Experimental and theoretical study of the mechanism for the kinetic of elimination of methyl carbazate in the gas phase

The elimination kinetic of methyl carbazate in the gas phase was determined in a static system over the temperature range of 340–390 °C and pressure range of 47–118 Torr. The reaction is homogeneous, unimolecular, and obeys a first order rate law. The decomposition products are methyl amine, nitrous acid, and CO gas. The variation of the rate coefficients with temperatures is given by the Arrhenius expression: log k₁ (s^?1) = (11.56 ± 0.34) ? (180.7 ± 4.1) kJ mol^?1(2.303 RT)^?1. The estimated kinetics and thermodynamics parameters are in good agreement to the experimental values using B3LYP/6‐31G (d,p), and MP2/6‐31G (d,p) levels of theory. These calculations imply a molecular mechanism involving a concerted non‐synchronous quasi three‐membered ring cyclic transition state to give an unstable intermediate, 1,2‐oxaziridin‐3‐one. Bond order analysis and natural charges implies that polarization of O (alkyl)? C (alkyl) bond of the ester is rate determining in this reaction. Copyright © 2008 John Wiley & Sons, Ltd.     

Non‐Hydrolyzable RNA–Peptide Conjugates: A Powerful Advance in the Synthesis of Mimics for 3′‐Peptidyl tRNA Termini

Translation of specific small peptides on the ribosome can confer resistance to macrolide antibiotics. To reveal the molecular details of this and related phenomena, stable RNA–peptide conjugates that mimic peptidyl‐tRNA would be desirable, especially for ribosome structural biology. A flexible solid‐phase synthesis strategy now allows efficient access to these highly requested derivatives without restriction on the RNA and peptide sequences.

     

Optical imaging of bacterial infection in living mice using a fluorescent near-infrared molecular probe

An optical imaging probe was synthesized by attaching a near-infrared carbocyanine fluorophore to an affinity group containing two zinc(II) dipicolylamine (Zn-DPA) units. The probe has a strong and selective affinity for the surfaces of bacteria, and it was used to image infections of Gram-positive S. aureus and Gram-negative E. coli bacteria in living nude mice. After intravenous injection, the probe selectively accumulates at the sites of localized bacterial infections in the thigh muscles of the mice.     

Synthesis of nanometer-scale polymeric structures on surfaces from template assisted admicellar polymerization: a comparative study with protein adsorption

A novel method for the formation of nanometer-scale polymer structures via template assisted admicellar polymerization (TAAP) is described. Admicellar polymerization uses a surfactant layer adsorbed on a surface to localize monomer to the surface prior to polymerization of the monomer. Nanostructures are formed by restricting adsorption to the uncovered sites of an already-templated surface, in this case to the interstitial sites between adsorbed latex spheres. Unlike most other process that form polymer nanostructures, polymer dimensions can be significantly smaller than the interstitial size because of sphere-surfactant interactions. Protein adsorption in the interstitial sites of colloidal arrays was also studied for three different proteins, and the results were compared with those obtained via admicellar polymerization.     

The mechanism of the gas-phase elimination kinetics of the β,γ-unsaturated aldehyde 2,2–dimethyl-3-butenal: a theoretical study

The study on the mechanism of the gas-phase elimination or thermal decomposition kinetics of 2, 2-dimethyl-3-butenal has been carried out by using theoretical calculation at MP2, combined ab initio CBSQB3 and DFT (B3LYP, B3PW91, MPW1PW91, PBEPBE, PBE1PBE, CAMB3LYP, M06, B97d) levels of theory. A good reasonable agreement between experimental and calculated parameters was obtained by using CAMB3LYP/6-311G(d,pd) calculations. The contrasted calculated parameters against experimental values suggested decarbonylation reaction to proceed through a concerted five-membered cyclic transition state type of mechanism, involving the hydrogen transfer from the carbonyl carbon to the gamma carbon, consistent with observed kinetic isotope effect. The breaking of alpha carbon–carbonyl carbon bond to produce carbon monoxide is 50% advanced in the transition state. The reaction mechanism may be described as a concerted moderately non-synchronous process. Examination of the Atoms in Molecules (AIM) analysis of electron density supports the suggested mechanism.     

Electrocyclic [1,5] hydrogen shift in the thermal elimination kinetics of phenyl acetate and p-tolyl acetate in the gas phase: a density functional theory study

The kinetics and mechanisms of thermal decomposition of phenyl acetate and p-tolyl acetate in the gas phase were studied by means of electronic structure calculations using density functional theory methods: B3LYP/6-31G(d,p), B3LYP/6-31++G(d,p), B3PW91/6-31G(d,p), B3PW91/6-31++G(d,p), MPW1PW91/6-31G(d,p), MPW1PW91/6-31++G(d,p), PBE/6-31G(d,p) and PBE/6-31++G(d,p). Two possible mechanisms have been considered: mechanism A is a stepwise process involving electrocyclic [1,5] hydrogen shift to eliminate ketene through concerted six-membered cyclic transition-state structure, followed by tautomerisation of cyclohexadienone or by 4-methyl cyclohexadienone intermediate to give the corresponding phenol. Mechanism B is a one-step concerted [1,3] hydrogen shift through a four-membered cyclic transition-state geometry, to produce ketene and phenol or p-cresol. Theoretical calculations showed reasonable agreement with experimental activation parameters when using the Perdew, Burke and Ernserhof (PBE)functional, through the stepwise [1,5] hydrogen-shift mechanism. For mechanism B, large deviation for the entropy of activation was observed. No experimental data were available for p-tolyl acetate; however, theoretical calculations showed similar results to phenyl acetate, thus supporting the stepwise mechanism for both phenyl acetate and p-tolyl acetate.     

Characterization of in vitro metabolic profiles of cinitapride obtained with liver microsomes of humans and various mammal species using UHPLC and chemometric methods for data analysis

An ultra-high performance liquid chromatographic method has been utilized to obtain metabolic profiles of cinitapride with liver microsomes of humans and various mammal species such as rats, mice, mini pigs, dogs, and monkeys. Metabolites have been generated by incubation of cinitapride in the presence of microsomes using nicotinamide adenine dinucleotide phosphate as a cofactor. Incubation times from 15 to 60 min have been assayed. Cinitapride and its metabolites have been separated by reversed-phase C₁₈ mode using ammonium formate aqueous solution (pH 6.5) and acetonitrile as the components of the mobile phase. Concentrations of metabolites in the incubated samples have resulted in an excellent source of multivariate data to be used to extract metabolic information. Statistic parameters and principal component analysis have been used to compare the in vitro metabolism of humans with the other species.     

Theoretical study of methoxy group influence in the gas‐phase elimination kinetics of methoxyalkyl chlorides

The unimolecular gas‐phase elimination kinetics of 2‐methoxy‐1‐chloroethane, 3‐methoxy‐1‐chloropropane, and 4‐methoxyl‐1‐chloroburane has been studied by using density functional theory (DFT) methods to propose the most reasonable mechanisms of decomposition of the aforementioned compounds. Calculation results of 2‐methoxy‐1‐chloroethane and 3‐methoxy‐1‐chloropropane suggest dehydrochlorination through a concerted nonsynchronous four‐centered cyclic transition state (TS) to give the corresponding olefin. In the case of 4‐methoxyl‐1‐chloroburane, in addition to the 1,2‐elimination mechanism, the anchimeric assistance by the methoxy group, through a polar five‐centered cyclic TS, provides additional pathways to give 4‐methoxy‐butene, tetrahydrofuran and chloromethane. The bond polarization of the C? Cl, in the direction of C^δ+ ··· Cl^δ?, is the limiting step of these elimination reactions. The significant increase in rate together with the formation of a cyclic product tetrahydrofuran in the gas‐phase elimination of 4‐methoxyl‐1‐chloroburane is attributed to neighboring group participation of the oxygen of the methoxy group in the TS. The theoretical calculations show a good agreement with the reported experimental results. © 2011 Wiley Periodicals, Inc. Int J Quantum Chem, 2011     

Controlled Release from and Tissue Response to Physically Bonded Hydrogel Nanoparticle Assembly

Our recent work on synthesis and application of thermally gelling nanoparticle dispersions is briefly reviewed here. These nanoparticles consist of interpenetrating polymer networks (IPN) of poly-acrylic acid (PAAc) and poly(N-isopropylacrylamide) (PNIPAM). The aqueous IPN nanoparticle dispersions with polymer concentrations above 2.5 wt % underwent an inverse thermoreversible gelation at about 33 °C. Dextran markers of various molecular weights as model macromolecular pseudodrugs were mixed with the IPN nanoparticle dispersion at room temperature. At body temperature, the dispersion became a gel. The dextran release profiles were then measured using UV-visible spectroscopy. The biocompatibility of this nanoparticle assembly was assessed using an animal implantation model.     

A multidomain discretization method with local mesh refinement

We introduce a nonconforming finite element formulation of asecond-order elliptic problem in the plane. The problem is posedon a domain which is partitioned into disjoint subregions andthe discrete problem is based on an independent triangulationby subregion. We use an integral matching condition at the interfaces.We prove quasi-optimal error estimates and propose an iterativesubstructuring algorithm to solve the system of linear equationsrelated to our discrete problem. The algorithm and its convergenceanalysis rely on an abstract framework of the additive Schwarzmethod.