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Observation of the neutrinoless double β decay is the only practical way to establish that neutrinos are their own antiparticles. Because of the small masses of neutrinos, the lifetime of neutrinoless double β decay is expected to be at least ten orders of magnitude greater than the typical lifetimes of natural radioactive chains, which can mimic the experimental signature of neutrinoless double β decay. The most robust identification of neutrinoless double β decay requires the definition of a signature signal—such as the observation of the daughter atom in the decay—that cannot be generated by radioactive backgrounds, as well as excellent energy resolution. In particular, the neutrinoless double β decay of Xe could be established by detecting the daughter atom, Ba, in its doubly ionized state. Here we demonstrate an important step towards a ‘barium-tagging’ experiment, which identifies double β decay through the detection of a single Ba ion. We propose a fluorescent bicolour indicator as the core of a sensor that can detect single Ba ions in a high-pressure xenon gas detector. In a sensor made of a monolayer of such indicators, the Ba dication would be captured by one of the molecules and generate a Ba-coordinated species with distinct photophysical properties. The presence of such a single Ba-coordinated indicator would be revealed by its response to repeated interrogation with a laser system, enabling the development of a sensor able to detect single Ba ions in high-pressure xenon gas detectors for barium-tagging experiments., We also acknowledge support from the following agencies and institutions: the European Research Council (ERC) under Advanced Grant 339787-NEXT; the Ministry of Science and Innovation of Spain and FEDER under grants FIS2014-53371-C04, FIS2016-76163-R, MAT2016-78293-C6-5-R, MINECO/FEDER CT2016-80955-P, CTQ2016-80375-P and CTQ2014-51912-REDC; Interred PCTEFA V-A Spain/France/Andorra Program (EFA 194/16/TNSI); the Basque Government (GV/EJ) under grants IT-1346-19 and IT-1180-19; andAgencia de Ciencia y Tecnología de la Región de Murcia (19897/GERM/15). The authors also thank the SGI/IZO-SGIker UPV/EHU, Fundación Séneca and DIPC for computational and analytical resources.

All possible demethylation reactions of a diverse family of quaternary alkaloids by means of DFT calculations are here described. We aim to develop a rational model that allows the explanation of the high selectivity observed experimentally and predicts the occurrence of new alkaloid derivatives. To this end, we have performed a detailed analysis of the initial reagents and products. In addition, as a proof of concept, an experimentally unknown demethylation reaction of coralyne has been carried out, thus verifying the reliability of the theoretical model presented here.

The αv β3 integrin receptor plays an important role in tumor metastasis and tumor-induced angiogenesis. The inhibition of this receptor with diverse ligands, antibodies, or cyclic peptides is a promising research field for the treatment of a variety of tumors. The replacement of Phe-(Me)Val dipeptide by a β-lactam ring in Cilengitide has led to new products that show higher inhibitory activity than the parent cyclopeptide. In particular, substitution of a peptide bond β-lactam-NH-Asp linkage by a β-lactam-O-Asp ester linkage increases the activity of the new cyclodepsipeptide. In the same way it has been found that open-chain compounds of the form Asp-β-lactam-Arg can interact with the receptor and inhibit its activity moderately. The integrin inhibitory activity of the synthesized compounds has been established by using the CGH array, a method that appears to be a more reliable trial than the classical adhesion test.

35 p.-14 fig.-4 tab., The exopolysaccharide (EPS)-producing Lactobacillus mali CUPV271 and Leuconostoc carnosum CUPV411 were isolated from Spanish ropy apple must and slimy ham, respectively. The polymers were purified from bacterial cultures’ supernatants and subjected to physicochemical and rheological characterization with the aim to evaluate their potential for future industrial utilization. Methylation analysis, Fourier-Transform Infrared Spectroscopy (FT-IR) and Nuclear Magnetic Resonance (NMR) revealed that both polymers were dextrans, partially branched at O-3 and O-4 positions of the main α-(1 → 6)-d-glucopyranose backbone. The molar masses of the EPS of L. mali and Lc. carnosum were of 1.23 × 108 g/mol and 3.58 × 108 g/mol, respectively. The bacterial strains were tested for binding to the human Caco-2 cell line in the presence and absence of their respective dextran, revealing that the EPS production by L. mali decreased the binding capacity of the bacterium while the adhesiveness of Lc. carnosum did not change. As the structure and molecular mass of both dextrans were comparable, other characteristics of the dextrans were studied to explain this behavior. Atomic force micrographs showed some differences at the supramolecular level, suggesting that the different spatial distribution of the dextrans might be on the basis of the results of the adhesion studies. Both polysaccharides resulted to be amorphous materials with Tg around 226 °C and showed slightly different thermal degradation patterns. Rheologically, they showed to have a pseudoplastic behavior, but very different critical concentrations: 3.8% for the EPS of L. mali and 0.4% for that of Lc. carnosum., This work was supported by a grant from de Department of Environment, Territorial Planification, Agriculture and Fishing from the Basque Government, by the Provincial Council of Gipuzkoa (Exp. 77/17) and by the Spanish Ministry of Science and Innovation (AGL 2015-65010-C3-1-R).

International audience; An unexpected 1,3-dioxa-[3,3]-sigmatropic rearrangement during the treatment of aryl-and alkenyl-substituted allylic alcohols with activated isocyanates is reported. The reorganization of bonds is highly dependent on the electron density of the aromatic ring and the nature of isocyanate used. This metal-free tandem reaction from branched allyl alcohols initiated by a carbamoylation reaction and followed by a sigmatropic rearrangement thus offers a new access to (E)-cinnamyl and conjugated (E,E)-diene carbamates, such as N-acyl and N-sulfonyl derivatives. A computational study was conducted in order to rationalize this phenomenon, and a rearrangement progress kinetic analysis was performed.

The hypothesis of rescuing FKBP12/RyR1 interaction and intracellular calcium homeostasis through molecular “reshaping” of FKBP12 was investigated. To this end, novel 4-arylthioalkyl-1-carboxyalkyl-1,2,3-triazoles were designed and synthesized, and their efficacy was tested in human myotubes. A library of 17 compounds (10a-n) designed to dock the FKBP12/RyR1 hot-spot interface contact residues, was readily prepared from free α-amino acids and arylthioalkynes using CuAAC “click” protocols amenable to one-pot transformations in high overall yields and total configurational integrity. To model nitro-oxidative stress, human myotubes were treated with the peroxynitrite donor SIN1, and evidence was found that some triazoles 10 were able to normalize calcium levels, as well as FKBP12/RyR1 interaction. For example, compound 10 b at 150 nM rescued 46% of FKBP12/RyR1 interaction and up to 70% of resting cytosolic calcium levels in human myotubes under nitro-oxidative stress. All compounds 10 analyzed showed target engagement to FKBP12 and low levels of cytotoxicity in vitro. Compounds 10b, 10c, 10h, and 10iR were identified as potential therapeutic candidates to protect myotubes in muscle disorders with underlying nitro-oxidative stress, FKBP12/RyR1 dysfunction and calcium dysregulation.

4-Alkynyl-1,2,3-triazolium cations undergo thermal [3 + 2] cycloaddition reactions with azides roughly 50- to 100-fold faster than comparable noncharged alkynes. Further, the reaction is highly 1,4-regioselective (dr up to 99:1) owing to the selective stabilization of 1,4-TS transition states via conjugative π-acceptor assistance of the alkyne triazolium ring. The novel cationic triazolium alkynes also accelerate the CuAAC reaction to provide bis(1,2,3-triazoles) in an “ultrafast” way (

Experimental and computational studies on dendrimers possessing a Fe(porphyrin) catalytic core and polyether dendritic arms show that these macromolecules promote efficiently the (2+1) cycloaddition between a model alkene and diazomethane. The reaction is kinetically efficient and competitive with smaller catalysts. Lower generations of dendrimers exhibit a normal hyperbolic kinetic behaviour, whereas third- and fourth-generation dendrimers show a sigmoidal kinetic profile, compatible with cooperative effects most likely due to aggregation phenomena. This behaviour resembles that observed for Fe(porphyrin) containing biomolecules such as cytochromes and haemoglobin.

1,3‐Dipolar cycloadditions (1,3‐DC) between imino esters (as precursors of N‐metallated azomethine ylides) and π‐deficient alkenes are promoted by cooperative asymmetric Lewis acid/Brønsted base catalysis. The components of these catalytic pairs are silver salts derived from enantiopure commercially available BINOL‐based phosphoric acids and Cinchona alkaloids. Chiral phosphoric silver(I) salts promote HOMO raising of in situ formed 1,3‐dipoles, whereas protonated cinchona alkaloids generate a LUMO lowering for the dipolarophiles resulting in a global acceleration of the 1,3‐DC. The best results were obtained with BINOL‐derived silver phosphate and hydrocinchonine. Matching between both cooperative metallo‐ and organocatalyst results in an enhanced enantiomeric excess, superior to that reached by both separate components. NOESY experiments and DFT calculations are compatible with a non‐covalent interaction (hydrogen bond) between both catalysts, which results in close contacts and mutually coupled chiral environments. We gratefully acknowledge financial support from the Spanish Ministerio de Economía y Competitividad (MINECO) (projects CTQ2013-43446-P and CTQ2014-51912-REDC) the Spanish Ministerio de Economía, Industria y Competitividad, Agencia Estatal de Investigación (AEI) and Fondo Europeo de Desarrollo Regional (FEDER, EU) (projects CTQ2016-76782-P, CTQ2016-80375-P and CTQ2016-81797-REDC), the Generalitat Valenciana (PROMETEOII/2014/017), the Gobierno Vasco/ Eusko Jaurlaritza (GV/EJ, Grant IT673-13) and the University of Alicante. This work was partially supported by a Grant-in-Aid for Scientific Research from JSPS (17H03060).

A thorough understanding of the morphology of the environmental sensitive nanogels was indispensable to obtain a deeper insight on their stimuli-responsive behavior. Therefore, in this work the colloidal characterization and the study of the inner morphology were related by using light scattering technique and 1H-nuclear magnetic resonance transverse relaxation measurements combined with the Flory–Rehner theory. Different biocompatible and dual-stimuli-sensitive nanogel particles based on poly(2-diethylaminoethyl) methacrylate were synthesized using three different crosslinkers: two bifunctional and one multifunctional. All the nanogels obtained had a core–shell type heterogeneous morphology, but they presented completely different swelling behaviors due to their different crosslinking points’ distribution and polymeric chains’ microstructure. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015, 53, 2017–2025

Financial support was provided by the Spanish Ministerio de Economia y Competitividad (MINECO) and the Fondo Europeo de Desarrollo Regional (FEDER) (projects CTQ2010-16959/BQU, CTQ2012-35535, CTQ2013-40855-R, CTQ2007-62771/BQU, CTQ2010-20387, CTQ2010-17436, and Consolider-Ingenio CSD2007-00006), the University of the Basque Country (UPV/EHU, UFI11/22 QOSYC), the Basque Government (GV/EJ, grant IT-324-07), the Generalitat Valenciana-FEDER (PROMETEO/2009/039), the Gobierno de Aragon-FSE (research group E40), and the University of Alicante. M. d. G. R. thanks the Donostia International Physics Center (DIPC) for a postdoctoral contract. M. S. and L. C. gratefully thank MINECO for a contract funding their PhD projects.

A novel catalytic system based on covalently modified DNA is described., A novel catalytic system based on covalently modified DNA is described. This catalyst promotes 1,3-dipolar reactions between azomethine ylides and maleimides. The catalytic system is based on the distortion of the double helix of DNA by means of the formation of Pt(ii) adducts with guanine units. This distortion, similar to that generated in the interaction of DNA with platinum chemotherapeutic drugs, generates active sites that can accommodate N-metallated azomethine ylides. The proposed reaction mechanism, based on QM(DFT)/MM calculations, is compatible with thermally allowed concerted (but asynchronous) [π4s + π2s] mechanisms leading to the exclusive formation of racemic endo-cycloadducts.

Herein we report the synthesis of “clickable” magnetic nanoparticles (MNPs) stable in suspension in physiological media for bioorthogonal click chemistry applications. These MNPs incorporate into their coating a cyclooctynyl derivative for strain-promoted azide–alkyne (SPAAC) cycloaddition and either a polyethylene glycol or a glucose moiety to ensure MNP stability in physiological media. Their reactivity towards azide-functionalised Si surfaces was investigated, demonstrating their potential as bioorthogonal probes., This work was supported by Fondo Social Europeo de la DGA (grupos DGA), Ministerio de la Economía y Competitividad del Gobierno de España for the public funding of Proyectos I + D + I – Programa Estatal de Investigación, Desarrollo e Innovación Orientada a los Retos de la Sociedad (project no. SAF2014-54763-C2-2-R) and Gobierno Vasco (project IT-1033-16). R. M. F. also acknowledges financial support from Universidad de Zaragoza (JIUZ-2014-CIE-03) and European Union (Marie Skłodowska-Curie grant agreement no. 657215 OUTstandINg).

The synthesis of new waterborne polymer latexes based on renewable linoleic acid (LA) was investigated. Methacrylic functionality was incorporated into the LA and the resulting monomer was successfully polymerized via miniemulsion polymerization. The effect of the initiator amount and type on microstructure was analyzed. Almost totally converted latexes with different microstructures were achieved. Furthermore, the effect of the presence of labile allylic hydrogens on the LA backbone was discussed in terms of microstructural properties, as well as final film properties. The results suggested that LA based latexes have great potential to replace petroleum based waterborne coating materials.

 Aziridines are known to undergo hydrolysis in the presence of cyclodextrins, whereas the latter are largely investigated as potential vectors of biologically active compounds. Despite this easy cyclodextrin-induced cleavage of aziridines in aqueous medium, it was of interest to find out a model aziridine derivative that would be sufficiently water-stable and form a stable complex with b-cyclodextrin in aqueous medium, so that it could be used as a reference in future formulations or vectorization work. Among compounds we have investigated, we found out that only (S)-2-isopropyl-1-(o-nitrophenyl)sulfonyl)aziridine complied with the above-mentioned solubility and stability requirements. NMR studies of the inclusion complex of this derivative with b-cyclodextrin provided useful parameters related to the stoichiometry of the complex and the association constant Ka. The geometry of the complex was assessed by 2D-ROESY experiments, suggesting a deep insertion of the aziridine into the cavity of b-cyclodextrin.

The synthesis of three families of sialyl LewisX (sLeX) mimetics based on triazole and bis-triazole scaffolds is reported. The flexibility of these mimetics is dictated by the scaffold and gradually increases from flexible to rigid. All three families were accessible by straightforward synthetic routes and by taking advantage of the unique features and high yields of CuI-catalyzed alkyne–azide cycloaddition (CuAAC) reaction. Glycopeptidomimetics 12–15 were submitted to an extensive evaluation of their binding affinities towards fucose-specific Ulex Europaeus lectin I by using conformational analysis (molecular dynamics), docking calculations, and saturation-transfer difference (STD) NMR experiments. The results reveal that the recognition of the ligands is mostly dictated by the fucose moiety and that semi-rigid ligands are better sLex mimic candidates because their degree of flexibility enables the modulation of their conformation to the best-fitting position.

Novel enantiopure pseudopeptide models containing a central -(β-lactam)-(Aa)- scaffold characterized by the combined presence of an α-alkyl-α-amino-β-lactam (i+1) residue and a α-substituted (i + 2) amino acid have been readily synthesized from α-alkyl serines. The conformational analysis of such β-lactam pseudopeptides conducted in CDCl(3) and DMSO-d(6) solutions using 1D- and 2D-NMR techniques revealed an equilibrium between β-II turn and γ-turn conformers, which was ultimately modulated by the relative configuration of the -(β-lactam)-(Aa)- residues. Long-range chiral effects on the α-lactam pseudopeptide conformers were also found when two (i) and (i + 3) chiral residues were attached to the termini of a central -(β-lactam)-(Aib)- segment. In such mimetics, heterochiral (i) and (i + 3) residues reinforced a β-II turn conformer, whereas homochiral corner residues stabilized an overlapped β-II/ β-I double turn motif. No β-hairpin nucleation was observed in any instance. In good agreement with the conformers found in solution, β-turned and open structures were also characterized by X-ray crystallography. Relative stabilities of the different conformers were estimated computationally at a B3LYP/6-31++G** calculation level, and finally, a conformation equilibrium model based on steric inter-residual interactions around the -(β-lactam)-(i + 2)- segment was proposed to account for the observed chiral effects.

The α

N3-Alkylation of 1-(pivaloyloxymethyl)-1,2,3-triazoles with alkyl triflates carrying latent “click” functionality, followed by a nucleophile-promoted N1-dealkylation of the resulting strongly electrophilic intermediate triazolium salts, provides an efficient route to 1,5-disubstituted 1,2,3-triazoles. The azide and alkyne groups incorporated by N-alkylation can be submitted to further copper-catalyzed azide–alkyne and Huisgen cycloadditions to provide bis(1,2,3-triazoles) with unprecedented 1,5/1,4 substitution patterns.

4-Alkynyl-1,2,3-triazolium cations undergo thermal [3 + 2] cycloaddition reactions with azides roughly 50- to 100-fold faster than comparable noncharged alkynes. Further, the reaction is highly 1,4-regioselective (dr up to 99:1) owing to the selective stabilization of 1,4-TS transition states via conjugative π-acceptor assistance of the alkyne triazolium ring. The novel cationic triazolium alkynes also accelerate the CuAAC reaction to provide bis(1,2,3-triazoles) in an “ultrafast” way (

N3-Alkylation of 1-(pivaloyloxymethyl)-1,2,3-triazoles with alkyl triflates carrying latent “click” functionality, followed by a nucleophile-promoted N1-dealkylation of the resulting strongly electrophilic intermediate triazolium salts, provides an efficient route to 1,5-disubstituted 1,2,3-triazoles. The azide and alkyne groups incorporated by N-alkylation can be submitted to further copper-catalyzed azide–alkyne and Huisgen cycloadditions to provide bis(1,2,3-triazoles) with unprecedented 1,5/1,4 substitution patterns.

Copper-catalyzed cycloaddition of ethynyltriazoles (I) with azides provides precursors (III) which can be converted into title compounds as shown for (IIIb).

Angiogenesis is a fundamental step in the transition of solid tumors from a dormant state to a malign one. Many of the low-molecular-weight anti-angiogenic drug candidates mimic the short peptide epitope Arg-Gly-Asp (RGD), disrupting the extracellular matrix/integrin adhesion and, ultimately, leading to tumor cell apoptosis. In contrast to the detailed structural information available for the extracellular adhesion inhibition of endothelial cells through the recognition of integrins (typically aVb3) by RGD peptidomimetics, [2] most aspects of possible intracellular angiogenic gene regulation caused by peptidomimetics remain unexplored. Importantly, dysfunction of this signaling system is suspected to be behind the resistance phenomena developed in anti-angiogenic therapies. Inside the endothelial cell, dozens of proteins mediate or control the signaling pathways of angiogenesis after integrin activation, but only a couple of kinases (JNK, ERK) and transcription factors (NFkB, FoxO) are able to promote gene regulation (Figure 1). In addition, large environmental ligands, such as vascular endothelial growth factors (VEGFs) or peptide hormones, are required to elicit proangiogenic gene regulation. In this context, we set out to design alternative lowmolecular-weight RGD probes for interaction with aVb3 integrin and gene regulation in HUVECs. Ideally, these peptidomimetics should: 1) contain a minimal scaffold to prevent undesired scaffold/integrin interactions, 2) have a uniform and predictable scaffold conformation, 3) bear a maximum of recognition groups, including hydrophobic or hydrophilic ones, and 4) permit the deletion of selected residues from the RGD triad without global shape change. We selected five-membered and four-membered small cyclic peptides for development. The residual flexibility of these cyclopeptides can be further constrained by incorporating lactam bridges between neighboring amino acids to stabilize protein secondary structure motifs characterized by combinations of b-turns and/or g-turns. Several lactam pseudopeptides resulting from such an extension of Freidinger’s concept (Scheme 1; 1!2) have been explored with the goals of mimicking receptor-bound conformations of bioactive peptides and of providing pharmacophore information for nonpeptide drug design. However, despite its apparent simplicity, this design is not always reliable for the precise positioning of a maximum number of recognition groups around the pseudopeptide cyclic core. Because the interresidual lactam bridge created by modification of the side chain (R) shares recognition and constraint functions, the design of mimetic libraries becomes difficult and non-general, when synthetically achievable. An alternative way to constrain cyclic peptides is based on the incorporation of a d-amino acid and an N-alkyl-amino acid into the macrocycle, as illustrated by the remarkable aVb3 antagonist cilengitide (3, cyclo-[Arg-Gly-Asp-d-Phe-N(Me)Val]) developed by Kessler et al. Here we report an alternative, more versatile solution to the above design problem, by introducing a-amino-b-lactam scaffolds originating from aCH/NH proton mimicry (Scheme 2; 1! 4). This “b-lactam scaffold-assisted design” (b-LSAD) approach is based on the separation of recognition and constraint groups, and has previously proven efficient for promotion of unusually stable type-II (II’) b-turn peptidomimetics from extended open native peptides. Accordingly, the straight application of the b-LSAD principle to RGD cyclic mimetics led us to the b-lactam pseudopeptides 4a–d, which fulfilled several structural requirements to trigger quite different signaling interactions with aVb3 integrin. The hydrophobic benzyl group in the d-Phe residue of cilengitide (3), for instance, was replaced by the strongly hydrophilic 1,2-dihydroxyethyl moiety in the mimetic 4a or by the poorly hydrophobic methyl group in compound 4b. Conversely, the hydrophobic R–R substituents Figure 1. Signaling pathways initiated by integrins affecting the gene regulation of angiogenesis. ERK=extracellular-signal-regulated kinase, FAK= focal adhesion kinase, FoxO= forkhead box O, JNK=c-Jun N-terminal kinase, NFkB=nuclear factor k of B-cells.

Conformationally restricted NADH peptidomimetics 4a–e, characterized by the presence of a (1,4-dihydronicotinamide)-(β-lactam) moiety, have been synthesized and used to study the Mg2+ cation-promoted asymmetric reduction of alkyl aroylformates in acetonitrile. Increasing the bulkiness of peripheral substituents at the nitrogen atom of the β-lactam ring, at the 1,4-dihydronicotinamide moiety, or at the aroylformate ester group, was found to cause weak but clearly detectable variations of the enantiomeric excess of the reaction. A rational for these observations was consistent with a chelated NADH/Mg2+/ArCOCO2R3 ternary complex model, according to DFT calculations computed at a B3LYP/6-31G∗ theory level.

Unsymmetrically 1,1'-disubstituted 4,4'-bis-1H-1,2,3-triazoles 4 have been prepared from 4-ethynyl-1,2,3-triazoles 5 and azides. Following a "double-click" strategy, two complementary approaches were implemented for the preparation of the key 4-ethynyltriazole intermediates 5: (a) the stepwise Swern oxidation/Ohira-Bestman alkynylation of readily available 4-hydroxymethyl-1,2,3-triazoles 8 and (b) the stepwise cycloaddition of TMS-1,4-butadiyne 9. The method is highlighted by its compatibility with orthogonally protected and functionalized saccharide-peptide hybrids and its ability to be extended to the trisubstituted counterparts 12.

The hydrolysis process suffered by vinylcaprolactam (VCL) monomer during polymerization and the way of avoiding it is a matter of considerable interest when the final material is used in biomedical applications. In this work, in order to study the hydrolysis process in the synthesis of VCL-based microgels, VCL was polymerized by emulsion polymerization in batch and semi-batch reactors by using N,N′-methylenebisacrylamide (BA) as cross-linker and potassium persulfate (KPS) as initiator. Moreover, the partial conversion evolutions of VCL and BA were analyzed by 1H NMR. The colloidal characterization was carried out by measuring the final average diameters as a function of temperature. The results showed that there were two competitive reactions (hydrolysis and propagation) in the polymerizations carried out in the absence of a buffer. However, VCL did not suffer hydrolysis by adding a buffer in the recipes. A new reliable method for the determination of the partial conversions was developed using the quantitative NMR method. The final cross-linked colloidal particles (microgel particles) obtained in the buffered reaction presented the conventional swelling de-swelling behavior corresponding to temperature sensitive microgels.

Lithium metal can be used to reduce single-walled carbon nanotubes (SWNT) to carbide-like species under the catalytic effect of di-tert-butyl-biphenyl (DTBP). The resulting nanotube polycarbanions show a significantly increased dispersability in THF and react "in situ" with trimethylchlorosilane, methyl methacrylate, and methyl N-acetamidoacrylate to afford covalently functionalized silyl nanotubes and polymer-wrapped SWNT. The density and average length of the polymer chains attached to the nanotube wall can be widely modified by varying the amount of monomer, lithium, and catalyst.

This report describes a simple strategy to produce copolymers of tetrahydrofuran (THF) and glycidyl phenyl ether (GPE) by using B(C6F5)3 as a catalyst. The control of the synthesis conditions, such as reaction time, catalyst concentration, and monomer concentration, allows the formation of copolymers with molecular weights in the range of 15-330 kg/mol. MALDI-TOF mass spectrometry revealed that with a low THF content in the feed cyclic copolymers are the major reaction products, whereas with a high THF content, linear copolymers are the main products. To explain these results, a zwitterionic ring-opening copolymerization mechanism was postulated based on DFT calculations and experimental results. Physical properties of the resulting copolymers demonstrated that by changing the relative amounts of monomers copolymers with tailored glass transition temperatures in a broad range of temperatures from-84 to-4 °C can be obtained and that crystallization of THF fragments can be suppressed. Rheological measurements showed that by controlling the degree of crystallization, copolymers with rubber-like behavior can be obtained in a broad temperature range below room temperature., We gratefully acknowledge support from MINECO (MAT2012-31088, CTQ2011-25572), Basque Government (IT-654-13, GVIT373-10), Diputacion Foral de Gipuzkoa (2011-CIEN-000085-01), University of the Basque Country (UFI 11/56), and Fundacion Domingo Martínez (Ayudas a la investigacion, 2012). Technical and human support provided by NMR facility and IZO-SGI, SGIker (UPV/EHU, MICINN, GV/EJ, ERDF and ESF), is also acknowledged.

[reaction: see text] Ring opening of alpha-substituted-alpha-methoxycarbonyl-N-nosylaziridines provides a practical access to enantiopure alpha,alpha'-disubstituted beta-lactam scaffolds, novel types of ditopic reverse turn surrogates. The procedure is general, short, and high yielding and starts from handy alpha-substituted serinates and alpha-amino acid derivatives.

The achiral bis(trimethylsilyl)methyl group acts as an efficient stereochemical determinant of the α-alkylation reaction in β-branched α-phenyloxazolidinyl- or α-diphenyloxazolidinyl-β-lactams and ...

This article introduces a method for the determination of chlorogenic acid in apple juices by measuring its signal at 7.20 ppm in the 1 H NMR spectrum. The method is direct and does not need any previous derivatization. The addition to the juice of 1,3,5-benzenetricarboxylic acid as internal standard allows the determination of the absolute concentration of chlorogenic acid. Ascorbic acid is also added to prevent enzymatic oxidation of the phenolic compounds and to adjust the pH to 2.74, since the chemical shifts of some compounds vary with the pH. A standard addition method performed with the juices of three different varieties of apples gave recoveries between 91 and 107%. The precision of the method was tested for repeatability (n=5) and reproducibility (n=15), obtaining coefficient of variation of 5.7 and 7.5%, respectively, for a sample of Gezamina apple juice (586 mg l−1 chlorogenic acid).

Mesoionic 4,4′-bis(1,2,3-triazole-5,5′-diylidene) Rh(I) complexes having a C2 chiral 4,4′-axis were accessed from 3-alkyltriazolium salts in virtually complete de. Their structure and configurational integrity were assessed by NMR spectroscopy, X-ray crystallography, and chiral HPLC. Computational analysis of the MICs involved in the reaction suggested the formation of a highly stable and unprecedented cation-carbene intermediate species, which could be evidenced experimentally by cyclic voltammetry analysis.

The stereocontrolled synthesis of the Angiotensin Converting Enzyme (ACE) inhibitor enalapril is reported. The key transformation of the synthesis is a formal carboxylation of imines, which lies in the sequence: imine-ketene (2+2) cycloaddition reaction, ring expansion of the resulting 3- hydroxy β-lactam to a N-carboxy α-amino acid anhydride (NCA), and final opening of the NCA with alcohols.

A new method of generating cyclic polyethers is reported. Glycidyl monomers react with B(C6F5)3 to generate cyclic polyethers under anhydrous conditions. In the presence of water, linear chains are formed. A zwitterionic ring-opening polymerization mechanism is postulated based on experimental evidence and DFT calculations. The obtained cyclic polyethers can be considered a new family of crown ethers, where peripheral functional groups such as phenyls, fluorinated aliphatic chains or hydroxyls decorate the rings.

α,α-Dichloro β-lactones, readily obtained by a highly diastereoselective cycloaddition of dichloroketene to N-Boc-α-amino aldehydes and α-(silyloxy) aldehydes, coupled efficiently with α-amino acid...

Short α,β,α-tripeptides comprising a central chiral trisubstituted β 2,2,3*-amino acid residue form unusual γ-turns and δ-turns in CDCl 3 and DMSO-d 6 solutions but do not form β-turns. Thermal coefficients of backbone amide protons, 2D-NMR spectra, and molecular modeling revealed that these motifs were strongly dependent on the configuration (chiral effect) of the central β-amino acid residue within the triad. Accordingly, SSS tripeptides adopted an intraresidual γ-turn like (C6) arrangement in the central β-amino acid, whereas SRS diastereomers preferred an extended δ-turn (C9) conformation. A different SRS-stabilizing bias was observed in the crystal structures of the same compounds, which shared the extended δ-turn (C9) found in solution, but incorporated an additional extended β-turn (C11) to form an overlapped double turn motif., We thank the Gobierno Vasco (Project SAIOTEK S-PR10BF02) and Ministerio de Ciencia e Innovación (Project CTQ2009-07109) for financial support and SGIker UPV/EHU for NMR facilities. C.J.S. thanks Gobierno de Canarias for a predoctoral fellowship.

Copper-catalyzed cycloaddition of ethynyltriazoles (I) with azides provides precursors (III) which can be converted into title compounds as shown for (IIIb).

The cycloaddition reaction of the Evans-Sjogren ketenes to imines, followed by α-hydroxylation of the resulting cycloadducts provides an efficient general asymmetric synthesis of α-keto β-lactams and derivatives.

A general access to 3-hydroxy-4-(1-hydroxyalkyl)-β-lactams with a C4–C1′ relative configuration unlike is provided. The subsequent oxidative ring expansion of the corresponding 3-hydroxy β-lactam smoothly affords an α-amino acid N-carboxy anhydride (NCA) formally derived from (2S,3S)-β-substituted serine, which upon sequential peptide coupling furnishes the tripeptide segment 2 , present in lysobactin.

The cycloaddition reaction of the Evans-Sjogren ketenes to imines, followed by α-hydroxylation of the resulting cycloadducts provides an efficient general asymmetric synthesis of α-keto β-lactams and derivatives.

A convenient route to the β-hydroxy α-aminoacid-derived tripeptides found in the macrocyclic peptide lactone antibiotic lysobactin from azetidin-2-one frameworks is provided for the first time.

α,α-Dichloro β-lactones, readily obtained by a highly diastereoselective cycloaddition of dichloroketene to N-Boc-α-amino aldehydes and α-(silyloxy) aldehydes, coupled efficiently with α-amino acid...

Unsymmetrically 1,1'-disubstituted 4,4'-bis-1H-1,2,3-triazoles 4 have been prepared from 4-ethynyl-1,2,3-triazoles 5 and azides. Following a "double-click" strategy, two complementary approaches were implemented for the preparation of the key 4-ethynyltriazole intermediates 5: (a) the stepwise Swern oxidation/Ohira-Bestman alkynylation of readily available 4-hydroxymethyl-1,2,3-triazoles 8 and (b) the stepwise cycloaddition of TMS-1,4-butadiyne 9. The method is highlighted by its compatibility with orthogonally protected and functionalized saccharide-peptide hybrids and its ability to be extended to the trisubstituted counterparts 12.

A straightforward method for the synthesis of polyhydroxylated α-amino acid N-carboxy anhydrides (NCAs) is described as the means by which short peptide segments comprised of a polyhydroxylated chain are easily affordable. The entire sequence lies in the preparation of nonracemic 3-hydroxy β-lactams through the highly diastereoselective Staudinger reaction of hydroxyketene equivalents with chiral α-oxyaldehyde-derived imines, followed by TEMPO radical assisted cycloexpansion to the corresponding NCA and subsequent peptide coupling with α-amino acid esters. The method has been applied to the synthesis of short peptide segments derived from carbamoylpolyoxamic acid, some glycoglycines, as well as C2 symmetric hydroxy amino acids.

A general access to 3-hydroxy-4-(1-hydroxyalkyl)-β-lactams with a C4–C1′ relative configuration unlike is provided. The subsequent oxidative ring expansion of the corresponding 3-hydroxy β-lactam smoothly affords an α-amino acid N-carboxy anhydride (NCA) formally derived from (2S,3S)-β-substituted serine, which upon sequential peptide coupling furnishes the tripeptide segment 2 , present in lysobactin.

The use of proton nuclear magnetic resonance ((1)H-NMR) for the quantification of additives in an electrolytic Zn bath is reported. A simple and quick method is described that does not need any prior sample preparation. Contrary to other analytical methods, the three additives in the bath, benzylidene acetone (BDA), benzoic acid (BA) and poly(ethylene glycol) (PE400), can be quantified. Two calibration methods were tried: integration of NMR signals with the use of an internal standard and partial least squares (PLS) regression applied to the characteristic NMR peaks. Both methods are compared and the univariate method was preferred because of simplicity, accuracy and precision. The following limits of detection were found: 0.30 g L(-1) BA, 0.08 g L(-1) BDA and 0.7 g L(-1) PE400 with dynamic ranges of at least 1.0-6.0, 0.1-0.6 and 3.0-18.0 g L(-1) respectively. Those concentration ranges are suitable to follow the concentration of additives in the bath in real time. (1)H-NMR spectra provide evidence for the BDA degradation pattern.

Mechanistic details of the Mg(2+) ion-activated enantioselective reduction of methyl benzoylformate have been investigated at a B3LYP/6-31G* theory level, using peptide NADH models 1 rigidified with a beta-lactam ring. Computation of the reaction pathway revealed important structural differences between the intermediate NADH/Mg(2+)/ArCOCO(2)R ternary complexes 3 and the corresponding transition states leading to enantiomeric methyl mandelates. Thus, ternary complexes showed the dihydronicotinamide moiety placed quasiequatorial to a seven-membered chelation pseudoplane including the two amide carbonyls and the Mg(2+) cation, whereas productive transition states were strongly deformed with the dihydronicotinamide group oriented quasiaxial to the chelation pseudoplane. This chelation model was further applied to acyclic nonrigidified NADH models and, based on the fluxional mobility of the peptide chain bonds, experimental enantioselectivities were correctly predicted. Parallel experiments were also conducted in deuterated acetonitrile, using NMR techniques, to study the structure of the binary complexes 2 (NADH/Mg(2+)) and ternary complexes 3 (NADH/Mg(2+)/PhCOCO(2)Me). Finally, owing to the incorporation of two diastereotopic trimethylsilyl NMR-tags in the beta-lactam-NADH peptidomimetics, a nonproductive ternary complex predicted by calculations could be observed and its structure characterized on the basis of ROESY experiments and molecular modeling.

Hybrid glycopeptide β-lactam mimetics designed to bind lectins or carbohydrate recognition domains in selectins have been prepared according to a “shape-modulating linker” design. This approach was implemented using the azide−alkyne “click” cycloaddition reaction, and as shown by NMR/MD experiments, binding of the resulting mimetics to Ulex Europaeus Lectin-1 (UEL-1) occurred after a “bent-to-extended” conformational change around a partially rotatable triazolylmethylene moiety.

4 páginas, 3 figuras, 2 tablas, 3 esquemas -- PAGS nros. 2227-2230, Hybrid glycopeptide beta-lactam mimetics designed to bind lectins or carbohydrate recognition domains in selectins have been prepared according to a "shape-modulating linker" design. This approach was implemented using the azide-alkyne "click" cycloaddition reaction, and as shown by NMR/MD experiments, binding of the resulting mimetics to Ulex Europaeus Lectin-1 (UEL-1) occurred after a "bent-to-extended" conformational change around a partially rotatable triazolylmethylene moiety, We thank the Ministerio de Educación y Ciencia (MEC, Spain) (Projects: CTQ2006-13891/BQU and CTQ10874-C02-01), UPV/EHU, and Gobierno Vasco (ETORTEK-BiomaGUNE IE-05/143) for financial support and SGIker UPV/EHU for NMR facilities. A grant from Gobierno Vasco to I.A. is acknowledged