Sequential one-pot glycosidations catalytically promoted: unprecedented strategy in oligosaccharide synthesis for the straightforward assemblage of the antitumor PI-88 pentasaccharide

The pentasaccharide sequence of the most active components of the antitumor drug PI-88, currently in phase II clinical trial, has been rapidly assembled in high overall yield and in only three steps starting from three monosaccharide building blocks. The procedure takes advantage of the first reported strategy of sequential one-pot glycosidations conducted exclusively under catalytic activation. In addition, the procedure relies only on shelf-stable and mild promoters such as Yb(OTf)(3) and Bi(OTf)(3).     

Computational DFT investigation of vicinal amide group anchimeric assistance in ether cleavage

Density functional theory (DFT) computations in solvent have been used to investigate the mechanism of anchimeric assistance (by a vicinal amide group) in the acid-induced ether cleavage. The calculations were carried out at the B3LYP/6-31G* level of theory via full geometry optimizations within the IEF-PCM continuum solvent model. Two different mechanisms have been investigated here that were previously hypothesized for the rate-determining step of this process: the first (mechanism A1) involves a protonated amide and an ethereal oxygen as the nucleophile, while the second (mechanism A2) involves protonation of the ethereal oxygen followed by a nucleophilic attack of the amide. Computations clearly show that the second (involving protonation of the less basic site) is the most favorite route and leads to the formation of an oxazolidinic intermediate that triggers ether hydrolysis. Results are produced that are in excellent agreement with the experiments, and a rationale for them is provided, which represents a general interpretative basis for similar anchimerically assisted processes, such as the ones characterizing the glycosidic activity of two very important classes of enzymes: beta-hexosaminidases and O-GlcNAcases.     

Palladium complexes of 8-(di-tert-butylphosphinooxy) quinoline

The preparation of the new ligand 8-(di-tert-butylphosphinooxy)quinoline (1) and the palladium derivatives [PdCl₂(1)] (2), [Pd(η³-all)(1)]⁺ [all = C₃H₅ (3a), 1-PhC₃H₄ (3b) and 1,3-Ph₂C₃H₃ (3c)] and [Pd(η²-ol)(1)] [ol = dimethyl fumarate (4a) and fumaronitrile (4b)] is reported. The cationic species 3a-3c have been isolated as salts. The complex 3a(BF₄) is obtained either from the reaction of 1 with [Pd(μ-Cl)(η³-C₃H₅)]₂ or from the reaction of ClP(CMe₃)₂ with [Pd(η³-C₃H₅)(8-oxyquinoline)], followed in both cases by chloride abstraction with NaBF₄. In the complexes, the ligand 1 is P,N chelated to the central metal, as shown by the X-ray structural analysis of 3a(BF₄). At 25 °C in solution, 3a(BF₄) and 3b(BF₄) undergo a fast η³−η¹−η³ dynamic process which brings about a syn-anti exchange only for the allylic protons cis to phosphorus, while for 4a and 4b a slow rotation of the olefin around its bond axis to palladium takes place. The complexes 2 and 3a(BF₄) are efficient catalyst precursors in the coupling of the phenylboronic acid with aryl bromides and chlorides.     

Bottom-up Solution Synthesis of Graphene Nanoribbons with Precisely Engineered Nanopores

The incorporation of nanopores into graphene nanostructures has been demonstrated as an efficient tool in tuning their band gaps and electronic structures. However, precisely embedding the uniform nanopores into graphene nanoribbons (GNRs) at the atomic level remains underdeveloped especially for in-solution synthesis due to the lack of efficient synthetic strategies. Herein we report the first case of solution-synthesized porous GNR ( pGNR ) with a fully conjugated backbone via the efficient Scholl reaction of tailor-made polyphenylene precursor ( P1 ) bearing pre-installed hexagonal nanopores. The resultant pGNR features periodic subnanometer pores with a uniform diameter of 0.6 nm and an adjacent-pores-distance of 1.7 nm. To solidify our design strategy, two porous model compounds ( 1 a , 1 b ) containing the same pore size as the shortcuts of pGNR , are successfully synthesized. The chemical structure and photophysical properties of pGNR are investigated by various spectroscopic analyses. Notably, the embedded periodic nanopores largely reduce the π-conjugation degree and alleviate the inter-ribbon π–π interactions, compared to the nonporous GNRs with similar widths, affording pGNR with a notably enlarged band gap and enhanced liquid-phase processability.     

Myoglobin modification by enzyme-generated dopamine reactive species

The generation of reactive quinone species (DAQ) from oxidation of dopamine (DA) is involved in neurodegenerative pathologies like Parkinson's disease (A. Borta, G. U. H?glinger, J. Neurochem. 2007, 100, 587-595). The oxidation of DA to DAQ can occur either in a single two-electron process or in two consecutive one-electron steps, through semiquinone radicals, giving rise to different patterns of reactions. The former type of reaction can be promoted by tyrosinase, the latter by peroxidases in the presence of H(2)O(2), which can be formed under oxidative stress conditions. Both enzymes were employed for the characterization of the thiol-catechol adducts formed by reaction of DA and cysteine or glutathione, and for the identification of specific amino acid residues modified by DAQs in two representative target proteins, human and horse heart myoglobin. Our results indicate that the cysteinyl-DA adducts are formed from the same quinone intermediate independently of the mechanism of DA oxidation, and that the hallmark of a radical mechanism is the formation of the cystine dimer. The reactivity of quinone species also controls the DA-promoted derivatization of histidine residues in proteins. However, for the modification of the cysteine residue in human myoglobin, a radical intramolecular mechanism has been proposed, in which the protein acts both as the catalyst and target of the reaction. Most importantly, the modification of myoglobins through DAQ linkages, and in particular by DA oligomers, has dramatic effects on their stability, as it induces protein unfolding and incorporation into insoluble melanic precipitates.     

Tricarbonyl rhenium(I) complexes containing a bridging 2,5-diphenyl-1,3,4-oxadiazole ligand: structural, spectroscopic, electrochemical, and computational characterization

The three complexes [Re2(mu-X1)(mu-X2)(CO)6(mu-ppd-kappaN3:kappaN4)] (X1, X2 ) H, 1; X1 ) H, X2 ) Cl, 2; X1, X2 ) Cl, 3; ppd) 2,5-diphenyl-1,3,4-oxadiazole) have been synthesized by different routes, involving the reaction of [Re4(mu3-H)4(CO)12]with ppd for 1, the reaction of 1 with HCl for 2, and the reaction of [ReCl(CO)5] with ppd for 3. The three complexes possess a different number of valence electrons, so the formal Re-Re bond order varies from 2 to 1 to 0 in complexes 1, 2, and 3, respectively. This is reflected in the Re-Re bond distance (277.9, 297.9, and 358.5 pm in the same series)and in the stability of the complexes in the coordinating solvent acetonitrile (t1/2 for ppd displacement 13.6, 4.5, and 3.7 h,for 1, 2, and 3, respectively). Both experimental and calculated structures indicates that coordination induces a distortion from planarity of the diphenyloxadiazole moiety due to the interaction of the equatorial carbonyls with the bridging ppd,which increases on going from 1 to 2 to 3 (dihedral angle between the oxadiazole and the phenyl rings 18.4 degrees, 23.3 degrees, and 45.0 degrees, respectively). The UV spectra show pi-pi* transitions of the oxadiazole ligand (which shift to higher energy on increasing the distortion from the planarity, from 252 to 267 nm) and metal-to-ligand charge transfer absorptions (from 300 to 362 nm). Upon irradiation between 340 and 380 nm, complex 2 only features a weak broad emission at 527 nm(phi)0.02%), whereas upon excitation at 300 nm, the emission typical of free ppd is observed, suggesting photodissociation.Cyclic voltammetry investigations in acetonitrile showed that the three complexes exhibit ligand-centered irreversible reduction peaks (from -1.83 to -1.93 V vs Fc+|Fc), shifted to more positive values with respect to free ppd (-2.50 V). The shift however is smaller than in the analogous derivatives containing 1,2-diazines, suggesting a smaller electron depletion of the heterocycle ligand upon coordination. The complexes also show a metal-centered, bi-electronic, irreversible oxidation peak (from 1.05 to 1.37 V vs Fc+/Fc). A combined density functional and time-dependent density functional (TD DFT)study allowed us to understand the factors affecting the stability of the three complexes and to rationalize their electrochemical and photophysical properties in terms of their electronic structure.     

Effect of charge distribution on the translocation of an inhomogeneously charged polymer through a nanopore

We investigate the voltage-driven translocation of an inhomogeneously charged polymer through a nanopore by utilizing discrete and continuous stochastic models. As a simplified illustration of the effect of charge distribution on translocation, we consider the translocation of a polymer with a single charged site in the presence and absence of interactions between the charge and the pore. We find that the position of the charge that minimizes the translocation time in the absence of pore-polymer interactions is determined by the entropic cost of translocation, with the optimum charge position being at the midpoint of the chain for a rodlike polymer and close to the leading chain end for an ideal chain. The presence of attractive and repulsive pore-charge interactions yields a shift in the optimum charge position toward the trailing end and the leading end of the chain, respectively. Moreover, our results show that strong attractive or repulsive interactions between the charge and the pore lengthen the translocation time relative to translocation through an inert pore. We generalize our results to accommodate the presence of multiple charged sites on the polymer. Our results provide insight into the effect of charge inhomogeneity on protein translocation through biological membranes.     

Carbynes phonons: a tight binding force field

Modeling the vibrational structure of linear carbon chains has proved to be a difficult task with present first-principles calculations. This limits their applicability for the interpretation of experimental data, such as Raman scattering experiments on linear carbon chains within nanotubes. These limitations can be overcome by means of a simple tight binding scheme for pi-electrons. In this work a force field for the calculation of longitudinal phonon dispersion branches is built on the basis of bond-bond polarizabilities and just three parameters. The so obtained phonon dispersion branches are in very good agreement with the experimental data on carbynes in different environments and polyynes of any length. The model is discussed in relation to the importance of long range vibrational interactions in carbynes. The physical phenomena affecting their vibrational properties (i.e., Kohn anomaly, electron-phonon coupling) can be accurately and analytically described by the present approach.     

Electronic and Steric Effects on L-Lactide Ring-Opening Polymerization with NSSN-type Zr(IV) Complexes

In this work the mechanism of L-lactide polymerization promoted by NSSN zirconium complexes was investigated through DFT methods with the aim to understand as the electronic and steric features of the ligand affect the energy reaction. It was observed that the rate determining step of the process is the opening of the L-lactide ring and that by increasing the steric hindrance, evaluated by changing geometric parameters and topographic steric maps, or the electron-withdrawing properties of the ligand, the corresponding energy barrier increases. On the other hand, calculations foresee that a small and electron-releasing substituent on the nitrogen atom of the ligand, such as the methyl group, is desirable in order to obtain NSSN zirconium based catalysts with improved activity in the ROP of the L-lactide.     

The role of dispersive forces determining the energetics of adsorption in Ti zeolites

Ti‐zeolites are interesting materials because of their key role in partial oxidation reactions, as well as under a fundamental point of view being regarded as single site catalysts. Both experimental and computational approaches have been widely applied to the characterization of their active sites, reaching a level of knowledge unmatchable by most other important catalysts. However, several questions are still open, being a proper energetic simulation of the adsorption process of simple molecules, fitting with the experimental outcomes, still missing. The present work wants to underline the role of dispersive forces in correctly determining the adsorption energies of H₂O and NH₃ in Ti chabazite: first dispersive contributions have been included through an ONIOM scheme, comparing the results from semiempirical Grimme scheme and fully ab initio MP2. Being the key contribution of dispersion proved, a fully periodic, Grimme dispersions inclusive approach has been applied, coming to results close to the experimental values. © 2016 Wiley Periodicals, Inc.