the puzzle. The ,-methylaspartate-,-decarboxylase (CrpG) from the cryptophycin biosynthetic pathway was cloned, over-expressed, and purified. We found that CrpG decarboxylates (2S,3R)-3-methylaspartic acid to form 3-amino-2(R)-methylpropionic acid, which is subsequently incorporated into Unit C of cryptophycins (see scheme). [source] Facile Synthesis of 2,4-Dinitrophenyl ,- D -Glycopyranosides as Chromogenic Substrates for ,-GlycosidasesCHEMBIOCHEM, Issue 7 2007Hong-Ming Chen Dr. Pure and simple. The efficient synthesis of chromogenic aryl glycoside substrates for N -acetyl-,-hexosaminidases, which were previously troublesome to prepare, is described (see scheme). This one-pot arylation/anomerisation sequence gives access to a range of aryl ,-glycosides, and minimizes decomposition of ,-linked intermediates in the case of the 2-acetamido sugars. [source] A Generic Approach to Monofunctionalized Protein-Like Gold Nanoparticles Based on Immobilized Metal Ion Affinity ChromatographyCHEMBIOCHEM, Issue 4 2006Raphaël Lévy Dr. Control of a peptide-capped gold-nanoparticle (NP) surface with single-molecule accuracy is demonstrated. Immobilized metal ion affinity chromatography (IMAC) has been used to separate peptide-capped NPs as a function of the number of molecular labels (see scheme). The method described in this paper is simple, quantitative and directly applicable to the preparation of monofunctionalized nanoparticles with any water-soluble chemical moieties. [source] Dissection of the Late Steps in Aureothin BiosynthesisCHEMBIOCHEM, Issue 1 2006Markus Müller Part of the queue. Biosynthesis of the cytostatic polyketide aureothin (1) in Streptomyces thioluteus was found to involve two tailoring steps (see scheme). Mutational biosynthesis of nor -deoxyaureothin (,- 2) and a hydroxylated derivative (3), together with biotransformation experiments revealed a well-defined order for the polyketide-tailoring steps. Regioselective ,-pyrone methylation was found to be the penultimate biosynthetic step prior to furan-ring formation. [source] 3,- Enolpyruvyl-UMP, a Novel and Unexpected Metabolite in Nikkomycin BiosynthesisCHEMBIOCHEM, Issue 11 2005Cristian Ginj Dipl.-Chem. An unexpected turn. NikO, the putative enolpyruvyl transferase involved in the formation of the aminohexuronic acid moiety of nikkomycins catalyzes the formation of 3,- enolpyruvyl-UMP from UMP (see scheme). This finding contradicts the current model for the biosynthesis of aminohexuronic acid. [source] Discovery of Mycobacterium Tuberculosis Protein Tyrosine Phosphatase A (MptpA) Inhibitors Based on Natural Products and a Fragment-Based ApproachCHEMBIOCHEM, Issue 10 2005Michael Manger Dr. Naturally inspired or fragment based. Mcyobacterium tuberculosis has two functional phosphatases, protein tyrosine phosphates A and B (MptpA and B), which are thought to mediate mycobacterial survival in the host. Here we describe the first inhibitors of MptpA (see scheme). Initial hits were identified in screening collections that were inspired by natural products and composed by fragment-based approach. [source] Luminescent Saccharide Biosensor by Using Lanthanide-Bound Lectin Labeled with FluoresceinCHEMBIOCHEM, Issue 8 2005Yoichiro Koshi A new luminescent biosensor for complicated glycoconjugates was engineered on the basis of a lanthanide-complexed sugar-binding protein (lectin) modified with a fluorophore. By using luminescence resonance energy transfer (LRET), ratiometric luminescent sensing can be carried out and successfully applied to a luminescent assay for an enzymatic trimming of a glycoprotein (see scheme). [source] Small-Molecule Inhibitors and Probes for Ubiquitin- and Ubiquitin-Like-Specific ProteasesCHEMBIOCHEM, Issue 2 2005Anna Borodovsky Dr. There's always a catch. The post-translational modification of proteins with ubiquitin (Ub) or ubiquitin-like (Ubl) modifiers is an important signal in the regulation of a variety of biological processes, such as degradation and regulation of gene expression. Here we report the synthesis of a panel of peptide vinyl sulfones (see scheme) harboring various portions of the Ub C terminus by using a safety-catch linker. Depending on their length, such compounds can efficiently target Ubl-specific proteases. [source] Chemical Approaches to Controlling Intracellular Protein DegradationCHEMBIOCHEM, Issue 1 2005John S. Schneekloth Jr. Inactive. Recent advances have yielded many ways to study proteins by means of inactivation. Traditional methods of genetic knockout are complimented by newer techniques, including RNAi and small molecules that induce proteolysis (see scheme). Although seemingly in competition, these techniques each offer solutions to specific problems in proteomic analysis. [source] Extended Target Sequence Specificity of PNA,Minor-Groove Binder ConjugatesCHEMBIOCHEM, Issue 1 2005Peter E. Nielsen Prof. ,Conjugal bliss. We show that a peptide nucleic acid,Hoechst conjugate (see scheme) kinetically and sequence preferentially guides the PNA moiety to target a binding site proximal to an A,T region that has an affinity for the minor-groove binder. These results demonstrate a new strategy for constructing DNA recognition ligands composed of a sequence-guiding domain that increases the target specificity and a DNA-modification domain that determines the biological activity of the conjugate. [source] Enzymatic Formation of Multiple Triterpenes by Mutation of Tyrosine 510 of the Oxidosqualene-Lanosterol Cyclase from Saccharomyces cerevisiaeCHEMBIOCHEM, Issue 12 2004Tung-Kung Wu Prof. Dr. The simultaneous formation of monocyclic and differentially deprotonated triterpenes by mutation of Tyr510 of the oxidosqualene-lanosterol cyclase (ERG7) from Saccharomyces cerevisiae is reported (see scheme). Possible dual functions of this residue involved in the cyclization and deprotonation steps of the oxidosqualene cyclization/rearrangement cascade are discussed. [source] Enhancing Membrane Permeability by Fatty Acylation of Oligoarginine PeptidesCHEMBIOCHEM, Issue 8 2004Wellington Pham Dr. A systematic study of fatty acylated polyarginines as drug-delivery modules is described. A remarkable uptake was observed when a myristate moiety was incorporated with a 7-mer polyarginine (see scheme). Microscopic studies suggest that the fatty acylated peptide is internalized into the cytoplasm, not the nucleus, thus providing an alternative method for drug delivery. [source] Catalytically Active Tetramodular 6-Deoxyerythonolide B Synthase Fusion ProteinsCHEMBIOCHEM, Issue 11 2003Corinne M. Squire Dr. Easy as 1, 2, 3? Erythromycin (see scheme) is biosynthesised on a polyketide synthase consisting of three discrete bimodular protein subunits which, in the natural system, must dock together to form the active system. This paper details an experiment in which either two or all three of these proteins are translationally fused through their C and N termini. The tetramodular fusions are shown to be competent in biosynthesis. [source] Rapid Diversity-Oriented Synthesis in Microtiter Plates for In Situ Screening of HIV Protease InhibitorsCHEMBIOCHEM, Issue 11 2003Ashraf Brik Dr. Click and go: By using click chemistry based on a new triazole forming reaction condition (see scheme), over 100 triazole compounds generated in microtiter plates from a core structure were screened for HIV protease inhibition in situ without product isolation. Potent inhibitors, active at nanomolar concentrations, against the wild type and drug resistant mutants were identified. [source] Conserved Amino Acid Residues Correlating With Ketoreductase Stereospecificity in Modular Polyketide SynthasesCHEMBIOCHEM, Issue 7 2003Patrick Caffrey Dr. Getting down to specifics: Key amino acid residues were found to correlate with ketoreductase domain stereospecificity in modular polyketide synthases. These residues may allow alcohol stereochemistry (see scheme; ACP, acyl carrier protein) in polyketides to be predicted from ketoreductase sequences. The results also suggest that polyketide synthase dehydratase domains have a preference for 3hydroxyacyl substrates with the same alcohol stereochemistry as the (3R)-hydroxyacyl chains used by dehydratases in fatty acid synthases. [source] Binding and Catalysis: A Thermodynamic Study on a Catalytic Antibody SystemCHEMBIOCHEM, Issue 6 2003Herschel Wade Dr. Binding versus catalysis: Attempts to obtain efficient catalysts by using conventional screening methods raise a question concerning the connection between binding and catalysis. To address this issue, we have determined the thermodynamic parameters for the binding of several phosphonates to the esterolytic antibody 17E8 (see scheme). Our results suggest that there may be thermodynamic differences between a binding site selected from a screen for tight transition-state-analogue binding and one that is designed for efficient catalysis. [source] Redox Potentials of Methanophenazine and CoB-S-S-CoM, Factors Involved in Electron Transport in Methanogenic Archaea,CHEMBIOCHEM, Issue 4 2003Mario Tietze Dr. Potentially important: The redox potentials of methanophenazine and CoB-S-S-CoM (see scheme), two cofactors from methanogenic archaea, strongly support the view that methanophenazine plays a central role in the electron transport system of methane-producing archaea. These redox potentials were measured with a hanging mercury drop electrode as the working electrode and were compared to those of several phenazine ethers. [source] | ||||||||||