4-carboxy-1,2-cyclohexanedionedioxime complexes of nickel(ii) in alkaline media

The reactions of 4-carboxy-1,2-cyclohexanedionedioxime and nickel(II) were studied in alkaline media. Spectrophotometric studies indicate the presence of a 1:1 complex ion, NiD^-. Magnetic susceptibility measurements on a series of solutions of varying ratios of vic-dioxime and nickel(II) showed that the 1:1 complex ion was diamagnetic and that two paramagnetic complexes, probably NiD₂^4- and NiD₃^7-, are present in solution. The stability constants for the three complexes were calculated from spectrophotometric and magnetic susceptibility data. The log K values were found to be log K₁ = 28.74 ± 0.60, log K₂ = 0.76 ± 0.15, and log K₃ = 3.67 ± 0.73, respectively.     

An electron-diffraction study of the molecular structure of gaseous perbromyl fluoride and calculation of its force field and vibrational amplitudes

The molecular structure of FBrO₃ has been studied by gas-phase electron diffraction. Least-squares refinements of the molecular geometry using fixed spectroscopic amplitudes revealed two geometrical minima. Initially, the amplitudes employed were derived from diagonal force fields obtained by spectroscopic least-squares refinements to fit observed and calculated wave numbers; for each geometry there are two spectroscopic minima. In the lowest geometrical minimum the wave number agreement is poor, however, the introduction of the ∠OBrO/∠FBrO interaction force constant removed the discrepancies; the resulting force field is F(Br-O) = 6.92 ± 0.02 mdyn Å^?1F(Br-F) = 3.22 ± 0.03 mdyn Å^?1, F(∠OBrO) = 1.06 ± 0.02 mdyn Å, F(∠FBrO) = 0.81 ± 0.03 mdyn Å, F(∠OBrO/∠FBrO) = ?0.19 ± 0.02 mdyn Å. In the corresponding geometrical minimum r_g(Br-O) = 1.582 ± 0.001 Å, r_g(Br-F) = 1.708 ± 0.003 Å, r_α(∠OBrO) = 114.9 ± 0.3°, r_α(∠FBrO) = 103.3 ± 0.3°. Perpendicular amplitude correction coefficients, calculated for each force field employed, were used throughout to relate the interatomic distances through the r_α-structure. The geometries of the r_α^o- and r_e-structures are estimated.     

Nonlinear dynamics of the heartbeat: I. The AV junction: Passive conduit or active oscillator?

Under physiologic conditions, the AV junction is traditionally regarded as a passive conduit for the conduction of impulses from the atria to the ventricles. An alternative view, namely that subsidiary pacemakers play an active role in normal electrophysiologic dynamics during sinus rhythm, has been suggested based on nonlinear models of cardiac oscillators. A central problem has been the development of a simple but explicit mathematical model for coupled nonlinear oscillators relevant both to stable and perturbed cardiac dynamics. We use equations describing an analog electrical circuit with an external d.c. voltage source (V₀) and two nonlinear oscillators with intrinsic frequencies in the ratio of 3:2, comparable to the SA node and AV junction rates. The oscillators are coupled by means of a resistor. 1:1 (SA:AV) phase-locking of the oscillators occurs over a critical range of V₀. Externally driving the SA oscillator at increasing rates results in 3:2 AV Wenckebach periodicity and a 2:1 AV block. These findings appear with no assumptions about conduction time or refractoriness. This dynamical model is consistent with the new interpretation that normal sinus rhythm may represent 1:1 coupling of two or more active nonlinear oscillators and also accounts for the appearance of an AV block with critical changes in a single parameter such as the pacing rate.     

The crystal structure of a tricarbonyliron-substituted cyclobutadiene complex: Tricarbonyl[1,2,2a,12a-η-5,10-dimethyldibenzo[a,c]cyclobuta[f]cyclooctene-3,12-dione] iron

The crystal structure of tricarbonyl[1,2,2a,12a-η-5,10-dimethyldibenzo[a,c] cyclobuta[f] cyclooctene-3,12-dione] iron, C₂₀O₂H₁₄Fe(CO)₃, has been determined by the single crystal X-ray diffraction technique using data collected with a fully automated diffractometer. The unit cell is monoclinic, space group P2₁/c with a = 12.025(2), b = 23.204(3), c = 14.614(2) Å, β = 102.16(2)°, and contains eight molecules (two per asymmetric unit). The structure was elucidated to study the coordination of the iron atom and to correlate the conformation of the eight-membered ring with an NMR study. The final structure was obtained by Patterson-superposition and Fourier techniques and refined by full-matrix least-squares to a crystallographic residual of 0.070. In both independent molecules the iron atom is 1.77 Å from the cyclobutadiene ring to which it is coordinated. The eight-membered ring is flattened from a boat conformation and the six-membered rings are twisted from coplanarity by an angle of 74°. The twist is such that if one ring points above the eight-membered ring, the other ring will point below it with concomitant pointing in the opposite sense by neighboring carbonyl groups. Such a structure has conformational chirality. It is postulated that the stability of each enantiometer is due to the particularly high energy of the transition state through which each would pass to achieve inter-conversion.     

Efficient resolution of profen ethyl ester racemates by engineered Yarrowia lipolytica Lip2p lipase

Enzyme-catalyzed enantiomer discrimination is still a great challenge for the development of industrial pharmaceutical processes. For the resolution of ibuprofen, naproxen and ketoprofen racemates, three major anti-inflammatory drugs, only lipases from Candida rugosa present a high selectivity if solvent and surfactant use is discarded. However, their catalytic activities are too low. In the present work, we demonstrate that the lipase Lip2p from the yeast Yarrowia lipolytica has a higher catalytic activity than C. rugosa lipases to hydrolyze the ethyl esters of ibuprofen, naproxen and ketoprofen, but its selectivity is not sufficient [E = 52 (S); 11 (S) and 1.5 (R) respectively]. The enantioselectivity was further improved by site-directed mutagenesis, targeted at the substrate binding site and guided by molecular modelling studies. By investigating the binding modes of the (R)- and (S)-enantiomers in the active site, two amino acid residues located in the hydrophobic substrate binding site of the lipase, namely residues 232 and 235, were identified as crucial for enantiomer discrimination and enzyme activity. The (S) enantioselectivity of Lip2p towards ethyl ibuprofen esters was rendered infinite (E ? 300) by replacing V232 by an A or C residue. Substitution of V235 by C, M, S, or T amino acids led to a great increase in the (S)-enantioselectivity (E ? 300) towards naproxen ethyl ester. Finally, the variant V232F enabled the efficient kinetic resolution of ethyl ketoprofen ester enantiomers [(R)-enantiopreference; E ? 300]. In addition to the increase in selectivity, a remarkable increase in velocity by 2.6, 2.7 and 2.5 times, respectively, was found for ibuprofen, naproxen and ketoprofen ethyl esters.     

Total synthesis,reactivity, and structural clarification of lindenatriene

The synthesis of lindenatriene (1) and iso-lindenatriene (12) were achieved, along with the des-hydroxy model compounds (10 and 18, respectively), and compared to reported ¹H NMR spectra in the literature (1a and 10a). These comparisons clarify the correct initial assignment of lindenatriene (1) as well as its instability and propensity to isomerize into the more thermodynamically favored iso-lindenatriene (12).     

The rhodophytin and chondriol natural products; structures of several new acetylenes from laurencia, and a reassignment of structure for cis-rhodophytin

The structures of five new halogenated vinyl acetylenes are described which are natural products from various species of the red seaweed Laurencia. The structure of epoxyrhodophytin (1) was determined by spectral, chemical, and X-ray diffraction analyses. The structures of trans-rhodophytin (5) and trans-chondriol (8) are based on chemical and spectral comparisons with the previously reported compounds cis-rhodophytin (4) and cis-chondriol (7). The structures of cis-chondrin (14) and trans-chondrin (15) were secured by synthesis from cis- and trans-chondriol, respectively. The reactivity of these enol-ethers to various conditions of catalytic hydrogenation has been examined in detail. Hydrogenation yields an unexpected and facile incorporation of oxygen into the reaction products. Based upon these studies, and upon combustion analysis, the structure of rhodophytin has been revised as the vinyl ether rather than the vinyl peroxide originally proposed.     

The vibrational spectra and structure of sodium bromoacetate and sodium bromoacetate-d2

The complete vibrational spectra of crystalline sodium bromoacetate and sodium bromoacetate-d₂ have been recorded and a vibrational assignmem proposed. The intermolecular coupling of these compounds is quite strong and the data are consistent with a centrosymmetric unit cell containing at least four molecules.The product rule calculations support a structure m which the bromine atom is rotated out of the plane of the remaining heavy atoms, but the frequency of the carbon-bromine stretching mode indicates that the degree of rotation is not large.     

Determination of thiosulphate in the presence of dithionite and sulphite

To determine thiosulphate in the presence of dithionite and sulphite, iodine dissolved in potassium bromide solution is used to oxidize thiosulphate to tetrathionate, and dithionite and sulphite to sulphate. The tetrathionate generated from the thiosulphate is then oxidized with potassium bromate-potassium bromide solution in the presence of hydrochloric acid. The bromine consumption of the tetrathionate is measured by titration of the excess of bromine with sodium thiosulphate after the addition of potassium iodide. For each equivalent of iodine used to determine thiosulphate by the Wollak method, fourteen equivalents of bromine are used to determine thiosulphate by this method.