The effect of alternate heating rates during cure on the structure-property relationships of epoxy/MMT clay nanocomposites

This paper investigates the effect of both the mixing technique and heating rate during cure on the dispersion of montmorillonite (MMT) clay in an epoxy resin. The combination of sonication and using a 10. °C/min heating rate during cure was found to facilitate the dispersion of nanoclay in epoxy resin. These processing conditions provided a synergistic effect, making it possible for polymer chains to penetrate in-between clay galleries and detach platelets from their agglomerates. As the degree of dispersion was enhanced, the flexural modulus and strength properties were found to decrease by 15% and 40%, respectively. This is thought to be due to individual platelets fracturing in the nanocomposite. Complementary techniques including X-ray diffraction (XRD), small angle X-ray scattering (SAXS), scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDX), transmission electron microscopy (TEM) and optical microscopy were essential to fully characterise localised and spatial regions of the clay morphologies.

The effect of a rapid heating rate, mechanical vibration and surfactant chemistry on the structure-property relationships of epoxy/clay nanocomposites

The role of processing conditions and intercalant chemistry in montmorillonite clays on the dispersion, morphology and mechanical properties of two epoxy/clay nanocomposite systems was investigated in this paper. This work highlights the importance of employing complementary techniques (X-ray diffraction, small angle X-ray scattering, optical microscopy and transmission electron microscopy) to correlate nanomorphology to macroscale properties. Materials were prepared using an out of autoclave manufacturing process equipped to generate rapid heating rates and mechanical vibration. The results suggested that the quaternary ammonium surfactant on C30B clay reacted with the epoxy during cure, while the primary ammonium surfactant (I.30E) catalysed the polymerisation reaction. These effects led to important differences in nanocomposite clay morphologies. The use of mechanical vibration at 4 Hz prior to matrix gelation was found to facilitate clay dispersion and to reduce the area fraction of I.30E clay agglomerates in addition to increasing flexural strength by over 40%.

Atomically resolved tomography to directly inform simulations for structure-property relationships

Microscopy encompasses a wide variety of forms and scales. So too does the array of simulation techniques developed that correlate to and build upon microstructural information. Nevertheless, a true nexus between microscopy and atomistic simulations is lacking. Atom probe has emerged as a potential means of achieving this goal. Atom probe generates three-dimensional atomistic images in a format almost identical to many atomistic simulations. However, this data is imperfect, preventing input into computational algorithms to predict material properties. Here we describe a methodology to overcome these limitations, based on a hybrid data format, blending atom probe and predictive Monte Carlo simulations. We create atomically complete and lattice-bound models of material specimens. This hybrid data can then be used as direct input into density functional theory simulations to calculate local energetics and elastic properties. This research demonstrates the role that atom probe combined with theoretical approaches can play in modern materials engineering.

Design of endoperoxides with anti-Candida activity

Broad antifungal structure-activity relationships governing epoxy-endoperoxides 2 and 3 and their parent endoperoxides 1 are reported. Their inhibitory activity against Candida albicans in conjunction with hemolytic activity and/or growth inhibition of cultured mammalian cells are reported. This information provided guidance for the further development of endoperoxide and epoxy-endoperoxides as topical antifungal agents.

Structure-property relationships in nylon 6 nanocomposites based on octaphenyl-, dodecaphenyl-POSS, montmorillonite, and their combinations

Binary and ternary nanocomposites were produced by incorporating, via melt compounding, two types of octa-and dodecaphenyl substituted polyhedral oligomeric silsesquioxanes (POSS), montmorillonite (MMT), and combinations of POSS with MMT into nylon 6. The tensile, flexural, and dynamic thermo-mechanical properties of these materials were characterized and their structure-property relationships discussed. The results show that the losses in ductility and toughness experienced after inclusion of MMT into nylon 6 can be balanced out by co-mixing MMT with the dodecaphenyl- POSS to produce a ternary nanocomposite. This trend however was less pronounced in the ternary MMT/octaphenyl-POSS system. Analysis of the microstructure organization in these materials using XRD and SEM sheds some light on understanding the differences in behavior. Both types of POSS particles mixed alone in nylon 6 were found to be polydisperse (500 nm to a few microns in size) and locally aggregated, yielding materials with similar mechanical performance. The co-mixing of MMT with the octaphenyl- POSS served to break down the POSS crystal aggregates, enhancing their micro-mechanical reinforcing action. On the other hand, the POSS crystals were not affected in the MMT/dodecaphenyl-POSS system, which led to improving their toughening ability.

Design of 1,2-dioxines with anti-Candida activity: aromatic substituted 1,2-dioxines

In an ongoing effort to rationally design new antimicrobials, 47 new 1,2-dioxines have been synthesised. Broad antifungal structure-activity relationships governing aromatically substituted epoxy-1,2-dioxines 2 and 3 and their parent 1,2-dioxines 1 were assessed primarily against the pathogenic yeast, Candida albicans, with haemolytic activity of selected examples also reported.

A tellurium-based cathepsin B inhibitor: Molecular structure, modelling, molecular docking and biological evaluation

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Understanding the Structure, Activity and Inhibition of Chorismate Synthase from Mycobacterium tuberculosis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Structure-activity relationship of compounds which are anti-schistosomiasis active

O método do orbital molecular AM1 foi empregado para calcular um conjunto de descritores moleculares para vinte neolignanas sintéticas com atividade anti-esquistossomose. O método de reconhecimento de padrão (análise de componentes principais ACP, análise de conglomerados AC e análise de discriminante) foi utilizado para obter a relação entre a estrutura molecular e a atividade biológica. O conjunto de moléculas foi classificado em dois grupos de acordo com seus graus de atividade biológica. Estes resultados permitem que, projete-se racionalmente novos compostos, potenciais candidatos à síntese e à avaliação biológica.

Structure-activity relationship of mastoparan analogs: effects of the number and positioning of Lys residues on secondary structure, interaction with membrane-mimetic systems and biological activity

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Structure- and ligand-based drug design approaches for neglected tropical diseases

Drug discovery has moved toward more rational strategies based on our increasing understanding of the fundamental principles of protein-ligand interactions. Structure( SBDD) and ligand-based drug design (LBDD) approaches bring together the most powerful concepts in modern chemistry and biology, linking medicinal chemistry with structural biology. The definition and assessment of both chemical and biological space have revitalized the importance of exploring the intrinsic complementary nature of experimental and computational methods in drug design. Major challenges in this field include the identification of promising hits and the development of high-quality leads for further development into clinical candidates. It becomes particularly important in the case of neglected tropical diseases (NTDs) that affect disproportionately poor people living in rural and remote regions worldwide, and for which there is an insufficient number of new chemical entities being evaluated owing to the lack of innovation and R&D investment by the pharmaceutical industry. This perspective paper outlines the utility and applications of SBDD and LBDD approaches for the identification and design of new small-molecule agents for NTDs.

Synthesis, Biological Evaluation, And Molecular Modeling of Chalcone Derivatives As Potent Inhibitors of Mycobacterium tuberculosis Protein Tyrosine Phosphatases (PtpA and PtpB)

Tuberculosis (TB) is a major infectious disease caused by Mycobacterium tuberculosis (Mtb). According to the World Health Organization (WHO), about 1.8 million people die from TB and 10 million new cases are recorded each year. Recently, a new series of naphthylchalcones has been identified as inhibitors of Mtb protein tyrosine phosphatases (PTPs). In this work, 100 chalcones were designed, synthesized, and investigated for their inhibitory properties against MtbPtps. Structure-activity relationships (SAR) were developed, leading to the discovery of new potent inhibitors with IC50 values in the low-micromolar range. Kinetic studies revealed competitive inhibition and high selectivity toward the Mtb enzymes. Molecular modeling investigations were carried out with the aim of revealing the most relevant structural requirements underlying the binding affinity and selectivity of this series of inhibitors as potential anti-TB drugs.

N-4-Phenyl-substituted 2-acetylpyridine thiosemicarbazones: Cytotoxicity against human tumor cells, structure-activity relationship studies and investigation on the mechanism of action

N-4-Phenyl 2-acetylpyridine thiosemicarbazone (H2Ac4Ph; N-(phenyl)-2-(1-(pyridin-2-yl)ethylidene) hydrazinecarbothioamide) and its N-4-ortho-, -meta- and -para-fluorophenyl (H2Ac4oFPh, H2Ac4mFPh, H2Ac4pFPh), N-4-ortho-, -meta- and -para-chlorophenyl (H2Ac4oClPh, H2Ac4mClPh, H2Ac4pClPh), N-4-ortho-, -meta- and -para-iodophenyl (H2Ac4oIPh, H2Ac4mIPh, H2Ac4pIPh) and N-4-ortho-, -meta- and -para-nitrophenyl (H2Ac4oNO(2)Ph, H2Ac4mNO(2)Ph, H2Ac4pNO(2)Ph) derivatives were assayed for their cytotoxicity against human malignant breast (MCF-7) and glioma (T98G and U87) cells. The compounds were highly cytotoxic against the three cell lineages (IC50: MCF-7, 52-0.16 nM; T98G, 140-1.0 nM; U87, 160-1.4 nM). All tested thiosemicarbazones were more cytotoxic than etoposide and did not present any haemolytic activity at up to 10(-5) M. The compounds were able to induce programmed cell death. H2Ac4pClPh partially inhibited tubulin assembly at high concentrations and induced cellular microtubule disorganization. (C) 2012 Elsevier Ltd. All rights reserved.