The reaction of aspirin with base

Aspirin anion appears to exist only fleetingly, rearranging via acetyl transfer to the ortho carboxylate group, as indicated by IR, UV and NMR. The resulting mixed anhydride cyclises to the more stable bicyclic orthoacetate isomer, a process facilitated by time and increasing pH. Mechanistic possibilities are discussed to explain these intriguing observations. (C) 2011 Elsevier Ltd. All rights reserved.

Real-time kinetic analysis of hCG-monoclonal antibody interaction using radiolabeled hCG probe: presence of two forms of Ag-mAb complex as revealed by solid phase dissociation studies

Real-time kinetics of ligand-ligate interaction has predominantly been studied by either fluorescence or surface plasmon resonance based methods. Almost all such studies are based on association between the ligand and the ligate. This paper reports our analysis of dissociation data of monoclonal antibody-antigen (hCG) system using radio-iodinated hCG as a probe and nitrocellulose as a solid support to immobilize mAb. The data was analyzed quantitatively for a one-step and a two-step model. The data fits well into the two-step model. We also found that a fraction of what is bound is non-dissociable (tight-binding portion (TBP)). The TBP was neither an artifact of immobilization nor does it interfere with analysis. It was present when the reaction was carried out in homogeneous solution in liquid phase. The rate constants obtained from the two methods were comparable. The work reported here shows that real-time kinetics of other ligand-ligate interaction can be studied using nitrocellulose as a solid support. (C) 2002 Elsevier Science B.V. All rights reserved.

Remarkable photocytotoxicity in hypoxic HeLa cells by a dipyridophenazine copper(II) Schiff base thiolate

Copper(II) complexes Cu(satp)(L)] (1-3) of a Schiff base thiolate (salicylidene-2-aminothiophenol, H(2)satP) and phenanthroline bases (L), viz. 1,10-phenanthroline (phen in 1), dipyrido3,2-d:2',3'-f]quinoxaline (dpq in 2) and dipyrido3,2-a:2',3'-c]phenazine (dppz in 3), were prepared, characterized and their anaerobic DNA photocleavage activity and hypoxic photocytotoxicity studied. The redox active complexes show the Cu(II)-Cu(I) couple near -0.5 V for 1 and near 0.0 V vs. SCE (saturated calomel electrode) for 2 and 3. The one-electron paramagnetic complexes (similar to 1.85 mu(B)) are avid DNA binders giving K(b) values within 1.0 x 10(5) - 8.0 x 10(5) M(-1). Thermal melting and viscosity data along with molecular docking calculations suggest DNA groove and/or partial intercalative binding of the complexes. The complexes show anaerobic DNA cleavage activity in red light under argon via type-I pathway, while DNA photocleavage in air proceeds via hydroxyl radical pathway. The DFT (density functional theory) calculations reveal a thyil radical pathway for the anaerobic DNA photocleavage activity and suggest the possibility of generation of a transient copper(I) species due to bond breakage between the copper and sulfur to generate the thyil radical. An oxidation of the copper(I) species is likely by oxygen in an aerobic medium or by the buffer medium in an anaerobic condition. Complex 3 exhibits significant photocytotoxicity in HeLa cells (IC(50) = 8.3(+/- 1.0) mu M) in visible light, while showing lower dark toxicity (IC(50) = 17.2(+/- 1.0) mu M). A significant reduction in the dark toxicity is observed under hypoxic cellular conditions (IC(50) = 30.0(+/- 1.0) mu M in dark), while retaining its photocytotoxicity (IC(50) = 8.0(+/- 1.0) mu M). (C) 2011 Elsevier Inc. All rights reserved.

Crystal structures of open and closed forms of D-serine deaminase from Salmonella typhimurium - implications on substrate specificity and catalysis

Metabolism of D-amino acids is of considerable interest due to their key importance in cell structure and function. Salmonella typhimurium D-serine deaminase (StDSD) is a pyridoxal 5' phosphate (PLP) dependent enzyme that catalyses degradation of D-Ser to pyruvate and ammonia. The first crystal structure of D-serine deaminase described here reveals a typical Foldtype II or tryptophan synthase beta subunit fold of PLP-dependent enzymes. Although holoenzyme was used for crystallization of both wild-type StDSD (WtDSD) and selenomethionine labelled StDSD (SeMetDSD), significant electron density was not observed for the cofactor, indicating that the enzyme has a low affinity for the cofactor under crystallization conditions. Interestingly, unexpected conformational differences were observed between the two structures. The WtDSD was in an open conformation while SeMetDSD, crystallized in the presence of isoserine, was in a closed conformation suggesting that the enzyme is likely to undergo conformational changes upon binding of substrate as observed in other Foldtype II PLP-dependent enzymes. Electron density corresponding to a plausible sodium ion was found near the active site of the closed but not in the open state of the enzyme. Examination of the active site and substrate modelling suggests that Thr166 may be involved in abstraction of proton from the C alpha atom of the substrate. Apart from the physiological reaction, StDSD catalyses a, b elimination of D-Thr, D-Allothr and L-Ser to the corresponding alpha-keto acids and ammonia. The structure of StDSD provides a molecular framework necessary for understanding differences in the rate of reaction with these substrates.

Synthesis and DNA binding studies of Ni(II), Co(II), Cu(II) and Zn(II) metal complexes of N(1),N(5)-bis[pyridine-2-methylene]-thiocarbohydrazone Schiff-base ligand

The thiocarbohydrazone Schiff-base ligand with a nitrogen and sulphur donor was synthesized through condensation of pyridine-2-carbaldehyde and thiocarbohydrazide. Schiff-base ligands have the ability to conjugate with metal salts. A series of metal complexes with a general formula [MCl(2)(H(2)L)]center dot nH(2)O (M=Ni, Co, Cu and Zn) were synthesized by forming complexes of the N(1),N5-bis[pyridine-2-methylene]thiocarbohydrazone (H2L) Schiff-base ligand. These metal complexes and ligand were characterized by using ultraviolet-visible (UV-Vis), Fourier Transform Infrared (FT-IR), (1)H and (13)C NMR spectroscopy and mass spectroscopy, physicochemical characterization, CHNS and conductivity. The biological activity of the synthesized ligand was investigated by using Escherichia coli DNA as target. The DNA interaction of the synthesized ligand and complexes on E. coli plasmid DNA was investigated in the aqueous medium by UV-Vis spectroscopy and the binding constant (K(b)) was calculated. The DNA binding studies showed that the metal complexes had an improved interaction due to trans-geometrical isomers of the complexes than ligand isomers in cis-positions. (C) 2011 Elsevier B.V. All rights reserved.

Laboratory simulations show diabatic heating drives cumulus-cloud evolution and entrainment

Clouds are the largest source of uncertainty in climate science, and remain a weak link in modeling tropical circulation. A major challenge is to establish connections between particulate microphysics and macroscale turbulent dynamics in cumulus clouds. Here we address the issue from the latter standpoint. First we show how to create bench-scale flows that reproduce a variety of cumulus-cloud forms (including two genera and three species), and track complete cloud life cycles-e.g., from a ``cauliflower'' congestus to a dissipating fractus. The flow model used is a transient plume with volumetric diabatic heating scaled dynamically to simulate latent-heat release from phase changes in clouds. Laser-based diagnostics of steady plumes reveal Riehl-Malkus type protected cores. They also show that, unlike the constancy implied by early self-similar plume models, the diabatic heating raises the Taylor entrainment coefficient just above cloud base, depressing it at higher levels. This behavior is consistent with cloud-dilution rates found in recent numerical simulations of steady deep convection, and with aircraft-based observations of homogeneous mixing in clouds. In-cloud diabatic heating thus emerges as the key driver in cloud development, and could well provide a major link between microphysics and cloud- scale dynamics.

On the fundamentally asynchronous nature of interference in cooperative base station systems

Cooperative transmission by base stations can significantly improve the spectral efficiency of multiuser, multi-cell multiple input multiple output systems. We show that in such systems the multiuser interference is asynchronous by nature, even when perfect timing-advance mechanisms ensure that the desired signal components arrive synchronously. We establish an accurate mathematical model for the asynchronism, and use it to show that the asynchronism leads to a significant performance degradation of existing linear preceding designs that assumed synchronous interference. We consider three different previously proposed precoding designs, and show how to modify them to effectively mitigate asynchronous interference.

Localization induced base isolation in fractionally damped non linear system

In the present article we take up the study of nonlinear localization induced base isolation of a 3 degree of freedom system having cubic nonlinearities under sinusoidal base excitation. The damping forces in the system are described by functions of fractional derivative of the instantaneous displacements, typically linear and quadratic damping are considered here separately. Under the assumption of smallness of certain system parameters and nonlinear terms an approximate estimate of the response at each degree of freedom of the system is obtained by the Method of Multiple Scales approach. We then consider a similar system where the nonlinear terms and certain other parameters are no longer small. Direct numerical simulation is made use of to obtain the amplitude plot in the frequency domain for this case, which helps us to establish the efficacy of this method of base isolation for a broad class of systems. Base isolation obtained this way has no counterpart in the linear theory.

Base excision and nucleotide excision repair pathways in mycobacteria

About a third of the human population is estimated to be infected with Mycobacterium tuberculosis. The bacterium displays an excellent adaptability to survive within the host macrophages. As the reactive environment of macrophages is capable of inducing DNA damage, the ability of the pathogen to safeguard its DNA against the damage is of paramount significance for its survival within the host. Analysis of the genome sequence has provided important insights into the DNA repair machinery of the pathogen, and the studies on DNA repair in mycobacteria have gained momentum in the past few years. The studies have revealed considerable differences in the mycobacterial DNA repair machinery when compared with those of the other bacteria. This review article focuses especially on the aspects of base excision, and nucleotide excision repair pathways in mycobacteria. (C) 2011 Elsevier Ltd. All rights reserved.