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

Tumor initiating cells (TIC) are resistant to conventional anticancer therapy and associated with metastasis and relapse in cancer. Although various TIC markers and their antibodies have been proposed, it is limited to the use of antibodies for in vivo imaging or treatment of TIC. In this study, we discovered heme oxygenase 2 (HMOX2) as a novel biomarker for TIC and developed a selective small molecule probe TiNIR (tumor initiating cell probe with near infrared). TiNIR detects and enriches the functionally active TIC in human lung tumors, and through the photoacoustic property, TiNIR also visualizes lung TIC in the patient-derived xenograft (PDX) model. Furthermore, we demonstrate that TiNIR inhibits tumor growth by blocking the function of HMOX2, resulting in significantly increased survival rates of the cancer model mice. The novel therapeutic target HMOX2 and its fluorescent ligand TiNIR will open a new path for the molecular level of lung TIC diagnosis and treatment. Copyright © 2019 American Chemical Society.

World University root node

(SoNS) School of Natural Sciences

Journal of the American Chemical Society

A Near-Infrared Probe Tracks and Treats Lung Tumor Initiating Cells by Targeting HMOX2

Alzheimer’s disease (AD) is now clinically considered as a chronic inflammation-based neurodegenerative disease. The CDnir7 probe was previously developed as an optical imaging probe to target macrophages in order to image mouse inflammation using in vivo optical imaging modalities such as In Vivo imaging system (IVIS) and fluorescent molecular tomography (FMT). Here, we demonstrate the application of CDnir7 in AD mouse brain imaging via multispectral optoacoustic tomography (MSOT). Longitudinal MSOT imaging of CDnir7 showed higher CDnir7 localization in AD mouse cerebral cortex compared to that of normal mice. MSOT signals of CDnir7 localization in mouse brain were verified by ex vivo near-infrared (NIR) imaging and immunohistochemistry. Histological evaluation showed strong CDnir7 staining in AD cerebral cortex, hippocampus, basal ganglia and thalamus area. Based on the supporting evidence, CDnir7 has great potential as a molecular imaging probe for AD brain imaging. © 2019, The Author(s).

Fulltext

Scientific Reports

Visualizing Alzheimer’s Disease Mouse Brain with Multispectral Optoacoustic Tomography using a Fluorescent probe, CDnir7

Antimicrobial drug resistance is one of the most critical problems that plagued the human race in modern times. Discovery of novel antibiotics is important to counter this threat. Accordingly, herein we have reported the discovery of substituted benzimidazole class of molecules with antimicrobial property (specifically against Staphylococcus aureus). They were initially identified through a random screening and a novel catalytic synthetic strategy was utilized to access them. in vitro screening and phenotypic profiling revealed the antimicrobial nature. De novo transcriptome and gene analyses predicted the putative targets. This work provides a solid foundation for developing the benzimidazoles as a target specific antimicrobial preclinical candidate. © 2019 Wiley Periodicals, Inc.

Life Sciences

Drug Development Research

Transcriptome analysis predicts mode of action of benzimidazole molecules against Staphylococcus aureus UAMS-1

Biobased phenols and amines are attractive feedstock in rapid emerging polybenzoxazine thermosets. Renewable benzoxazines are mainly monofunctional due to structure limitation of raw materials, especially amines. Here, we report fully naturally sourced bifunctional benzoxazines by a simple one-step solventless microwave synthesis using cardanol/guaiacol- and carbohydrate-based isomannide diamine (ima). Chirality of ima led to complicated 1H NMR spectra of monomers. Heteronuclear single-quantum coherence (HSQC) and two-dimensional correlated spectroscopy (COSY) NMR and single-crystal X-ray diffraction confirmed the structure and formation of monomers. Polymerization and thermal stability of monomers and polymers were found to be either better than or comparable to widely studied fully and partly petro-based polybenzoxazines. Incorporation of rigid core ima in fully biobased polybenzoxazines showed a glass-transition temperature comparable to their petro-based aromatic diamine counterparts. Exploration of adhesive behavior revealed that the designed polybenzoxazine framework showed 2-fold higher lap shear strength than bisphenol-A (BPA) aniline polybenzoxazine. The current work highlights the utility of higher functionality renewable amines as promising candidates to design future high-performance fully biobased BPA-free polybenzoxazines. Copyright © 2019 American Chemical Society.

ACS Sustainable Chemistry and Engineering

Isomannide-Derived Chiral Rigid Fully Biobased Polybenzoxazines

Isobutyraldehyde underwent auto-oxidation in the presence of molecular oxygen to generate an acyloxy radical under a "metal-free" environment. They were subsequently exploited in situ to afford hypervalent iodines with p-anisolyl iodide which generated substituted 1,3,4-oxadiazoles in moderate to excellent yields from N′-arylidene acetohydrazides. The reaction strategy tolerated diverse substitution on the hydrazide substrates. Control experiments and literature precedence supported the formation of an in situ iodosylarene complex that facilitates the formation of products. © 2019 American Chemical Society.

Organic Letters

Harnessing Autoxidation of Aldehydes: In Situ Iodoarene Catalyzed Synthesis of Substituted 1,3,4-Oxadiazole, in the Presence of Molecular Oxygen

An aromatic oligoamide sequence composed of a light-responsive diazaanthracene-based aromatic $\beta$-sheet flanked by two variable diameter helical segments was prepared. Structural investigations revealed that such oligomers adopt two distinct conformations: a canonical symmetrical conformation with the two helices stacked above and below the sheet and an unanticipated unsymmetrical conformation in which one helix has flipped to directly stack with the first helix. Photoirradiation of the foldamer led to the quantitative and thermally reversible, formation of a single photoproduct resulting from the [4+4] cycloaddition of two diazaanthracenes within the aromatic $\beta$-sheet. NMR and crystallographic studies revealed a parallel arrangement of the diazaanthracene photoproduct and a complete conversion into a symmetrical conformation requiring a rearrangement of all unsymmetrical conformers. These results highlight the potential of foldamers, with structures more complex than isolated helices, for the design of photoswitches showing nontrivial nanometer scale shape changes.

Angewandte Chemie - International Edition

Light-Controlled Conformational Switch of an Aromatic Oligoamide Foldamer

Malaria, one of the most severe global diseases, infects nearly 300 million people causing death of about a million population annually. Herein we have reported design, synthesis and biological evaluation of potent antimalarial compounds that target melatonin hormone as a potential pathway for the inhibition of the parasite proliferation. The molecular design is based on melatonin and indole based synthetic and natural antimalarial agents. The library of compounds was accessed via an iodine catalyzed one pot organocatalytic ring opening of 1-aryltetrahydro-β-carbolines followed by in situ imination of the resulting C2-aroyl intermediates. Inhibition of parasite growth progression (3D7 and chloroquine resistant RKL9 strain) in the presence of the tested compounds indicated that few of the compounds substantially inhibited the parasite survival and the most potent compound 2j blocked the parasite growth at the trophozoite stage. Compound 2j also disrupted the melatonin induced synchronization of the parasite culture in vitro. The active compounds were screened against melatonin receptor MT1 to demonstrate substantial binding. © 2019 Elsevier Masson SAS

European Journal of Medicinal Chemistry

Indole based antimalarial compounds targeting the melatonin pathway: Their design, synthesis and biological evaluation

Full control over the selectivity of carbon-carbon double-bond migrations would enable access to stereochemically defined olefins that are central to the pharmaceutical, food, fragrance, materials and petrochemical arenas. The vast majority of double-bond migrations investigated over the past 60 years capitalize on precious-metal hydrides that are frequently associated with reversible equilibria, hydrogen scrambling, incomplete E/Z stereoselection and/or high cost. Here, we report a fundamentally different, radical-based approach.We showcase a nonprecious, reductant-free and atom-economical nickel (Ni)(I)-catalyzed intramolecular 1,3-hydrogen atom relocation to yield E-olefins within 3 hours at room temperature. Remote installations of E-olefins over extended distances are also demonstrated.

Science

E-Olefins through intramolecular radical relocation

Among 2-D nanostructures, graphene oxide is considered as the most attractive precursor nanomaterial for the utility of graphene in a variety of applications. There are problems associated with its mass production, which demands development of better and easier synthetic protocols. In addition, a chemical approach with a better control over degree of oxidation and nature of functionalities is simultaneously crucial for designing their structural modifications and the corresponding applications. Herein, three types of GOs are prepared by Hummers’, Intermediate and Improved method. A primary reaction step in GO synthesis is the formation of graphite intercalation compounds (GICs). The efficiency of oxidation and intercalant efficiency, non-oxidative Bronsted acid H 3 PO 4 /H 2 SO 4 and H 2 SO 4 are studied and properties are compared with the classical intercalant, H 2 SO 4 /NaNO 3 . A modulation in degree and nature of oxidative defects, flake size and stability of aqueous dispersion is observed, as supported by various analytical techniques. Depending upon the reaction conditions, the synthesized GOs revealed predominance of different type of oxidative functionalities and thereby reflected in associated physical properties, which is helpful to guide their usage for specific applications. © 2019 Elsevier B.V.

FlatChem

A comparative study of graphene oxide: Hummers, intermediate and improved method

Highly efficient oxidative annulation of alkynes furnished diversely substituted pyran[2,3,4-de]chromene-2-one derivatives and related polycycles in moderate to high yield. The reaction is catalyzed by nontoxic, air-stable, and inexpensive Cp∗Co(CO)I 2 catalyst. The hydroxyl moiety at the substrate acts as the directing group for the C-H bond activation. © 2019 American Chemical Society.