Search for singlet-triplet bistability or biradicaloid properties in polycyclic conjugated hydrocarbons: a valence-bond analysis

Two classes of molecules displaying singlet-triplet biradical bistability (i.e. species having significant biradicaloid properties) can be designed as follows. Alternant conjugated polycyclic hydrocarbons with numerous fixed double bonds (double bonds that remain unchanged in all its Kekulé resonance structures), a large number of Dewar resonance structures which measures the corresponding diradical resonance, and a small HOMO-LUMO band gap which measures the ease of thermal spin inversion are candidates for singlet triplet biradical bistability. Chichibabin's hydrocarbon ( 1 ) is an example. In addition, in the search for candidate molecules having singlet triplet bistability, one should also examine polycyclic conjugated systems having nonalternant induced spin frustration. Spin frustrated nonalternant polycyclic conjugated hydrocarbons will display singlet-triplet bistability (biradicaloid properties) and are generated from alternant valence-bond diradicals or Hückel molecular orbital diradicals having classical Kekulé structures by appropriate intramolecular joining of two starred or nonstarred positions with bonds, respectively.     

Indestructibility of compact spaces

In this article we investigate which compact spaces remain compact under countably closed forcing. We prove that, assuming the Continuum Hypothesis, the natural generalizations to _ω1${\omega }_1$-sequences of the selection principle and topological game versions of the Rothberger property are not equivalent, even for compact spaces. We also show that Tall and Usuba?s “_ℵ1${\aleph }_1$-Borel Conjecture” is equiconsistent with the existence of an inaccessible cardinal.     

Selection of intensity modulated radiation therapy treatment beam directions using radial basis functions within a pattern search methods framework

The selection of appropriate radiation incidence directions in radiation therapy treatment planning is important for the quality of the treatment plan, both for appropriate tumor coverage and for better organ sparing. The objective of this paper is to discuss the benefits of using radial basis functions within a pattern search methods framework in the optimization of the highly non-convex beam angle optimization (BAO) problem. Pattern search methods are derivative-free optimization methods that require few function value evaluations to converge and have the ability to avoid local entrapment. These two characteristics gathered together make pattern search methods suited to address the BAO problem. The pattern search methods framework is composed by a search step and a poll step at each iteration. The poll step performs a local search in a mesh neighborhood and assures convergence to a local minimizer or stationary point. The search step provides the flexibility for a global search since it allows searches away from the neighborhood of the current iterate. Radial basis functions are used and tested in this step both to influence the quality of the local minimizer found by the method and to obtain a better coverage of the search space in amplitude. A set of retrospective treated cases of head-and-neck tumors at the Portuguese Institute of Oncology of Coimbra is used to discuss the benefits of using this approach in the optimization of the BAO problem.     

p53‐Dependent and p53‐Independent Responses of Cells Challenged by Photosensitization

The p53 protein exerts fundamental roles in cell responses to a variety of stress stimuli. It has clear roles in controlling cell cycle, triggering apoptosis, activating autophagy and modulating DNA damage response. Little is known about the role of p53 in autophagy‐associated cell death, which can be induced by photoactivation of photosensitizers within cells. The photosensitizer 1,9‐dimethyl methylene blue (DMMB) within nanomolar concentration regimes has specific intracellular targets (mitochondria and lysosomes), photoinducing a typical scenario of cell death with autophagy. Importantly, in consequence of its subcellular localization, photoactive DMMB induces selective damage to mitochondrial DNA, saving nuclear DNA. By challenging cells having different p53 protein levels, we investigated whether p53 modulates DMMB/light‐induced phototoxicity and cell cycle dynamics. Cells lacking p53 activity were slightly more resistant to photoactivated DMMB, which was correlated with a smaller sub‐G1 population, indicative of a lower level of apoptosis. DMMB photosensitization seems to induce mostly autophagy‐associated cell death and S‐phase cell cycle arrest with replication stress. Remarkably, these responses were independent on the p53 status, indicating that p53 is not involved in either process. Despite describing some p53‐related responses in cells challenged by photosensitization, our results also provide novel information on the consequences of DMMB phototoxicity.     

Growth of CuS platelet single crystals by the high-temperature solution growth technique

Millimeter size CuS single crystals with a dark indigo blue color and a plate hexagonal shape have been successfully grown by the high-temperature solution growth technique using the KCl–LiCl eutectic as solvent. Surface microtopographic studies of the crystals indicated that the growth is made by the lateral spreading of the layers. Electrical resistivity measurements clearly show an anomaly at T55 K, related with the low-temperature structural transition, a high residual resistivity ratio of 400 and a sharp superconducting transition at T≈1.7 K confirming the very good quality of the crystals.     

New di‐ and triorganotin(IV) carboxylates derived from a Schiff base: synthesis,characterization and in vitro antimicrobial activities

A new carboxylic acid, 2‐{[5‐(2‐nitrophenyl)furan‐2‐yl]methyleneamino}benzoic acid (HOBZ), has been produced by reacting 5‐(2‐nitrophenyl)furfural with 2‐aminobenzoic acid. Reactions of NaOBZ with organotin chlorides led to formation of [Me₃Sn(OBZ)] ( 1 ), [Bu₃Sn(OBZ)] ( 2 ), [Me₂Sn(OBZ)₂] ( 3 ) and [Bu₂Sn(OBZ)₂] ( 4 ). Complexes 1 , 2 , 3 , 4 have been characterized using elemental analyses and infrared, ¹H NMR, ¹³C NMR, ¹¹⁹Sn NMR and ¹¹⁹Sn Mössbauer spectroscopies. In the solid state, the OBZ ligands might coordinate to tin in an anisobidentate fashion via the carboxylate group. The in vitro antimicrobial activity of all compounds has been screened against the following fungi: Aspergillus niger, A. flavus, A. parasiticus, Penicillium citrinum, Candida dubliniensis, C. lusitaniae, C. albicans, C. tropicalis, C. parapsilosis and C. glabrata; and against the following bacteria: Staphylococcus aureus, Listeria monocytogenes, Bacillus cereus, Streptococcus sanguinis, Escherichia coli, Citrobacter frendii, Salmonella typhimurium and Pseudomonas aeruginosa. Complexes 2 and 4 exhibited higher biocide activity in comparison to 1 and 3 and to the control drugs nystatin and miconazole nitrate for the yeasts, and chloramphenicol and ampicillin for the bacteria. The biological activity of 2 was superior to that of 4 . In addition, the toxicity of HOBZ, NaOBz and 1 , 2 , 3 , 4 were determined using Chlorella vulgaris, revealing low toxicity of the complexes at MIC₅₀ concentrations. We also performed cell viability studies, using XTT assay, displaying no change in the mitochondrial function after 2–4 h of exposure of the microorganism to the complexes at MIC₅₀ concentrations. The butyl‐containing complexes 2 and 4 display greater lipophilicities than do the methyl analogues 1 and 3 , thereby endowing 2 and 4 with superior abilities to cross the microbe cell membrane, the possible mechanism of action. Copyright © 2015 John Wiley & Sons, Ltd.     

The Plasticity of the Carbohydrate Recognition Domain Dictates the Exquisite Mechanism of Binding of Human Macrophage Galactose-Type Lectin

The human macrophage galactose-type lectin (MGL), expressed on macrophages and dendritic cells (DCs), modulates distinct immune cell responses by recognizing N-acetylgalactosamine (GalNAc) containing structures present on pathogens, self-glycoproteins, and tumor cells. Herein, NMR spectroscopy and molecular dynamics (MD) simulations were used to investigate the structural preferences of MGL against different GalNAc-containing structures derived from the blood group A antigen, the Forssman antigen, and the GM2 glycolipid. NMR spectroscopic analysis of the MGL carbohydrate recognition domain (MGL-CRD, C181-H316) in the absence and presence of methyl α-GalNAc (α-MeGalNAc), a simple monosaccharide, shows that the MGL-CRD is highly dynamic and its structure is strongly altered upon ligand binding. This plasticity of the MGL-CRD structure explains the ability of MGL to accommodate different GalNAc-containing molecules. However, key differences are observed in the recognition process depending on whether the GalNAc is part of the blood group A antigen, the Forssman antigen, or GM2-derived structures. These results are in accordance with molecular dynamics simulations that suggest the existence of a distinct MGL binding mechanism depending on the context of GalNAc moiety presentation. These results afford new perspectives for the rational design of GalNAc modifications that fine tune MGL immune responses in distinct biological contexts, especially in malignancy.     

Interaction of PiB‐Derivative Metal Complexes with Beta‐Amyloid Peptides: Selective Recognition of the Aggregated Forms

Metal complexes are increasingly explored as imaging probes in amyloid peptide related pathologies. We report the first detailed study on the mechanism of interaction between a metal complex and both the monomer and the aggregated form of Aβ_1–40 peptide. We have studied lanthanide(III) chelates of two PiB‐derivative ligands (PiB=Pittsburgh compound B), L¹ and L², differing in the length of the spacer between the metal‐complexing DO3A macrocycle (DO3A= 1,4,7,10‐tetraazacyclododecane‐1,4,7‐triacetic acid) and the peptide‐recognition PiB moiety. Surface plasmon resonance (SPR) and saturation transfer difference (STD) NMR spectroscopy revealed that they both bind to aggregated Aβ_1–40 (K_D=67–160 μM ), primarily through the benzothiazole unit. HSQC NMR spectroscopy on the ¹⁵N‐labeled, monomer Aβ_1–40 peptide indicates nonsignificant interaction with monomeric Aβ. Time‐dependent circular dichroism (CD), dynamic light scattering (DLS), and TEM investigations of the secondary structure and of the aggregation of Aβ_1–40 in the presence of increasing amounts of the metal complexes provide coherent data showing that, despite their structural similarity, the two complexes affect Aβ fibril formation distinctly. Whereas GdL¹, at higher concentrations, stabilizes β‐sheets, GdL² prevents aggregation by promoting α‐helical structures. These results give insight into the behavior of amyloid‐targeted metal complexes in general and contribute to a more rational design of metal‐based diagnostic and therapeutic agents for amyloid‐ associated pathologies.