Chemical reaction dynamics of PeCB and TCDD decomposition: A tight‐binding quantum chemical molecular dynamics study with first‐principles parameterization

The decomposition reaction dynamics of 2,3,4,4′,5‐penta‐chlorinated biphenyl (2,3,4,4′,5‐PeCB), 3,3′,4,4′,5‐penta‐chlorinated biphenyl (3,3′,4,4′,5‐PeCB), and 2,3,7,8‐tetra‐chlorinated dibenzo‐p‐dioxin (2,3,7,8‐TCDD) was clarified for the first time at atomic and electronic levels, using our novel tight‐binding quantum chemical molecular dynamics method with first‐principles parameterization. The calculation speed of our new method is over 5000 times faster than that of the conventional first‐principles molecular dynamics method. We confirmed that the structure, energy, and electronic states of the above molecules calculated by our new method are quantitatively consistent with those by first‐principles calculations. After the confirmation of our methodology, we investigated the decomposition reaction dynamics of the above molecules and the calculated dynamic behaviors indicate that the oxidation of the 2,3,4,4′,5‐PeCB, 3,3′,4,4′,5‐PeCB, and 2,3,7,8‐TCDD proceeds through an epoxide intermediate, which is in good agreement with the previous experimental reports and consistent with our static density functional theory calculations. These results proved that our new tight‐binding quantum chemical molecular dynamics method with first‐principles parameterization is an effective tool to clarify the chemical reaction dynamics at reaction temperatures. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2005     

Nitration Products of 5‐Amino‐1H‐tetrazole and Methyl‐5‐amino‐1H‐tetrazoles – Structures and Properties of Promising Energetic Materials

The nitration of 5‐amino‐1H‐tetrazole ( 1 ), 5‐amino‐1‐methyl‐1H‐tetrazole ( 3 ), and 5‐amino‐2‐methyl‐2H‐tetrazole ( 4 ) with HNO₃ (100%) was undertaken, and the corresponding products 5‐(nitrimino)‐1H‐tetrazole ( 2 ), 1‐methyl‐5‐(nitrimino)‐1H‐tetrazole ( 5 ), and 2‐methyl‐5‐(nitramino)‐2H‐tetrazole ( 6 ) were characterized comprehensively using vibrational (IR and Raman) spectroscopy, multinuclear (¹H, ¹³C, ¹⁴N, and ¹⁵N) NMR spectroscopy, mass spectrometry, and elemental analysis. The molecular structures in the crystalline state were determined by single‐crystal X‐ray diffraction. The thermodynamic properties and thermal behavior were investigated by using differential scanning calorimetry (DSC), and the heats of formation were determined by bomb calorimetric measurements. Compounds 2, 5 , and 6 were all found to be endothermic compounds. The thermal decompositions were investigated by gas‐phase IR spectroscopy as well as DSC experiments. The heats of explosion, the detonation pressures, and velocities were calculated with the software EXPLO5, whereby the calculated values are similar to those of common explosives such as TNT and RDX. In addition, the sensitivities were tested by BAM methods (drophammer and friction) and correlated to the calculated electrostatic potentials. The explosion performance of 5 was investigated by Koenen steel sleeve test, whereby a higher explosion power compared to RDX was reached. Finally, the long‐term stabilities at higher temperatures were tested by thermal safety calorimetry (FlexyTSC). X‐Ray crystallography of monoclinic 2 and 6 , and orthorhombic 5 was performed.     

Low-temperature bath/coupled-capillary/sweeping-micellar electrokinetic capillary chromatography for the separation of naphthalene-2,3-dicarboxaldehyde-derivatized dopamine and norepinephrine

The use of a low-temperature (0 degrees C) bath-assisted coupled capillary for the separation of naphthalene-2,3-dicarboxaldehyde (NDA)-derivatized dopamine and norepinephrine using the sweeping-micellar electrokinetic capillary chromatography (MEKC) mode is described. In this technique, a capillary consisting of two portions with different inside diameters is used. Therefore, the field strength inside the capillary is different. Hence, the electrophoretic migration velocities of the analytes and the electro-osmotic flow (EOF) also are different. Furthermore, when a portion of the capillary (wide portion, used for sweeping) is immersed in a low-temperature bath, the viscosity of the buffer and the retention factor of the analytes inside are increased. Thus, not only are the interactions between the SDS micelles and the analytes increased, but the SDS-analytes also move more slowly. As a result, a more complete separation can be achieved, even when the sample injection volume is large, up to approximately 2 microL. In general, when the volume of an injected sample is larger, the effects of sweeping and separation would become insufficient, especially when the retention values (k) of the analytes are quite different. However, this limitation can be improved when the low-temperature bath/coupled capillary/sweeping-MEKC mode is used.     

Enantioseparation in capillary electrophoresis using 2-O-(2-hydroxybutyl)-beta-CD as a chiral selector

The resolving ability of 2-O-(2-hydroxybutyl)-beta-CD (HB-beta-CD) with different degrees of substitution (DS = 2.9 and 4.0) as a chiral selector in CZE is reported in this work. Fourteen chiral drugs belonging to different classes of compounds of pharmaceutical interest such as beta-agonists, antifungal agents, ageneric agents, etc., were resolved. The effects of the DS of HB-beta-CD on separations were also investigated. The chiral resolution (R(s)) was strongly influenced by the concentrations of the CD derivative, the BGE, and the pH of the BGE. Under the conditions of 50 mmol/L Tris-phosphate buffer at pH 2.5 containing 5 mmol/L HB-beta-CD, all 14 analytes were separated. The very low concentration necessary to obtain separation was particularly impressive. The DS had a significant effect on the resolution of the chiral drugs and the ionic strength of the separation media; hence, the use of a well-characterized CD derivative is crucial.     

Synthesis, crystal structure and in vitro antitumor activity of di-n-butyltin 4′-(7-oxabicyclo [2,2,1]-5-heptane-2,3-dicarboximide) benzoates

Dibutyltin(IV) oxide reacts with the cantharidin analogue, 4′-(7-oxabicyclo [2,2,1]-5-heptane-2,3-dicarboximide) benzoic acid, A, to give the complexes [(p-C₈H₈NO₃-C₆H₄-COOBu₂Sn)₂O]₂ (1) and (p-C₈H₈NO₃-C₆H₄-COO)₂SnBu₂ (2) which had been characterized by IR and ¹H, ¹³C, ¹¹⁹Sn NMR. Single X-ray crystal structure analysis has been determined for compound (1), which was analogue to most other [(RCOOBu₂Sn)₂O]₂. The dimer features central of Bu₄Sn₂O₂ unit with the two Bu₂Sn groups being linked via bridging oxygen atom. Each tin atom adopts distorted trigonal bipyramidal structures via two carbons from a dibutyl moiety and three oxygen atoms from cantharidin derivative and bridging oxygen atom. In vitro tests show compounds 1 and 2 exhibit high cytotoxicity against P388 and HL-60.     

Development of an Enzymeless/Mediatorless Glucose Sensor Using Ruthenium Oxide‐Prussian Blue Combinative Analogue

Presented in this work is the first step towards an enzymeless/mediatorless glucose sensor. We first observed remarkable electrocatalytic oxidation of glucose using combinative ruthenium oxide (RuOx)‐Prussian blue (PB) analogues (designated as mvRuOx‐RuCN, mv: mixed valent) at ca. 1.1 V (vs. Ag/AgCl) in acidic media (pH 2 Na₂SO₄/H₂SO₄). Individual RuOx and PB analogs failed to give any such catalytic response. A high ruthenium oxidation state (i.e., oxy/hydroxy‐Ru^VII, E°≈1.4 V vs. RHE), normally occurring in strong alkaline conditions at RuOx‐based electrodes, was electrogenerated and stabilized (without any conventional disproportionation reaction) in the mvRuOx‐RuCN matrix for glucose catalysis. Detail X‐ray photoelectron spectroscopic studies can fully support the observation. The catalyst was chemically modified onto a disposable screen‐printed carbon electrode and employed for the amperometric detection of glucose via flow injection analysis (FIA). This system has a linear detection range of 0.3–20 mM with a detection limit and sensitivity of 40 μM (S/N=3) and 6.2 μA/(mM cm²), respectively, for glucose. Further steps towards the elimination of interference and the extendibility to neutral pHs were addressed.     

Determination of the uronic acid composition of seaweed dietary fibre by HPLC

A high-performance liquid chromatographic (HPLC) method is described for determination of the ratio of beta-d-mannuronic acid to alpha-l-guluronic acid (M/G ratio) in dietary fibre of edible seaweeds. Total dietary fibre (TDF) content was determined gravimetrically. The TDF fraction was hydrolysed with 12 m and 1 m H(2)SO(4), then neutralized with AG 4 x 4 resin. The uronic acids were separated in a Tracer Extrasil SAX 5 micro m column (25 cm x 4 mm) at 35 degrees C, with 2 mm KH(2)PO(4) containing 5% methanol as mobile phase at a fl ow rate of 1.5 mL/min. The detection wavelength was UV 210 nm. The chromatographic identifications of beta-d-mannuronic acid and alpha-l-guluronic acid were confirmed by liquid chromatography-mass spectrometry (LC-MS). The method precision was 1.4% for beta-d-mannuronic acid and 3.5% for alpha-l-guluronic acid. The method was used to determine M/G ratio in canned seaweeds (Saccorhiza polyschides and Himanthalia elongata) and in dried seaweeds (H. elongata, Laminaria ochroleuca, Undaria pinnatifida, Palmaria sp. and Porphyra sp.).     

Preparation and Characterization of Trimethylsilylpyridylacetylene Bridged,Dicobalt Carbonyl Complexes Containing Bis(diphenylphosphino)methylene or Bis(diphenylphosphino)ethylene Ligand

Reaction of an alkyne‐bridged dicobalt complex, [Co₂(CO)₆(μ‐Me₃SiC=Cpy)] 4 , with bis(diphenylphosphino)methylene (DPPM) or bis(diphenylphosphino)ethylene (DPPE) in THF at 55 °C yielded a DPPM or DPPE doubly bridged dicobalt compound, [{μ‐P,P‐PPh₂CH₂PPh₂}Co₂(CO)₄(μ‐Me₃SiC=Cpy)] 5 or [{μ‐P,P‐PPh₂CH₂CH₂PPh₂}Co₂(CO)₄(μ‐Me₃SiC≡Cpy)] 6 . Compound 5 and 6 were characterized by spectroscopic means as well as X‐ray crystal structure determination.     

Open-access liquid chromatography/mass spectrometry in a drug discovery environment

The use of open-access mass spectrometry to monitor synthetic chemistry reactions, and also the integrity and purity of new chemical entities, has been a part of the medicinal chemist's tool-box for more than 5 years. Originally in our group at Wyeth Research there were two open-access methods available to the chemists, flow injection analysis (FIA) and liquid chromatography/mass spectrometry (LC/MS). The FIA method was approximately 3 min long, while the LC/MS method was approximately 20 min long (including an 8 min gradient). Within the first 2 years, the total number of open-access analyses increased by approximately 125%. It is interesting, however, that the number of LC/MS analyses increased by more than 285%. This is attributed to the fact that the chemists began using the LC/MS data to monitor reactions and also to check final product integrity and purity. In addition, the number of chemists performing parallel synthesis reactions has increased; thus, individual chemists can produce sample sets of up to 100 vials. This paper describes the implementation of new methodology, which accommodates the need for much faster run times and also the ability to acquire alternating positive and negative ion spectra within the same run. In addition, the instrument has been configured to e-mail the resulting processed data report to the submitting chemist. Several methods have been developed, including structure elucidation using in-source collision-induced dissociation (CID) and night-time analysis. The LC/MS methods for this system are described herein and are applicable to both industrial and academic synthetic chemistry optimization efforts.