Atmospheric chemistry of isoflurane, desflurane, and sevoflurane: kinetics and mechanisms of reactions with chlorine atoms and OH radicals and global warming potentials

The smog chamber/Fourier-transform infrared spectroscopy (FTIR) technique was used to measure the rate coefficients k(Cl + CF(3)CHClOCHF(2), isoflurane) = (4.5 ± 0.8) × 10(-15), k(Cl + CF(3)CHFOCHF(2), desflurane) = (1.0 ± 0.3) × 10(-15), k(Cl + (CF(3))(2)CHOCH(2)F, sevoflurane) = (1.1 ± 0.1) × 10(-13), and k(OH + (CF(3))(2)CHOCH(2)F) = (3.5 ± 0.7) × 10(-14) cm(3) molecule(-1) in 700 Torr of N(2)/air diluent at 295 ± 2 K. An upper limit of 6 × 10(-17) cm(3) molecule(-1) was established for k(Cl + (CF(3))(2)CHOC(O)F). The laser photolysis/laser-induced fluorescence (LP/LIF) technique was employed to determine hydroxyl radical rate coefficients as a function of temperature (241-298 K): k(OH + CF(3)CHFOCHF(2)) = (7.05 ± 1.80) × 10(-13) exp[-(1551 ± 72)/T] cm(3) molecule(-1); k(296 ± 1 K) = (3.73 ± 0.08) × 10(-15) cm(3) molecule(-1), and k(OH + (CF(3))(2)CHOCH(2)F) = (9.98 ± 3.24) × 10(-13) exp[-(969 ± 82)/T] cm(3) molecule(-1); k(298 ± 1 K) = (3.94 ± 0.30) × 10(-14) cm(3) molecule(-1). The rate coefficient of k(OH + CF(3)CHClOCHF(2), 296 ± 1 K) = (1.45 ± 0.16) × 10(-14) cm(3) molecule(-1) was also determined. Chlorine atoms react with CF(3)CHFOCHF(2) via H-abstraction to give CF(3)CFOCHF(2) and CF(3)CHFOCF(2) radicals in yields of approximately 83% and 17%. The major atmospheric fate of the CF(3)C(O)FOCHF(2) alkoxy radical is decomposition via elimination of CF(3) to give FC(O)OCHF(2) and is unaffected by the method used to generate the CF(3)C(O)FOCHF(2) radicals. CF(3)CHFOCF(2) radicals add O(2) and are converted by subsequent reactions into CF(3)CHFOCF(2)O alkoxy radicals, which decompose to give COF(2) and CF(3)CHFO radicals. In 700 Torr of air 82% of CF(3)CHFO radicals undergo C-C scission to yield HC(O)F and CF(3) radicals with the remaining 18% reacting with O(2) to give CF(3)C(O)F. Atmospheric oxidation of (CF(3))(2)CHOCH(2)F gives (CF(3))(2)CHOC(O)F in a molar yield of 93 ± 6% with CF(3)C(O)CF(3) and HCOF as minor products. The IR spectra of (CF(3))(2)CHOC(O)F and FC(O)OCHF(2) are reported for the first time. The atmospheric lifetimes of CF(3)CHClOCHF(2), CF(3)CHFOCHF(2), and (CF(3))(2)CHOCH(2)F (sevoflurane) are estimated at 3.2, 14, and 1.1 years, respectively. The 100 year time horizon global warming potentials of isoflurane, desflurane, and sevoflurane are 510, 2540, and 130, respectively. The atmospheric degradation products of these anesthetics are not of environmental concern.     

Rate coefficients for reactions of OH radicals with CH3D,CH2D2, CHD3, and CD4

Fourier transform infrared (FTIR) smog chamber techniques were used to investigate the atmospheric chemistry of the isotopologues of methane. Relative rate measurements were performed to determine the kinetics of the reaction of the isotopologues of methane with OH radicals in cm³ molecule⁻¹ s⁻¹ units: k(CH₃D + OH) = (5.19 ± 0.90) × 10⁻¹⁵, k(CH₂D₂ + OH) = (4.11 ± 0.74) × 10⁻¹⁵, k(CHD₃ + OH) = (2.14 ± 0.43) × 10⁻¹⁵, and k(CD₄ + OH) = (1.17 ± 0.19) × 10⁻¹⁵ in 700 Torr of air diluent at 296 ± 2 K. Using the determined OH rate coefficients, the atmospheric lifetimes for CH_4–xD_x (x = 1–4) were estimated to be 6.1, 7.7, 14.8, and 27.0 years, respectively. The results are discussed in relation to previous measurements of these rate coefficients.     

Petasis three-component coupling reactions of hydrazides for the synthesis of oxadiazolones and oxazolidinones

An application of readily available hydrazides in the Petasis 3-component coupling reaction is presented. An investigation of the substrate scope was performed to establish a general, synthetically useful protocol for the formation of hydrazido alcohols, which were selectively converted to oxazolidinone and oxadiazolone ring systems through triphosgene-mediated cyclization reactions.     

Optical constants of HNO3/H2O and H2SO4/HNO3/H2O at low temperatures in the infrared region

The complex index of refraction of liquid HNO3/H2O and H2SO4/HNO3/H2O has been obtained at different temperatures and acid concentrations. FT-IR specular reflectance spectra were obtained for 30, 54, and 64 wt % aqueous HNO3 and for four different H2SO4/HNO3/H2O mixtures in the temperature region from 293 to 183 K. The complex index of refraction was obtained from the reflectance spectra with the Kramers-Kronig transformation. The optical constants of the binary and ternary mixtures vary with the acid concentration and the temperature. The results demonstrate that vibrational bands originating from the sulfate species are more sensitive to changes in temperature than the bands originating from vibrations in the nitrate species; only minor changes in the nitrate vibrational bands are observed as the temperature decreases below 248 K.     

Formation of long-lived fluorofullerene trianions in collisions with Na

The first experimental observation of long-lived triply charged fluorofullerene anions in the gas phase obtained from C60F48 is reported. The existence of a Coloumb barrier trapping the third electron in the trianion is supposed to be responsible for detection of the species which is estimated to have negative third electron affinity.     

Synthesis of <Emphasis Type="Italic">N</Emphasis>-1-(Indanyloxymethyl) and <Emphasis Type="Italic">N</Emphasis>-1-(4-Hydroxybut-2-enyloxymethyl) Analogues of the HIV Drugs Emivirine and GCA-186

Summary. A series of Emivirine and GCA-186 analogues substituted at N-1 with indan-1-yloxymethyl (6a–6c) and indan-2-yloxymethyl (6d–6f) were synthesized by reaction of the corresponding bis(indanyloxy)methans with uracils having 5-ethyl or 5-isopropyl and 6-benzyl or 6-(3,5-dimethylbenzyl) substituents. A route to the corresponding N-1 substituted 4-hydroxybut-2-enyloxymethyl analogue was also devised. All newly synthesized compounds showed potent activity against wild-type HIV-1, the most active compound being 5-ethyl-1-(indan-1-yloxymethyl)-6-(3,5-dimethylbenzyl)uracil (6b), which was 50-fold more active than Emivirine.Present address: Chemistry Department, Faculty of Science, Tanta University, Tanta, EgyptA research center funded by The Danish National Research Foundation for studies on nucleic acid chemical biology     

HPLC Method for Determination of Rosiglitazone in Plasma

A fast and sensitive high performance liquid chromatography method for quantitative determination of rosiglitazone in human plasma has been developed. The extraction from plasma was performed using solid-phase extraction (SPE) on C4 silica (100 mg) disposable extraction cartridges (DEC). The separation of rosiglitazone and two metabolites was achieved on a Phenomenex® Synergi 4 µm MAX-RP (150 × 4.6 mm) column, protected by a guard column. The mobile phase was 0.01 M ammonium acetate, pH 7.0 - acetonitrile (65:35, v/v). (3S)-3-OH-quinidine was used as internal standard. The analytes were detected using fluorescence detection. The method was validated. The limit of quantitation was 1 ng mL⁻¹ and the detection limit was 0.25 ng mL⁻¹ for rosiglitazone in human plasma. The recovery was 90% for rosiglitazone. Linearity was observed over a range of 1-1000 ng mL⁻¹ (r²=0.9959). The intra- and inter-day precision (C.V.) did not exceed 8.7 %. Applicability of the method was demonstrated by a clinical pharmacokinetic study. A healthy volunteer received in two separate phases 4 mg and 8 mg rosiglitazone maleate as a single oral dose. Plasma concentrations were measured for 24 h in both phases.     

A ruler for determining the position of proteins in membranes

Both the oxygen diffusion rate and the oxygen solubility vary with depth into the interior of biological membranes. The product of these two gradients generates a single gradient, a permeability gradient, which is a smooth continuous function of the distance from the center of the membrane. Using electron paramagnetic resonance and the spin-probe method, the relaxation gradient of oxygen, which is directly proportional to the permeability gradient, is the quantity that can be directly measured in membranes under physiological conditions. The gradient obtained provides a calibrated ruler for determining the membrane depth of residues either from loop regions of membrane-binding proteins or from the membrane-exposed residues of transmembrane proteins. We have determined the relaxation gradient of oxygen in zwitterionic and anionic phospholipid membranes by attaching a single nitroxide probe to a transmembrane alpha-helical polypeptide at specific residues. The peptide ruler was used to determine the depth of penetration of the calcium-binding loops of the C2 domain of cytosolic phospholipase A(2). The positions of selected residues of this membrane-binding protein that penetrate into the membrane, determined using this ruler, compared favorably with previous determinations using more complex methods. The relaxation gradient constrains the possible values of the membrane-dependent oxygen concentration and the oxygen diffusion gradients. The average oxygen diffusion coefficient is estimated to be at least 2-fold smaller in the membrane than that in water.     

Crystal structure of a partly self-complementary peptide nucleic acid (PNA) oligomer showing a duplex-triplex network

The X-ray structure of a partly self-complementary peptide nucleic acid (PNA) decamer (H-GTAGATCACT-l-Lys-NH(2)) to 2.60 A resolution is reported. The structure is mainly controlled by the canonical Watson-Crick base pairs formed by the self-complementary stretch of four bases in the middle of the decamer (G(4)A(5)T(6)C(7)). One right- and one left-handed Watson-Crick duplex are formed. The two PNA units C(9)T(10) change helical handedness, so that each PNA strand contains both a right- and a left-handed section. The changed handedness in C(9)T(10) allows formation of Hoogsteen hydrogen bonding between C(9)T(10) and G(4)A(5) of a PNA strand in an adjacent Watson-Crick double helix of the same handedness. Thereby, a PNA-PNA-PNA triplex is formed. The PNA unit A(3) forms a noncanonical base pair with A(8) in a symmetry-related strand of opposite handedness; the base pair is of the A-A reverse Hoogsteen type. The structural diversity of this PNA demonstrates how the PNA backbone is able to adapt to structures governed by the stacking and hydrogen-bonding interactions between the nucleobases. The crystal structure further shows how PNA oligomers containing limited sequence complementarity may form complex hydrogen-bonding networks.     

SYNTHESIS OF SOME NEW 4-AMINO-1,2,4-TRIAZOLE DERIVATIVES AS POTENTIAL ANTI-HIV AND ANTI-HBV

Some novel [1,2,4]triazolo[3,4-b][1,3,4]thiadiazolylisoindole-1,3-dione 2a–c were prepared by heating 4-amino-5-aryl-1,2,4-triazole-3-thiones 1a–c with different (1,3-dioxo-1,3-dihydro-isoindol-2-yl) carboxylic acids in POCl₃. Compounds 2a, b were hydrolyzed using HCl to yield [1,2,4]triazolo[3,4-b][1,3,4]thiadiazolyl-alkylamines 3a, b. Coupling 1a, c with 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide (ABG) afforded the corresponding S-glucosides 4a, b, which on oxidation with KMnO₄ gave the corresponding sulfone 5. Treatment 1b, c with diphenyl diazomethane afforded benzhydrylsulfanyltriazolylamines 7a, b. 1,8-Bis-(4-chloro-phenyl)-bis[1,2,4]triazolo[3,4-c-,4′,3′-e][1,2,4,5]dithiadiazine 8 was formed by oxidation of 1b with lead tetracetate. Compound 1c reacted with morpholine in the presence of KI and I₂ to give the triazolodisulfide ⁹ El-Barbary, A. A., Fahmy, M., El-Badawi, M., El-Brembaly, K. and El-Brollosi, N. R. 1991. Rev. Roum. Chim., 36(619) [Google Scholar].