New dicationic porphyrin ligands suited for intercalation into B-form DNA

This paper describes the synthesis and characterization of a new series of sterically nondemanding, dicationic porphyrins that exhibit novel DNA-binding interactions. Cationic porphyrins continue to be the focus of a great deal of effort because of the promise they have for use in photodynamic, antiviral, and anticancer therapies. The systems explored here include 5,15-di(N-methylpyridinium-4-yl)porphyrin (H2D4), 5,15-di(N-methylpyridinium-3-yl)porphyrin (H2D3), and 5,15-di(N-methylpyridinium-2-yl)porphyrin (H2D2), as well as Zn(D4) and Zn(D3), the zinc(II)-containing derivatives of H2D4 and H2D3, respectively. Viscometry studies, in conjunction with various spectroscopic techniques, reveal the nature of the adducts formed with DNA. Irrespective of the base composition, H2D4 and H2D3 bind to DNA by intercalation. The zinc derivatives Zn(D4) and Zn(D3) are also intercalators; however, the binding constants are smaller because uptake requires the loss of an axial ligand. The decisive roles that steric factors and structural rigidity play in shaping the adducts with DNA become clear. Sequences that contain mainly adenine-thymine base pairs easily depart from the canonical B-form DNA structure and generally accommodate bulky porphyrins in external binding sites. However, with the H2D3 and H2D4 systems, the steric requirements are so minimal that intercalation becomes the preferred mode of binding, even in [poly(dA-dT)]2. The intercalated form of the H2D2 isomer is less stable, probably because of frontal strain associated with the (N-methyl)pyridinium-2-yl groups. A qualitative energy-level diagram is useful for assessing the forces that influence binding and could guide the design of new porphyrin ligands.     

Synthesis of new 3'-, 5-, and N(4)-modified 2'-O-methylcytidine libraries on solid support

A versatile solid phase combinatorial approach was developed and utilized for the rapid synthesis of new 2'-O-methylcytidine nucleoside libraries 1-7 containing 672 compounds with 3'-deoxy-3'-C-methyl, 3'-deoxy-3'-C-hydroxymethyl, and 5-alkyl/alkynyl modifications. The modified uridine scaffolds 8-10, 23-25, and 31 were loaded onto the 4-methoxytrityl chloride (MMT-Cl) polystyrene resin through the hydroxyl groups at the 5'-position as well as on the substituents at the 3'- and 5-positions. The scaffolds loaded on the resin were orthogonally protected by MMT group on the resin itself and TBDMS or acetyl protecting groups. The 4-position of the uridine derivatives was activated by 2,4,6-triisopropyl benzene sulfonyl chloride for further derivatization. The resins 14-16, 28-30, and 32 loaded with the corresponding activated scaffolds were reacted with the selected and validated amino building blocks in the 96 well format on the semiautomated synthesizer. The high-quality 2'-O-methylcytidine libraries 1-7 were thus generated and characterized by liquid chromatography-mass spectrometry (LC-MS) analysis with 63-99% successful rates.     

First Observation of Hyperfine Structure in K(2)

The hyperfine structure of the (v'-v") = (27-0) band of the b(3)Pi(u0(+)) <-- X(1)Sigma(+)(g) transition has been observed by laser excitation spectroscopy in a highly collimated molecular beam. Hyperfine parameters for magnetic dipole and electric quadrupole interaction are derived from least-squares fitting of the hyperfine pattern and deperturbation between A(1)Sigma(+)(u) and b(3)Pi(u0(+)). Copyright 2000 Academic Press.     

Finite element modelling of the elastic-plastic stress and strain state and lifetime of the belt chamber

Abstract

A special finite element method (FEM) programme has been developed, reflected all significant phenomena connected with assembly and exploration of the Belt chamber. A nonhomogeneous temperature field is taken into account. Isotropic, kinematic and mixed hardening rules can be considered.     

Use of an internal control for matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis of bacteria

A method to aid in the analysis of bacterial samples of unknown concentration by matrix-assisted laser desorption/ionization (MALDI) mass spectrometry is demonstrated. It is shown that in MALDI analysis of bacteria, the intensities of resulting peaks in spectra are sensitive to the microbial concentration. At the high and low ends of the concentration range, no signal can be obtained, leaving very concentrated or very dilute samples indistinguishable. The addition of cytochrome c as an internal control allows the differentiation of these concentrated and dilute samples. The presence of the internal control causes only a 20% to 30% decrease in signal intensity when the bacterial concentration is optimum. However, the signal quality is improved when the internal control is added to some low concentrations of bacteria.     

Topologische Typen reeller kubischer Flächen

Zusammenfassung 4.11. Die topologischen Typen reeller kubischer Flächen werden durch (4.4)-(4.6) und Liste 4, die äquisingulären Isotopieklassen hierdurch und durch (4.11) vollständig klassifiziert. Für Flächen mit nur rationalen Doppelpunkten bestimmt man die Zahl der reellen Geraden nach (2.8), die Topologie aus (3.3) und (3.6).     

Asymmetric fermi surfaces for magnetic schrödinger operators

We consider Schrödinger operators with periodic magnetic field having zero flux through a fundamental cell of the period lattice. We show that, for a generic small magnetic field and a generic small Fermi energy, the corresponding Fermi surface is convex and not invariant under inversion in any point.