alpha-L-LNA (alpha-L-ribo configured locked nucleic acid) recognition of DNA: an NMR spectroscopic study

We have used NMR and CD spectroscopy to study and characterise two alpha-L-LNA:DNA duplexes, a nonamer that incorporates three alpha-L-LNA nucleotides and a decamer that incorporates four alpha-L-LNA nucleotides, in which alpha-L-LNA is alpha-L-ribo-configured locked nucleic acid. Both duplexes adopt right-handed helical conformations and form normal Watson-Crick base pairing with all nucleobases in the anti conformation. Deoxyribose conformations were determined from measurements of scalar coupling constants in the sugar rings, and for the decamer duplex, distance information was derived from 1H-1H NOE measurements. In general, the deoxyriboses in both of the alpha-L-LNA:DNA duplexes adopt S-type (B-type structure) sugar puckers, that is the inclusion of the modified alpha-L-LNA nucleotides does not perturb the local native B-like double-stranded DNA (dsDNA) structure. The CD spectra of the duplexes confirm these findings, as these display B-type characteristic features that allow us to characterise the overall duplex type as B-like. The 1H-1H NOE distances which were determined for the decamer duplex were employed in a simulated annealing protocol to generate a model structure for this duplex, thus allowing a more detailed inspection of the impact of the alpha-L-ribo-configured nucleotides. In this structure, it is evident that the malleable DNA backbone rearranges in the vicinity of the modified nucleotides in order to accommodate them and present their nucleobases in a geometry suitable for Watson-Crick base pairing.     

The magnetic circular dichroism of five-membered ring heterocycles

The MCD spectra of pyrrole, furan, thiophene, selenophene and teburophene and some of their derivatives are reported and the corresponding energies, oscillator strengths, transition moment directions, and MCD terms are calculated from semi-empirical quantum mechanical calculations hi the π-electron approximation. The MCD spectrum of thiophene is only slightly perturbed by substituents, and this is also expected to be true of the quite similar MCD spectra of selenophene and tellurophene. These molecules can then be classified as “hard” chromophores. On the other hand, pyrrole and furan have different and much weaker MCD spectra which change shape considerably when substituents are introduced. The implications of these observations are further discussed.     

Ligand field-actuated redox-activity of acetylacetonate

The quest for simple ligands that enable multi-electron metal–ligand redox chemistry is driven by a desire to replace noble metals in catalysis and to discover novel chemical reactivity. The vast majority of simple ligand systems display electrochemical potentials impractical for catalytic cycles, illustrating the importance of creating new strategies towards energetically aligned ligand frontier and transition metal d orbitals. We herein demonstrate the ability to chemically control the redox-activity of the ubiquitous acetylacetonate (acac) ligand. By employing the ligand field of high-spin Cr(ii) as a switch, we were able to chemically tailor the occurrence of metal–ligand redox events via simple coordination or decoordination of the labile auxiliary ligands. The mechanism of ligand field actuation can be viewed as a destabilization of the d_z² orbital relative to the π* LUMO of acac, which proffers a generalizable strategy to synthetically engineer redox-activity with seemingly redox-inactive ligands.

Tailoring the chemical surroundings of chromium(ii) allows reversible electron-transfer to the ubiquitous, purportedly redox-inactive acetylacetonate.     

Limitations of current proteomics technologies

Application of proteomics technologies in the investigation of biological systems creates new possibilities in the elucidation of biopathomechanisms and the discovery of novel drug targets and early disease markers. A proteomic analysis involves protein separation and protein identification as well as characterization of the post-translational modifications. Proteomics has been applied in the investigation of various disorders, like neurological diseases, and the application has resulted in the detection of a large number of differences in the levels and the modifications of proteins between healthy and diseased states. However, the current proteomics technologies are still under development and show certain limitations. In this article, we discuss the major drawbacks and pitfalls of proteomics we have observed in our laboratory and in particular during the application of proteomics technologies in the investigation of the brain.     

Excess enthalpies,heat capacities,and excess heat capacities as a function of temperature in liquid mixtures of ethanol + toluene,ethanol + hexamethyldisiloxane,and hexamethyldisiloxane + toluene

The heat capacities of liquid ethanol, toluene, and hexamethyldisiloxane, and of 14 binary mixtures of these were measured at atmospheric pressure at a series of temperatures between 298 and 348 K. In addition, the excess enthalpy was measured for each of the 14 mixtures at room temperature and corrected with the aid of the heat capacities to 298.15 K. The results were represented by empirical equations of a polynomial form. From these equations, the excess heat capacity was derived and the excess enthalpy was calculated, and fitted to equations, as a function of composition at temperatures between 298 and 348 K. All the mixtures are non-ideal as evidenced by the substantial excess enthalpy. The excess enthalpy for the mixtures containing ethanol showed a strong positive temperature dependence, while the variation of temperature between 298 and 348 K had little effect on the excess enthalpy of toluene + hexamethyldisiloxane.     

New polymer syntheses. LXVI. Copolyester of 4-hydroxybenzoic acid and 3-(4'-hydroxyphenoxy)benzoic acid or 4-(3'-hydroxyphenoxy)benzoic acid

Copolyesters of 4-hydroxybenzoic acid (HBA) and 3-(4'-hydroxyphenoxy)benzoic acid were prepared by two different procedures. Either the acetyl derivatives were polycondensed in bulk at temperatures up to 300°C or they were polycondensed in an inert reactions medium (Marlotherm-S) at 340°C. Two analogous series of copolyesters were synthesized from 4-acetoxybenzoic acid (4-HBA) and 4-(3'-acetoxyphenoxy)benzoic acid. The copolyesters were characterized by elemental analyses, inherent viscosities, ¹H- and ¹³C-NMR spectroscopy, WAXS and DSC measurements, and by optical microscopy. All copolyesters synthesized in solution were highly crystalline materials which were neither meltable nor soluble. Part of the copolyesters prepared by polycondensation in bulk were semi-crystalline, meltable, and soluble. The copolyester derived from 3-(4'-hydroxyphenoxy)benzoic acid proved to be thermotropic forming a nematic melt, whereas the isomeric copolyesters of 4-(3'-hydroxyphenoxy)benzoic acid only formed isotropic melts. © 1993 John Wiley & Sons, Inc.     

Ternäre Halogenide vom Typ A3MX6. VI [1]. Ternäre Chloride der Selten-Erd-Elemente mit Lithium,Li3MCl6 (M  Tb?Lu,Y, Sc): Synthese,Kristallstrukturen und Ionenbewegung

Ternary Halides of the A₃MX₆ Type. VI. Ternary Chlorides of the Rare-Earth Elements with Lithium, Li₃MCl₆ (M ? Tb? Lu, Y, Sc): Synthesis, Crystal Structures, and Ionic Motion Single crystal X-ray studies on the ternary chlorides Li₃ErCl₆, Li₃YbCl₆ and Li₃ScCl₆ show that they crystallize in three different structure types. Li₃ErCl₆ (trigonal, P3 ml, Z = 3, a = 1117.7(2); c = 603.6(2) pm; the chlorides with M ? Tb? Tm, Y are isotypic) and Li₃YbCl₆ (orthorhombic, Pnma, Z = 4, a = 1286.6(1); b = 1113.2(1); c = 602.95(8) pm; Li₃LuCl₆ is isotypic) have very similar structures that may be derived from hexagonal closest packings of chloride ions with the cations occupying octahedral holes in part statistically. Li₃ScCl₆ (monoclinic, C2/m, Z = 2, a = 639.8(1); b = 1104.0(2); c = 639,1(1) pm; β = 109.89(1)°) crystallizes isotypic with Na₃GdI₆ and Li₃ErBr₆, structures that may be derived from a cubic closes packings of anions. The ionic movement in Li₃YCl₆ and Li₃YbCl₆ has been investigated by impedance and ⁷Li-NMR spectroscopy.     

Mixed Ligand Complexes of Cobalt(II) – Synthesis,Structure, and Properties of Co4(thd)4(OEt)4

Synthesis, crystal structure, thermal stability, and magnetic properties of mixed‐ligand complexes of cobalt(II) with ß‐diketonato (thd = C₁₁H₁₉O₂^?) and alkoxides (OR mainly OMe = methoxide = CH₃O^? or OEt = ethoxide = C₂H₅O^?) are reported. Direct reaction between Co(thd)₂ ( 1 ) and EtOH gives a new complex with the structural formula [Co₄(thd)₄(OEt)₄] ( 2 ) whereas MeOH correspondingly reacts to [Co₄(thd)₄(OMe)₄(MeOH)₄] ( 3 ). The yield of these products decreases with increasing size of the R group owing to increased solubility of 1 in the alcohol. The structure of 2 is determined from single‐crystal X‐ray diffraction data. At 100 K 2 takes a monoclinic structure (space group C2/c): a = 15.108(2), b = 19.428(2), c = 21.240(3) Å, and β = 108.882(2)°. At 295 K 2 has transformed to a closely related orthorhombic structure (space group Fddd): a = 15.233(3), b = 19.712(3), c = 40.916(7) Å. Protracted hydrolysis accompanied by oxygenation of complexes 2 and 3 in laboratory air (viz. simultaneous exposure to moisture and oxygen) leads to a new complex 4 with empirical formula corresponding to [Co(thd)(OH)(O₂)]. Magnetic susceptibility data show that Co takes the valence state II in all complexes 1 – 4 . For 4 this implies that dioxygen has to form an adduct‐like association to the rest of the complex. Unfortunately complex 4 has hitherto only been obtained in the amorphous state, but all here produced evidences point at 4 as a distinct entity and that products of 4 obtained from 2 and 3 are chemically identical (but differ somewhat with regard to short‐ and longer‐range order in the atomic arrangement). The interatomic distances in the crystal structure of complexes 1 – 3 are briefly discussed in terms of the bond‐valence concept.     

Synthesis and Properties of a pH‐Insensitive Fluorescent Nitric Oxide Cheletropic Trap (FNOCT)

The synthesis and properties of the new fluorescent nitric oxide cheletropic trap (FNOCT) 14 , designed for the trapping and quantification of nitric oxide (NO) production in chemical and biological systems, is described (Scheme 3). The dicarboxylic acid 14 and the corresponding bis[(acetyloxy)methyl] ester derivative 15 of the FNOCT contain a 2‐methoxy‐substituted phenanthrene group as fluorophoric unit. The fluorescence of the reduced NO adduct of this FNOCT (λ_exc 320 nm, λ_em 380 nm) is pH‐independent. Trapping experiments were carried out in aqueous buffer solution at pH 7.4 with nitric oxide being added as a bolus as well as being released from the NO donor compound MAHMA NONOate (= (1Z)‐1‐{methyl[6‐(methylammonio)hexyl]amino}diazen‐1‐ium‐1,2‐diolate), indicating a trapping efficiency of ca. 50%. In a biological application, nitric oxide was scavenged from a culture of lipopolysaccharide‐stimulated rat alveolar macrophages. Under the applied conditions, a production of 11.1 ± 1.5 nmol of NO per hour and per 10⁵ cells was estimated.     

Column chromatographic prefractionation leads to the detection of 543 different gene products in human fetal brain

In a previous publication a large series of proteins were identified in fetal human brain by the use of two-dimensional electrophoresis (2-DE) with subsequent matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) and MALDI-tandem time-of-flight (TOF/TOF) analysis. Further identification of many more different spots by traditional 2-DE without additional step such as narrow immobilized ph gradient (IPG) strips or prefractionation seems unlikely and we therefore decided to separate extracted brain proteins by ion-exchange chromatography using a TSK gel DEAE-5PW column followed by 2-DE of individual fractions and analysis by MALDI-TOF/TOF with LIFT technology in fetal brain of the early second trimester. About 1880 protein spots corresponding to 543 different gene products were identified. These proteins included housekeeping, signaling, cytoskeletal, metabolic, antioxidant, and neuron/synaptosomal specific proteins. Among these, 314 gene products (314/543, 57.8%), which have never been detected in traditional 2-DE of human fetal brain, were observed by this method. This updated map of fetal brain proteins may serve as data base and reference map for fetal brain proteins, and the methodology applied may be used as a valuable analytical tool for the basis of protein expressional studies in health and disease.