The use of liquid chromatography-atmospheric pressure chemical ionization mass spectrometry to explore the in vitro metabolism of cyanoalkyl piperidine derivatives

A LC/MS method using atmospheric pressure chemical ionization, positive ion mode and full scan to measure the in vitro metabolic stability of cyanoalkyl functionalized compounds with the human liver microsomes was employed. Percentage metabolism examined for the five cyanoalkyl piperidines revealed the optimal chain length and positioning of these functions to produce the most metabolically stable compound. The 4-cyanomethyl piperidine derivative was the most stable compound with 15% metabolism after 15 min incubation with human liver microsomes. In general, the major metabolites formed from the cyanoalkyl piperidine derivatives were due to oxidation of the cyanoalkyl chain or the piperidine fragment, resulting in a M+16 ion. However, the 2-cyanomethyl piperidine derivative exhibited an interesting biotransformation pathway with unusual metabolite peaks corresponding to M+5, M-11 and M+21 ions. Data-dependent MS/MS scanning was used to generate daughter ion spectra from the parent compound and its metabolite peaks. Based on the fragmentation analysis, a carboxylic acid, aldehyde and oxidative metabolite of the carboxylic acid structure have been proposed for M+5, M-11 and M+21 ions, respectively.     

Water liquid-vapor equilibria predicted by refined ab initio derived potentials

Coexistence properties for water near the critical point using several ab initio models were calculated using grand canonical Monte Carlo simulations with multiple histogram reweighting techniques. These models, that have proved to yield a good reproduction of the water properties at ambient conditions, perform rather well, improving the performance of a previous ab initio model. It is also shown that bulk geometry and dipole values, predicted by the simulation, can be used and a good approximation obtained with a polarizable rigid water model but not when polarization is excluded.     

Interactions in large, polyaromatic hydrocarbon dimers: application of density functional theory with dispersion corrections

The interactions within two models for graphene, coronene and hexabenzocoronene (HBC), and (H 3C(CH 2) 5) 6-HBC, a synthesizable model for asphaltenes, were studied using density functional theory (DFT) with dispersion corrections. The corrections were implemented using carbon atom-centered effective core-type potentials that were designed to correct the erroneous long-range behavior of several DFT methods. The potentials can be used with any computational chemistry program package that can handle standard effective core potential input, without the need for software modification. Testing on a set of common noncovalently bonded dimers shows that the potentials improve calculated binding energies by factors of 2-3 over those obtained without the potentials. Binding energies are predicted to within ca. 15%, and monomer separations to within ca. 0.1 A, of high-level wave function data. The application of the present approach predicts binding energies and structures of the coronene dimer that are in excellent agreement with the results of other DFT methods in which dispersion is taken into account. Dimers of HBC show extensive binding in pi-stacking arrangements, with the largest binding energy, 44.8 kcal/mol, obtained for a parallel-displaced structure. This structure is inline with the published crystal structure. Conformations in which the monomers are perpendicular to one another are much more weakly bound and have binding energies less than 10 kcal/mol. For dimers of (H 3C(CH 2) 5) 6-HBC, which contain 336 atoms, we find that a slipped-parallel structure with C s symmetry has a binding energy of 52.4 kcal/mol, 8.9 kcal/mol lower than that of a bowl-like, C 6 v -symmetric structure.     

Quantum chemical study of low temperature oxidation mechanism of dibenzofuran

A density functional theory (DFT) study of the reaction of dibenzofuranyl radical with oxygen molecule has been made. The geometries, energies, and vibrational frequencies of the reactant, transition states, intermediates, and products have been calculated at the B3LYP/6-311+G(3df,2p)//B3LYP/6-31G(d) level of theory. The initial reaction of dibenzofuran (DBF) with molecular oxygen results in the formation of the 1-dibenzofuranylperoxy radical. The stability of this adduct toward decomposition at low to intermediate temperatures results in it undergoing several possible rearrangements. The lowest energy pathway with a barrier of 24.2 kcal/mol involves a rearrangement to the 1,1-dioxadibenzofuran radical. The next lowest energy pathway involves fission of the O-O linkage whose reaction energy was found to be 37.6 kcal/mol. Transition state theory (TST) calculations indicate that the lowest energy pathway should predominate at temperatures up to about 1200 K. Two other unimolecular reaction pathways with barriers of 45.5 and 91.1 kcal/mol have also been discovered. The latter pathway leads to the formation of a para-quinone (dibenzofuran quinone) which has been detected experimentally in the low-temperature oxidation of DBF [Marquaire, P. M.; Worner, R.; Rambaud, P.; Baronnet, F. Organohalogen Compd. 1999, 40, 519]. Our quantum calculations, however, do not support this latter pathway to quinone formation. Instead, the quinone is most probably formed as a consequence of recombination of the 1-dibenzofuranyloxy radical (produced by peroxy fission) with an O atom in the para position. Each of the unimolecular reaction pathways have been subjected to detailed quantum chemical investigation and transition states and intermediates leading to the final products (principally CO, CO2, and C2H2 with traces of benzofuran and benzene) have been identified. For certain stable intermediates, their possible reactions with molecular oxygen have been further investigated quantum chemically. The present work therefore presents a detailed quantum chemical investigation of the reaction pathways in the low-temperature oxidation mechanism of DBF. Since the dibenzofuran moiety is present in the polychlorinated DBFs, our conclusions should be generally applicable to this family of compounds.     

Shock tube pyrolysis of pyrrole and kinetic modeling

The kinetics of pyrolysis of pyrrole dilute in argon have been studied in a single pulse shock tube, using capillary column GC, together with GC/MS and FTIR for product identification, over the temperature range 1200–1700 K, total pressures of 7.5–13.5 atm and nominal mixture compositions of pyrrole of 5000 and 700 ppm (nominal concentrations of 5 × 10^?7 and 7 × 10^?8 mol cm^?3). Time-resolved measurements of the rate of disappearance of pyrrole behind reflected shock waves have been made by absorption spectroscopy at 230 nm, corresponding to the lowest ¹π* ← ¹π transition of pyrrole at pressures of 20 atm and mixture compositions between 1000–2000 ppm pyrrole (1.7–3.0 × 10^?7 mol cm^?3) over the temperature range of 1300 to 1700 K. At the lower end of the studied temperature range, the isomers of pyrrole, allyl cyanide and cis- and trans-crotononitrile, were the principal products, together with hydrogen cyanide and propyne/allene. At elevated temperatures, acetylene, acetonitrile, cyanoacetylene, and hydrogen became important products. The rate of overall disappearance of pyrrole, as measured by absorption spectrometry, was found to be first order in pyrrole concentration, with a rate constant k_dis(pyrrole) = 10^14.1±0.7 exp(?74.1 ± 3.0 kcal mol^?1/RT) s^?1 between 1350–1600 K and at a pressure of 20 atm. First order dependence of pyrrole decomposition and major product formation was also observed in the single pulse experiments over the range of mixture compositions studied. A 75-step reaction model is presented and shown to substantially fit the observed temperature profiles of the major product species and the reactant profile. In the model the initiation reaction is postulated to be the reversible formation of pyrrolenine, (2H-pyrrole). Pyrrolenine can undergo ring scission at the C2? N bond forming a biradical which can rearrange to form allyl cyanide and crotononitrile or undergo decomposition to form HCN and C₃H₄ or acetylene and a precursor of acetonitrile. The model predicts an overall rate of disappearance of pyrrole in agreement with the experimental measurements.     

Extended-cavity grating-tuned operation of mid-infrared InAsSb diode lasers

2 cryostat that permits placement of both the collimation optics and the extended-cavity elements within a vacuum chamber. We have observed tuning of the laser frequency over a 1.44 THz (48 cm^-1) range by rotation of the external grating. This result was obtained without anti-reflection coating of the laser output facet. Received: 8 July 1997/Revised version: 31 July 1997     

Theoretical investigation into the low-temperature oxidation of ethylbenzene

The classical topic on the oxidation of alkylbenzene has been revisited via performing accurate theoretical calculations to address the salient features for the initial oxidation of ethylbenzene. Potential energy surfaces are mapped out for all possible reactions in the systems of (1-phenylethyl + O₂ and 2-phenylethyl + O₂). Reaction rate constants at the high-pressure limit are calculated for all possible reactions in these two systems. Direct H abstraction from 1-phenylethyl radical by oxygen molecule appears to be an important route for the formation of styrene from the oxidation of ethylbenzene. Concerted elimination of HO₂ is predicted to contribute significantly the production of styrene from system of 2-phenylethyl + O₂; especially at the atmospheric pressure and intermediate temperatures. Formation of the other major experimental product, benzaldehyde, is attributed to the unimolecular decomposition of C₆H₅CH₂(O)CH₃ rather than to unimolecular isomerisation of the two initial peroxy adducts. Kinetic and mechanistic data presented herein are instrumental for better understanding of the oxidative decomposition of ethylbenzene, i.e., major constituents of commonly formulated fuel surrogates.     

Dispersion interactions in density‐functional theory

Density‐functional theory (DFT) allows for the calculation of many chemical properties with relative ease, thus making it extremely useful for the physical organic chemistry community to understand and focus on various experiments. However, density‐functional techniques have their limitations, including the ability to satisfactorily describe dispersion interactions. Given the ubiquitous nature of dispersion in chemical and biological systems, this is not a trivial matter. Recent advances in the development of DFT methods can treat dispersion. These include dispersion‐corrected DFT (using explicit, attractive dispersion terms), parameterized functionals, and dispersion‐correcting potentials, all of which can dramatically improve performance for dispersion‐bound species. In this perspective, we highlight the achievements made in modeling dispersion using DFT. We hope that this will provide valuable insight to both computational chemists and experimentalists, who aim to study physical processes driven by dispersion interactions. Copyright © 2009 John Wiley & Sons, Ltd.