Radioactivity characterization of 125I brachytherapy seeds used in prostate cancer treatment

Journal of Radioanalytical and Nuclear Chemistry - A procedure for characterizing the activity amount of 125I seed was developed in order to establish a secondary standard activity measurement...     

A Covalent Binding Mode of a Pyrazole-Based CD38 Inhibitor

Brain concentrations of nicotinamide adenine dinucleotide (NAD⁺), an important cellular co-factor, tend to decrease with age and in neurodegeneration. As the NADase cluster of differentiation 38 (CD38) significantly contributes to NAD⁺ consumption, we reasoned that CD38 inhibition may be of therapeutic value for CNS disorders. The new pyrazole compound was designed based on a known CD38 inhibitor and showed good inhibitory potency. Several attempts to co-crystallise this pyrazole with CD38 and cyclic adenosine diphosphate ribose (cADPR) culminated in a high-resolution X-ray structure, in which the pyrazolyl group in the new compound formed a covalent bond with one of the ribosyl units of cADPR. This reaction proceeded under retention of configuration and resulted in a neutral ribosyl-pyrazole conjugate that is embedded within the active site of the enzyme. An analysis of this structural complex gave rise to design principles that enabled the preparation of more potent CD38 inhibitors with drug-like properties.     

Growth under Visible Light Increases Conidia and Mucilage Production and Tolerance to UV‐B Radiation in the Plant Pathogenic Fungus Colletotrichum acutatum

Light conditions can influence fungal development. Some spectral wavebands can induce conidial production, whereas others can kill the conidia, reducing the population size and limiting dispersal. The plant pathogenic fungus Colletotrichum acutatum causes anthracnose in several crops. During the asexual stage on the host plant, Colletototrichum produces acervuli with abundant mucilage‐embedded conidia. These conidia are responsible for fungal dispersal and host infection. This study examined the effect of visible light during C. acutatum growth on the production of conidia and mucilage and also on the UV tolerance of these conidia. Conidial tolerance to an environmentally realistic UV irradiance was determined both in conidia surrounded by mucilage on sporulating colonies and in conidial suspension. Exposures to visible light during fungal growth increased production of conidia and mucilage as well as conidial tolerance to UV. Colonies exposed to light produced 1.7 times more conidia than colonies grown in continuous darkness. The UV tolerances of conidia produced under light were at least two times higher than conidia produced in the dark. Conidia embedded in the mucilage on sporulating colonies were more tolerant of UV than conidia in suspension that were washed free of mucilage. Conidial tolerance to UV radiation varied among five selected isolates.     

Development of a high‐performance liquid chromatography method with fluorescence detection for the routine quantification of tamoxifen,endoxifen and 4‐hydroxytamoxifen in plasma from breast cancer patients

To date, several methods for the quantification of tamoxifen and its metabolites have been developed, most of which employ liquid chromatography tandem–mass spectrometry (LC–MS/MS). These methods are highly sensitive and reproducible, but are also time‐consuming and require expensive equipment; one of their main disadvantages is matrix ionization effects. A more viable option, particularly in developing countries, is high‐performance liquid chromatography coupled with UV or fluorescence detection. We developed and validated a method for simultaneous quantification of tamoxifen, endoxifen and 4‐hydroxytamoxifen based on high‐performance liquid chromatography with fluorescence detection in a reverse‐phase column. The method is rapid (16 min plus 5 min of column re‐equilibrium), accurate (80–100%) and precise (0.23–6.00%), and does not require any additional irradiation process. Sample pretreatment consists of protein precipitation with acetonitrile under alkaline conditions, employing only 200 μL plasma. The validated method's wide range allowed quantification of steady‐state levels in patients under standard tamoxifen treatment (20 mg/day). This assay is ready for application in clinical studies and routine quantification of tamoxifen, endoxifen and 4‐hydroxytamoxifen in healthcare institutions.     

Electrochemical characterisation of a Zn/(PEO)4ZnCl2/Nb2O5 solid-state cell

The (PEO)₄ZnCl₂ electrolyte (PEO, polyethylene oxide) was studied in view of its potential application in a solid-state rechargeable zinc cell. The electrochemical stability window was established, and decomposition voltage values between 3.19 (20 °C) and 1.44 V (150 °C) were estimated. Cyclic voltammetry studies using a Pt/(PEO)₄ZnCl₂/Pt cell indicated reversibility of the Zn²⁺/Zn couple at the electrode/electrolyte interface. Laboratory cells Zn(−)/(PEO)₄ZnCl₂/Nb₂O₅(+) were assembled and studied at 55 °C, under various discharge current densities. Results of cell discharge profiles, capacity values, charge–discharge cycles and cell stabilities are reported.     

Kinetics and dynamics study of the H + CCl4?��?HCl(v��, j��)?+?CCl3 reaction

Based on a previous potential energy surface describing the H?+?CCl₄ reaction, a new analytical surface named PES-2010 was developed modifying both the functional form to give it more flexibility, and the calibration process in which exclusively theoretical information was used. Thus, the surface is completely symmetric with respect to the permutation of the four methane chlorine atoms, and no experimental information is used in the process. For the kinetics, the thermal rate constants were calculated using variational transition-state theory with semiclassical transmission coefficients over a wide temperature range, 300?C2,500?K. The theoretical results reproduce the experimental variation with temperature. The influence of the tunneling factor is small, since the abstraction reaction involves the motion of a heavy particle (a chlorine atom) that cannot easily tunnel through the reaction barrier. The coupling between the reaction coordinate and the vibrational modes shows qualitatively that the HCl stretching mode in the products appears vibrationally excited. The dynamics study was performed using quasi-classical trajectory calculations, including corrections to avoid the zero-point energy problem. First, we found that the HCl(????, j??) product mostly appears with small rotational energy and vibrational population inversion. Second, the state-specific scattering distributions show backward scattering, which becomes more noticeable as the HCl(????) vibrational state increases. Unfortunately, no experimental dynamics data are available for the title reaction, but the comparison with the kinematically similar and well-studied H?+?Cl₂ reaction shows good agreement, indicative of similar mechanisms. These kinetics and dynamics results seem to indicate that the potential energy surface is adequate to describe this reaction, and the reasonable agreement with experiment lends further confidence to this new surface.     

Chemical Antibody Mimics Inhibit Cadherin-Mediated Cell–Cell Adhesion: A Promising Strategy for Cancer Therapy

One of the most promising strategies to treat cancer is the use of therapeutic antibodies that disrupt cell–cell adhesion mediated by dysregulated cadherins. The principal site where cell–cell adhesion occurs encompasses Trp2 found at the N-terminal region of the protein. Herein, we employed the naturally exposed highly conserved peptide Asp1-Trp2-Val3-Ile4-Pro5-Pro6-Ile7, as epitope to prepare molecularly imprinted polymer nanoparticles (MIP-NPs) to recognize cadherins. Since MIP-NPs target the site responsible for adhesion, they were more potent than commercially available therapeutic antibodies for inhibiting cell–cell adhesion in cell aggregation assays, and for completely disrupting three-dimensional tumor spheroids as well as inhibiting invasion of HeLa cells. These biocompatible supramolecular anti-adhesives may potentially be used as immunotherapeutic or sensitizing agents to enhance antitumor effects of chemotherapy.     

Sequential injection methodology for carbon speciation in bathing waters

A sequential injection method (SIA) for carbon speciation in inland bathing waters was developed comprising, in a single manifold, the determination of dissolved inorganic carbon (DIC), free dissolved carbon dioxide (CO₂), total carbon (TC), dissolved organic carbon and alkalinity. The determination of DIC, CO₂ and TC was based on colour change of bromothymol blue (660 nm) after CO₂ diffusion through a hydrophobic membrane placed in a gas diffusion unit (GDU). For the DIC determination, an in-line acidification prior to the GDU was performed and, for the TC determination, an in-line UV photo-oxidation of the sample prior to GDU ensured the conversion of all carbon forms into CO₂. Dissolved organic carbon (DOC) was determined by subtracting the obtained DIC value from the TC obtained value. The determination of alkalinity was based on the spectrophotometric measurement of bromocresol green colour change (611 nm) after reaction with acetic acid. The developed SIA method enabled the determination of DIC (0.24–3.5 mg C L⁻¹), CO₂ (1.0–10 mg C L⁻¹), TC (0.50–4.0 mg C L⁻¹) and alkalinity (1.2–4.7 mg C L⁻¹ and 4.7–19 mg C L⁻¹) with limits of detection of: 9.5 μg C L⁻¹, 20 μg C L⁻¹, 0.21 mg C L⁻¹, 0.32 mg C L⁻¹, respectively. The SIA system was effectively applied to inland bathing waters and the results showed good agreement with reference procedures.     

Isomeric effects on the self‐assembly of a plausible prebiotic nucleoside analogue: A theoretical study

The self‐assembly properties of N(9)‐(2,3‐dihydroxypropyl adenine) (DHPA), a plausible prebiotic nucleoside analogue of adenosine, were investigated using density functional theory. Two different isomers were considered, and it is found that while both isomers can form a variety of structures, including chains, one of them is also able to form cages and helixes. When these results were put in the context of substrate supported molecular self‐assembly, it is concluded that gas‐phase self‐assembly studies that consider isomer identity and composition not only can aid interpreting the experimental results, but also reveal structures that might be overlooked otherwise. In particular, this study suggest that a double‐helical structure made of DHPA molecules which could have implications in prebiotic chemistry and nanotechnology, is stable even at room temperature. For example electrical properties (energy gap of 4.52eV) and a giant permanent electrical dipole moment (49.22 Debye) were found in our larger double‐helical structure (3.7 nm) formed by 14 DHPA molecules. The former properties could be convenient for construction of organic dielectric‐based devices.     

Photoconductivity,photoluminescence and optical Kerr nonlinear effects in zinc oxide films containing chromium nanoclusters

Chromium doped zinc oxide thin solid films were deposited on soda–lime glass substrates. The photoconductivity of the material and its influence on the optical behavior was evaluated. A non-alkoxide sol–gel synthesis approach was used for the preparation of the samples. An enhancement of the photoluminescence response exhibited by the resulting photoconductive films with embedded chromium nanoclusters is presented. The modification in the photoconduction induced by a 445 nm wavelength was measured and then associated with the participation of the optical absorptive response. In order to investigate the third order optical nonlinearities of the samples, a standard time-resolved Optical Kerr Gate configuration with 80 fs pulses at 830 nm was used and a quasi-instantaneous pure electronic nonlinearity without the contribution of nonlinear optical absorption was observed. We estimate that from the inclusion of Cr nanoclusters into the sample results a strong optical Kerr effect originated by quantum confinement. The large photoluminescence response and the important refractive nonlinearity of the photoconductive samples seem to promise potential applications for the development of multifunctional all-optical nanodevices.