Chemistry

<p>Shiv Nadar University is a comprehensive, multidisciplinary, research-focused, and student-centric University offering a full range of academic programs at the undergraduate, postgraduate and doctoral level. With state-of-the-art infrastructure, the University comprises of academic wings, sophisticated labs, international standard sports facilities, amphitheaters, auditorium, conference rooms and smart classrooms. The University&rsquo;s goal is to become internationally recognized for the quality of its research and creative endeavors and their applicability to improving quality of life, generating new insights and expanding the boundaries of human knowledge creativity. Committed to excellence in teaching, research and service, the University aims to serve the higher education needs of India and the world beyond.</p>

Shiv Nadar University

Conjugates of poly(amidoamine) (PAMAM) with modified graphene oxide (GO) are attractive nonviral vectors for gene-based cancer therapeutics. GO protects siRNA from enzymatic cleavage and showed reasonable transfection efficiency along with simultaneous benefits of low cost and large scale production. PAMAM is highly effective in siRNA delivery but suffers from high toxicity with poor in vivo efficacy. Co-reaction of GO and PAMAM led to aggregation and more importantly, have detrimental effect on stability of dispersion at physiological pH preventing their exploration at clinical level. In the current work, we have designed, synthesized, characterized and explored a new type of hybrid vector (GPD), using GO synthesized via improved method which was covalently tethered with poly(ethylene glycol) (PEG) and PAMAM. The existence of covalent linkage, relative structural changes and properties of GPD is well supported by Fourier transform infrared (FTIR), UV-visible (UV-vis), Raman, X-ray photoelectron (XPS), elemental analysis, powder X-ray diffraction (XRD), thermogravimetry analysis (TGA), dynamic light scattering (DLS), and zeta potential. Scanning electron microscopy (SEM), and transmission electron microscopy (TEM) of GPD showed longitudinally aligned columnar self-assembled ∼10 nm thick polymeric nanoarchitectures onto the GO surface accounting to an average size reduction to ∼20 nm. GPD revealed an outstanding stability in both phosphate buffer saline (PBS) and serum containing cell medium. The binding efficiency of EPAC1 siRNA to GPD was supported by gel retardation assay, DLS, zeta potential and photoluminescence (PL) studies. A lower cytotoxicity with enhanced cellular uptake and homogeneous intracellular distribution of GPD/siRNA complex is confirmed by imaging studies. GPD exhibited a higher transfection efficiency with remarkable inhibition of cell migration and lower invasion than PAMAM and Lipofectamine 2000 suggesting its role in prevention of breast cancer progression and metastasis. A significant reduction in the expression of the specific protein against which siRNA was delivered is revealed by Western blot assay. Furthermore, a pH-triggered release of siRNA from the GPD/siRNA complex was studied to provide a mechanistic insight toward unloading of siRNA from the vector. Current strategy is a way forward for designing effective therapeutic vectors for gene-based antitumor therapy. © 2018 American Chemical Society.

Life Sciences

(SoNS) School of Natural Sciences

ACS Applied Materials and Interfaces

Stable Dispersions of Covalently Tethered Polymer Improved Graphene Oxide Nanoconjugates as an Effective Vector for siRNA Delivery

High-energy electrochemical storage containing earth abundant materials could be a choice for future battery development. Recent research reports indicated the possibility of room-temperature sodium-ion-sulfur chemistry for large storage including smart grids. Here, we report a room-temperature sodium-sulfur battery cathode that will address the native downsides of a sodium-sulfur battery, such as polysulfide shuttling and low electrical conductivity of elemental sulfur. In this Letter, we use a sustainable route which ensures a large sulfur confinement (i.e., ∼90 wt \%) in the cathode structure. The sulfur-embedded polymer is realized via thermal ring-opening polymerization of benzoxazine in the presence of elemental sulfur (CS90) and later composite with reduced graphene oxide (rGO). The resulting CS90 allows a homogeneous distribution of sulfur due to in situ formation of the polymer backbone and allows maximum utilization of sulfur. This unique electrode structure bestows CS90-rGO with an excellent Coulombic efficiency (99\%) and healthy cycle life. © 2017 American Chemical Society.

World University root node

ACS Energy Letters

Sulfur Copolymer: A New Cathode Structure for Room-Temperature Sodium-Sulfur Batteries

Catalytic cerium chloride was found to activate 2-iodoxybenzoic acid (IBX) for the oxidative dehydrogenation of tetrahydroisoquinolines, tetrahydro-β-carbolines, and thiazolidines to their dehydrogenated and aromatic forms at room temperature in moderate to excellent yields. The robustness of the protocol was demonstrated by scaling up the reactions to multigram quantities. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

European Journal of Organic Chemistry

Cerium Chloride Catalyzed, 2-Iodoxybenzoic Acid Mediated Oxidative Dehydrogenation of Multiple Heterocycles at Room Temperature

We study the stability of drum-shaped transition metal (TM)-doped boron clusters, M@Bn with n = 14 and 16, and M = 3d, 4d, and 5d TM atom using ab initio calculations. Our results show that drum-shaped M@B14 clusters are favored for M = Cr, Mn, Fe, Co, and Ni, while in other cases, open conical or bowl shaped structures become more favorable. The isoelectronic Ni@B14 and Co@B14- clusters have large highest occupied molecular orbital-lowest unoccupied molecular orbital gaps and these are magic clusters. Their stability has been correlated with the occurrence of magic behavior with 24 valence electrons in a disk jellium model, while for Fe@B14 case the drum structure is deformed and the stability occurs at 22 delocalized valence electrons. The bonding nature in these clusters has been studied by analyzing the electron density at bond and ring critical points, the Laplacian distribution of the electron density, the electron localization function, the source function, and electron localization-delocalization indices, all of which suggest two- and three-center σ bonding within and between the two B7 rings, respectively, and hybridization between the TM d orbitals and the π bonded molecular orbitals of the drum. The infrared and Raman spectra of these magic clusters show all real frequencies, suggesting the dynamical stability of the drum-shaped structures. There is a low frequency mode associated with the M atom. Results of the electronic spectra of the anion clusters are also presented that may help to identify these species in future experiments. Further, we discuss the stability of 24 delocalized valence electron systems Mn@B16 anion, Fe@B16, Co@B16 cation, and other related clusters. Assembly of Co@B14 clusters has been shown to stabilize a carbon nanotube-like nanotube of boron with Co atomic nanowire inside while a nanotube of boron with triangular network has been obtained with the assembly of Fe@B16 drum-shaped clusters. Both the nanotubes are metallic. © 2017 American Chemical Society.

Center for Informatics

Fulltext

Journal of Physical Chemistry C

Electronic Origin of the Stability of Transition-Metal-Doped B14 Drum-Shaped Boron Clusters and Their Assembly into a Nanotube

Lignin is an amorphous biopolymer consisting of hydroxyphenyl propane units, which are interlinked with ether and biphenyl linkages. The widespread abundance and variation in the substitution of phenolic units in the nature of plant species present them as a viable source for phenolic raw materials. This chapter aims to list the major phenolic components available from lignin and its utility as a synthon for benzoxazine monomer synthesis. The presence of additional functionalities in the monomer dictates the polymer properties and its utility in various applications. © 2017 Elsevier Inc. All rights reserved.

Advanced and Emerging Polybenzoxazine Science and Technology

Lignin-Based Phenols: Potential Feedstock for Renewable Benzoxazines

The acid/base-catalysed Kemp elimination of 5-nitro-benzisoxazole forming 2-cyano-4-nitrophenol has long served as a design platform of enzymes with non-natural reactions, providing new mechanistic insights in protein science. Here we describe an alternative concept based on redox catalysis by P450-BM3, leading to the same Kemp product via a fundamentally different mechanism. QM/MM computations show that it involves coordination of the substrate's N-atom to haem-Fe(II) with electron transfer and concomitant N-O heterolysis liberating an intermediate having a nitrogen radical moiety Fe(III)-N· and a phenoxyl anion. Product formation occurs by bond rotation and H-transfer. Two rationally chosen point mutations cause a notable increase in activity. The results shed light on the prevailing mechanistic uncertainties in human P450-catalysed metabolism of the immunomodulatory drug leflunomide, which likewise undergoes redox-mediated Kemp elimination by P450-BM3. Other isoxazole-based pharmaceuticals are probably also metabolized by a redox mechanism. Our work provides a basis for designing future artificial enzymes. © The Author(s) 2017.

Nature Communications

A redox-mediated Kemp eliminase

The entry of the dengue virus is mediated by the conformational change in the envelope protein due to change in the endosomal pH. The structural study reveals that domain-III of the dengue envelope protein (DENV) shows the largest shift in its position during the entry of the virus. Therefore, targeting the hinge region of the domain-III may block the conformational changes in the DENV. In the present work, we have targeted the domain I/III hinge region using four known ligands used for the dengue envelope protein (serotype-2) and have intended to explore the specificity of one ligand R1 (5-(3-chlorophenyl)-N-(2-phenyl-2H-benzo[d][1,2,3]triazol-6-yl)furan-2-carboxamide) that succeeded the dengue inhibition by the molecular dynamics (MD) simulations in conjunction of the molecular docking and the binding free energy calculations. The residue interactions map shows Lys 296 of domain-III of the DENV-2, which might be responsible for binding small molecules between domain I/III interface, as an important residue conserved in all the dengue serotypes. © 2017, Springer-Verlag Berlin Heidelberg.

Journal of Molecular Modeling

Targeting domain-III hinging of dengue envelope (DENV-2) protein by MD simulations, docking and free energy calculations

Adv. Mater. 2017, 29, 1700244 In Figure 2d of the originally published article, the (+) and (−) labels denoting the presence or absence of linker DNA were placed over the wrong samples. The figure is corrected here:. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Advanced Materials

Correction to: Gold and Hairpin DNA Functionalization of Upconversion Nanocrystals for Imaging and In Vivo Drug Delivery (Advanced Materials, (2017), 29, 18, (1700244), 10.1002/adma.201700244)

Nitrogen heteroarenes form an important class of compounds which can be found in natural products, synthetic drugs, building blocks etc. Among the diverse strategies that were developed for the synthesis of nitrogen heterocycles, oxidative dehydrogenation is extremely effective. This review discusses various oxidative dehydrogenation strategies of C-C and C-N bonds to generate nitrogen heteroarenes from their corresponding heterocyclic substrates. The strategies are categorized under stoichiometric and catalytic usage of reagents that facilitate such transformations. The application of these strategies in the synthesis of nitrogen heteroarene natural products and synthetic drug intermediates are also discussed. We hope this review will arouse sufficient interest among the scientific community to further advance the application of oxidative dehydrogenation in the synthesis of nitrogen heteroarenes. © 2017 Hati et al.; Licensee Beilstein-Institut.

Beilstein Journal of Organic Chemistry

Oxidative dehydrogenation of C-C and C-N bonds: A convenient approach to access diverse (dihydro)heteroaromatic compounds

Visceral Leishmaniasis is a deadly parasitic disease caused by Leishmania donovani. Paucity exists in the discovery of novel chemotherapeutics against Leishmaniasis. In this study, we synthesized a natural product inspired Diversity Oriented Synthesis library of L. donovani Trypanothione reductase (LdTR) inhibitor β-carboline-quinazolinone hybrids, which are different in stereochemical architecture and diverse in the bioactive chemical space. It is noteworthy that chirality affects drug-to-protein binding affinity since proteins in any living system are present only in one of the chiral forms. Upon evaluation of the hybrids, one of the chiral forms i.e. Compound 1 showed profound cytotoxic effect in micromolar range as compared to its other chiral form i.e. Compound 2. In-silico docking studies confirmed high binding efficiency of Compound 1 with the catalytic pocket of LdTR. Treatment of L. donovani parasites with Compound 1 inhibits LdTR activity, induces imbalance in redox homeostasis by enhancing ROS, disrupts the mitochondrial membrane potential, modifies actin polymerization and alters the surface topology and architecture. All these cellular modifications eventually led to apoptosis-like death of promastigotes. Furthermore, we synthesized the analogues of Compound 1 and found that these compounds show profound antileishmanial activity in the nanomolar range both in promastigotes and intracellular amastigotes. The enhanced inhibitory potential of these compounds was further supported by in-silico analysis of protein-ligand interactions which revealed high binding efficiency towards the catalytic pocket of LdTR. Taken together, this study reports the serendipitous discovery of β-carboline-quinazolinone hybrids with enhanced antileishmanial activity along with the in-depth structure-activity relationships and mechanism of action of these analogues. © 2016 Elsevier Inc.