The study of reaction mechanism for the transformation of nitronate into nitrile by phosphorus trichloride

Nitronate was generated using β-nitrostyrene and the anion of dimethyl malonate in THF at 0 °C. Subsequent treatment with PCl₃ in the presence/absence of DMAP either in THF or pyridine afforded nitroalkane, chloroxime, and nitrile. Pyridine, THF, and THF-pyridine co-solvent as solvents were investigated under different conditions. With different anions of malonates containing dipolarphiles, cyclic compounds were obtained as major products indicating nitrile oxides were generated during the reaction. Based on the results, compared to that of the one reported in literature, a plausible mechanism involving nitrile oxide intermediate was proposed.     

Theoretical and matrix-isolation experimental study of the infrared spectra of 5-azauracil and 6-azauracil

The infrared absorption spectra of 5-azauracil and 6-azauracil isolated in low-temperature Ar and N₂ matrices are reported. Within the limits of accuracy of spectroscopic measurements, both compounds appear to exist, in Ar and N₂ matrices, exclusively in dioxo tautomeric forms. An assignment of the observed infrared absorption bands is proposed based on the comparison of experimental frequencies and intensities with those calculated theoretically at ab initio Hartree-Fock level with 6-31G** basis set. Infrared spectra predicted at this level of theory reproduce the experimental spectra sufficiently accurately to enable a reliable assignment. Basis set dependency (6-31G**, 3–21G) of the theoretical result was also accounted for and it turned out that for accurate prediction of frequencies and intensities the use of basis set augmented with polarization functions is of crucial importance.     

A simple synthesis of dimethyl 2-pyridone-4, 5-dicarboxylate derivatives

1-Hydroxyphenyl-2-pyridone derivatives 8, 10 and 11 were easily prepared by treatment of methyl isocro-tonate derivatives 6 with base at room temperature in good yields.     

Theoretical and experimental study of nonlinear electrophoresis

Linear and nonlinear electrophoresis of conducting and nonconducting spherical disperse particles is studied. A comparative analysis is performed for the regularities of nonlinear electrophoresis in the stationary and pulsed modes at small and large Peclet numbers.     

Measurement of N-methyl-2-pyridone-5-carboxamide in urine by high performance liquid chromatography

We have previously described a simple and reproducible method for the measurement of nicotinamide and its major metabolite N-methyl-2-pyridone-5-carboxamide (2-pyr) in human plasma. We now describe a low-cost high-throughput method for measurement of urinary 2-pyr, and demonstrate that Isolute C18 bulk can replace use of the column to clean up the samples prior to injection into the HPLC apparatus. Using a standard curve together with an internal standard for each sample, with mean recovery of 2-pyr greater than 95%, the assay has proved reproducible, with considerable savings in cost and time. The principal advantages of this method are the rapid column clean up of samples prior to injection and the simple but effective methodology.     

Theoretical investigation of the first-shell mechanism of nitrile hydratase

The first-shell mechanism of nitrile hydratase (NHase) is investigated theoretically using density functional theory. NHases catalyze the conversion of nitriles to amides and are classified into two groups, the non-heme Fe(III) NHases and the non-corrinoid Co(III) NHases. The active site of the non-heme iron NHase comprises a low-spin iron (S=1/2) with a remarkable set of ligands, including two deprotonated backbone nitrogens and both cysteine-sulfenic and cysteine-sulfinic acids. A widely proposed reaction mechanism of NHase is the first-shell mechanism in which the nitrile substrate binds directly to the low-spin iron in the sixth coordination site. We have used quantum chemical models of the NHase active site to investigate this mechanism. We present potential energy profiles for the reaction and provide characterization of the intermediates and transition-state structures for the NHase-mediated conversion of acetonitrile. The results indicate that the first-shell ligand Cys114-SO- could be a possible base in the nitrile hydration mechanism, abstracting a proton from the nucleophilic water molecule. The generally suggested role of the Fe(III) center as a Lewis acid, activating the substrate toward nucleophilic attack, is shown to be unlikely. Instead, the metal is suggested to provide electrostatic stabilization to the anionic imidate intermediate, thereby lowering the reaction barrier.     

Theoretical and experimental studies of substitution of cadmium into hydroxyapatite

Substitution of cadmium into bulk hydroxyapatite Ca((10-x))Cd(x)(PO(4))(6)(OH)(2) (CdHA: x = 0.12, 1.3, 2.5) is studied by combining X-ray diffraction data from synchrotron radiation, Fourier transform infra-red spectroscopy (FTIR) and density functional theory (DFT) calculations. Energetic and electronic analyses are carried out for several configurations of Cd substitution for Ca at both cationic sites. Rietveld analysis shows preferential occupation of the Ca2 site by cadmium. FTIR data suggest a non-negligible covalent character of Cd-OH. The much-discussed cation site preference for substitution is determined on the basis of relaxed-lattice energetics, and interpreted in terms of chemical concepts; theory indicates that the Ca2 site is clearly favored and this preference is related to the more covalent character of this site compared to that of site 1.     

Theoretical and experimental study of weakly bound CO2-(pH2)2 trimers

The infrared spectrum of CO(2)-(pH(2))(2) trimers is predicted by performing exact basis-set calculations on a global potential energy surface defined as the sum of accurately known two-body pH(2)-CO(2) (J. Chem. Phys. 2010, 132, 214309) and pH(2)-pH(2) potentials (J. Chem. Phys. 2008, 129, 094304). These results are compared with new spectroscopic measurements for this species, for which 13 transitions are now assigned. A reduced-dimension treatment of the pH(2) rotation has been employed by applying the hindered-rotor averaging technique of Li, Roy, and Le Roy (J. Chem. Phys. 2010, 133, 104305). Three-body effects and the quality of the potential are discussed. A new technique for displaying the three-dimensional pH(2) density in the body-fixed frame is used, and shows that in the ground state the two pH(2) molecules are localized much more closely together than is the case for the two He atoms in the analogous CO(2)-(He)(2) species. A clear tunneling splitting is evident for the torsional motion of the two pH(2) molecules on a ring about the CO(2) molecular axis, in contrast to the case of CO(2)-(He)(2) where a more regular progression of vibrational levels reflects the much lower torsional barrier.     

Simultaneous micro-determination of nicotinamide and its major metabolites, N1-methyl-2-pyridone-5-carboxamide and N1-methyl-4-pyridone-3-carboxamide, by high-performance liquid chromatography

A simultaneous micro-determination of nicotinamide and its major metabolites, N1-methyl-2-pyridone-5-carboxamide (2-py) and N1-methyl-4-pyridone-3-carboxamide (4-py) by high-performance liquid chromatography is described. The method employs a 7-ODS-L (250 mm X 4.6 mm I.D., particle size 7 microns) column eluted with 10 mM potassium dihydrogenphosphate-acetonitrile (96:4, v/v; pH adjusted to 3.0 by the addition of concentrated phosphoric acid) at a flow-rate of 1.0 ml/min. The UV detector was set at 260 nm. The detection limits for nicotinamide, 2-py and 4-py were 10 pmol (1.22 ng), 2 pmol (304 pg) and 2 pmol (304 pg), respectively, at a signal-to-noise ratio 5:1. Isonicotinamide was used as an internal standard. The technique was applied to the analysis of rat and human urines. The total analysis time was ca. 15 min.     

Theoretical and experimental study of the vibrational spectrum of N-acetyl-L-alanine

The energies, vibrational frequencies and IR intensities of cis- and trans-N-acetyl-L-alanine (NAAL) are computed using the density functional theory (B3LYP) combined with the 6-311G(d, p) basis set. The trans conformer is characterized by an intramolecular NH ... O hydrogen bond leading to the formation of a five-membered ring and is by 23 kJ mol(-1) more stable than the cis conformer. The difference between the vibrational frequencies and IR intensities computed for the two conformers is discussed. The IR spectra at different temperatures and the Raman spectra of solid NAAL and its deuterated counterpart are investigated and discussed. The frequencies of the v(OH) vibration and the isotopic ratio suggest the formation of short OH ... O hydrogen bonds in the solid state. The NH group seems also to be involved in a weak hydrogen bond.     

Theoretical study of the thermal decomposition of the 5-methyl-2-furanylmethyl radical

The thermal decomposition of the 5-methyl-2-furanylmethyl radical (R(1)), the most important primary radical formed during the combustion and thermal decomposition of 2,5-dimethylfuran (a promising next-generation biofuel), was studied using CBS-QB3 calculations and master equation (ME)/RRKM modeling. Because very little information is available in the literature, the detailed potential energy surface (PES) was investigated thoroughly. Only the main pathways, having a kinetic influence on the decomposition of R(1), were retained in the final ME/RRKM model. Among all the channels studied, the ring-opening of the 5-methyl-2-furanylmethyl radical, followed by ring enlargement to form cyclohexadienone molecules is predicted to be the easiest decomposition channel of R(1). The C(6) cyclic species formed can undergo unimolecular reactions to yield phenol and to a lesser extent cyclopentadiene and CO. Our calculations predict that these species are important products formed during the pyrolysis of 2,5-dimethylfuran (DMF). Other channels involved in the decomposition of R(1) lead directly to the formation of linear and cyclic unsaturated C(5) species and constitute an additional source of cyclopentadiene and CO. High-pressure limit rate constants were computed as well as thermochemical properties for important species. ME/RRKM analysis was performed to probe the influence of pressure on the rate coefficients and pressure dependent rate coefficients were proposed for pressures and temperatures ranging, respectively, from 10(-2) bar to 10 bar and 1000 to 2000 K.     

Theoretical studies of bond dissociation energies for removal of the nitrile group in some nitrile compounds

The CCN bond distances and bond dissociation energies (BDEs) are estimated by utilizing quantum chemical calculations for 16 nitrile compounds. Since DFT methods have been researched to have low basis sets sensitivity for small and medium molecules in our earlier work [Jun Zhao, Xinlu Cheng, Xiangdong. Yang, J. Mol. Struct. (Theochem) 766 (2006) 87] 16 nitrile compounds are studied by employing the hybrid density functional theory (B3LYP, B3PW91, B3P86) and the complete basis set (CBS-Q) method in conjunction with the 6-311G^** basis set. The obtained results are compared with the available experimental data. It is demonstrated that CBS-Q method, which can produce reasonable BDEs for some systems, seems unable to predict accurate BDEs here. While, the B3P86 calculated results agree very well with the experimental values. So B3P86 method is suitable for computing the reliable BDEs of CCN bond for nitrile compounds.     

Theoretical and kinetic study of the H + C2H5CN reaction

The reaction of H radical with C₂H₅CN has been studied using various quantum chemistry methods. The geometries were optimized at the B3LYP/6‐311+G(d,p) and B3LYP/6‐311++G(2d,2p) levels. The single‐point energies were calculated using G3 and BMC‐CCSD methods based on B3LYP/6‐311++G(2d,2p) geometries. Four mechanisms were investigated, namely, hydrogen abstraction, C‐addition/elimination, N‐addition/elimination and substitution. The kinetics of this reaction were studied using the transition state theory and multichannel Rice‐Ramsperger‐Kassel‐Marcus methodologies over a wide temperature range of 200–3000 K. The calculated results indicate that C‐addition/elimination channel is the most feasible over the whole temperature range. The deactivation of initial adduct C₂H₅CHN is dominant at lower temperature with bath gas H₂ of 760 Torr; whereas C₂H₅+HCN is the dominant product at higher temperature. Our calculated rate constants are in good agreement with the available experimental data. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2010     

Molybdenum-catalyzed transformation of molecular dinitrogen into silylamine: experimental and DFT study on the remarkable role of ferrocenyldiphosphine ligands

A molybdenum-dinitrogen complex bearing two ancillary ferrocenyldiphosphine ligands, trans-[Mo(N(2))(2)(depf)(2)] (depf = 1,1'-bis(diethylphosphino)ferrocene), catalyzes the conversion of molecular dinitrogen (N(2)) into silylamine (N(SiMe(3))(3)), which can be readily converted into NH(3) by acid treatment. The conversion has been achieved in the presence of Me(3)SiCl and Na at room temperature with a turnover number (TON) of 226 for the N(SiMe(3))(3) generation for 200 h. This TON is significantly improved relative to those ever reported by Hidai's group for mononuclear molybdenum complexes having monophosphine coligands [J. Am. Chem. Soc.1989, 111, 1939]. Density functional theory (DFT) calculations have been performed to figure out the mechanism of the catalytic N(2) conversion. On the basis of some pieces of experimental information, SiMe(3) radical is assumed to serve as an active species in the catalytic cycle. Calculated results also support that SiMe(3) radical is capable of working as an active species. The formation of five-coordinate intermediates, in which one of the N(2) ligands or one of the Mo-P bonds is dissociated, is essential in an early stage of the N(2) conversion. The SiMe(3) addition to a "hydrazido(2-)" intermediate having the NN(SiMe(3))(2) group will give a "hydrazido(1-)" intermediate having the (Me(3)Si)NN(SiMe(3))(2) group rather than a pair of a nitrido (≡N) intermediate and N(SiMe(3))(3). The N(SiMe(3))(3) generation would not occur at the Mo center but proceed after the (Me(3)Si)NN(SiMe(3))(2) group is released from the Mo center. The flexibility of the Mo-P bond between Mo and depf would play a vital role in the high catalysis of the Mo-Fe complex.     

Theoretical study on the inhibition of ribonucleotide reductase by 2'-mercapto-2'-deoxyribonucleoside-5'-diphosphates

Ribonucleotide reductase (RNR) is responsible for the reduction of ribonucleotides into the correspondent 2'-deoxyribonucleotides in the only physiological process that yields the monomers of DNA. The enzyme has thus become an attractive target for chemotherapies that fight proliferation-based diseases, specifically cancer and infections by some viruses and parasites. 2'-Mercapto-2'-deoxyribonucleoside-5'-diphosphates (SHdNDP) are mechanism-based inhibitors of RNR and therefore potential chemotherapeutic agents for those indications. Previous experimental studies established the in vitro and in vivo activity of SHdNDP. In the in vitro studies, it was observed that the activity was dependent on the oxidative status of the medium, with the inactivation of RNR only occurring when molecular oxygen was available. To better understand the mechanism involved in RNR inactivation by SHdNDP, we performed theoretical calculations on the possible reactions between the inhibitors and the RNR active site. As a result, we propose the possible mechanistic pathways for the chemical events that occur in the absence and in the presence of O2. They correspond to a refinement and a complement of those proposed in the literature.     

Theoretical study of the [2+3] cycloaddition of nitrones to nitriles-influence of nitrile substituent,solvent and Lewis acid coordination

The [2+3] cycloaddition of nitrone PhCHdoublebondN(Me)O to nitriles RCtriplebondN (R=Me, Ph, CF(3)) was studied using quantum chemical calculations at the HF/6-31G* and B3LYP/6-31G* level of theory. With MeCN and PhCN, the reaction occurs through a concerted mechanism and leads selectively to Delta(4)-1,2,4-oxadiazolines rather than Delta(2)-1,2,5-oxadiazolines. Electron withdrawing substituents such as CF(3) at the nitrile provoke a non-synchronous bond formation, with the C-O bond being established on an earlier stage than the C-N bond. Additionally, the reaction becomes thermodynamically and kinetically more favourable. In the reaction of adducts of MeCN with BH(3) or BF(3) as model Lewis acids, the mechanism was found to change from fully concerted in the case of free MeCN towards a two-step reaction in the presence of BF(3), in which C-O bond formation occurs first. The BH(3)-mediated reaction occupies an intermediate stage where ring formation occurs in one-step but non-simultaneously, similar to the reaction of CF(3)CN. Interaction of the Lewis acid with the nitrile in the course of the reaction facilitates the cycloaddition by stabilizing transition states, intermediate and product rather than by activating the nitrile. The solvent influences the organic reaction mainly by lowering the energy of the reagents, thus leading to a higher activation barrier in a more polar solvent. In the Lewis acid mediated reaction, in contrast, the intermediate is strongly stabilised by a polar solvent and with that the synchronicity of the reaction changes in favour of a two-step mechanism.     

Novel synthesis of 2-aminopentanedinitriles from 2-(bromomethyl)aziridines and their transformation into 2-imino-5-methoxypyrrolidines and 5-methoxypyrrolidin-2-ones

1-Arylmethyl-2-(bromomethyl)aziridines were transformed into 2-[N-(arylmethyl)amino]pentanedinitriles upon treatment with an excess of potassium cyanide in DMSO through an unprecedented and peculiar reaction mechanism, involving base-induced ring opening of intermediate 2-(cyanomethyl)aziridines into allylamines, followed by migration of the double bond out of the conjugation towards aldimines via enamine intermediates. The resulting aminopentanedinitriles served as substrates for the synthesis of novel 2-imino-5-methoxypyrrolidines upon treatment with sodium methoxide in methanol, which were either acetylated at the free imino group to afford the more stable N-acetylimino derivatives or hydrolyzed towards the corresponding synthetically relevant 5-methoxypyrrolidin-2-ones.     

Theoretical study on the mechanism and kinetics for the self-reaction of C2H5O2 radicals

Oxygen-to-oxygen coupling, direct H-abstraction and oxygen-to-(α)carbon nucleophilic substitution processes have been investigated for both the singlet and triplet self-reaction of C(2)H(5)O(2) radicals at the CCSD(T)/cc-pVDZ//B3LYP/6-311G(2d,2p) level to evaluate the reaction mechanisms, possible products and rate constants. The calculated results show that the title reaction mainly occurs through the singlet oxygen-to-oxygen coupling mechanism with the formation of entrance tetroxide intermediates, and the most dominant product is C(2)H(5)O + HO(2) + CH(3)CHO (P5) generated in channel R5. Beginning from the radical products of P5 (C(2)H(5)O, HO(2)) and reactant (C(2)H(5)O(2)), five secondary reactions HO(2) + HO(2) (a), HO(2) + C(2)H(5)O (b), C(2)H(5)O + C(2)H(5)O (c), HO(2) + C(2)H(5)O(2) (d), and C(2)H(5)O + C(2)H(5)O(2) (e) mainly proceed on the triplet potential energy surface. Among these reactions, (a), (b), and (d) are kinetically favorable because of lower barrier heights. The calculated rate constants of channel R5 between 200 and 295 K are almost independent of the temperature, which is in agreement with the experimental report. With regard to the final products distribution, CH(3)CHO, C(2)H(5)OH, C(2)H(5)OOH, H(2)O(2), and (3)O(2) are predicted to be major, whereas C(2)H(5)OOC(2)H(5) should be in minor amount.     

2-phenoxathiinyl-5-phenyloxazole and 5-phenoxathiinyl-2-phenyloxazole derivatives: experimental and theoretical study of emission properties

The absorption and emission spectra in cyclohexane and methanol of the title phenoxathiinyl-phenyloxazole derivatives are presented and discussed. Comparing to the unsubstituted diphenyloxazole (PPO), the experimental results show a bathochromic shift of the emission band, a significant dependence of the maximum on the solvent polarity and a drastic decrease of the fluorescence quantum yield. Semiempirical MO calculations (AM1) in both the ground and excited states support the experimental findings. A charge transfer from the phenoxathiin fragment to the oxazole ring is predicted in the excited state explaining the solvatochromism of the compounds. The values for the singlet-triplet gap, 3500-5000 cm-1 point to an enhanced probability of intersystem crossing (ISC) non-radiative deactivation processes, in agreement with the low fluorescence quantum yields.