A fullerene-paclitaxel chemotherapeutic: synthesis, characterization, and study of biological activity in tissue culture

A fullerene-paclitaxel conjugate has been synthesized as a slow-release drug for aerosol liposome delivery of paclitaxel for lung cancer therapy. The conjugate was designed to release paclitaxel via enzymatic hydrolysis and subsequently has shown a half-life of release of 80 min in bovine plasma. A liposome formulation of the conjugate has been prepared using dilauroylphosphatidylcholine (DLPC), and its IC50 is virtually identical to the IC50 for a paclitaxel-DLPC formulation in human epithelial lung carcinoma A549 cells. With both clinically relevant kinetics of hydrolysis and significant cytotoxicity in tissue culture, the conjugate holds promise for enhanced therapeutic efficacy of paclitaxel in vivo.     

Three polar derivatives of N‐ethylcarbazole: materials for optical applications

Three N‐ethyl­carbazole derivatives have been synthesized and tested for non‐linear optical (NLO) properties. The compounds are 2‐(9‐ethyl‐9H‐carbazol‐3‐yl­methyl­ene)­malono­nitrile, C₁₈H₁₃N₃, (IIIa), 2‐cyano‐3‐(9‐ethyl‐9H‐carba­zol‐3‐yl)­thio­acryl­amide, C₁₈H₁₅N₃S, (IIIb), and 3‐(9‐ethyl‐9H‐carbazol‐3‐yl)‐2‐(4‐phenyl‐1,3‐thia­zol‐2‐yl)­acrylo­nitrile, C₂₆H₁₉N₃S, (V). It was found that the mol­ecules of (IIIa) and (V) are nearly planar, while non‐planarity is more pronounced for (IIIb). Molecules of (IIIa) and (V) exhibit herring‐bone packing motifs. In (IIIb), the mol­ecules form layers coplanar with (01), within which they form centrosymmetric dimers via N—H?S hydrogen bonds.     

Cyclization of N,N-dialkylditiocarbamate and alkylxanthate derivatives of polyhalogenated pyridines in gas and liquid phases

The intramolecular cyclization of 31 polyhalogen substituted pyridines containing N,N-dialkyldithiocarbamate or alkylxanthate groups has been compared in reaction in solution with sodium N,N-dialkyldithiocarbamates or potassium carbetoxydithiolate and in the gas phase under electron ionization (EI). The scheme of fragmentation of the studied compounds has been proposed. An influence of the nature of leaving groups (Cl, F, CF(3), CN, COOEt), of the presence of electron withdrawing groups (Cl, F, CN, CCl(3), CF(3), COOEt) in ortho-,meta or para-positions to the leaving halogen, of the position of a dithio group toward pyridine nitrogen atom and of the role of oxygen and nitrogen in corresponding alkylxanthates and N,N-dialkyldithiocarbamates on the cyclization process has been investigated.     

Gel-like lyomesophases formed in organic solvents by self-assembled guanine ribbons

Lipophilic guanosine derivatives are self-assembled into ribbonlike aggregates, both in the crystal state and in solution. The structure of the ribbons has been characterised by single-crystal X-ray diffraction and, in solution, by NMR spectroscopy and ESI-MS. Two different ribbons with different patterns of hydrogen bonds are present in the solid state and in chloroform solutions. The gel-like phases obtained in hexadecane, toluene and chloroform have been investigated by optical microscopy and small-angle X-ray diffraction: the type of phase observed is related to the molecular structure of the compounds and depends dramatically on the solvent. The structures of the phases are discussed, with the presence of the two different ribbons being taken into account.     

Use of iridium plus rhodium as permanent modifier to determine As, Cd and Pb in acids and ethanol by electrothermal atomic absorption spectrometry

The most severe interferences in atomic absorption spectrometry are caused by the presence of anions when they are in different concentrations in the samples and in the calibration solutions. The analyte addition technique or matrix matching calibration can be employed to minimize or compensate the non-spectral interferences, but they are time consuming or difficult to be carried out. The use of chemical modifiers usually allows higher pyrolysis temperatures and consequently the removal of components of the sample matrix, equalizing the analyte signal in the sample and in the calibration solution. In this work, a mixture of Ir and Rh is proposed as permanent modifier to determine As, Cd and Pb in diluted hydrochloric, sulfuric and phosphoric acids and in ethanol and methanol by electrothermal atomic absorption spectrometry (ET AAS) with calibration against 1% v/v nitric acid aqueous solutions. The performance of the proposed permanent modifier was compared to that of Pd plus Mg nitrates in solution. Better recoveries, low background levels and faster analysis were obtained with the permanent modifier. The permanent modifier was also successfully employed for the determination of As, Cd and Pb in different concentrations of sulfuric and hydrochloric acids. For the phosphoric acid, the proposed modifier was only efficient for acid concentrations up to 2% v/v for As and up to 5% v/v for Cd and Pb. The precision, expressed as the relative standard deviation (n=3), was lower than 10%, for all samples, including ethanol and methanol.     

Deubiquitinating enzymes: their functions and substrate specificity

Conjugation of one or more molecules of ubiquitin to target proteins can signify one of several fates, including degradation by the 26S proteasome, or trafficking via the secretory or endocytic pathways. Whereas much attention in recent years has focussed on the mechanisms of forming these different ubiquitin conjugates, far less is known about the removal of ubiquitin, which is performed by deubiquitinating enzymes (DUBs). While it has been appreciated for some 10 years that DUBs constitute large gene families in eukaryotes, and known for much longer that ubiquitination is a reversible process, information on the exact role of DUBs has been slow in coming. This review will attempt to summarise results from the last few years that shows that DUBs are an essential regulatory step of both protein degradation by the proteasome, and of other ubiquitin-dependent processes, by virtue of their ability to regulate protein ubiquitination in a target-specific manner.     

DSC and adiabatic calorimetry study of the polymorphs of paracetamol

Monoclinic (I) and orthorhombic (II) polymorphs of paracetamol were studied by DSC and adiabatic calorimetry in the temperature range 5 - 450 K. At all the stages of the study, the samples (single crystals and powders) were characterized using X-ray diffraction. A single crystal → polycrystal II→ I transformation was observed on heating polymorph II, after which polymorph I melted at 442 K. The previously reported fact that the two polymorphs melt at different temperatures could not be confirmed. The temperature of the II→I transformation varied from crystal to crystal. On cooling the crystals of paracetamol II from ambient temperature to 5 K, a II→ I transformation was also observed, if the 'cooling-heating' cycles were repeated several times. Inclusions of solvent (water) into the starting crystals were shown to be important for this transformation. The values of the low-temperature heat-capacity of the I and II polymorphs of paracetamol were compared, and the thermodynamic functions calculated for the two polymorphs. This revised version was published online in July 2006 with corrections to the Cover Date.     

Study of the conformation of γ-zeins in purified maize protein bodies by FTIR and NMR spectroscopy

The γ-zeins are a mixture of 16, 27, and 50-kDa polypeptides which are important in the formation and stabilization of protein bodies (PB). These organelles are used for deposition of zeins, the water-insoluble storage proteins in maize. The nature of the physical interaction between proteins in the assembly and stabilization of PB are fairly well known. It is suggested the repeated hexapeptide sequence (PPPVHL)₈ in the N-terminus is responsible for aggregation of the γ-zeins on the PB surface. Despite this importance, there is little information about the native conformation of γ-zeins. In this work, we have analyzed the secondary structures of γ-zeins in purified protein bodies from two maize cultivars, in the solid state, by FTIR and NMR spectroscopy. The results revealed that γ-zeins in their physiological state are comprise similar proportions of α-helix and β-sheet, 33 and 31% as determined by FTIR. It was not possible to state if the polyproline II (PPII) conformation is present in the solid-state structure of γ-zeins, as has been demonstrated for the hexapeptide in solution. Because of the similarity of the solid-state NMR spectra of γ and α-zeins in the α carbon region we attributed their contributions to the β-sheet structures rather than to the PPII conformation or a mixture of these extended structures.     

A polarity dependent fluorescence "switch" in live cells

The spectroscopic properties, ultrafast kinetics and utilization of a photochromic molecule as a bi-stable fluorescing sensor of polarity in live cells are described. This molecule is a photochromic fulgimide, 2,3-dialkylidenesuccinimide, which emits fluorescence that can be switched optically on and off. The fluorescence intensity is a function of the polarity of the molecular environment, namely it fluoresces strongly when the molecule is in its polar isomeric structure form. We demonstrate that this molecule enters live cells without inducing damage, it binds primarily to internal membranous organelles (mitochondria) and its fluorescence can be switched optically "on" and "off" repeatedly while inside the living cell. A possible use as a bi-stable, on/off sensor is discussed.     

Some properties of ion trajectories in the radial plane of an axially symmetric ion trap

In this article we analyse the trajectories of externally generated ions injected in the radial plane into the ion trap. The shape of the envelope curves for two-dimensional (2D) ion trajectories is determined. Conditions under which these envelope curves can be transformed into circles are found. We show that the amplitude of ion oscillations is a minimum in this case and that this mode corresponds to optimised ion trapping conditions. Also we discuss a ring-shaped ion trap mass spectrometer electrode system which consists of two ring electrodes, and which utilises ion trajectories with circular envelope curves.