Antiparallel triple helices. Structural characteristics and stabilization by 8-amino derivatives

The structural, dynamical, and recognition properties of antiparallel DNA triplexes formed by the antiparallel d(G#G.C), d(A#A.T), and d(T#A.T) motifs (the pound sign and dot mean reverse-Hoogsteen and Watson-Crick hydrogen bonds, respectively) are studied by means of "state of the art" molecular dynamics simulations. Once the characteristics of the helix are defined, molecular dynamics and thermodynamic integration calculations are used to determine the expected stabilization of the antiparallel triplex caused by the introduction of 8-aminopurines. Finally, oligonucleotides containing 8-aminopurine derivatives are synthesized and tested experimentally using several approaches in a variety of systems. A very large stabilization of the triplex is found experimentally, as predicted by simulations. These results open the possibility for the use of oligonucleotides carrying 8-aminopurines to bind single-stranded nucleic acids by formation of antiparallel triplexes.     

Performance of SuSi: a method for generating atomistic models of amorphous polymers based on a random search of energy minima

The performance of a recently developed method to generate representative atomistic models of amorphous polymers has been investigated. This method, which is denoted SuSi, can be defined as a random generator of energy minima. The effects produced by different parameters used to define the size of the system and the characteristics of the generation algorithm have been examined. Calculations have been performed on poly(L,D-lactic) acid (rho = 1.25 g/cm3) and nylon 6 (rho = 1.084 g/cm(3)), which are important commercial polymers.     

Conformational mobility of thianthrene-5-oxide

[reaction: see text] Data on the apparent dipole moment of thianthrene-5-oxide (1) and (1)H NMR spectra in different solvents support the conformational mobility of 1, which flaps between two limit boat conformations with the sulfinyl group in pseudoequatorial and pseudoaxial positions, respectively. The conformational equilibrium of 1 occurs too fast for the (1)H NMR (500 MHz) time-scale even at -130 degrees C, and the equilibrium constant has not been determined. The apparent dipole moments of 1 in n-hexane and 1,4-dioxane and the (1)H NMR spectra of 1 and the model compounds cis- and trans-thianthrene-5,10-dioxides (2) and thianthrene (5) in different solvents and at various temperatures confirm that the relative position of the conformational equilibrium of 1 is solvent-dependent, and more polar solvents favor the conformation with the sulfoxide group in the pseudoaxial position (1(')(ax)). Variable-temperature (1)H NMR spectra have established the interconversion barrier of trans-2 and confirmed that the conformational equilibrium of cis-2 is strongly displaced toward the conformation with both sulfinyl groups in the pseudoequatorial position. The (1)H NMR data support the transannular interaction of the functional groups in 1 and trans-2.     

Screening for the beta-39 mutation in thalassemia by capillary electrophoresis in free solution in strongly acidic, isoelectric buffers

A novel method is reported for screening for point mutations in genomic DNA: free-zone capillary electrophoresis in very acidic buffers. This method exploits the charge difference among the four different bases (C, T, A, G) in a pH window between 2.5 and 3.5, where the four titration curves fan out. The method is applied to the detection of the beta-39 missense mutation in the beta-globin gene in thalassemias. A 60-mer fragment straddling the mutation site has been amplified. In an isoelectric buffer (iminodiacetic acid) of pH 3.3, partial resolution between the wild type and mutated strands is obtained. In a pH 3.0 phosphate buffer, baseline resolution is achieved between the two strands in a heterozygous individual. Due to the short size of the amplified fragment, this method can only be applied to routine screening for known mutations because resolution was lost in a fragment 100 bases long.     

Gas-phase structure of protonated histidine and histidine methyl ester: combined experimental mass spectrometry and theoretical ab initio study

Gas-phase H/D exchange experiments with CD3OD and D2O and quantum chemical ab initio G3(MP2) calculations were carried out on protonated histidine and protonated histidine methyl ester in order to elucidate their bonding and structure. The H/D exchange experiments show that both ions have three equivalent fast hydrogens and one appreciably slower exchangeable hydrogen assigned to the protonated amino group participating in a strong intramolecular hydrogen bond (IHB) with the nearest N(sp2) nitrogen of the imidazole fragment and to the distal ring NH-group, respectively. It is taken for granted that the proton exchange in the IHB is much faster than the H/D exchange. Unlike in other protonated amino acids (glycine, proline, phenylalanine, tyrosine, and tryptophan) studied earlier, the exchange rate of the carboxyl group in protonated histidine is slower than that of the amino group. The most stable conformers and the enthalpies of neutral and protonated histidine and its methyl ester are calculated at the G3(MP2) level of theory. It is shown that strong intramolecular hydrogen bonding between the amino group and the imidazole ring nitrogen sites is responsible for the stability and specific properties of the protonated histidine. It is found that the proton fluctuates between the amino and imidazole groups in the protonated form across an almost vanishing barrier. Proton affinity (PA) of histidine calculated by the G3(MP2) method is 233.2 and 232.4 kcal mol(-1) for protonation at the imidazole ring and at the amino group nitrogens, respectively, which is about 3-5 kcal mol(-1) lower than the reported experimental value.     

Elucidation of the pore structure of SBA-2 using Monte Carlo simulation to interpret experimental data for the adsorption of light hydrocarbons

We have measured the adsorption of methane and ethane to high pressure on SBA-2, a structured mesoporous silica composed of spheres connected by narrow channels. The experimental data were analyzed by carrying out Monte Carlo simulations of adsorption in pore structure models of different complexity and then adjusting the parameters of the models to match the Monte Carlo results to the experimental data. We found that a model based on single-sized spherical cavities was inadequate and that it is necessary to explicitly account for the interconnecting channels. Further, we found that despite the basic regularity of the SBA-2 structure, it is necessary to allow for a distribution of the sizes of both the cavities and the channels. These size distributions were obtained by fitting the parameters of the model to the experimental adsorption data, revealing detailed structural information not previously known for this material. The channels were found to be 5-15 A in diameter, while the cavities were 40-50 A in diameter. There is some evidence that the distribution of channel sizes leads to a percolation effect whereby the pore structure is not equally accessible to all adsorptives.     

Die Bildungswärmen von MnSi1,73, MnSi,Mn5Si3 und Mn3Si

By means of vapor pressure measurements using theTorker method (Torsion-Knudsen Effusion Recoil) as well as theKnudsen tanspiration technique in connection with a mass spectrometer, the heats of formation of the following compounds were found to be –6.5±0.7 kcal/g atom (Mn_0.366Si_0.634), –7.8±0.6 kcal/g atom (Mn_0.50Si_0.50), –7.3±0.6 kcal/g atom (Mn_0.625Si_0.375), and –6.6±0.6 kcal/g atom (Mn_0.75Si_0.25).

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Monitoring some phenoxyl-type N-methylcarbamate pesticide residues in fruit juices using high-performance liquid chromatography with peroxyoxalate-chemiluminescence detection

A systematic investigation of optimal conditions for determining three of the most common phenoxyl-type N-methylcarbamate pesticides (carbaryl, carbofuran and propoxur) in fruit juices by HPLC with peroxyoxalate-chemiluminescence detection is described. The required pre-column hydrolysis of pesticides and derivatization of their hydrolytic metabolites with dansyl chloride was simultaneously carried out in a short time thanks to the micellar catalytic effect provided by cetyltrimethyl ammonium bromide micelles on the hydrolysis step. The liquid chromatographic separation of the dansylated phenols was performed on a reversed-phase C18 column with isocratic elution. The analytes were detected by using an integrated derivatization chemiluminescence detection unit based on the bis(2,4,6-trichlorophenyl)oxalate-hydrogen peroxide system. Fruit juice samples containing 4.0-1500 microg/l pesticides were analysed with a precision of ca. 6.5%. After contamination of the fruit juice samples, average recovery > 93% at fortification levels of 10-100 microg/l was obtained.     

A Comparative Study of Naproxen – Beta Cyclodextrin Complexes Prepared by Conventional Methods and Using Supercritical Carbon Dioxide

Naproxen is a poorly soluble anti-inflammatorydrug, the solubility of which canbe enhanced by complexation withbeta-cyclodextrin. Besides that, the inclusioncomplex reduces the incidence of gastrointestinal side effects of the drug. The aim of this work was to compare the physicochemical characteristics of the solid complexes prepared by traditional methods (kneading, freeze-drying and spray-drying) and using a supercritical fluid technology. The unusual solvent properties of carbon dioxide above their critical temperature and pressure were exploited in order to prepare inclusion compounds. Complexes prepared using supercritical fluid technology showed similar properties to those of freeze-drying andspray-drying complexes as proved by DSC, FT-IRand UV.     

Ag(I) complexes with alkylidene-bis(2-aminopyrimidines) as building units for discrete metallomacrocyclic frames. A structural and solution study

Alkylidene-bis(2-aminopyrimidines) (pyr2Cx, x = 2-5) are useful ligands to interact with Ag(I) yielding discrete metallocycles. Crystal structures of the [(pyr2C2)Ag(NO3)]2 and [(H-pyr2C4)Ag(NO3)2]2 have been isolated where each macrocyclic moiety interacts with their surroundings through weak interactions, yielding 3D discrete structures, On the other hand, the solution study shows that the equilibrium constants for the formation of Ag(pyr2Cx)+ complexes are higher than the literature values for Ag(I) complexes with single pyrimidines, although the differences could be explained by invoking the solid-state structures of the Ag(I)-pyr2Cx complexes.