Stereoselective 1,3-dipolar cycloadditions of nitrones derived from amino acids. Asymmetric synthesis of N-(alkoxycarbonylmethyl)-3-hydroxypyrrolidin-2-ones

Diastereoselective asymmetric 1,3-dipolar cycloadditions of N-(alkoxycarbonylmethyl) nitrones derived from glycine, alanine and phenylalanine have been studied both experimentally and theoretically. Asymmetric induction is evaluated by either introducing a chiral group at the nitrone nitrogen atom or by using Oppolzer's sultam acrylamide. In both cases the sense of the asymmetric induction is the same, the (3R,5R)-isomer being preferentially obtained. The best results were observed with the chiral dipolarophile, which afforded an only isomer in all cases. The obtained isoxazolidines are easily transformed into the corresponding 5-substituted-3-hydroxypyrrolidin-2-ones. DFT studies are in a qualitative agreement with the observed experimental results.     

Approximation of RNA multiple structural alignment

In the context of non-coding RNA (ncRNA) multiple structural alignment, Davydov and Batzoglou (2006) introduced in [7] the problem of finding the largest nested linear graph that occurs in a set G of linear graphs, the so-called Max-NLS problem. This problem generalizes both the longest common subsequence problem and the maximum common homeomorphic subtree problem for rooted ordered trees.In the present paper, we give a fast algorithm for finding the largest nested linear subgraph of a linear graph and a polynomial-time algorithm for a fixed number (k) of linear graphs. Also, we strongly strengthen the result of Davydov and Batzoglou (2006) [7] by proving that the problem is NP-complete even if G is composed of nested linear graphs of height at most 2, thereby precisely defining the borderline between tractable and intractable instances of the problem. Of particular importance, we improve the result of Davydov and Batzoglou (2006) [7] by showing that the Max-NLS problem is approximable within ratio in O(kn²) running time, where mopt is the size of an optimal solution. We also present O(1)-approximation of Max-NLS problem running in O(kn) time for restricted linear graphs. In particular, for ncRNA derived linear graphs, a -approximation is presented.     

Acyclically pushable bipartite permutation digraphs: An algorithm

Given a digraph D=(V,A) and an X⊆V, D^X denotes the digraph obtained from D by reversing those arcs with exactly one end in X. A digraph D is called acyclically pushable when there exists an X⊆V such that D^X is acyclic. Huang, MacGillivray and Yeo have recently characterized, in terms of two excluded induced subgraphs on 7 and 8 nodes, those bipartite permutation digraphs which are acyclically pushable. We give an algorithmic proof of their result. Our proof delivers an O(m²) time algorithm to decide whether a bipartite permutation digraph is acyclically pushable and, if yes, to find a set X such that D^X is acyclic. (Huang, MacGillivray and Yeo's result clearly implies an O(n⁸) time algorithm to decide but the polynomiality of constructing X was still open.)We define a strongly acyclic digraph as a digraph D such that D^X is acyclic for every X. We show how a result of Conforti et al [Balanced cycles and holes in bipartite graphs, Discrete Math. 199 (1-3) (1999) 27-33] can be essentially regarded as a characterization of strongly acyclic digraphs and also provides linear time algorithms to find a strongly acyclic orientation of an undirected graph, if one exists. Besides revealing this connection, we add simplicity to the structural and algorithmic results first given in Conforti et al [Balanced cycles and holes in bipartite graphs, Discrete Math. 199 (1-3) (1999) 27-33]. In particular, we avoid decomposing the graph into triconnected components.We give an alternate proof of a theorem of Huang, MacGillivray and Wood characterizing acyclically pushable bipartite tournaments. Our proof leads to a linear time algorithm which, given a bipartite tournament as input, either returns a set X such that D^X is acyclic or a proof that D is not acyclically pushable.     

Nuclear magnetic resonance spectra of psychotherapeutic agents. V*—conformational analysis of 1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-ones

The conformational analysis of biologically active lofendazam (7-chloro-5-phenyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-one) is carried out by means of lanthanide shift reagent assisted ¹H NMR spectroscopy: the lanthanide induced shift computer simulation suggests that in deuteriochloroform the heterocyclic ring of lofendazam assumes a cycloheptene-like chair conformation, where 1-N moves away from trigonal stereochemistry to a very flattened pyramidal structure. At room temperature the conformational equilibrium is markedly shifted (85%) towards the conformer showing pseudoaxial H-1 and 5-Ph. The remarkable influence of steric requirements in controlling conformation, and the importance of 3- and/or 4-methyl groups in hindering the ring inversion at room temperature, have been verified by conformational analysis of suitable analogous 1,3,4,5-tetraydro-2H-1,5-benzodiazepin-2-ones.     

Synchronized fluxional motion and cyclometalation of ligands in platinum(II) complexes

Oscillation of the 2,9-dimethyl-1,10-phenanthroline (dmphen) ligand between nonequivalent exchanging sites in [Pt(Me)(dmphen)(P(o-tolyl)3)]+ and phosphane rotation around the Pt-P bond take place at the same rate. Thus, this cationic complex behaves as a molecular gear, exhibiting a fascinating synchronism between two otherwise independent fluxional motions. The process (DeltaG(3330)(#) = 68.5 +/- 0.2 kJ mol(-1)) was found to be unaffected by (i) the nature of various counteranions (X = PF6- 1, SbF6- 2, CF3SO3- 3, BF4- 4, BArf- 5), (ii) the polarity or the electron-donor properties of the solvent and, (iii) the addition of weak nucleophiles. Restricted phosphane rotation around the Pt-P bond impedes free dmphen oscillation in a 14-electron three-coordinate T-shaped intermediate, containing eta1-coordinated dmphen, generated by easy Pt-N bond dissociation from [Pt(Me)(dmphen)(P(o-tolyl)3)]+. 1-5 undergo easy orthoplatination, leading to new [Pt(dmphen){CH2C6H4P(o-tolyl)2-kappaC,P}]X cyclometalated Pt(II) compounds (X = PF6- 1, SbF6- 2, CF3SO3- 3, BF4- 4, BArf- 5). The kinetics of the cyclometalation of 3 and 4 were followed in tetrachloroethane by both 1H NMR and spectrophotometric techniques (kobs = 1.7 x 10-4 s(-1) at 333 K, DeltaH = 59.3 +/- 3 kJ mol(-1), and DeltaS = -141 +/- 8 J K(-1) mol(-1)). Ring opening of dmphen is again a prerequisite for C-H bond activation, which takes place through a multistep oxidative-addition reductive-elimination pathway. The molecular structure of cyclometalated 10 shows a butterfly shape with two o-tolyl rings projected above and below the coordination plane. Variable-temperature 1H NMR spectra revealed hindered rotation around the P-Cipso(o-tolyl) bonds at rather mild temperatures (DeltaG(3330)(#) = 55.2 +/- 0.4 kJ mol(-1)). Dmphen oscillation results very slowly and is dependent on the nature of the counteranions, of the solvents, and is strongly accelerated by the presence of weak nucleophiles that act as catalysts, according to an associative mode of activation.     

Synthesis and properties of alkynethiolate gold(I) complexes

A series of alkynethiolate gold(I) derivatives have been synthesised by the cleavage of 4-monosubstituted 1,2,3-thiadiazoles in the presence of strong bases. The syntheses of the 1.2,3-thiadiazoles with p-cyanophenyl, p-tolyl, 2-thienyl, 3-thienyl and 9,9-dimethylfluoren-2-yl fragments are also described. All the complexes have been characterised by spectroscopic techniques and the complexes [Au(p-CH3-C6H4-C[triple bond]C-S)PPh3], [Au(3-C4H3S-C[triple bond]C-S)PPh3] and PPN[Au(p-CH3-C6H4-C[triple bond]C-S)(C6F5)] by X-ray analysis. The electrochemically polymerizable mononuclear bis(alkynethiolate) gold(I) complex PPN[Au(3-C4H3S-C[triple bond]C-S)2] is also described, including its electropolymerization and electrochemical properties.     

On the approximability of the minimum strictly fundamental cycle basis problem

We consider the problem of finding a strictly fundamental cycle basis of minimum weight in the cycle space associated with an undirected connected graph G, where a nonnegative weight is assigned to each edge of G and the total weight of a basis is defined as the sum of the weights of all the cycles in the basis. Several heuristics have been proposed to tackle this NP-hard problem, which has some interesting applications. In this paper we show that this problem is APX-hard, even when restricted to unweighted graphs, and hence does not admit a polynomial-time approximation scheme, unless P=NP. Using a recent result on the approximability of lower-stretch spanning trees (Elkin et al. (2005) [7]), we obtain that the problem is approximable within O(log²nloglogn) for arbitrary graphs. We obtain tighter approximability bounds for dense graphs. In particular, the problem restricted to complete graphs admits a polynomial-time approximation scheme.     

Alcohols immobilization onto 2-chlorotritylchloride resin under microwave irradiation

The immobilization of alcohols onto 2-chlorotritylchloride resin using microwave irradiation was studied. Three different Fmoc-aminoalcohols were tested: the phenol-like Fmoc-tyramine, the primary alcohol Fmoc-ethanolamine, and the secondary alcohol Fmoc-4-hydroxypiperidine. Several reaction conditions were evaluated: different bases, reaction times, temperatures, and concentrations. Microwave immobilization resulted is effective in binding to the resin all three types of alcohols with loadings which were superior or comparable to the ‘classical’ methods in shorter time and without employing toxic and racemizing reagents. This method resulted also useful for the immobilization, through the hydroxyl group, of FmocTyrOAll, FmocSerOAll, and FmocThrOAll, important building blocks for the synthesis of cyclic peptides.     

Universal features of the melt elasticity of interacting polymer nanocomposites

We study the structure and linear viscoelasticity of interacting polymer nanocomposites based on mixtures of poly(ethylene oxide) and fumed silica particles. The filler is dispersed within the polymer using two different techniques which lead to different dispersion states. The analysis of the dynamic response of our systems highlights the formation of a stress-bearing network above a critical volume fraction, Φ(c). Extending a two-phase model used to describe weakly interacting systems, we show that above Φ(c) the melt-state elasticity of the composites arises from the independent contributions of a polymer-particle network and a viscous matrix. We also find that, although Φ(c) depends on the initial state of dispersion, the network elasticity scales with volume fraction following a universal power-law, with an exponent ν ≈ 1.8. Such a scaling law has been recently predicted for the stress-bearing mechanism governed by polymer-mediated interactions.     

Development of a new flow reactor for kinetic studies. Application to the ozonolysis of a series of alkenes

A new flow reactor has been developed to study ozonolysis reactions at ambient pressure and room temperature (297 ± 2 K). The reaction kinetics of O(3) with 4-methyl-1-pentene (4M1P), 2-methyl-2-pentene (2M2P), 2,4,4-trimethyl-1-pentene (tM1P), 2,4,4-trimethyl-2-pentene (tM2P) and α-pinene have been investigated under pseudo-first-order conditions. Absolute measurements of the rate coefficients have been carried out by recording O(3) consumption in excess of organic compound. Alkene concentrations have been determined by sampling adsorbent cartridges that were thermodesorbed and analyzed by gas-chromatography coupled to flame ionization detection. Complementary experimental data have been obtained using a 250 L Teflon smog chamber. The following ozonolysis rate coefficients can be proposed (in cm(3) molecule(-1) s(-1)): k(4M1P) = (8.23 ± 0.50) × 10(-18), k(2M2P) = (4.54 ± 0.96) × 10(-16), k(tM1P) = (1.48 ± 0.11) × 10(-17), k(tM2P) = (1.25 ± 0.10) × 10(-16), and k(α-pinene) = (1.29 ± 0.16) × 10(-16), in very good agreement with literature values. The products of tM2P ozonolysis have been investigated, and branching ratios of (21.4 ± 2.8)% and (73.9 ± 7.3)% have been determined for acetone and 2,2-dimethyl-propanal, respectively. Additionally, a new nonoxidized intermediate, 2-methyl-1-propene, has been identified and quantified. A topological SAR analysis was also performed to strengthen the consistency of the kinetic data obtained with this new flow reactor.