THE USE OF SPIN LABEL OXIMETRY IN THE STUDY OF PHOTODYNAMIC INACTIVATION OF CHINESE HAMSTER OVARY CELLS

Spin label oximetry has been used to study the effects of photosensitizer hematoporphyrin on oxygen consumption in Chinese hamster ovary cells. These measurements demonstrate that, in the presence of the sensitizer, there occurs (i) an increase in total oxygen consumption during irradiation and (ii) a decrease in oxygen consumption following irradiation. These results are attributed to the effects of photosensitized oxygen consumption and decreased cellular respiration due to cell inactivation. Thus the inhibition of oxygen consumption after irradiation was shown to correlate with decreased cell survival measured in cell culture experiments. Possible mechanisms of inactivation and extensions of the oximetric approach are discussed.     

A copper-catalyzed C-N bond formation involving sp-hybridized carbons. A direct entry to chiral ynamides via N-alkynylation of amides

A copper-catalyzed new C-N bond formation involving a sp-hybridized carbon is described here leading to a facile entry for syntheses of chiral ynamides. This direct N-alkynylation of amides should have a significant impact on the future development of synthetic methodologies employing ynamides.     

Superoxide radical anion adduct of 5,5-dimethyl-1-pyrroline N-oxide (DMPO). 2. The thermodynamics of decay and EPR spectral properties

The formation of the superoxide radical anion (O2*-) adduct of the nitrone 5,5-dimethyl-1-pyrroline N-oxide (DMPO) as detected by electron paramagnetic resonance (EPR) spectroscopy is one of the most common techniques for O2*- detection in chemical and biological systems. However, the nature of DMPO-O2H has confounded spin-trapping investigators over the years, since there has been no independently synthesized DMPO-O2H to date. A density functional theory (DFT) approach was used to predict the isotropic hyperfine coupling constants arising from the N, beta-H, and gamma-H nuclei of DMPO-O2H using explicit interactions with water molecules as well as via a bulk dielectric effect employing the polarizable continuum model (PCM). Theoretical calculation on the thermodynamics of DMPO-O2H decay shows favorable intramolecular rearrangement to form a nitrosoaldehyde and a hydroxyl radical as products, consistent with experimental observations. Some pathways for the bimolecular decomposition of DMPO-O2H and DMPO-OH have also been computed.     

Novel alkyl-modified anionic siloxanes as pseudostationary phases for electrokinetic chromatography. III. Performance in organic-modified buffers

Anionic water-soluble siloxanes modified with different amounts of alkyl chains have been used as pseudostationary phases in electrokinetic chromatography. Ionic siloxane polymers with attached alkyl chains of C8 and C12 and having different alkyl chain densities have been employed previously to achieve selective and efficient separations with a range of electrophoretic mobilities and methylene selectivities. In this study, the performance of three alkyl-modified siloxanes is examined in different organic-modified buffers and at differing amounts of organic modifier. The organic modifiers used are acetonitrile and methanol. The siloxanes are stable in these organic solvents and show good mobility and good methylene selectivities even at high concentration of organic solvent. Siloxanes have also been used to separate a mixture of 14 polynuclear aromatic hydrocarbons in an acetonitrile-modified buffer.     

Iron(II) and zinc(II) monohelical binaphthyl salen complexes

A new chiral binaphthyl salen ligand with rigid polyaromatic sidearms gives monohelical complexes (Fe(II) and Zn(II)) of predetermined handedness.     

Synthesis of the methanesulfonates of α-(4-chlorophenyl)-α-[1-(2-chlorophenyl)emenyl]-1H-1,2,4-triazole-1-ethanol and α-[1-(2-chlorophenyl)ethenyl]-α-(2,4-difluorophenyl)-1H-1,2,4-triazole-1-ethanol,alpha styryl carbinol antifungal agents

The methanesulfonates of (α-(4-chlorophenyl)-α-[1-(2-chlorophenyl)ethenyl]-1H-1,2,4-triazole-1-ethanol and α-[1-(2-chlorophenyl)ethenyl]-α-(2,4-difluorophenyl)-1H-1,2,4-triazole-1-ethanol ( 1a, b ) are orally effective α-styryl carbinol derivatives developed for the treatment and prevention of systemic fungal infections. Practical new processes amenable for the large-scale production of these compounds are described. Of note is the selection of dichlorostyrene as a convenient precursor of the styryl portion, modification of a sensitive Grignard addition into a realistic preparative reaction and the use of 1,2,4-triazole simultaneously as a base transfer agent and nucleophile.     

PM3-SM3: A general parameterization for including aqueous solvation effects in the PM3 molecular orbital model

Our recently proposed scheme for including aqueous solvation free energies in parameterized NDDO SCF models is extended to the Parameterized Model 3 semiempirical Hamiltonian. The solvation model takes accurate account of the hydrophobic effect for hydrocarbons, as well as electric polarization of the solvent, the free energy of cavitation, and dispersion interactions. Eight heteroatoms are included (along with H and C), and the new model is parameterized accurately for the water molecule itself, which allows meaningful treatments of specifically hydrogen bonded water molecules. The unphysical partial charges on nitrogen atoms predicted by the Parameterized Model 3 Hamiltonian limit the accuracy of the predicted solvation energies for some compounds containing nitrogen, but the model may be very useful for other systems, especially those for which PM3 is preferred over AM1 for the solute properties of the particular system under study. © 1992 by John Wiley & Sons, Inc.     

Studies on the mechanism of action of azinomycin B: definition of regioselectivity and sequence selectivity of DNA cross-link formation and clarification of the role of the naphthoate

Evaluation of the sequence selectivity, noncovalent association, and orientation of the DNA cross-linking agent azinomycin B on its duplex DNA receptor is described. A strong correlation between sequence nucleophilicity and cross-linking yield was observed, and steric effects due to the thymine C5-methyl group were identified. Detailed studies on the role of the azinomycin naphthoate using viscometry, fluorescence contact energy transfer, and DNA unwinding assays point to a nonintercalative binding mode for this group. A kinetic assay for agent regioselectivity was used to determine the orientation of binding and covalent cross-link formation.     

Asymmetric synthesis and applications of beta-amino Weinreb amides: asymmetric synthesis of (S)-coniine

Conjugate addition of lithium (S)-N-benzyl-N-alpha-methylbenzylamide to a range of alpha, beta-unsaturated Weinreb amides proceeds with high levels of diastereoselectivity (>95% de). The beta-amino Weinreb amide products may be transformed into beta-amino ketones via reactions with Grignard reagents, while treatment with DIBAL-H furnishes beta-amino aldehydes. Trapping of the aldehyde via Wadsworth-Emmons reaction and subsequent manipulation offers an efficient route to homochiral delta-amino acid derivatives and 2-substituted piperidines. The application of this methodology for the synthesis of (S)-coniine is demonstrated.