Chemistry

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Graphene oxide (GO) is an attractive precursor for graphene, provided by the well-known wet-chemical oxidative process. The intercalation of acid in graphite is considered as a crucial step, and its subsequent oxidation holds special relevance in synthesis. So far, the above chemistry is dominated by usage of H2SO4. Recently, H3PO4 appeared as a suitable intercalant for graphite. However, its role is not well understood in the formation of GO, especially when present as a co-acid with H2SO4. Additionally, a relatively lower toxicity of H3PO4 as compared to H2SO4, elimination of toxic NaNO3 usage, and a facile purification protocol are encouraging in terms of low-cost production of GO with a reduced environmental impact. Here, we report the systematic synthesis and characterization of GOs prepared with the variation in the ratio of H2SO4 and H3PO4. Ab initio simulations revealed that intercalation is primarily affected because of the usage of a mixture of co-acids. Interestingly, the ratio of the acids dictated the nature of the functionalities, extent of the defects, and morphology of the GOs, accounting for a pronounced effect on thermal stability, contact angle, zeta potential, and hydrodynamic size. The oxidation mechanism showed a predominance of H2SO4 content, whereas H3PO4 is found to mainly govern the intercalation of graphite, thereby affecting the acid-based intercalation-oxidation chemistry of graphite. The as-prepared GO suspension exhibited a high adsorption capacity for methylene blue dye removal in water, suggesting its potential as an adsorbent material in water treatment. The utility of the two acids affects the acid-based intercalation-oxidation chemistry of graphite and simultaneously may open up new opportunities for synthesized GOs, on tenets of green chemistry, in a wide arena of applications. © 2019 American Chemical Society.

Physics

(SoNS) School of Natural Sciences

Fulltext

ACS Omega

Control of Functionalities in GO: Effect of Bronsted Acids as Supported by Ab Initio Simulations and Experiments

Background: Artesunate the most potent antimalarial is widely used for the treatment of multidrug-resistant malaria. The antimalarial cytotoxicity of artesunate has been mainly attributed to its selective, irreversible and iron- radical-mediated damage of parasite biomolecules. In the present research, iron oxide nanoparticle fortified artesunate was tested in P. falciparum and in an experimental malaria mouse model for enhancement in the selectivity and toxicity of artesunate towards parasite. Artesunate was fortified with nontoxic biocompatible surface modified iron oxide nanoparticle which is specially designed and synthesized for the sustained pH-dependent release of Fe2+ within the parasitic food vacuole for enhanced ROS spurt. Methods: Antimalarial efficacy of Iron oxide nanoparticle fortified artesunate was evaluated in wild type and artemisinin-resistant Plasmodium falciparum (R539T) grown in O + ve human blood and in Plasmodium berghei ANKA infected swiss albino mice. Internalization of nanoparticles, the pH-dependent release of Fe2+, production of reactive oxygen species and parasite biomolecule damage by iron oxide nanoparticle fortified artesunate was studied using various biochemical, biophysical, ultra-structural and fluorescence microscopy. For determining the efficacy of ATA-IONP+ART on resistant parasite ring survival assay was performed. Results: The nanoparticle fortified artesunate was highly efficient in the 1/8th concentration of artesunate IC50 and led to retarded growth of P. falciparum with significant damage to macromolecules mediated via enhanced ROS production. Similarly, preclinical In vivo studies also signified a radical reduction in parasitemia with ~8–10-fold reduced dosage of artesunate when fortified with iron oxide nanoparticles. Importantly, the ATA-IONP combination was efficacious against artemisinin-resistant parasites. Interpretation: Surface coated iron-oxide nanoparticle fortified artesunate can be developed into a potent therapeutic agent towards multidrug-resistant and artemisinin-resistant malaria in humans. Fund: This study is supported by the Centre for Study of Complex Malaria in India funded by the National Institute of Health, USA. © 2019

World University root node

EBioMedicine

Pre-clinical study of iron oxide nanoparticles fortified artesunate for efficient targeting of malarial parasite

Traditionally, lead and heavy metal containing inorganic oxides dominate the area of ferroelectricity. Although, recently, lightweight non-toxic organic ferroelectrics have emerged as excellent alternatives, achieving higher temperature up to which the ferroelectric phase can persist has remained a challenge. Moreover, only a few of those are single-component molecular ferroelectrics and were discovered upon revisiting their crystal structures. Here we report a novel phenanthroimidazole derivative, which not only displays notable spontaneous and highly stable remnant polarizations with a low coercive field but also retains its ferroelectric phase up to a record-high temperature of ∼521 K. Subsequently, the crystal undergoes phase transition to form non-polar and centrosymmetric polymorphs, the first study of its kind in a single-component ferroelectric crystal. Moreover, the compound exhibits a significantly high thermal stability. Given the excellent figures-of-merit for ferroelectricity, this material is likely to find potential applications in microelectronic devices pertaining to non-volatile memory. © The Royal Society of Chemistry 2019.

Center for Informatics

Chemical Communications

Record-high thermal stability achieved in a novel single-component all-organic ferroelectric crystal exhibiting polymorphism

Bioisosterism is a useful strategy in rational drug design to improve pharmacodynamic and pharmacokinetic properties of lead compounds. Imidazolidinones have been reported as potent kinase inhibitors and antileishmanial agents. In this study, bioisosteres of imidazolidinones (compounds 1–3) were evaluated for their antileishmanial properties. The modified imidazolidinones exhibited potent antileishmanial activity against extracellular as well as intracellular Leishmania donovani parasites in nanomolar concentrations. The selectivity index of these compounds on host cells was found to be more than 1000, emphasizing their specificity toward the parasite. Using SwissTargetPrediction software, we assessed the potential targets of these compounds and found MAPK as the most probable target. To in vitro validate, we developed a novel in vitro kinase assay that mimics the in vivo nature of the functional kinome. Compounds 1–3 displayed specific inhibition of parasite kinase activity accompanied by an increase in intracellular sodium levels in the parasites. This might be the effect of kinase inhibition that regulates sodium homeostasis through Na-ATPases. Finally, the compound-treated parasites underwent apoptosis-like death. This study represents bioisoterism as a novel approach for drug design to establish the structure–activity relationship, which in turn helps to improve the therapeutic activity of lead compounds. © 2019 Deutsche Pharmazeutische Gesellschaft

Archiv der Pharmazie

Design and synthesis of imidazolidinone derivatives as potent anti-leishmanial agents by bioisosterism

ConspectusThis Account addresses the catalytic cycle of the enzyme cytochrome P450 (CYP450) as a prototypical biological machine with automatic features. CYP450 is a nanomachine that uses dioxygen and two reducing and two proton equivalents to oxidize a plethora of molecules (so-called substrates) as a means of supplying bio-organisms with essential molecules (e.g., brain neurotransmitters, sex hormones, etc.) and protecting biosystems against poisoning. An enticing property of CYP450s is that entrance of an oxidizable substrate into the active site initiates a series of events that constitute the catalytic cycle, which functions "automatically" in a regulated sequence of events culminating in the production of the oxidized substrates (e.g., hydroxylated, epoxidized, etc.), oftentimes with remarkable stereo- and regioselectivities. It is timely to demonstrate how theory uses molecular dynamics (MD) simulations and quantum-mechanical/molecular-mechanical (QM/MM) calculations to complement experiments and elucidate the choreography by which the protein regulates the catalytic cycle.CYP450 is a heme enzyme that contains a ferric ion (Fe III ) coordinated by a porphyrin ligand, a water molecule, and a cysteinate ligand that is provided by a strategic residue of the encapsulating protein. While many of the individual steps are sufficiently well-understood, we shall provide here an overview of the factors that cause all of the steps to be sequentially coordinated. To this end, we use examples from three different CYP450 enzymes: the bacterial ones CYP450 BM3 and CYP450 CAM and the mammalian enzyme CYP450 3A4 . The treatment is limited to the catalytic cycle, as aspects of two-state reactivity were reviewed previously (e.g., Shaik, S.; et al. Chem. Rev. 2005, 105, 2279).What are the principles that govern the seeming automatic feature? For example, how do substrate entrance and binding gate the enzyme? How does the reductase attachment to the enzyme affect the next steps? What triggers the attachment of the reductase? How does the electron transfer (ET) that converts Fe III to Fe II occur? Is the ET coordinated with the entrance of O 2 into the active site? What is the mechanism of the latter step? Since the entrance of the substrate expels the water molecules from the active site, how do water molecules re-enter to form a proton channel, which is necessary for creating the ultimate oxidant Compound I? How do mutations that disrupt the water channel nevertheless create a competent oxidant? By what means does the enzyme produce regio- and stereoselective oxidation products? What triggers the departure of the oxidized product, and how does the exit occur in a manner that generates the resting state ready for the next cycle? This Account shows that the entrance of the substrate triggers all of the ensuing events. © Copyright 2019 American Chemical Society.

Accounts of Chemical Research

Cytochrome P450 - The Wonderful Nanomachine Revealed through Dynamic Simulations of the Catalytic Cycle

A lightweight organic material, trans-4′-dimethylamino-4-nitro-α-cyanostilbene, exhibits notable charge carrier mobility (∼10 -4 cm 2 V -1 s -1 ). The non-centrosymmetric material also displays moderate second harmonic generation activity. This is one of the rarest examples of small organic materials displaying semiconductor characteristics. The charge-transfer pathway as elucidated via high-resolution single-crystal X-ray diffraction data based "energy frameworks" and "experimental charge density" analyses is assessed by measuring the charge carrier mobility using the space charge limited current technique on pure single-crystal diode devices. These advanced structural analyses clearly demonstrate that charge transport in organic crystals is purely governed by its molecular packing, especially the π-π stacking geometry. The balanced ambipolar charge transport behavior makes this highly soluble and thermally stable organic crystal promising for applications in optoelectronic devices. Moreover, this report introduces the crucial role of energy frameworks and charge density analyses for fundamental understanding of the structure-property relationship in organic semiconductors. Copyright © 2019 American Chemical Society.

Crystal Growth and Design

Structure-Property Relationship in an Organic Semiconductor: Insights from Energy Frameworks, Charge Density Analysis, and Diode Devices

In recent years, covalent organic frameworks (COFs) have attracted considerable attention due to their crystalline and porous nature, which positions them as intriguing candidates for diverse applications such as catalysis, sensing, or optoelectronics. The incorporation of dyes or semiconducting moieties into a rigid two-dimensional COF can offer emergent features such as enhanced light harvesting or charge transport. However, this approach can be challenging when dealing with dye molecules that exhibit a large aromatic backbone, since the steric demand of solubilizing side chains also needs to be integrated into the framework. Here, we report the successful synthesis of DPP2-HHTP-COF consisting of diketopyrrolopyrrole (DPP) diboronic acid and hexahydroxytriphenylene (HHTP) building blocks. The well-known boronate ester coupling motif guides the formation of a planar and rigid backbone and long-range molecular DPP stacks, resulting in a highly crystalline and porous material. DPP2-HHTP-COF exhibits excellent optical properties including strong absorption over the visible spectral range, broad emission into the NIR and a singlet lifetime of over 5 ns attributed to the formation of molecular stacks with J-type interactions between the DPP subcomponents in the COF. Electrical conductivity measurements of crystalline DPP2-HHTP-COF pellets revealed conductivity values of up to 10 -6 S cm -1 .

Chemistry of Materials

Scaffold-Induced Diketopyrrolopyrrole Molecular Stacks in a Covalent Organic Framework

The influences of naphthyl and/or phenyl rings at the 2,4-positions of the quinolinyl fragments in carbazole-quinoline conjugates are studied. The centric phase of one of the conjugates (β-CQNN) revealed both thermally activated delayed fluorescence (TADF) and room-temperature phosphorescence (RTP), while prompt fluorescence and RTP were observed in the non-centric phase (α-CQNN) that can regenerate the emission features of β-CQNNvia mechanical grinding. This unique observation is explained by the modulation of the higher-lying triplet (T2) energy level caused by conformational change. © The Royal Society of Chemistry.

Thermally activated delayed fluorescence and room-temperature phosphorescence in naphthyl appended carbazole-quinoline conjugates, and their mechanical regulation

Polybenzoxazines are evolving as a new class of phenolic resins with a tremendous amount of applications. The ease of structural designing, synthetic procedure, and polymerization reactions are attractive to affect their properties ensuing as an effective substitute for many existing polymers. The nonrenewable origin, toxicity, and increasing cost of petro-based raw materials are alarming issues. Therefore, the emergence of sustainable benzoxazines, especially based on naturally abundant, agro-waste origin cardanol is encouraging as it allows both solventless synthesis of monomers and processing to form highly thermally stable thermoset resins. The inherent functionalities in cardanol benzoxazine provide a platform for further structural modifications to advance their applications as adhesives, composites, and energy storage devices. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Macromolecular Chemistry and Physics

Cardanol Benzoxazines: A Versatile Monomer with Advancing Applications

Azidothymidine (AZT) is a first anti-HIV drug namely Zidovudine used for HIV treatment, which binds to the viral DNA primer and inhibits the HIV reverse transcription. The side effects of this powerful drug are severe and the detailed understanding of its electronic structure helps to design new drugs from the AZT molecule. Present study aims to determine the structure of AZT at electronic level from the experimental charge density analysis as well as the solid state DFT calculations. AZT was crystallized and low temperature high resolution X-ray diffraction intensity data has been measured up to sin (θ/λ) max = 1.1 Å −1 at 100.0 (2) K. The crystal structure of AZT was determined, which reveals the information that the AZT compound crystallizes with two molecules in the asymmetric unit which are conformationally different and linked through strong hydrogen bonding interactions (dimer). The Hirshfeld surface of both molecules shows the locations of weak and strong interactions. Further, a multipole model refinement was carried out using Hansen-Coppens multipole formalism. The experimental topological properties of electron density of AZT molecules were determined and compared with the results of theoretical DFT calculations based on solid state and gas phase studies. The charge density distribution of the two molecules in the asymmetric unit is unequal and shows some difference. The topological properties of O–H⋅⋅⋅O, O–H⋅⋅⋅N, C–H⋅⋅⋅N, H⋅⋅⋅H and azide⋅⋅⋅azide group interactions are also determined. The electrostatic potential (ESP) surface of both AZT molecules in the crystal exhibits high electronegative regions around the O, N atoms and also around the azide group, however, ESP regions of molecules (I) and (II) are not similar. © 2018 Elsevier B.V.

Journal of Molecular Structure

Topology of electron density and electrostatic potential of HIV reverse transcriptase inhibitor zidovudine from high resolution X-ray diffraction and charge density analysis