Stereoselective enzymatic synthesis of monoglucosyl-myo-inositols with in vivo anti-inflammatory activity

The monoglucosyl-inositols α-d-glucopyranosyl-(1→4)-4d-myo-inositol 3 and α-d-glucopyranosyl-(1→1)-1d-myo-inositol 4 were synthesized by a combined enzymatic transglucosylation and hydrolysis strategy, using cyclodextrin glucosyl transferase (CGTase) from Thermoanaerobacter sp., followed by hydrolysis with Aspergillus niger glucoamylase. The glucosides were separated by preparative HPLC and fully characterized by extensive 1D and 2D NMR studies. The structure of the regioisomer 4 was confirmed by X-ray crystallography of its perbenzoylated derivative 4a. Both isomers demonstrated in vivo anti-inflammatory activity at comparative levels to corticosterone on mouse ear oedema induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) and in rat hind paw oedema induced by carrageenan.     

Resolution and uniqueness of estimated parameters of a model of thin filament regulation in solution

The estimation of chemical kinetic rate constants for any non-trivial model is complex due to the nonlinear effects of second order chemical reactions. We developed an algorithm to accomplish this goal based on the Damped Least Squares (DLS) inversion method and then tested the effectiveness of this method on the McKillop–Geeves (MG) model of thin filament regulation. The kinetics of MG model is defined by a set of nonlinear ordinary differential equations (ODEs) that predict the evolution of troponin–tropomyosin–actin and actin–myosin states. The values of the rate constants are estimated by integrating these ODEs numerically and fitting them to a series of stopped-flow pyrene fluorescence transients of myosin-S1 fragment binding to regulated actin in solution. The accuracy and robustness of the estimated rate constants are evaluated for DLS and two other methods, namely quasi-Newton (QN) and simulated annealing (SA). The comparison of these methods revealed that SA provides the best estimates of the model parameters because of its global optimization scheme. However it converges slowly and does quantify the uniqueness of the estimated parameters. On the other hand the QN method converges rapidly but only if the initial guess of the parameters is close to the optimum values, otherwise it diverges. Overall, the DLS method proves to be the most convenient method. It converges fast and was able to provide excellent estimates of kinetic parameters. Furthermore, DLS provides the model resolution matrix, which quantifies the interdependence of model parameters thereby evaluating the uniqueness of their estimated values. This property is essential for estimating of the dependence of the model parameters on experimental conditions (e.g. Ca²⁺ concentration) when it is assessed from noisy experimental data such as pyrene fluorescence from stopped-flow transients. The advantages of the DLS method observed in this study should be further examined in other physicochemical systems to firmly establish the observed effectiveness of DSL vs. the other parameter estimation methods.     

Relative energy of organic compounds I. Hydrocarbons and their oxygen derivatives

The energies of the following types of compounds are characterized by their calculated relative enthalpies: alkanes and cycloalkanes, alkenes and cycloalkenes, polyolefins and cyclic polyolefins, aromatic hydrocarbons, alcohols and phenols, ethers, peroxides, aldehides and ketones, acetals, carboxylic acids esters, and anhydrides. Stabilization energies of conjugated olefins, benzene, and furan have been estimated.     

Exploiting the Multidentate Nature of Chiral Disulfonimides in a Multicomponent Reaction for the Asymmetric Synthesis of Pyrrolo[1,2‐a]indoles: A Remarkable Case of Enantioinversion

A new multicomponent coupling reaction for the enantioselective synthesis of pyrrolo[1,2‐a]indoles under the catalysis of a chiral disulfonimide is described. The high specificity of the reaction is a consequence of the multidentate character of the Brønsted acid catalyst. Insights from DFT calculations helped explain the unexpected high enantioselectivity observed with the simplest 3,3′‐unsubstituted binaphthyl catalyst as a result of transition‐state stabilization by a network of cooperative noncovalent interactions. The remarkable enantioinversion resulting from the simple introduction of substituents at 3‐ and 3′‐positions, the first reported example of this phenomenon in the context of binaphthalene‐derived Brønsted acid catalysis, was instead attributed to destabilizing steric interactions.     

Structural Diversity in Alkali Metal and Alkali Metal Magnesiate Chemistry of the Bulky 2,6‐Diisopropyl‐N‐(trimethylsilyl)anilino Ligand

Bulky amido ligands are precious in s‐block chemistry, since they can implant complementary strong basic and weak nucleophilic properties within compounds. Recent work has shown the pivotal importance of the base structure with enhancement of basicity and extraordinary regioselectivities possible for cyclic alkali metal magnesiates containing mixed n‐butyl/amido ligand sets. This work advances alkali metal and alkali metal magnesiate chemistry of the bulky arylsilyl amido ligand [N(SiMe₃)(Dipp)]^? (Dipp=2,6‐iPr₂‐C₆H₃). Infinite chain structures of the parent sodium and potassium amides are disclosed, adding to the few known crystallographically characterised unsolvated s‐block metal amides. Solvation by N,N,N′,N′′,N′′‐pentamethyldiethylenetriamine (PMDETA) or N,N,N′,N′‐tetramethylethylenediamine (TMEDA) gives molecular variants of the lithium and sodium amides; whereas for potassium, PMDETA gives a molecular structure, TMEDA affords a novel, hemi‐solvated infinite chain. Crystal structures of the first magnesiate examples of this amide in [MMg{N(SiMe₃)(Dipp)}₂(μ‐nBu)]_∞ (M=Na or K) are also revealed, though these breakdown to their homometallic components in donor solvents as revealed through NMR and DOSY studies.     

Simultaneous Determination of Ascorbic Acid and Uric Acid by Using a PVC/TTF‐TCNQ Composite Electrode as Detector in a FIA System

A PVC/TTF‐TCNQ composite electrode has been employed as detector in a flow injection system. The proposed method allows the simultaneous detection of ascorbic acid (AA) and uric acid (UA) in mixtures by using a FIA system in a simple manner, without pre‐treatment or modified electrode. This method is based on the amperometric determination of (a) ascorbic acid at 0.15 V and (b) both analytes at 0.35 V, being the response linear in the range 1×10^?2–4×10^?4 M for both analytes with detection limits (S/N=3) of 1.2×10^?4 M and 8.1×10^?5 M for AA and UA, respectively.     

Pseudohexagonal crystallinity and thermal and tensile properties of ethene–propene copolymers

Structural (X‐ray diffraction), melting (differential scanning calorimetry), as well as mechanical (tensile tests) characterizations on uncrosslinked ethene–propene copolymer samples, obtained using a metallocene‐based catalytic system and having an ethene content in the range 80–50% by mol, are reported. Samples with an ethene content in the range 80–60% by mol present a disordered pseudohexagonal crystalline phase, whose melting moves from ≈ 40°C down to ≈ −20°C as the ethene content is reduced. The dramatic influence of the crystalline phase on tensile properties of uncrosslinked ethene–propene copolymers is shown. In particular, highest elongation at break values are obtained for samples being essentially amorphous in the unstretched state and partially crystallizing under stretching. On the other hand, lowest tension set values (most elastic behavior) are observed for samples presenting, already in the unstretched state, microcrystalline domains acting as physical crosslinks in a prevailing amorphous phase. © 1999 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 37: 1095–1103, 1999