Chemistry

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Shiv Nadar University

An agro-waste origin cardanol benzoxazine monomer (Ca) has shown potential as a suitable sustainable linker to chemically bind petroleum industry generated waste, elemental sulphur (S) to form random copolymers poly(S-r-Ca). A series of random copolymers with varied weight percent of elemental sulphur (20–95\%) were synthesised via bulk polymerisation methodology. The Ca monomer offered several reaction sites to facilitate the formation of sulphur rich copolymers as supported by FT-IR, 1H NMR, Raman spectroscopy, XRD, DSC and TGA studies. The curing temperature of Ca was found to be lowered to reaction temperature i.e. 185 °C from 242 °C using elemental sulphur as co-reactant. Preliminary studies of random poly(S-r-Ca) copolymers with a very high sulphur loadings (&gt;80\% w/w) demonstrated inverse vulcanisation and suggest their utility as an efficient substitute to elemental sulphur as a cathode material in Li-S battery. © 2016 Elsevier Ltd

World University root node

(SoNS) School of Natural Sciences

Polymer

Cardanol benzoxazines – A sustainable linker for elemental sulphur based copolymers via inverse vulcanisation

A library of arylidenefuropyridinediones was discovered as potent inhibitors of Leishmania donovani Topoisomerase 1 (LdTop1) where the active molecules displayed considerable inhibition with single digit micromolar EC 50 values. This molecular library was designed via intuitive scaffold hopping and bioisosteric modification of known topoisomerase 1 inhibitors such as camptothecin, edotecarin and etc. The design was rationalized by molecular docking analysis of the compound prototype with human topoisomerase 1 (HTop1) and Leishmania donovani topoisomerase 1(LdTop1). The most active compound 4 displayed no cytotoxicity against normal mammalian COS7 cell line (∼100 fold less inhibition at the EC 50). Similar to camptothecin, 4 interacted with free LdTop1 as observed in the preincubation DNA relaxation inhibition experiment. It also displayed anti-protozoal activity against Leishmania donovani promastigote. Crystal structure investigation of 4 and its molecular modelling with LdTop1 revealed putative binding sites in the enzyme that could be harnessed to generate molecules with better potency.

Fulltext

Scientific Reports

Identification of Leishmania donovani Topoisomerase 1 inhibitors via intuitive scaffold hopping and bioisosteric modification of known Top 1 inhibitors

We have demonstrated a facile synthesis of diversely substituted quinazolines and 3,4-dihydroquinazolines through the o-iodoxybenzoic acid (IBX) mediated tandem reaction of readily available o-aminobenzylamine and aldehydes. The yield of the reactions generally ranged from 70\% to 95\%. This mild protocol provides an efficient strategy toward the synthesis of these classes of heterocycles. © Georg Thieme Verlag Stuttgart.

Synthesis (Germany)

Synthesis of Quinazolines and Dihydroquinazolines: o-Iodoxybenzoic Acid Mediated Tandem Reaction of o-Aminobenzylamine with Aldehydes

Benzoxazine resins, although exhibiting attractive properties; particularly high thermal stability and near zero- shrinkage, suffer from a major drawback associated with its high curing temperature. In view of the Lewis acidity associated with the Zn4O nodes in a zinc based metal organic framework [Zn4O(BDC)3, MOF5], we considered it of interest to explore its potential as a curing accelerator for a representative biobased benzoxazine resin. MOF 5 was solvothermally synthesized and characterized using different techniques including powder X-ray diffraction (PXRD), Scanning Electron Microscopy (SEM), Thermogravimetric Analysis (TGA), Fourier transform infrared spectroscopy (FT-IR) and Nitrogen physisorption measurements. Bio-based benzoxazine resin was synthesized by mannich type condensation of cardanol and aniline with formaldehyde under solventless conditions, the structure of which was confirmed using FT-IR and 1H-NMR. The curing behavior of the synthesized resin was systematically investigated using non-isothermal Differential Scanning Calorimetry (DSC). Introduction of MOF 5 led to a shift in the curing profile to lower temperature, the extent of which was proportional to the amount of MOF 5 in the formulation. DSC studies were performed at different heating rates to establish the kinetic parameters associated with the curing of the resin. Activation energy, as calculated using Kissinger Akahira Sunose method, was found to concomitantly decrease from 98 kJ/mol to 58 kJ/mol upon addition of MOF 5 (5 \% w/w). © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

ChemistrySelect

Metal-Organic Frameworks as curing accelerators for benzoxazines

Early detection of gastric cancers saves lives, but remains a diagnostic challenge. In this study, we aimed to identify cell-surface biomarkers of early gastric cancer. We hypothesized that a subset of plasma membrane proteins induced by the Helicobacter pylori oncoprotein CagA will be retained in early gastric cancers through non-oncogene addiction. An inducible system for expression of CagA was used to identify differentially upregulated membrane protein transcripts in vitro. The top hits were then analyzed in gene expression datasets comparing transcriptome of gastric cancer with normal tissue, to focus on markers retained in cancer. Among the transcripts enriched upon CagA induction in vitro, a significant elevation of CEACAM6 was noted in gene expression datasets of gastric cancer. We used quantitative digital immunohistochemistry to measure CEACAM6 protein levels in tissue microarrays of gastric cancer. We demonstrate an increase in CEACAM6 in early gastric cancers, when compared to matched normal tissue, with an AUC of 0.83 for diagnostic validity. Finally, we show that a fluorescently conjugated CEACAM6 antibody binds avidly to freshly resected gastric cancer xenograft samples and can be detected by endoscopy in real time. Together, these results suggest that CEACAM6 upregulation is a cell surface response to H. pylori CagA, and is retained in early gastric cancers. They highlight a novel link between CEACAM6 expression and CagA in gastric cancer, and suggest CEACAM6 to be a promising biomarker to aid with the fluorescent endoscopic diagnosis of early neoplastic lesions in the stomach.

Oncotarget

CEACAM6 is upregulated by Helicobacter pylori CagA and is a biomarker for early gastric cancer

A diradical approach to obtain stable organic dyes with intense absorption around λ=1100 nm is reported. The para- and meta-quinodimethane-bridged BODIPY dimers BD-1 and BD-2 were synthesized and were found to have a small amount of diradical character. These molecules exhibited very intense absorption at λ=1088 nm (ε=6.65×105 M-1 cm-1) and 1136 nm (ε=6.44×105 M-1 cm-1), respectively, together with large two-photon-absorption cross-sections. Structural isomerization induced little variation in their diradical character but distinctive differences in their physical properties. Moreover, the compounds showed a selective fluorescence turn-on response in the presence of the hydroxyl radical but not with other reactive oxygen species. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA.

Angewandte Chemie - International Edition

A Diradical Approach towards BODIPY-Based Dyes with Intense Near-Infrared Absorption around λ=1100 nm

In this report, the issue related to nanoparticle (NP) agglomeration upon increasing their loading amount into metal-organic frameworks (MOFs) has been addressed by functionalization of MOFs with alkyne groups. The alkynophilicity of the Pd2+ (or other noble metals) ions has been utilized successfully for significant loading of Pd NPs into alkyne functionalized MOFs. It has been shown here that the size and loading amount of Pd NPs are highly dependent on the surface area and pore width of the MOFs. The loading amount of Pd NPs was increased monotonically without altering their size distribution on a particular MOF. Importantly, the distinct role of alkyne groups for Pd2+ stabilization has also been demonstrated by performing a control experiment considering a MOF without an alkyne moiety. The preparation of NPs involved two distinct steps viz. adsorption of metal ions inside MOFs and reduction of metal ions. Both of these steps were monitored by microscopic techniques. This report also demonstrates the applicability of Pd@MOF NPs as extremely efficient heterogeneous catalysts for Heck-coupling and hydrogenation reactions of aryl bromides or iodides and alkenes, respectively.

Inorganic Chemistry

High Loading of Pd Nanoparticles by Interior Functionalization of MOFs for Heterogeneous Catalysis

The Cu-catalyzed oxidation of ketones with O2 has recently been extensively utilized to cleave the $\alpha$-C-C bond. This report examines the selective aerobic hydroxylation of tertiary $\alpha$-C-H bonds in ketones without C-C cleavage. We set out to understand the underlying mechanisms of these two possible reactivity modes. Using experimental, in situ IR spectroscopic and computational studies, we investigated several mechanisms. Our data suggest that both C-C cleavage and C-H hydroxylation pathways proceed via a common key intermediate, i.e., an $\alpha$-peroxo ketone. The fate of this peroxide dictates the ultimate product selectivity. Specifically, we uncovered the role of hppH [=1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-a]pyrimidine] to act not only as a base in the transformation but also as a reductant of the peroxide to the corresponding $\alpha$-hydroxy ketone. This reduction may also be accomplished through exogenous phosphine additives, therefore allowing the tuning of reduction efficiency toward higher driving forces, if required (e.g., for more-activated substrates). The likely competitive pathway is the cleavage of peroxide to the $\alpha$-oxy radical (likely catalyzed by Cu), which is computationally predicted to spontaneously trigger C-C bond cleavage. Increasing the susceptibility of this deperoxidation step via (i) the removal of reductant (use of different base, e.g., DBU) or the modulation of (ii) the substitution pattern toward greater activation (substrate control) and (iii) the nature of Cu catalyst (counterion and solvent dependence) will favor the C-C cleavage product.

Journal of the American Chemical Society

Factors That Control C-C Cleavage versus C-H Bond Hydroxylation in Copper-Catalyzed Oxidations of Ketones with O2

The synthesis of a new library of 5-arylidenethiazolidinone compounds using an efficient three component reaction with thiazolidine-2,4-dione, piperidine and appropriate aldehydes is reported. This reaction is excellently high yielding, tolerant towards a variety of aldehydes and provides access to these compounds in a single step (in comparison to low yielding multistep syntheses reported in the literature). Once the reaction is complete, the desired product precipitates out of the reaction mixture and is isolated by filtration and purified by washing and recrystallization. These compounds revealed anti-proliferative activities against human breast cancer cells (MCF7 and MDA). Phenotypic profiling established the most active compound 17i (EC50 = 4.52 μM) as an apoptotic agent. A novel chemical proteomics approach identified β-actin-like protein 2, γ-enolase and macrophage migration inhibitory factor (MMIF) as putative cellular binding partners of 17i. © 2016 The Royal Society of Chemistry.

Organic and Biomolecular Chemistry

Synthesis of novel 5-arylidenethiazolidinones with apoptotic properties: Via a three component reaction using piperidine as a bifunctional reagent

A series of benzoxazine monomers with varied benzoxazine functionality from 1 to 3 (mono, bis, and tris) is prepared by reacting agrowaste-derived cardanol with higher functionality amines. The ring opening polymerization study of cardanol-based benzoxazine monomers is investigated by three modes, namely, solution (nuclear magnetic resonance and gel permeation chromatography), bulk (differential scanning calorimetry), and theoretical (B3LYP and 6–31+G**) calculations to analyze the role of number of benzoxazine functionality in curing behavior of the monomers. It is found that the presence of higher and close vicinity of benzoxazine functionality in the monomer promotes faster ring opening, rapid polymerization conversion, and enhancement in the average molecular weight buildup. The activation energy for the curing process is found to decrease from 144–113 kJ mol−1 from mono- to tris-benzo­xazine monomer. Thermodynamically, the presence of higher benzoxazine moiety reveals the curing process is highly exergonic as supported by theoretical calculations. Free energy for successive protonation varies from −9.54 to −24.68 eV for mono- to tris-functionalized monomer. The effect of number of functionality in monomer on its curing behavior – a complete study is reported to offer sustainable monomers/polymers for futuristic materials applications. (Figure presented.) . © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim