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The synthesis of the first conjugates of acridine with cobalt bis(dicarbollide) are reported. A novel 9-azido derivative of acridine was prepared through the reaction of 9-methoxyacridine with N3CH2CH2NH2, and its solid-state molecular structure was determined via single-crystal X-ray diffraction. The azidoacridine was used in a copper (I)-catalyzed azide-alkyne cycloaddition reaction with cobalt bis(dicarbollide)-based terminal alkynes to give the target 1,2,3-triazoles. DNA interaction studies via absorbance spectroscopy showed the weak binding of the obtained conjugates with DNA. The antiproliferative activity (IC50) of the boronated conjugates against a series of human cell lines was evaluated through an MTT assay. The results suggested that acridine derivatives of cobalt bis(dicarbollide) might serve as a novel scaffold for the future development of new agents for boron neutron capture therapy (BNCT).

Synthesis, NMR spectral data and crystal structure of 9,12-dibromo derivative of ortho-carborane are reported.

No setor rodoviário, a atividade de cadastro e integração das informações é tarefa contínua, podendo ser realizada com a utilização de Sistemas de Referenciamento Linear (SRL) e/ou de Sistemas de Informações Geográficas (SIG). Os SRL são baseados na determinação unidimensional de um ponto desconhecido considerando uma referência, direção e distância conhecidas. Os SIG são baseados em geometrias bidimensionais e apresentam conceitos, algoritmos e modelos de dados próprios, sendo ferramentas indispensáveis no desenvolvimento dos processos de transportes. SRL e SIG são complementares tendo suas vantagens e desvantagens particulares. O desafio por décadas tem sido desenvolver práticas e modelos de dados genéricos para SRL que sejam adaptáveis, flexíveis e personalizáveis para atender a diferentes ambientes. Infelizmente, não há um consenso com relação à metodologia e padrões a serem seguidos para a integração das informações rodoviárias no Brasil. Por exemplo, muitos aspectos das normativas vigentes no âmbito da Comissão Nacional de Cartografia são diferentes das adotadas pelo Departamento Nacional de Infraestrutura de Transportes. Nos EUA, diversas modelagens conceituais de dados foram propostas ao longo dos anos, comprovando uma preocupação constante na padronização e integração das informações rodoviárias. Internacionalmente, foi desenvolvida a norma ISO 19148 para SRL. Diante deste cenário e da ausência de normativas e especificações no Brasil para SRL, o presente artigo apresenta uma revisão a respeito das principais definições e modelos de dados para SRL existentes que possam ser aplicados ao sistema rodoviário. Diversos aspectos da normativa internacional são discutidos, como por exemplo métodos (absoluto – quilometragem, milhagem, etc. –, relativo, interpolativo) e elementos (curva, feição, aresta direcionada) para SRL. Um estudo de caso preliminar no âmbito do Departamento Autônomo de Estradas de Rodagem do estado do Rio Grande do Sul também é descrito.

Novel fluorescent 7-methoxy- and 7-(diethylamino)-coumarins modified with azido-group on the side chain have been synthesized. Their photophysical properties and single crystals structure characteristics have been studied. In order to demonstrate the possibilities of fluorescent labeling, obtained coumarins have been tested with closo-dodecaborate derivative bearing terminal alkynyl group. CuI catalyzed Huisgen 1,3-dipolar cycloaddition reaction has led to fluorescent conjugates formation. The absorption–emission spectra of the formed conjugates have been presented. The antiproliferative activity and uptake of compounds against several human cell lines were evaluated.

Мета. Визначити ступінь впливу незалежних один від одного передопераційних чинників на єдиний залежний чинник - тривалість госпіталізації пацієнтів із гострим коронарним синдромом після екстреної ендоваскулярної реваскуляризації міокарда. Матеріали і методи. Зібрано та статистично опрацьовано дані історій хвороб 40 пацієнтів віком до 60 років (1-ша група) та 40 пацієнтів віком 60 років і старше (2-га група). Методом статистичного опрацювання даних обрано кореляційно-регресійний аналіз. Результати. У пацієнтів 1-ї групи на тривалість госпіталізації впливали (в порядку зменшення значущості): передопераційні показники гемоглобіну та гематокриту, рівні тропоніну І та загального холестерину, ступінь оклюзії коронарних артерій, індекс маси тіла, фракція викиду лівого шлуночка та об’єм післяопераційної крововтрати. У пацієнтів 2-ї групи єдиним фактором, що істотно вплинув на тривалість госпіталізації, був вік. Висновки. Предикторами тривалості госпіталізації у віковій групі до 60 років слугують майже всі включені до дослідження незалежні фактори, тоді як у віковій групі 60 років і старше стійка кореляція характерна лише для фактора віку.

A series of novel cobalt bis(dicarbollide)—curcumin conjugates were synthesized. Two conjugates were obtained through the nucleophilic ring-opening reaction of the 1,4-dioxane and tetrahydropyran derivatives of cobalt bis(dicarbollide) with the OH group of curcumin, and using two equiv. of the oxonium derivatives, two other conjugates containing two cobalt bis(dicarbollide) units per molecule were obtained. In contrast to curcumin, the conjugates obtained were found to be non-cytotoxic against both tumor and normal cell lines. The analysis of the intracellular accumulation of the conjugates by flow cytometry showed that all cobalt bis(dicarbollide)—curcumin conjugates entered HCT116 colorectal carcinoma cells in a time-dependent manner. New non-cytotoxic conjugates contain a large amount of boron atoms in the biomolecule and can potentially be used for further biological research into boron neutron capture therapy (BNCT).

A series of novel conjugates of cobalt bis(dicarbollide) and closo-dodecaborate with curcumin were synthesized by copper(I)-catalyzed azide-alkyne cycloaddition. These conjugates were tested for antibacterial activity. It was shown that all derivatives are active when exposed to Bacillus cereus ATCC 10702 and are not active against Gram-negative microorganisms and Candida albicans at the maximum studied concentration of 1000 mg/L. The conjugate of alkynyl-curcumin with azide synthesized from the tetrahydropyran derivative of cobalt bis(dicarbollide) exhibited activity against Gram-positive microorganisms: Staphylococcus aureus ATCC 29213, Enterococcus faecalis ATCC 29212 and the clinical isolate MRSA 17, that surpassed curcumin by 2–4 times.

CXCR1 and CXCR2 signaling play a critical role in neutrophil migration, angiogenesis, and tumorigenesis and are therefore an attractive signaling axis to target in a variety of indications. In human, a total of seven chemokines signal through these receptors and comprise the ELR+CXC chemokine family, so named because of the conserved ELRCXC N-terminal motif. To fully antagonize CXCR1 and CXCR2 signaling, an effective therapeutic should block either both receptors or all seven ligands, yet neither approach has been fully realized clinically. In this work, we describe the generation and characterization of LY3041658, a humanized monoclonal antibody that binds and neutralizes all seven human and cynomolgus monkey ELR+CXC chemokines and three of five mouse and rat ELR+CXC chemokines with high affinity. LY3041658 is able to block ELR+CXC chemokine-induced Ca2+ mobilization, CXCR2 internalization, and chemotaxis in vitro as well as neutrophil mobilization in vivo without affecting other neutrophil functions. In addition to the in vitro and in vivo activity, we characterized the epitope and structural basis for binding in detail through alanine scanning, crystallography, and mutagenesis. Together, these data provide a robust preclinical characterization of LY3041658 for which the efficacy and safety is being evaluated in human clinical trials for neutrophilic skin diseases.

Antibody therapeutics are one of the most important classes of drugs. Antibody structures have become an integral part of predicting the behavior of potential therapeutics, either directly or as the basis of modeling. Structures of Fab:antigen complexes have even greater value. While the crystallization and structure determination of Fabs is easy relative to many other protein classes, especially membrane proteins, broad screening and optimization of crystalline hits is still necessary. Through a comprehensive review of rabbit Fab crystal contacts and their incompatibility with human Fabs, we identified a small secondary structural element from the rabbit light chain constant domain potentially responsible for hindering the crystallization of human Fabs. Upon replacing the human kappa constant domain FG loop (HQGLSSP) with the two residue shorter rabbit loop (QGTTS), we dramatically improved the crystallization of human Fabs and Fab:antigen complexes. Our design, which we call "Crystal Kappa", enables rapid crystallization of human fabs and fab complexes in a broad range of conditions, with less material in smaller screens or from dilute solutions.

9-HC≡CCH2Me2N-nido-7,8-C2B9H11, a previously described carboranyl terminal alkyne, was used for the copper(I)-catalyzed azide-alkyne cycloaddition with azido-3β-cholesterol to form a novel zwitter-ionic conjugate of nido-carborane with cholesterol, bearing a 1,2,3-triazol fragment. The conjugate of nido-carborane with cholesterol, containing a charge-compensated group in the linker, can be used as a precursor for the preparation of liposomes for BNCT (Boron Neutron Capture Therapy). The solid-state molecular structure of a nido-carborane derivative with the 9-Me2N(CH2)2Me2N-nido-7,8-C2B9H11 terminal dimethylamino group was determined by single-crystal X-ray diffraction.

Novel zwitter-ionic nido-carboranyl azide 9-N3(CH2)3Me2N-nido-7,8-C2B9H11 was prepared by the reaction of 9-Cl(CH2)3Me2N-nido-7,8-C2B9H11 with NaN3. The solid-state molecular structure of nido-carboranyl azide was determined by single-crystal X-ray diffraction. 9-N3(CH2)3Me2N-nido-7,8-C2B9H11 was used for the copper(I)-catalyzed azide-alkyne cycloaddition with phenylacetylene, alkynyl-3β-cholesterol and cobalt/iron bis(dicarbollide) terminal alkynes to form the target 1,2,3-triazoles. The nido-carborane-cholesterol conjugate 9-3β-Chol-O(CH2)C-CH-N3(CH2)3Me2N-nido-7,8-C2B9H11 with charge-compensated group in a linker can be used as a precursor for preparation of liposomes for Boron Neutron Capture Therapy (BNCT). A series of novel zwitter-ionic boron-enriched cluster compounds bearing a 1,2,3-triazol-metallacarborane-carborane conjugated system was synthesized. Prepared conjugates contain a large amount of boron atom in the biomolecule and potentially can be used for BNCT.

This paper presents one of the ways in which the ideas of active learning, problem solving, using history of science, probing students' ideas and other approaches can be implemented to bring about meaningful learning. The example is taken from the plant chemistry and is suitable for the lower secondary level. In this paper we wanted to show how, from a seemingly simple question "What's inside a sweet pepper fruit", one can develop a complex teaching situation that leads to the realisation of teaching goals in a unique way. It shows merely one approach as an example of how to connect content (i.e. declarative knowledge, practical skills) and understanding of scientific processes (i.e. process-based knowledge), as well as the understanding of their own thought processes (i.e. metacognitive knowledge). The chemical analysis of the gases in the sweet pepper fruit showed that there was an increased concentration of carbon dioxide which is around 200 times greater than in the air and this is perhaps a good starting point for new problem-based teaching. (Contains 8 figures.)