Showing papers by "Claus J. Nielsen published in 1992"

A Surprising Ring Opening Mechanism in the Formation of α-D-Arabinofuranosyl Nucleosides from 5-Substituted Uracils

Abstract: Reaction of silylated 5-substituted uracil derivatives 6 with methyl 2,3,5-tri-O-benzoyl-α-D-arabinofuranoside (3) in the presence of trimethylsilyl trifluoromethanesulfonate afforded a mixture of the corresponding 5-substituted 1-(2,3,5-tri-O-benzoyl-α-D-arabinofuranosyl)uracils 7 and the acyclo 2,3,5-tri-O-benzoyl-1-O-methyl-1-(uracil-1-yl)-D-arabinitols 9 with the methoxy group intact at C-1. Compound 7 was deprotected with methanolic ammonia. Compound 7 was also reacted With Lawesson's reagent to generate the corresponding 4-thio-α-D-arabinofuranoside nucleoside which was deprotected by treatment with methanolic ammonia

Recent advances in infrared matrix isolation spectroscopy. Invited lecture

Abstract: The matrix isolation technique has been employed for producing and trapping chemical species in inert matrices, typically in the ratio 1 : 1000 at 5–20 K. The matrices can be studied by a variety of spectroscopic techniques, including infrared (IR), Raman, visible, ultraviolet, fluorescence, Mossbauer, magnetic circular dichroism and electron spin resonance. This paper will be restricted to IR studies, as this is by far the most common technique for identifying the matrix isolated species. Convenient closed cycle He-cooled cryostats have made matrix isolation spectroscopy a common technique for various analytical applications. Combining these cryostats with Fourier transform IR spectrometers, matrix isolation spectroscopy is no longer a speciality employed by only a few specialists, but is now within the reach of many molecular spectroscopists. Some applications take advantage of the stabilization of free radicals and reactive species in the matrices; in others the reduced intermolecular interactions and absence of rotational fine structure make the matrices; suitable for high resolution spectra, frequently showing isotopic splitting. Weak H-bonds and charge transfer complexes can conveniently be studied in matrices. Various applications of IR isolation spectroscopy will be reviewed including studies of: (i) molecular ions; (ii) free radicals; (iii) complexes; (iv) clusters; (v) photochemical reactions with ozone; (vi) photoselection and infrared dichroism; and (vii) conformational equilibria. Studies of conformational equilibria will be discussed in some detail. Here the solute–matrix gas mixture is heated in a Knudsen cell or in a quartz nozzle to temperatures as high as 900 K before being quenched on the cold window. The high temperature thermodynamic equilibrium can be trapped and maintained in the matrix and evaluated from the spectra. By annealing (heating) the matrices, new thermodynamic equilibria can be achieved.

Vibrational spectra of seven halomethanes

Abstract: Seven halogenated methanes CX2YZ(with X, Y and Z being H, F, Cl, Br or I), all with a plane of symmetry, were synthesized and studied by infrared (IR) and Raman techniques. They belong to point group Cs and have six fundamentals of species a′ and three of species a″. Some of these molecules were investigated 30–40 years ago, but very little spectroscopic work has been carried out since. The IR spectra were recorded in the region from 3100 to 100 cm–1 in the vapour, liquid and crystalline states. Raman spectra, including semi-quantitative polarization measurements on the liquids, were obtained, additional vapour spectra were recorded, and the liquid spectra were also given in the R(ω) representation. Accurate Raman spectra were recorded of the crystalline phases at temperatures above 78 K, and the external modes in the range 200–10 cm–1 were investigated as probes for the phase transitions. The fundamentals of chloroiodomethane have been listed and two crystalline phases were observed for this compound, while only one crystal phase was observed for the other molecules. No plastic phases were detected in any of the compounds. Preliminary results of these investigations are presented.

Solid phases of bicyclohexyl studied with vibrational spectroscopy and calorimetry

Abstract: Bicyclohexyl, (C6H11)2(BCH), is a simple hydrocarbon and is the backbone of a group of compounds that form nematic (and sometimes smectic) liquid crystals. The infrared (IR) spectra of BCH, studied some years ago, have been re-investigated. Low-temperature, and also high-pressure spectra, at room temperature, of the amorphous phase and of three crystalline phases were obtained. Raman spectra of the liquid and of the crystalline solids were also recorded. Bicyclohexyl has a number of phase transitions. They are reversible in terms of temperature and pressure variations, and they were carefully investigated by differential scanning calorimetry (DSC) and by the variable-temperature X-ray powder technique. In the low-temperature and also in the high-pressure crystals, BCH existed in three phases: in phase 1 (274–277 K) all conformers were present; in phase 2 (256.5–274 K) only the equatorial–equatorial anti conformer and in phase 3 (below 256.5 K) the equatorial–equatorial gauche conformer was present. An additional phase transition was observed at 266.5 K by DSC and X-ray methods, but no noticeable changes were observed in the spectra. A single crystal of the high-pressure phase 1 was investigated by polarized radiation, and the order parameters for various bands were determined in the IR region. From these data it is argued that phase 1 could be a smectic liquid crystal rather than a plastic crystalline phase.

Trend towards decreased survival in patients infected with HIV resistant to zidovudine.

Abstract: The survival of 35 patients with AIDS or advanced HIV infection on treatment with zidovu-dine was related to the viral sensitivity to the drug and to the CD4+ cell count. 14 patients died, the survivors were followed up for an average of 804 days. In a univariate Cox model, survival was strongly related to Iog IC90 (p = 0.0003) and to the CD4+ count (p = 0.0002). In a bivariate model, Iog IC90 and the CD4+ count contributed to the prediction of survival (p = 0.12 and 0.06, respectively). Large studies of combination or alternation therapy with several anti-HIV drugs should be given high priority.

Synergistic antiviral effect in vitro of azidothymidine and amphotericin B methyl ester in combination on HIV infection.

Abstract: The nucleoside analogue azidothymidine (AZT) and the methyl ester of amphotericin B (AME) were assayed for antiviral effect on HIV infection singly and in combination. Both compounds were effective in inhibiting HIV infection of MT-4 cells. At concentrations where either compound alone had no significant effect on infection, the compounds in combination were potent inhibitors of HIV as evaluated by reduction in HIV antigen production and HIV induced cytopathic effect. These results indicate that a combination therapy employing compounds with different modes of action like AZT and AME may have synergistic antiviral properties. Amphotericin B itself significantly reduced HIV infectivity in vitro and should not be used as an antifungal agent in cultures intended to propagate HIV.

Vibrational spectra and conformation of 1-chloro-4-fluorobut-2-yne and ab initio calculations on 1,4-dihalobut-2-ynes

Abstract: Raman spectra were recorded in the 3200-5 cm−1 range for 1-chloro-4-fluorobut-2-yne as a liquid at various temperatures and as amorphous and different crystalline solids at low temperature. In the liquid, the Raman spectra showed broad, asymmetrical band shapes as previously reported for other 1,4-dihalobut-2-ynes. Additional IR and far-IR spectra were obtained of the liquid, vapour, amorphous and crystalline solids at low temperature, and of the compound isolated in argon and nitrogen matrices at 13 K. The vapour and liquid spectra were interpreted in terms of a low barrier to internal rotation and the crystal spectra of a single conformer, gauche. The unusual band shapes in the low-frequency Raman spectra of the 1,4-dihalobut-2-ynes are discussed and are reproduced fairly well by a simple model of a molecule exhibiting nearly free internal rotation. The agreement between the observed and calculated spectra is good for all the molecules studied when ab initio potentials are applied in the model calculations. Temperature effects in the Raman spectra of liquid 1-chloro-4-fluorobut-2-yne can also be derived from the model. Internal rotation in 1,4-difluoro-, 1,4-dichloro-, 1-chloro-4-fluoro-, 1,4-dibromo- and 1,4-diiodobut-2-yne was studied with the aid of ab initio calculations. The barriers were found to be low and decreasing through the series from 1,4-difluoro- to 1,4-diiodobut-2-yne accompanied by an increase in the equilibrium dihedral angle, XCCCCY, from 101° in 1,4-difluorobut-2-yne to 180° in 1,4-diiodobut-2-yne. The systematic variations through the series were correlated with the local dipole moments of the halomethyl groups and the electronegativities of the halogen substituents.

Conformational equilibria and infrared matrix isolation spectra of bromoacetyl chloride and bromoacetyl bromide

Abstract: IR spectra of the title compounds were investigated in argon and nitrogen matrices at 14 K with nozzle temperatures from 313 to 900 K. After annealing to 30 - 34 K the spectra changed considerably and the high energy conformer (gauche) nearly vanished. The matrix spectra supported the assignments into anti and gauche conformer bands, based upon bands disappearing on crystallization, and due to the small band widths various instances of overlapping bands were detected. Raman spectra were recorded as liquids at various temperatures and as amorphous and crystalline solids. The matrix spectra recorded at different nozzle temperatures gave as an average (Delta) HO (gauche - anti) equals 1.7 +/- 0.6 in bromoacetyl chloride and 2.9 +/- 0.6 kJ mol-1 in bromoacetyl bromide which are lower than in isothermal vapor cells, indicating that the high energy conformer (gauche) was partly converted to anti during deposition. The corresponding (Delta) HO values in the liquid (Raman) were 4.7 +/- 0.4 and 6.6 +/- 0.4 kJ mol-1, respectively.© (1992) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Vibrational spectra and conformations of 1, 4-dibromobut-2-yne and 1,4-diiodobut-2-yne

Abstract: The Raman spectra of 1,4-dibromobut-2-yne (BrBr) as a liquid at various temperatures and as an amorphous and crystalline solid at low temperatures were recorded in the 3200-10 cm−1 region. IR spectra of the liquid at room temperature and of the amorphous and crystalline solids at low temperatures (4000-50 cm−1) were obtained. Additional IR spectra of the vapour were recorded (4000-500 cm−1). The spectra of the liquid phase showed characteristic, broad bands below 500 cm−1. No temperature dependence was detected in these, and the spectra of the amorphous solid at 90 K are almost identical with the room temperature spectra of the liquid. A shoulder on the Rayleigh line was observed at ca. 20 cm−1 in the Raman spectrum of the amorphous BrBr at 90 K which tentatively, has been interpreted as the torsional mode. In the crystal an anti conformer was present, while the spectra of the vapour and the liquid were interpreted in terms of large torsional freedom. The Raman and IR spectra of the very unstable 1,4-diiodobut-2-yne (II) as a crystalline solid were recorded in the 4000-20 cm−1 range at low temperatures. Spectra of carbon disulphide solutions at temperatures 250–260 K were obtained and additional IR spectra of II in Nujol mulls and in KBr pellets were also recorded. In the region below 500 cm−1, Where other 1,4-dihalobut-2-ynes have characteristic, broad bands, a high irregular background was observed in the Raman spectrum of II in solution. The spectra agree with an anti conformer present in the crystal and nearly free internal rotation in the liquid. The vibrational assignments are supported by force constant calculations and by a correlation diagram for the vibrations of the six skeletal bending modes in 1,4-dichlorobut-2-yne, BrBr and II.