Racemisation in Chemistry and Biology

The two enantiomers of a compound often have profoundly different biological properties and thus their liability to racemisation in aqueous solutions is an important piece of information. The authors reviewed the available data concerning the process of racemisation in vivo, in the presence of biological molecules (e.g., racemase enzymes, serum albumin, cofactors and derivatives) and under purely chemical but aqueous conditions (acid, base and other aqueous systems). Mechanistic studies are described critically in light of reported kinetic data. The types of experimental measurement that can be used to effectively determine rate constants of racemisation in various conditions are discussed and the data they provide is summarised. The proposed origins of enzymatic racemisation are presented and suggest ways to promote the process that are different from processes taking place in bulk water. Experimental and computational studies that provide understanding and quantitative predictions of racemisation risk are also presented.     

Kinetic evidence for hydrophobically stabilized encounter complexes formed by hydrophobic esters in aqueous solutions containing monohydric alcohols.

The pH-independent hydrolysis of four esters, p-methoxyphenyl 2,2-dichloroethanoate (1a), p-methoxyphenyl 2,2-dichloropropanoate (1b), p-methoxyphenyl 2,2-dichlorobutanoate (1c), and p-methoxyphenyl 2,2-dichloropentanoate (1d), in dilute aqueous solution has been studied as a function of the molality of added cosolutes ethanol, 1-propanol, and 1-butanol. The rate constants for the neutral hydrolysis decrease with increasing cosolute concentration. These kinetic medium effects respond to both the hydrophobicity of the ester and of the monohydric alcohol. The observed rate effects were analyzed using both a thermodynamic and a kinetic model. The kinetic model suggests a molecular picture of a hydrophobically stabilized encounter complex, with equilibrium constants K(ec) often smaller than unity, in which the cosolute blocks the reaction center of the hydrolytic ester for attack by water. The formation of these encounter complexes leads to a dominant initial-state stabilization as follows from the thermodynamic model. Decreases in both apparent enthalpies and entropies of activation for these hydrolysis reactions correspond to unfavorable enthalpies and favorable entropies of complexation, which confirms that the encounter complexes are stabilized by hydrophobic interactions.     

Quantitative Prediction of Rate Constants for Aqueous Racemization To Avoid Pointless Stereoselective Syntheses

Racemization has a large impact upon the biological properties of molecules but the chemical scope of compounds with known rate constants for racemization in aqueous conditions was hitherto limited. To address this remarkable blind spot, we have measured the kinetics for racemization of 28 compounds using circular dichroism and ¹H NMR spectroscopy. We show that rate constants for racemization (measured by ourselves and others) correlate well with deprotonation energies from quantum mechanical (QM) and group contribution calculations. Such calculations thus provide predictions of the second‐order rate constants for general‐base‐catalyzed racemization that are usefully accurate. When applied to recent publications describing the stereoselective synthesis of compounds of purported biological value, the calculations reveal that racemization would be sufficiently fast to render these expensive syntheses pointless.     

Scale size of magnetic turbulence in tokamaks probed with 30-MeV electrons

Measurements of synchrotron radiation emitted by 30-MeV runaway electrons in the TEXTOR-94 tokamak show that the runaway population decays after switching on neutral beam injection (NBI). The decay starts only with a significant delay, which decreases with increasing NBI heating power. This delay provides direct evidence of the energy dependence of runaway confinement, which is expected if magnetic modes govern the loss of runaways. Application of the theory by Mynick and Strachan [Phys. Fluids 24, 695 (1981)] yields estimates for the "mode width" (delta) of magnetic perturbations: delta<0.5 cm in Ohmic discharges, increasing to delta = 4.4 cm for 0. 6 MW NBI.     

Co-ordination behaviour of a novel bisthiourea tripodal ligand: structural, spectroscopic and electrochemical properties of a series of transition metal complexes

The synthesis of a thiourea substituted derivative of tris(pyridyl-2-methyl)amine (TPA) is reported. Two of the three pyridine rings are substituted in the 6-position with benzoylthiourea groups. These thiourea groups undergo intramolecular hydrogen bonding to form six-membered rings which leaves one N-H group available to form hydrogen bonds with other molecules. This reports details how the complexation of this new ligand with transition metal ions yields complexes with differing geometries. Seven co-ordinate Mn(II) and Cd(II), six co-ordinate Ni(II) and five co-ordinate Co(II), Cu(II) and Zn(II) complexes have been isolated.     

Polypyrrole-palladium nanocomposite coating of micrometer-sized polymer particles toward a recyclable catalyst

A range of near-monodisperse, multimicrometer-sized polymer particles has been coated with ultrathin overlayers of polypyrrole-palladium (PPy-Pd) nanocomposite by chemical oxidative polymerization of pyrrole using PdCl(2) as an oxidant in aqueous media. Good control over the targeted PPy-Pd nanocomposite loading is achieved for 5.2 μm diameter polystyrene (PS) particles, and PS particles of up to 84 μm diameter can also be efficiently coated with the PPy-Pd nanocomposite. The seed polymer particles and resulting composite particles were extensively characterized with respect to particle size and size distribution, morphology, surface/bulk chemical compositions, and conductivity. Laser diffraction studies of dilute aqueous suspensions indicate that the polymer particles disperse stably before and after nanocoating with the PPy-Pd nanocomposite. The Fourier transform infrared (FT-IR) spectrum of the PS particles coated with the PPy-Pd nanocomposite overlayer is dominated by the underlying particle, since this is the major component (>96% by mass). Thermogravimetric and elemental analysis indicated that PPy-Pd nanocomposite loadings were below 6 wt %. The conductivity of pressed pellets prepared with the nanocomposite-coated particles increased with a decrease of particle diameter because of higher PPy-Pd nanocomposite loading. "Flattened ball" morphologies were observed by scanning/transmission electron microscopy after extraction of the PS component from the composite particles, which confirmed a PS core and a PPy-Pd nanocomposite shell morphology. X-ray diffraction confirmed the production of elemental Pd and X-ray photoelectron spectroscopy studies indicated the existence of elemental Pd on the surface of the composite particles. Transmission electron microscopy confirmed that nanometer-sized Pd particles were distributed in the shell. Near-monodisperse poly(methyl methacrylate) particles with diameters ranging between 10 and 19 μm have been also successfully coated with PPy-Pd nanocomposite, and stable aqueous dispersions were obtained. The nanocomposite particles functioned as an efficient catalyst for the aerobic oxidative homocoupling reaction of 4-carboxyphenylboronic acid in aqueous media for the formation of carbon-carbon bonds. The composite particles sediment in a short time (相似文献   

Synthesis and characterization of biocompatible, thermoresponsive ABC and ABA triblock copolymer gelators

The synthesis of doubly thermoresponsive PPO-PMPC-PNIPAM triblock copolymer gelators by atom transfer radical polymerization using a PPO-based macroinitiator is described. Provided that the PPO block is sufficiently long, dynamic light scattering and differential scanning calorimetry studies confirm the presence of two separate thermal transitions corresponding to micellization and gelation, as expected. However, these ABC-type triblock copolymers proved to be rather inefficient gelators: free-standing gels at 37 degrees C required a triblock copolymer concentration of around 20 wt%. This gelator performance should be compared with copolymer concentrations of 6-7 wt% required for the PNIPAM-PMPC-PNIPAM triblock copolymers reported previously. Clearly, the separation of micellar self-assembly from gel network formation does not lead to enhanced gelator efficiencies, at least for this particular system. Nevertheless, there are some features of interest in the present study. In particular, close inspection of the viscosity vs temperature plot obtained for a PPO43-PMPC160-PNIPAM81 triblock copolymer revealed a local minimum in viscosity. This is consistent with intramicelle collapse of the outer PNIPAM blocks prior to the development of the intermicelle hydrophobic interactions that are a prerequisite for macroscopic gelation.     

Kinetics of hydrolysis of 1-benzoyl-1,2,4-triazole in aqueous solution as a function of temperature near the temperature of maximum density,and the isochoric controversy

At temperatures above and below the temperature of maximum density, TMD, for water at ambient pressure, pairs of temperatures exist at which the molar volumes of water are equal. First-order rate constants for the pH-independent hydrolysis of 1-benzoyl-1,2,4-triazole in aqueous solution at pairs of such isochoric temperatures show no unique features. Taken together with previously published kinetic data for the hydrolysis of a range of simple organic solutes in both water and D2O near their respective TMDs, we conclude that special significance in the context of rates of chemical reactions in aqueous solutions should not be attached to the isochoric condition.