Oxymethylene Bridges Research Articles

Synthesis and biophysical properties of C5-functionalized LNA (locked nucleic acid).

Oligonucleotides modified with conformationally restricted nucleotides such as locked nucleic acid (LNA) monomers are used extensively in molecular biology and medicinal chemistry to modulate gene expression at the RNA level. Major efforts have been devoted to the design of LNA derivatives that induce even higher binding affinity and specificity, greater enzymatic stability, and more desirable pharmacokinetic profiles. Most of this work has focused on modifications of LNA’s oxymethylene bridge. Here, we describe an alternative approach for modulation of the properties of LNA: i.e., through functionalization of LNA nucleobases. Twelve structurally diverse C5-functionalized LNA uridine (U) phosphoramidites were synthesized and incorporated into oligodeoxyribonucleotides (ONs), which were then characterized with respect to thermal denaturation, enzymatic stability, and fluorescence properties. ONs modified with monomers that are conjugated to small alkynes display significantly improved target affinity, binding specificity, and protection against 3′-exonucleases relative to regular LNA. In contrast, ONs modified with monomers that are conjugated to bulky hydrophobic alkynes display lower target affinity yet much greater 3′-exonuclease resistance. ONs modified with C5-fluorophore-functionalized LNA-U monomers enable fluorescent discrimination of targets with single nucleotide polymorphisms (SNPs). In concert, these properties render C5-functionalized LNA as a promising class of building blocks for RNA-targeting applications and nucleic acid diagnostics.

Crystal structure, conformation, vibration and optical band gap analysis of bis[ rac-propranolol nitrate

The crystal structure of the title rac-propranolol salt, C 16 H 22 NO 2 + · NO 3 - , consists of two protonated propranolol residues and nitrate anions. Three virtually flat fragments, characteristics of most of the β-adrenolytics with oxy-methylene bridge are present in both the cations (A and B). The plane of the propranolol chain is twisted with respect to the plane of the aromatic ring in both the cations. Present study investigates the conformation and hydrogen bonding interactions, which play an important role in biological functions. A gauche conformation is observed for the oxo-methylene bridge of cation A, while a trans conformation prevails in cation B. These conformations are found in majority of β-blockers. Presence of twenty intermolecular hydrogen bonds mediating through the anions stabilizes the crystal packing. Vibration analysis and earlier theoretical predictions complement the structure analysed. From the UV–Vis spectral analysis for the crystal, the optical band gap is found to be E g = 5.12 eV, where as the chloride salt has E g = 3.81 eV. The increase in the band gap may be attributed by the increase in the number of intermolecular hydrogen bonds. Good optical transmittance in the entire visible region and the direct band gap property suggest that it is a suitable candidate for optical applications in UV region.

Novel diadenosine polyphosphate analogs with oxymethylene bridges replacing oxygen in the polyphosphate chain

Dinucleoside polyphosphates (Np(n)N's; where N and N' are nucleosides and n = 3-6 phosphate residues) are naturally occurring compounds that may act as signaling molecules. One of the most successful approaches to understand their biological functions has been through the use of Np(n)N' analogs. Here, we present the results of studies using novel diadenosine polyphosphate analogs, with an oxymethylene group replacing one or two bridging oxygen(s) in the polyphosphate chain. These have been tested as potential substrates and/or inhibitors of the symmetrically acting Ap(4)A hydrolase [bis(5'-nucleosyl)-tetraphosphatase (symmetrical); EC 3.6.1.41] from E. coli and of two asymmetrically acting Ap(4)A hydrolases [bis(5'-nucleosyl)-tetraphosphatase (asymmetrical); EC 3.6.1.17] from humans and narrow-leaved lupin. The six chemically synthesized analogs were: ApCH(2)OpOCH(2)pA (1), ApOCH(2)pCH(2)OpA (2), ApOpCH(2)OpOpA (3), ApCH(2)OpOpOCH(2)pA (4), ApOCH(2)pOpCH(2)OpA (5) and ApOpOCH(2)pCH(2)OpOpA (6). The eukaryotic asymmetrical Ap(4)A hydrolases degrade two compounds, 3 and 5, as anticipated in their design. Analog 3 was cleaved to AMP (pA) and beta,gamma-methyleneoxy-ATP (pOCH(2)pOpA), whereas hydrolysis of analog 5 gave two molecules of alpha,beta-oxymethylene ADP (pCH(2)OpA). The relative rates of hydrolysis of these analogs were estimated. Some of the novel nucleotides were moderately good inhibitors of the asymmetrical hydrolases, having K(i) values within the range of the K(m) for Ap(4)A. By contrast, none of the six analogs were good substrates or inhibitors of the bacterial symmetrical Ap(4)A hydrolase.

Hydroxyalkylation of barbituric acid. III. Product analysis and reaction pathway

AbstractPolyetherols containing a thermally stable pyrimidine ring were obtained upon the reaction of hydroxymethyl derivatives of barbituric acid with an excess of ethylene or propylene oxide. The reaction was monitored by 1H‐NMR and IR spectroscopy for the systems with variable starting molar ratios of reagents. We found that formaldehyde rearranged from N‐hydroxymethyl and oxymethylene bridges into the end of the polyetherol chain during the reaction. Simultaneously, the O‐hydroxymethyl groups underwent blocking by oxirane. The structures of the polyetherols was deduced on the basis of the course of the reaction and the analytical data. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009

An Aryldihydronaphthalene Lignan with a Novel Type of Ring System and Further New Lignans from Linum perenne L.

From the dichloromethane extract of aerial parts of Linum perenne L. (Linaceae), in addition to three lignans of the arylnaphthalene type (justicidin B, isojusticidin B and retrohelioxanthin), we isolated four lignans of the aryldihydronaphthalene type. The major constituent contains a novel type of ring closure, formed by additional cyclisation between rings A and D of the aryldihydronaphthalene skeleton via an oxymethylene bridge, yielding a novel 2,8-dihydro-3 H-benzo[ E]naphtho[1,8- BC]oxepine ring system hitherto unreported for a lignan or any other natural product. We named this novel unusual lignan linoxepin. In addition, three further aryldihydronaphthalenes (one new and two known) were isolated. The absolute stereochemistry at C-8 of linoxepin and the related dihydronaphthalene lignans was established as R on grounds of CD spectra which were in good agreement with results of time dependent density functional (TDDFT) quantum mechanical simulations. The occurrence of aryldihydronaphthalenes in the genus Linum or the Linaceae has not been reported before.

Synthesis and acid catalyzed hydrolysis of B 2,5 type conformationally constrained glucopyranosides: incorporation into a cellobiose analogue

Isopropyl and p-nitrophenyl α- and β- d-glucopyranosides, restrained in a conformation close to B 2,5 via an oxymethylene bridge have been synthesized. These four glucopyranosides were found to be hydrolyzed at similar rates, close to those observed for the parent unconstrained glucosides. In such derivatives, either α or β, the exocyclic cleaved bond is synperiplanar to an endocyclic oxygen lone pair. This conformationally locked glucopyranosyl moiety was also incorporated into a disaccharide, affording a conformationally restrained cellobiose analogue which was assayed against various glycosidases.

Effect of LNA Modifications on Small Molecule Binding to Nucleic Acids

Locked nucleic acid (LNA) is a conformationally constrained DNA analogue that exhibits exceptionally high affinity for complementary DNA and RNA strands. The deoxyribose sugar is modified by a 2′-O, 4′-C oxymethylene bridge, which projects into the minor groove. In addition to changing the distribution of functional groups in the groove and the overall helical geometry relative to unmodified DNA, the bridge likely alters the hydration of the groove. Each of these factors will impact the ability of small molecules, proteins and other nucleic acids to recognize LNA-containing hybrids. This report describes the ability of several DNA-intercalating ligands and one minor groove binder to recognize LNA-DNA and LNA-RNA hybrid duplexes. Using UV-vis, fluorescence and circular dichroism spectroscopies, we find that the minor groove binder as well as the intercalators exhibit significantly lower affinity for LNA-containing duplexes. The lone exception is the alkaloid ellipticine, which intercalates into LNA-DNA and LNA-RNA duplexes with affinities comparable to unmodified DNA-DNA and RNA-DNA duplexes.

Curing of urea-formaldehyde adhesives with collagen type hydrolysates under acid condition

Condensation of dimethylol urea and its mixtures with urea or hydrolysate of chrome-tanned leather waste (mass fraction in mixture 0.05) in the presence of a variable quantity of phthalic acid, as acid curing agent (within mass fraction limits 0.01-0.1), was studied through TG technique. During condensation of sole dimethylol urea or of its mixture with urea, oxy-methylene as well as methylene cross-links are produced at a ratio of approx. 1:1, presence of leather waste hydrolysate reduces this ratio to approx. 1:2 in favour of more stable methylene bridges. Higher concentrations of phthalic acid (above mass fraction 0.05) lead to formation of a new TG mass decrement wave in the 150-180°C temperature interval, which probably relates to transition of more unstable oxy-methylene bridges to more stable methylene bridges, with splitting-off of formaldehyde. Oxy-methylene bridges may be regarded as a potential source of formaldehyde emissions by cured urea-formaldehyde adhesive films. Hydrolysate of chrome-tanned leather waste and a suitable concentration of acid curing agent distinctly reduce formaldehyde emission from cured urea-formaldehyde adhesive films.

The structure of ligands and effects of the europium luminescence excitation

Results of studies of the luminescence excitation spectra of europium compounds: β-diketonates, aromatic carboxylates, nitrates with sulfoxides are presented. The processes of transfer and degradation of the excitation energy are discussed. Alteration of the relative contribution of two inequivalent ligands to the luminescence excitation of europium β-diketonates with 1,10-phenanthroline derivatives upon modification of ligand radicals and variation of relative binding strength of ligands by metal ion was investigated. The participation of the ligand–metal charge transfer states both in degradation of the excitation energy and in enhancement of Eu3+ luminescence excitation was analyzed. Increase of intraligand charge transfer upon introduction of a ligand's acceptor substituent such as nitro-group, decreasing the ligand–metal charge transfer, was demonstrated. Blocking effect of methylene or oxymethylene bridges on the energy transfer from ligand to Eu3+ ion was observed. This phenomenon witnesses about the electron exchange mechanism of the interaction between the disjuncted parts of the ligand.

Viscoelastic properties of the matrix substance of chemically treated wood

The temperature variations of the storage modulus and the loss tangent along the grain for four kinds of chemically modified Sitka spruce (Picea sitchensis Carr.) woods were measured at 11 Hz over a temperature range of −150 to 200 °C. By using a cell-wall model in which the amorphous matrix substance is disposed parallel to the axis of cellulose fibrils inclined at an angle to the grain direction of the wood, the storage modulus, Em, and the loss tangent, tan δm of the matrix substance were estimated, and the relaxation processes detected were discussed. In formalization, the restriction of the micro-Brownian motion of the main chains due to oxymethylene bridges between the hydroxyl groups resulted in a decrease in tan δm above 0 °C. In acetylation and propylene oxide treatment, a marked reduction in Em was observed over the temperature range tested, by the introduction of bulky side chains, and the tan δm remarkably increased in the high-temperature range. In polyethylene glycol (PEG) impregnation, the Em increased below 20 °C due to the freezing of the micro-Brownian motion of PEG molecules in the cell lumens as well as in the cell walls, while it was reduced above this temperature by the melting of PEG molecules.

The cyclization of 8′-hydroxy abscisic acid to phaseic acid in vivo

The cyclization of 8′-hydroxyabscisic acid to phaseic acid was investigated by feeding RS-[3′,5,7- 2D 6]abscisic acid to tomato ( Lycopersicon esculentum) shoots, the 1′- S-enantiomer was metabolized to dihydrophaseic acid-4′- O-β- d-glucopyranoside (DPAGS) which was isolated as the acetylated methyl ester and subjected to 500 MHz 1H NMR. The 2H atom from C-3′ of abscisic acid (ABA) was confined to the axial 3′- pro-S position of DPAGS (numbered as in ABA) and so the carbanion presumed to be formed at C-3′ during cyclization is protonated from the oxymethylene bridge, β-face. Enolization of the 3′-hydrogen atoms of phaseic acid in D 2O at pH 10.55 exchanged the axial hydrogen atom (α-face) preferentially. Thus the carbanion present at this position during cyclization is protonated from the opposite side. This suggests that the reaction that gives rise to phaseic acid is catalysed enzymically.

石炭の熱分解による液状成分の生成

The formation of liquid products such as BTX and tar from the pyrolysis of coal was reviewed from a chemical point of view. First, the dissociation of bonds in coal during heat treatment was discussed. Polymethylene and/or oxymethylene bridges play important roles for the tar formation, because of their relatively low bond energies. The radicals produced in the above stage should be stabilized by hydrogen supplied either from other parts of coal molecule or from ambient atmosphere to yield liquid products. The factors which affect the final product yields were discussed. The secondary reaction of primary volatile matter is essential in this respect. The temperature, heating rate, residence time, coal particle size, gas pressure and minerals in coal all influence the secondary reaction. A molecular model of a bituminous coal and the reaction model during pyrolysis were proposed

Crosslinking of Gelatin with Formaldehyde; a 13C NMR Study

The different species formed when gaseous formaldehyde is dissolved in aqueous medium are investigated by a 13C NMR flow-through technique and the spectra of commercial aqueous form­aldehyde solutions containing methanol completely interpreted. 13CH2O was used to study the crosslinking reaction with gelatin which leads to methylene and oxymethylene bridges between gelatin-amino-groups. On ageing, hardened gelatin shows an increase in the number of methylene bridges.

Structure de l'opigénine: triterpène pentacyclique isolé d'Opilia celtidifolia

The structure of opigenin, an aglycone from the glycosidic fraction of Opiliaceltidifolia, has been established by study of the genin and its derivatives by means of ir, mass spectroscopy, and 1H and 13C nmr spectroscopy. This is a new triterpene whose skeleton resembles that of 3β-hydroxy lupane but with an isopropyl group in position 20 and an oxymethylene bridge in position 20–28.

Estimation of the Length of the Oxymethylene Bridges Introduced into Cotton Cellulose by Formaldeh de and by Methylenedisulfuric Acid

The average values of n in cellulose-O(CH2O)n-cellulose, inter- and intramolecular bridges not differentiated, have been estimated in cotton fabrics treated by various methods. These values were obtained from n = 0.6 ÷ (1 - R), where R is the ratio of dry weight lost to formaldehyde lost, when formaldehyde was removed from the fabric by exposure to moist HCl vapor. The values estimated for n were 2.5, 2.4, 1.7, and 1.1 for Form W', Form D', Form V, and the alkaline methylenedisulfuric acid methods, respectively.