Structural and Surface Properties of pH-Varied Fe2O3 Nanoparticles: Correlation with Antibacterial Properties.

Hematite (Fe2O3) nanoparticles were synthesized using a hydrothermal synthesis route under different pH conditions (pH ∼8,10,11.5) (i.e., different ratios of H+/OH- ions). The sample synthesized at pH 10 had better motility toward the bacterial surface due to having an overall positive charge (ξ-potential = +11.10), leading to a minimal hydrodynamic size (Dτ = 186.6). The results are discussed in light of the relative ratio of H+/OH- that may affect bond formation by influencing the electronic clouds of the participating ions that can modify the structure. This, in turn, modifies crystallinity, strain, disorder, surface termination, and thereby, the surface charge, which has been correlated to the antibacterial properties of the nanoparticles due to the interaction between the respective opposite charges on the nanoparticle surface and bacterial cell wall. The structural modifications were correlated to all of these parameters in this work.

Intermolecular interactions underlie protein/peptide phase separation irrespective of sequence and structure at crowded milieu.

Liquid-liquid phase separation (LLPS) has emerged as a crucial biological phenomenon underlying the sequestration of macromolecules (such as proteins and nucleic acids) into membraneless organelles in cells. Unstructured and intrinsically disordered domains are known to facilitate multivalent interactions driving protein LLPS. We hypothesized that LLPS could be an intrinsic property of proteins/polypeptides but with distinct phase regimes irrespective of their sequence and structure. To examine this, we studied many (a total of 23) proteins/polypeptides with different structures and sequences for LLPS study in the presence and absence of molecular crowder, polyethylene glycol (PEG-8000). We showed that all proteins and even highly charged polypeptides (under study) can undergo liquid condensate formation, however with different phase regimes and intermolecular interactions. We further demonstrated that electrostatic, hydrophobic, and H-bonding or a combination of such intermolecular interactions plays a crucial role in individual protein/peptide LLPS.

Transition-metal catalyzed C-H activation as a means of synthesizing complex natural products.

Over the past few decades, the advent of C-H activation has led to a rethink among chemists about the synthetic strategies employed for multi-step transformations. Indeed, deploying innovative and masterful tricks against the numerous classical organic transformations has been the need of the hour. Despite this, the immense importance of C-H activation remains unfulfilled unless the methodology can be deployed for large-scale industrial processes and towards the concise, step-economic synthesis of prodigious natural products and pharmaceutical drugs. Lately, the growing potential of C-H activation methodology has indeed driven the pioneers of synthetic organic chemists into finding more efficient methods to accelerate the synthesis of such complex molecular scaffolds. This review aims to draw a general overview of the various C-H activation procedures that have been adopted for synthesizing these vast majority of structurally complicated natural products. Our objective lies in drawing a complete picture and taking the readers through the synthesis of a series of such complex organic compounds by simplified techniques, making it step-economic on a larger scale and thus instigating the readers to trigger the use of such methodology and uncover new, unique patterns for future synthesis of such natural products.

Transition-metal-catalyzed C-H bond alkylation using olefins: recent advances and mechanistic aspects.

Transition metal catalysis has contributed immensely to C-C bond formation reactions over the last few decades, and alkylation is no exception. The superiority of such methodologies over traditional alkylation is evident from minimal reaction steps, shorter reaction times, and atom economy while also allowing control over regio- and stereo-selectivity. In particular, hydrocarbonation of alkenes has grabbed increased attention due its fundamental ability to effectively and selectively synthesise a wide range of industrially and pharmaceutically relevant moieties. This review attempts to provide a scientific viewpoint and a systematic analysis of the recent developments in transition-metal-catalyzed alkylation of various C-H bonds using simple and activated olefins. The key features and mechanistic studies involved in these transformations are described briefly.

C-CN bond formation: an overview of diverse strategies.

Nitrile or cyano compounds are an important part of structural motifs in dyes, agrochemicals, medicinal compounds, and electronic materials. Also, aryl nitrile is an important intermediate in the preparation of numerous compounds via transformations such as hydrolysis, hydration, reduction, cycloadditions, and nucleophilic additions. Such methods are beneficial for introducing sensitive functional groups in various positions in the multi-step synthesis of natural products and medicinal compounds. In the past decades, various cyanation methods have been reported in the vast arena of chemistry, which have made several building blocks accessible. Previously reported cyanation reviews, letters, and perspectives are written in parts. Thus, today a comprehensive review that will be able to guide readers through the vast pool of C-CN bond forming reactions via different approaches is obligatory. The present feature article depicts the various areas of cyanation methodologies that are based on the metal catalyst used, directed, non-directed, electrochemical, photochemical, asymmetric, and radical based approaches. This feature article will serve as a comprehensive tool to navigate the C-CN (cyanation) reactions across the vast area in synthetic chemistry.

Edible Tuber Amorphophallus paeoniifolius (Dennst.) Extract Induces Apoptosis and Suppresses Migration of Breast Cancer Cells.

Medicinal plants offer enormous possibilities in the quest of novel bioactive formulation for cancer therapy. Here, we studied the anticancer efficacy of the extract of edible tuber Amorphophallus paeoniifolius (Dennst.) (APTE) against estrogen positive MCF-7 and triple negative MDA-MB-231 breast cancer cell lines. APTE showed significant cytotoxic activity in both MCF-7 and MDA-MB-231 cells in a dose and time-dependent manner. The effect of APTE on metastatic parameters e.g., migration, adhesion, and invasion in MCF-7 and MDA-MB-231 cells were studied using wound healing, collagen adhesion, and transwell matrigel invasion assays, respectively. APTE significantly reduced migration in both the cell lines, however, its effect on the inhibition of adhesion and invasion was higher in MDA-MB-231 cells. Annexin V-Cy3 staining suggested that APTE induced apoptosis in these cells which was further validated by attenuation of antiapoptotic Bcl-2 and induction of pro-apoptotic Bax, Caspase-7 expression and cleavage of PARP. High resolution-liquid chromatography mass spectroscopy analysis with bioactive ethyl acetate and butanol fractions of APTE detected several compounds with anticancer activities. Overall, the study described the mechanism of anticancer activity of a common edible tuber A. paeoniifolius and contributes to growing list of naturally occurring chemo-preventive strategies.

α-Synuclein aggregation nucleates through liquid-liquid phase separation.

α-Synuclein (α-Syn) aggregation and amyloid formation is directly linked with Parkinson's disease pathogenesis. However, the early events involved in this process remain unclear. Here, using the in vitro reconstitution and cellular model, we show that liquid-liquid phase separation of α-Syn precedes its aggregation. In particular, in vitro generated α-Syn liquid-like droplets eventually undergo a liquid-to-solid transition and form an amyloid hydrogel that contains oligomers and fibrillar species. Factors known to aggravate α-Syn aggregation, such as low pH, phosphomimetic substitution and familial Parkinson's disease mutations, also promote α-Syn liquid-liquid phase separation and its subsequent maturation. We further demonstrate α-Syn liquid-droplet formation in cells. These cellular α-Syn droplets eventually transform into perinuclear aggresomes, the process regulated by microtubules. This work provides detailed insights into the phase-separation behaviour of natively unstructured α-Syn and its conversion to a disease-associated aggregated state, which is highly relevant in Parkinson's disease pathogenesis.

Cobalt-Catalyzed C(sp2)-H Allylation of Biphenyl Amines with Unbiased Terminal Olefins.

Unactivated olefins usually react poorly in conventional alkenylation reactions. Their introduction via C-H activation is limited to aromatic acids. Herein, we disclose a C-H functionalization protocol of aromatic amines with unactivated olefins, which shows exclusive allylic selectivity for the distal ring of the biphenyl system by exploiting a readily available cobalt(II) catalyst. The allylation proceeds smoothly involving a broad set of unbiased olefins and biaryls, giving access to the functionalization of the biphenyl scaffold.

Rhodium catalyzed template-assisted distal para-C-H olefination.

Rhodium catalysis has been extensively used for ortho-C-H functionalization reactions, and successfully extended to meta-C-H functionalization. Its application to para-C-H activation remains an unmet challenge. Herein we disclose the first example of such a reaction, with the Rh-catalyzed para-C-H olefination of arenes. The use of a Si-linked cyanobiphenyl unit as a traceless directing group leads to highly para-selective arene-olefin couplings.

Regioselective Synthesis of Fused Furans by Decarboxylative Annulation of α,ß-Alkenyl Carboxylic Acid with Cyclic Ketone: Synthesis of Di-Heteroaryl Derivatives.

α,ß-Alkenyl carboxylic acids undergo CuII -mediated decarboxylative annulation reactions with aliphatic cyclic ketones to provide synthetically valuable di-heterocycles. The annulation process tolerates a variety of aliphatic ketones and heterocyclic alkenyl carboxylic acids, producing substituted fused furan derivatives with complete regioselectivity. The current protocol offers a synthetically applicable pathway to construct a variety of oligo-heterocycles through Cu-mediated single-electron transfer and decarboxylation. Notably, synthesis of relatively inaccessible di-heterocycles has been achieved successfully using this protocol.

Direct meta-C-H Perfluoroalkenylation of Arenes Enabled by a Cleavable Pyrimidine-Based Template.

The development of efficient and mild methods for the synthesis of organofluorine compounds is of foremost interest in various fields of chemistry. A direct pyrimidine-based selective meta-C-H perfluoroalkenylation of arenes involving several commercially available perfluoroolefins is described. The synthetic versatility of the protocol is demonstrated by an extensive substrate scope including different benzylsulfonyl, alkylarene and phenylacetic acid scaffolds. The generality of this methodology including the meta-C-H perfluoroalkenylation of Ibuprofen, the facile cleavage of the directing group and gram-scale reactions are presented.

Palladium-Catalyzed Directed meta-Selective C-H Allylation of Arenes: Unactivated Internal Olefins as Allyl Surrogates.

Palladium(II)-catalyzed meta-selective C-H allylation of arenes has been developed utilizing synthetically inert unactivated acyclic internal olefins as allylic surrogates. The strong σ-donating and π-accepting ability of pyrimidine-based directing group facilitates the olefin insertion by overcoming inertness of the typical unactivated internal olefins. Exclusive allyl over styrenyl product selectivity as well as E stereoselectivity were achieved with broad substrate scope, wide functional-group tolerance, and good to excellent yields. Late-stage functionalisations of pharmaceuticals were demonstrated. Experimental and computational studies shed light on the mechanism and point to key steric control in the palladacycle, thus determining product selectivities.

Palladium-Catalyzed Template Directed C-5 Selective Olefination of Thiazoles.

An efficient method has been developed to afford highly C-5 selective olefination of thiazole derivatives utilizing a bifunctional template in an intermolecular fashion. Coordinative interaction between the substrates and the metal chelated template backbone plays a crucial role in high C-5 selectivity. Excellent selectivity for the C-5 position was observed while mono substituted (2- or 4-) or even more challenging unsubstituted thiazoles were employed.

Reaction-based turn-on fluorescent probes with magnetic responses for Fe(2+) detection in live cells.

Iron is the most abundant nutritionally essential transition metal found in the human body. It plays important roles in various biological processes such as oxygen delivery, electron transport, enzymatic reactions and DNA synthesis and repair. However, iron can also catalyze the production of free radicals, which are linked to quite a few diseases such as cancer, neurodegenerative diseases, and cardiovascular diseases. Both iron deficiency and iron overload are related to various health problems. Thus, precisely monitoring iron ions (Fe(2+) and Fe(3+)) in biological systems is important in understanding the detailed biological functions of iron and its trafficking pathways. However, effective tools for monitoring labile Fe(2+) in biological systems have not yet been established. Reported herein are turn on, reaction-based coumarin and rhodamine-linked nitroxide probes (Cou-T and Rh-T) for selective detection of Fe(2+) in solution and in living cells. Rh-T displayed a unique change in the EPR signal as well as enhancement of the fluorescence signal resulting from a specific redox reaction between the probe and Fe(2+). The turn-on fluorescence response towards Fe(2+) allows the subcellular imaging of endogenous Fe(2+) as well as imaging under conditions of external iron supplementation or depletion, with a labile Fe(2+) pool located in the mitochondria of human fibroblast primary cells. The detection and mechanism were verified by the magnetic properties of the probe via electron paramagnetic resonance (EPR) spectroscopy in solution and in cells.