Comparison of gas chromatographic and high-performance liquid chromatographic assays for the determination of debrisoquine and its 4-hydroxy metabolite in human fluids

A comparison of an established gas chromatographic assay for 4-hydroxydebrisoquine and debrisoquine and a modified high-performance liquid chromatographic assay was made. Both assays used guanoxan as the internal standard and required derivatization of all three compounds with acetylacetone at 96 degrees C for 2.5 h and subsequent ethereal extraction and cleaning steps before chromatographic analysis. For detailed pharmacokinetic studies the gas chromatographic assay was more sensitive in the measurement of low concentrations in plasma, but the liquid chromatographic assay was adequate for phenotyping the 4-hydroxylation of debrisoquine in a population. In the latter assay a mobile phase consisting of 70% methanol in water at pH 3.5 (adjusted with orthophosphoric acid containing 10 mM 1-pentanesulphonic acid was employed (flow-rate 1.5 ml/min) with a pre-column (C8) linked to a reversed-phase muBondapak C18 cartridge in a Z-module. The eluate was detected at 248 nm. With this assay it was observed that the buccal absorption of debrisoquine and 4-hydroxy-debrisoquine was affected by the pH of the buccal medium. This indicates that urinary pH may influence the excretion of both substances at high pH. The debrisoquine-to-4-hydroxydebrisoquine ratio may be dose-dependent.     

Macrocyclic polycther sulfide syntheses. The preparation of thia-crown-5, 6 and 7 compounds

Macroeyclic polyether sulfides have been prepared by reacting an oligoethylene glycol dichloride with a dimercaptan or sodium sulfide as reported in a previous paper (6). The following new compounds were prepared: 1,4,7-trithia(15-crown-5) (1); 1,4,10-trithia(15-crown-5) (II): 1,4,7,10-tetrathia(15-crown-5) (III); I-thia(18-crown-6) (IV); 1,4-dithia(18-crown-6) (V); 1,7-dithia(18-crown-6) (VI); 1,4,7-trithia(18-crown-6) (VII); 1,7-dithia(21-crown-7) (VIII); and 1,4,7-trithia(21-crown-7) (IX). The melting points of these and previously reported thia-crown compounds correlate with their structures. X-ray analyses of two thia-crown compounds indicate that the large sulfur atoms are directed away from the center of the ring.     

Octahedral cobalt(III) complexes of the chloropentammine type. XXVII. Effects of Methyl Substituents on reactivities of the cis-chloro-n-propylaminebis(ethylenediamine)-cobalt(III) cation

Salts of one isomeric form of the chloro-n-butylamine-, chloro-iso-butyl-amine- and chloro-sec-butylamine-bis(ethylenediamine)cobalt(III) cations have been prepared and characterised to have a cis-configuration (IR and VIS spectroscopy). Rate constants for their spontaneous aquation, mercury(II)-induced aquation and base hydrolysis have been determined and the activation parameters calculated. The results are compared with data obtained for the n-propylamine complex with a view to investigate the effects of methyl (α, β, γ) substituents on reactivities. The rate-determining dissociation of the outgoing group (Cl^? or HgCl⁺) takes place via either a square-pyramidal or a trigonal-bipyramidal intermediate, depending on whether the activation entropy is negative or positive.     

Solution properties of polyoxymethylene

Light scattering and viscosity have been measured at 25°C. for dilute solutions of six unfractionated polyoxymethylene samples in the mixed solvent hexafluoroacetone–water (mole ratio 1/1.7) slightly buffered with triethylamine. Dialysis equilibrium through porous Vycor glass thimbles indicates that the polymer is strongly solvated by the hydrate (CF₃)₂C(OH)₂, and this must be taken into account in evaluating weight-average molecular weights from the light-scattering data. Over the molecular weight range 23,000–185,000, the intrinsic viscosities (in deciliter per gram) follow the relation The corresponding unperturbed dimensions are σ = 2.3 ± 0.2 or r₀²/nl² = 10.5 ± 1.5.     

Palladium-catalyzed C-O bond formation: direct synthesis of phenols and aryl/alkyl ethers from activated aryl halides

A simple and efficient palladium-catalyzed carbon-oxygen bond formation is reported. The palladium-tri-tert-butylphosphine complex was found to be effective in converting haloarenes to corresponding substituted phenols. This methodology offers a direct transformation of aryl halides to phenols, as well as the straightforward application to generate a wide variety of diaryl or alkyl/aryl ethers.     

Broadband rotational resonance in solid state NMR spectroscopy

A new technique for restoring nuclear magnetic dipole-dipole couplings under magic-angle spinning (MAS) in solid state nuclear magnetic resonance (NMR) spectroscopy is described and demonstrated. In this technique, called broadband rotational resonance (BroBaRR), the coupling between a pair of nuclear spins with NMR frequency difference close (but not necessarily equal) to the MAS frequency is restored by the application of a train of weak radio-frequency pulses at a carrier frequency close to the average of the two NMR frequencies. Phase or amplitude modulation of the pulse train at half the MAS frequency splits the carrier into sidebands close to the two NMR frequencies. The pulse train then removes offsets from the exact rotational resonance condition, leading to dipolar recoupling over a bandwidth controlled by the amplitude of the pulse train. (13)C NMR experiments on uniformly (15)N,(13)C-labeled L-valineHClH(2)O powder validate the theoretical analysis. BroBaRR will be useful in studies of molecular structures by solid state NMR, for example in the detection of long-range couplings between carbons in uniformly labeled organic and biological materials.