Oxidative cyclization of 2-pyrrolidinyl-acetamide and 2-pyrrolidinyl-propionamide local anaesthetics

2 - Pyrrolidinyl - acetamide and -propionamide local anaesthetics (1a–d) on oxidation with mercuric acetate, potassium hexacyanoferrate(III) and potassium permanganate underwent oxidative cyclization to give new bicyclic compounds, hexahydro - 1H - pyrrolo[1,2 - a]imidazolin - 2 - ones (2a–d). The propionamides (1c–d) yielded mixtures of the two possible diastereoisomers of 2c and 2d. These were separated; in solution and above their melting points they epimerized via ring opening and reclosure between the 7a-carbon and 1-nitrogen atoms.     

Simultaneous determination of radionuclides separable into natural decay series by use of time-interval analysis

A delayed coincidence method, time-interval analysis (TIA), has been applied to successive – decay events on the millisecond time-scale. Such decay events are part of the ²²⁰Rn²¹⁶Po (T_1/2 145 ms) (Th-series) and ²¹⁹Rn²¹⁵Po (T_1/2 1.78 ms) (Ac-series). By using TIA in addition to measurement of ²²⁶Ra (U-series) from -spectrometry by liquid scintillation counting (LSC), two natural decay series could be identified and separated. The TIA detection efficiency was improved by using the pulse-shape discrimination technique (PSD) to reject -pulses, by solvent extraction of Ra combined with simple chemical separation, and by purging the scintillation solution with dry N₂ gas. The U- and Th-series together with the Ac-series were determined, respectively, from alpha spectra and TIA carried out immediately after Ra-extraction. Using the ²²¹Fr²¹⁷At (T_1/2 32.3 ms) decay process as a tracer, overall yields were estimated from application of TIA to the ²²⁵Ra (Np-decay series) at the time of maximum growth. The present method has proven useful for simultaneous determination of three radioactive decay series in environmental samples.     

Comparative bioanalytical study of3H-deramciclane in dog plasma, using a gas chromatography-nitrogen-selective detection (GC-NPD), a new GC-radiochemical detection (GC-RD) and a liquid scintillation method

Summary A new, highly sensitive and selective gas chromatography method, using radiochemical detection (GC-DR) was developed for the selective determination of³H-labelled deramciclane and its N-desmethyl metabolite in dog plasma. Inter-day accuracy and precision, as well as system suitability of the GC-RD method was investigated during the method validation. The calibration curve was proved to be linear (r=0.9986) in a wide concentration range (13–1000 ngeqv mL⁻¹) The lower limit of quantitation (LLOQ) was 13.7 ngeqv mL⁻¹, and the limit of the detection (LOD) was 1 ngeqv mL⁻¹. Using this new GC-RD method, plasma levels of³H-labelled deramciclane and its metabolite were determined in dogs, after the administration of a single 10 mg kg⁻¹ oral dose. Pharmacokinetic curves and the calculated pharmacokinetic parameters were compared to those obtained using a previously elaborated gas chromatography-nitrogen selective detection method (GC-NPD) and to those obtained by measuring the plasma level of total radioactivity (liquid scintillation counting, LSC). Pharmacokinetic curves and the calculated pharmacokinetic parameters obtained with the two different gas chromatography detection methods (NPD and RD) showed good correlation. Comparison of these results to those acquired by total radioactivity measurement demonstrated that deramciclane was intensively metabolised. Moreover, the biological half-life (t ₁ ^2/β ) of the unknown metabolites proved to be more than a magnitude longer than the half-life of the parent compound or that of N-desmethyl metabolite. Presented at: Balaton Symposium on High-Performance Separation Methods, Siófok, Hungary, September 3–5, 1997.     

On the convergence of interior-reflective Newton methods for nonlinear minimization subject to bounds

We consider a new algorithm, an interior-reflective Newton approach, for the problem of minimizing a smooth nonlinear function of many variables, subject to upper and/or lower bounds on some of the variables. This approach generatesstrictly feasible iterates by using a new affine scaling transformation and following piecewise linear paths (reflection paths). The interior-reflective approach does not require identification of an activity set. In this paper we establish that the interior-reflective Newton approach is globally and quadratically convergent. Moreover, we develop a specific example of interior-reflective Newton methods which can be used for large-scale and sparse problems.Research partially supported by the Applied Mathematical Sciences Research Program (KC-04-02) of the Office of Energy Research of the U.S. Department of Energy under grant DE-FG02-86ER25013.A000, and in part by NSF, AFOSR, and ONR through grant DMS-8920550, and by the Advanced Computing Research Institute, a unit of the Cornell Theory Center which receives major funding from the National Science Foundation and IBM Corporation, with additional support from New York State and members of its Corporate Research Institute.Corresponding author.     

Conformational studies of 1,2,3-trichloro- and 1,2,3-tribromopropane by nuclear magnetic resonance spectroscopy: attractive parallel (1:3) halogen-hydr

Analysis of the NMR spectra of 1,2,3-trichloropropane and 1,2,3-tribromopropane in various media shows the most stable conformer to be AG_-. The populations of several conformera have been estimated by using pure trans and gauche coupling constants obtained from closely similar molecules. The calculated populations found in non-polar solvents agree well with those obtained by electron diffraction studies in the gas phase. It is suggested that the AG_- form is stabilised relative to AG₊ by the former having two parallel (1:3) halogen-hydrogen attractions against one in the AG₊ form. Comparison is made to related molecules where the most stable conformers also have the greatest number of parallel (1:3) halogen-hydrogen interactions.     

Photochemistry of β, γ-unsaturated ketones-V: The direct irradiation of some γ-phenyl β, γ-enones

The photochemistry of some members of the two series of γ-phenyl substituted acyclic β, γ-unsaturated ketones 1 and 2 upon direct irradiation with γ 310nm has been investigated, viz 1c–1h and 2b+2c.The alkyl substituted (E)-5-phenyl-4-penten-2-ones 1c–1h yield the corresponding 1,3-acyl shift products and (Z)-isomers, and 1g and 1h in addition two decarbonylated products. 2b only yields the (Z)-isomer and some benzaldehyde, but 2c yields the 1,3-acyl shift product, the ODPM product, three hydrocarbons formed by disproportionation of the allyl radical, and some benzaldehyde. The β-phenyl β, γ-UK 3a proved to be photostable. The 1,3-acyl shift products of 1c–1h result mainly from the singlet excited state in a cage radical process. The exclusive formation of the (E)-configuration of the 1,3-acyl shift product is explained in terms of conformational preference of the intermediate allyl radical. It is proposed that the formation of the (Z)-isomer proceeds from ¹T(π -π^*) which is populated according to

. Evidence is presented which supports the proposed mechanism.The β,γ-UK 2b containing a benzoyl moiety leads to a higher degree of (E)-(Z) isomerization than the corresponding 1d which has an acetyl moiety.The triplet energies of (E)- and (Z)-1h are 56 and ca 70 kcal/mol respectively.     

Determination/estimation of an optimal replacement interval under minimal repair

In this paper the problem of estimation of an optimal replacement interval for a system which is minimally repaired at failures is studied. The problem is investigated both under a parametric and a nonparametric form of the failure intensity of the system. It is assumed that observational data from n systems are available. Some asymptotic results are shown. A graphical procedure for determining/estimating an optimal replacement interval is presented. The procedure is particularly valuable for sensitivity analyses, for example with respect to the costs involved.     

Application of a Laplace Transform Method to the Study of Binary Mixtures of Spherical and Rod-Like Particles for Low Intensity Levels.

A Laplace Transform (LT) method is used to improve the results obtained in a quasi-elastic scattering (QELS) experiment. This is designed to determine the characteristic parameters of a bimodal solution of spherical and rod-like macromolecules. The theoretical study and the experimental simulation are carried out for low light levels and the results show that the LT technique provides a real alternative to the second order correlation function, g⁽²⁾(τ), in QELS measurements for these particularly difficult experimental conditions.     

Some Remarks on One-dimensional Functions and Their Riemann–Liouville Fractional Calculus

A one-dimensional continuous function of unbounded variation on [0,1] has been constructed.The length of its graph is infnite,while part of this function displays fractal features.The Box dimension of its Riemann–Liouville fractional integral has been calculated.