Anti-Inflammatory Dysidazirine Carboxylic Acid from the Marine Cyanobacterium Caldora sp. Collected from the Reefs of Fort Lauderdale,Florida

Dysidazirine carboxylic acid (1) was isolated from the lipophilic extract of a collection of the benthic marine cyanobacterium Caldora sp. from reefs near Fort Lauderdale, Florida. The planar structure of this new compound was determined by spectroscopic methods and comparisons between HRMS and NMR data with its reported methyl ester. The absolute configuration of the single chiral center was determined by the conversion of 1 to the methyl ester and the comparison of its specific rotation data with the two known methyl ester isomers, 2 and 3. Molecular sequencing with 16S rDNA indicated that this cyanobacterium differs from Caldora penicillata (Oscillatoriales) and represents a previously undocumented and novel Caldora species. Dysidazirine (2) showed weak cytotoxicity against HCT116 colorectal cancer cells (IC₅₀ 9.1 µM), while dysidazirine carboxylic acid (1) was non-cytotoxic. Similar cell viability patterns were observed in RAW264.7 cells with dysidazirine only (2), displaying cytotoxicity at the highest concentration tested (50 µM). The non-cytotoxic dysidazirine carboxylic acid (1) demonstrated anti-inflammatory activity in RAW264.7 cells stimulated with LPS. After 24 h, 1 inhibited the production of NO by almost 50% at 50 µM, without inducing cytotoxicity. Compound 1 rapidly decreased gene expression of the pro-inflammatory gene iNOS after 3 h post-LPS treatment and in a dose-dependent manner (IC₅₀ ~1 µM); the downregulation of iNOS persisted at least until 12 h.     

Synthesis and anti-leukaemic activity of pyrrolo[3,2,1-hi]indole-1,2-diones,pyrrolo[3,2,1-ij]quinoline-1,2-diones and other polycyclic isatin derivatives

To further expand the structure–cytotoxic activity relationships of isatin derivatives and to reduce flexibility in substituent groups at nitrogen, 20 analogues incorporating a ring system between the N1 and C7 atoms of isatin were prepared using a variety of synthetic strategies. This yielded pyrroloindole-, pyrroloquinoline-, pyrroloacridine-, pyrrolophenanthridine- and benzopyrrolophenanthridine-based systems with embedded isatin moieties, the latter possessing a novel carbon skeleton. These compounds were subsequently assessed for their in vitro cytotoxicity against human U937 lymphoma cells, with the brominated pyrroloacridine dione 27 showing the most promising activity (IC₅₀ 3.01 μM) after 24 h.     

Multi-Fractal Formalism for Quasi-Self-Similar Functions

The study of multi-fractal functions has proved important in several domains of physics. Some physical phenomena such as fully developed turbulence or diffusion limited aggregates seem to exhibit some sort of self-similarity. The validity of the multi-fractal formalism has been proved to be valid for self-similar functions. But, multi-fractals encountered in physics or image processing are not exactly self-similar. For this reason, we extend the validity of the multi-fractal formalism for a class of some non-self-similar functions. Our functions are written as the superposition of similar structures at different scales, reminiscent of some possible modelization of turbulence or cascade models. Their expressions look also like wavelet decompositions. For the computation of their spectrum of singularities, it is unknown how to construct Gibbs measures. However, it suffices to use measures constructed according the Frostman's method. Besides, we compute the box dimension of the graphs.     

Dihydroxamate based siderophore model, piperazine-1,4-bis-(N-methyl-acetohydroxamic acid (PIPDMAHA), as a chelating agent of molybdenum(VI)

Equilibrium studies based on pH-potentiometric and spectrophotometric measurements as well as some theoretical simulations are reported for the complexes of Mo(VI) with a dihydroxamate type siderophore analogue, the piperazine-1,4-bis-(N-methyl-acetohydroxamic acid) (PIPDMAHA). It has been found that the complexation process starts below pH 2 and that PIPDMAHA forms more stable O,O-hydroxamate bis-chelated complexes with Mo(VI) than any of the formerly studied dihydroxamic acids. The experimental data were fitted with two complexation models based either on dinuclear or on mononuclear species. However, ESI-MS showed that the dimmer is much more abundant than the monomer. This feature was further suggested by theoretical simulation studies, which indicated the dimeric species is more stable than the monomeric one.     

Structural investigation of the bridged activated complex in the reaction between hexachloroiridate(IV) and pentacyanocobaltate(II)

Time resolved energy dispersive X-ray absorption spectroscopy has been used to follow the structural evolution of the inner-sphere electron transfer reaction between [IrCl6]2- and [Co(CN)5]3-, and to characterise the local structure of the iridium metal centre in the bridged activated complex formed during the reaction.     

Lipopeptides incorporated into supported phospholipid monolayers have high specific activity at low incorporation levels

The ability to present cell adhesion molecule (CAM) ligands in controlled amounts on a culture surface would greatly facilitate the control of cell growth and differentiation. Supported lipid monolayer/bilayer systems have previously been developed that allow for presentation of CAM ligands for cell interaction; however, these systems have employed peptide loadings much higher than those used in poly(ethylene glycol) (PEG)-based immobilization systems. We report the development of synthetic methods that can be used for the efficient and versatile creation of many linear and cyclic lipid-linked peptide moieties. Using RGD-based peptides for the alpha5beta1 integrin as a model system, we have demonstrated that these lipopeptides support efficient cell binding and spreading at CAM ligand loadings as low as 0.1 mol %, which is well below that previously reported for supported lipid systems. Engineered lipopeptide-based surfaces offer unique presentation options not possible with other immobilization systems, and the high activity at low loadings we have shown here may be extremely useful in presenting multiple CAM ligands for studying cell growth, differentiation, and signaling.     

Substrate electric dipole moment exerts a pH-dependent effect on electron transfer in Escherichia coli photolyase

Transient absorption spectroscopy is used to demonstrate that the electric dipole moment of the substrate cyclobutane thymine dimer affects the charge recombination reaction between fully reduced flavin adenine dinucleotide (FADH-) and the neutral radical tryptophan 306 (Trp306*) in Escherichia coli DNA photolyase. At pH 7.4, the charge recombination is slowed by a factor of 1.75 in the presence of substrate, but not at pH 5.4. Photolyase does bind substrate at pH 5.4, and it seems that this pH effect originates from the conversion of FADH- to FADH2 at lower pH. The free-energy changes calculated from the electric field parameters and from the change in electron transfer rate are in good agreement and support the idea that the substrate electric dipole is responsible for the observed change in electron transfer rate. It is expected that the substrate electric field will also modify the physiologically important from excited 1FADH- to the substrate in the DNA repair reaction.     

Investigation of energy and structural changes of Lin (n=3, 4) microclusters based on temperature

The energy and structural changes of lithium microclusters based on temperature has been investigated by using Molecular-Dynamic simulation Method. Two and three-body interacted semi-empiric potential energy formula that characterized the interaction has been used. It has been calculated that the dissociation of atoms from cluster has started after 1300 K for Li₃ and 1350 K for Li₄, respectively. Dissociations at the fixed temperatures are very close to the expected values of the lithium metal. Additionally, it has been observed that Li₄ microclusters above 1000 K and Li₃ clusters above 700 K temperatures have steady structures in two different energy values.     

Calculation of Two-Center Nuclear Attraction Integrals over Integer and Noninteger n-Slater Type Orbitals in Nonlined-Up Coordinate Systems

Two-center nuclear attraction integrals over Slater type orbitals with integer and noninteger principal quantum numbers in nonlined up coordinate systems have been calculated by means of formulas in our previous work (T. Özdoan and M. Orbay, Int. J. Quant. Chem. 87 (2002) 15). The computer results for integer case are in best agreement with the prior literature. On the other hand, the results for noninteger case are not compared with the literature due to the scarcity of the literature, but also compared with the limit of integer case and good agreements are obtained. The proposed algorithm for the calculation of two-center nuclear attraction integrals over Slater type orbitals with noninteger principal quantum numbers in nonlined-up coordinate systems permits to avoid the interpolation procedure used to overcome the difficulty introduced by the presence of noninteger principal quantum numbers. Finally, numerical aspects of the presented formulae are analyzed under wide range of quantum numbers, orbital exponents and internuclear distances.