Carbon-13 magnetic resonance spectroscopy

High-resolution, natural-abundance ¹³C spectra have been obtained from a wide variety of organic compounds; ¹³C chemical shifts and coupling constants have been correlated with other molecular properties.

Geminal and vicinal, carbon-proton couplings in benzene and the five- and six-membered aromatic heterocycles have been related to the corresponding proton-proton couplings in substituted ethylenes. The carbon-proton coupling constants in benzene are J_CCH = + 1.0, J_CCCH = +7.4 and J_CCCH = -1.1 Hz. Extended Hückel wavefunctions are uniformly poor in explaining the long-range, carbon-proton couplings in aromatic systems.

Couplings between carbon and elements other than hydrogen have been observed in proton decoupled ¹³C spectra. All of the carbons in fluorobenzene and 1-fluoronaphthalene, but only six of the carbons in 2-fluoronaphthalene are coupled to the fluorine. One-bond, carbon-phosphorus coupling in trialkylphosphines is negative, while one-bond, carbon-phosphorus coupling in tetra-alkylphosphonium ions is positive. Atoms which do not use hybrid orbitals to form bonds to carbon (F, P(III), Se, Te) may have negative, one-bond coupling constants because of the failure of the average energy approximation. One-bond couplings between carbon and carbon, silicon, tin, lead and mercury appear to be explainable in terms of an effective nuclear charge and the s-bond order of the metal. Couplings between carbon and nitrogen and phosphorus (IV) have significant negative contributions to the Fermi contact coupling expression, though, within one series, correlations with s-bond order may be valid. Carbon-carbon coupling in cyclopropane derivatives (10-15 Hz) is consistent with a high degree of p character in the interior orbitals. Some two- and three-bond carbon-carbon coupling constants have also been observed.

Substituent effects of hydroxyl groups on the ¹³C chemical shifts of continuous-chain alkanes depend both on steric and electronic factors. The hydroxyl substituent effects in the long-chain, primary alcohols are α = -48.3, β = -10.2, and γ = +6.0 ppm. The upfield γ effect is attributed to steric crowding in the gauche conformations. Additivity of the hydroxyl and carbonyl and alkyl substituent effects in alkyl-substituted cyclohexanols and cyclohexanones has been demonstrated.

Synthesis and Reactions of Enantiopure Substituted Benzene cis-Hexahydro-1,2-diols

Enantiopure cis-dihydro-1,2-diol metabolites, obtained from toluene dioxygenase-catalysed cis-dihydroxylation of six monosubstituted benzene substrates, have been converted to their corresponding cis-hexahydro-12-diol derivatives by catalytic hydrogenation via their cis-tetrahydro-1,2-diol intermediates. Optimal reaction conditions for total catalytic hydrogenation of the cis-dihydro-1,2-diols have been established using six heterogeneous catalysts. The relative and absolute configurations of the resulting benzene cis-hexahydro-1,2-diol products have been unequivocally established by X-ray crystallography and NMR spectroscopy. Methods have been developed to obtain enantiopure cis-hexahydro-1,2-diol diastereoisomers, to desymmetrise a meso-cis-hexahydro-1,2-diol and to synthesise 2-substituted cyclohexanols. The potential of these enantiopure cyclohexanols as chiral reagents was briefly evaluated through their application in the synthesis of two enantiomerically enriched phosphine oxides from the corresponding racemic phosphine precursors.

A ring-closing metathesis approach to the bicyclo[4.3.1]decane core of caryolanes

A synthesis of highly substituted and sterically congested bicyclo[4.3.1]decenes, a structure embedded in the core 4,7,6-tricyclic system of natural caryolanes, was successfully achieved via a ring-closing metathesis (RCM) reaction of syn-1,3-diene substituted cyclohexanols. The construction of the diene substrates, starting from 4-acetoxy-3-methyl-2-cyclohexen-1-one, employed diastereoselective copper-mediated conjugate addition and Grignard reactions. An X-ray crystal structure determination of a key synthetic intermediate confirmed the relative stereochemistry of the RCM bicyclic product.

Double-blind comparison of venlafaxine and amitriptyline in outpatients with major depression with or without melancholia

The purpose of this study was to compare the efficacy and tolerability of venlafaxine and amitriptyline in outpatients with major depression with or without melancholia. This was an 8-week, multicentre, randomized, double-blind, parallel-group comparison of venlafaxine and amitriptyline. Outpatients with DSM-IV major depression, a minimum score of 20 on the 21-item Hamilton Depression Rating Scale (HAM-D), and depressive symptoms for at least 1 month were eligible. Patients were randomly assigned to venlafaxine or amitriptyline, both drugs titrated to a maximum of 150 mg/day until study day 15. The primary efficacy variables were the final on-therapy scores on the HAM-D, Montgomery-Asberg Depression Rating Scale and Clinical Global Impression severity scales. Data were evaluated on an intent-to-treat basis using the LOCF method. One hundred and 16 patients were randomized, and 115 were evaluated for efficacy. Both drugs showed efficacy in the treatment of depression with or without melancholia. No significant differences were noted between treatments for any efficacy parameter. However, significantly (p < 0.05) more patients in the amitriptyline group had at least one adverse event. These results should support the efficacy and tolerability of venlafaxine in comparison with amitriptyline for treating major depression with or without melancholia.

Efficacy of hormone therapy with and without methyltestosterone augmentation of venlafaxine in the treatment of postmenopausal depression: A double-blind controlled pilot study

Objective: This study evaluated the augmentation of venlafaxine with hormone therapy in the treatment of postmenopausal depression. The hormones evaluated were estrogen (0.625 mg) in combination with medroxyprogesterone acetate (2.5 mg) and methyltestosterone (2.5 mg). Design: Seventy-two menopausal women (mean age: 53.6 ± 4.27 years) diagnosed with depression (Montgomery-Åsberg Depression Rating Scale [MADRS] scores ≥ 20) were treated with venlafaxine and one of the following hormone therapy combinations, in a double-blind regimen: estrogen + medroxyprogesterone + methyltestosterone (group 1, n = 20); estrogen + medroxyprogesterone acetate (group 2, n = 20); methyltestosterone only (group 3, n = 16); and no hormone therapy (group 4, n = 16). Study duration was 24 weeks. Primary efficacy outcome was remission according to the MADRS, whereas secondary efficacy measures included the Clinical Global Impression (CGI), Blatt-Kupperman Index, and Women's Health Questionnaire (WHQ). Results: Forty-eight patients completed the study. All groups showed significant improvement from baseline. Group 3 demonstrated significant improvement on the MADRS compared with placebo (group 4) at weeks 20 (P = 0.048) and 24 (P = 0.030); effect size 8.04 (0.83; 15.26) (P = 0.029), but also had the highest dropout rate. Groups 1 and 3 had significant CGI improvement rates compared with placebo: 42.23% (P = 0.012) and 44.45% (P = 0.08), respectively. There were no differences in the WHQ or BKI scores among the groups. Conclusions: Methyltestosterone 2.5 mg had the highest effect size compared with placebo, but the high dropout rate prevented its efficacy from being determined. Estrogen plus medroxyprogesterone, combined with methyltestosterone or otherwise, demonstrated a trend toward increased efficacy of venlafaxine. Further larger-scale clinical trials are needed to elucidate the findings of this pilot study. © 2006 by The North American Menopause Society.

In vitro cytotoxic and non-genotoxic effects of gutta-percha solvents on mouse lymphoma cells by single cell gel (comet) assay

Chloroform and eucalyptol are widely used in clinical dentistry as gutta-percha solvents. However, these compounds may represent a hazard to human health, especially by causing injury to genetic apparatus and/or inducing cellular death. In this study, the genotoxic and cytotoxic potentials associated with exposure to chloroform and eucalyptol were assessed on mouse lymphoma cells in vitro by the single cell gel (comet) assay and trypan blue exclusion test, respectively. Both gutta-percha solvents proved to be cytotoxic at the same levels in concentrations of 2.5, 5 and 10 μL/mL (p<0.05). On the other hand, neither of the solvents induced DNA breakage. Taken together, these results suggest that although both tested compounds (chloroform and eucalyptol) are strong cytotoxicants, it seems that they are not likely to increase the level of DNA damage on mammalian cells.

Solvent capacity of different substances on gutta-percha and resilon

The aim of this study was to evaluate the effectiveness of 3 solvents (eucalyptol, orange oil, and xylol) on 2 types of gutta-percha (conventional and thermoplastic) and Resilon. Specimens (10 mm diameter × 1 mm thick; n=7 per condition) were prepared and maintained at 37°C for 48 h. Each specimen was weighed on a precision scale every 24 h until its mass was stable, at which time the initial mass was determined. Specimens (n=7) were then immersed in the solvent solutions and, after 48 h at 37°C, they were reweighed at 24- h intervals, until stabilization (final mass). The difference between the final and the initial mass determined the solvent capacity of each solvent. Data were subjected to analysis of variance and Tukey's test at 5% significance level. The results demonstrated that xylol was the most effective, especially on conventional gutta-percha and Resilon (p<0.05). Eucalyptol and orange oil were more effective on thermoplastic gutta-percha than the other materials (p<0.05). It was concluded that all evaluated substances presented solvent action, but xylol was the most effective on both gutta-percha or Resilon.

Effectiveness of three solvents and two associations of solvents on gutta-percha and Resilon

This study evaluated the effectiveness of 3 solvents (Citrol orange oil, Eucalyptol and Tetrachloroethylene) and 2 associations of solvents (Citrol orange oil+Tetrachloroethylene and Eucalyptol+Tetrachloroethylene) on 3 types of gutta-percha (conventional, thermoplastic and EndoREZ) and Resilon. Ten discs (10 mm diameter x 1 mm thick) from each material were prepared using standard metallic molds. Each specimen was weighed to determinate its initial mass. The specimens were immersed in the solvents for 10 min, followed by immersion in distilled water for 20 min, and were then reweighed to obtain the final mass. The mean weight loss determined the solvent capacity. Data were analyzed by ANOVA and Tukey's test at 5% significance level. Tetrachloroethylene was the most effective on conventional gutta-percha (p<0.05). Tetrachloroethylene was also the most effective on thermoplastic gutta-percha, but it was not significantly different (p>0.05) from Eucalyptol+Tetrachloroethylene, Citrol+Tetrachloroethylene, and Citrol. All solvents and associations presented little effectiveness on Resilon. The association Eucalyptol+Tetrachloroethylene was the most effective on EndoREZ, but it did not differ significantly (p>0.05) from Citrol+Tetrachloroethylene and Tetrachloroethylene. All evaluated substances presented solvent action. Tetrachloroethylene improved the effectiveness of both Citrol and Eucalyptol.