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Cancer is a multifaceted disease involving various pathological processes, including uncontrolled proliferation, development of resistance, angiogenesis, metastasis, etc. Therefore, chemotherapeutic agents capable of simultaneously inhibiting proliferation, circumventing chemoresistance, and inhibiting angiogenesis can address multiple aspects of cancer progression. We recently identified a highly promising kinetically inert platinum antitumor agent, namely, Pt-1 , that can circumvent cisplatin resistance and showed negligible nephrotoxicity. In this study, we explored the antiangiogenic potential and elucidated the detailed mechanism of cell death through which it exerts its antitumor activity. Pt-1 strongly inhibited angiogenesis in a zebrafish in vivo model at its therapeutically relevant nontoxic dose. Further, Pt-1 exerted antitumor activity through necroptosis- and paraptosis-mediated cell death. Taken together, the combination of antitumor activity with antiangiogenic property in Pt-1 makes it a highly promising antitumor candidate., Competing Interests: The authors declare no competing financial interest., (© 2024 American Chemical Society.)

We have devised a highly diastereoselective formal [2 + 1] annulation reaction of arylidene/alkylidine-pyrazolones with in situ-generated supported as well as standard pyridinium ylides to construct spirocyclopropanyl-pyrazolones. The cascade approach exhibits a wide range of functional group tolerance, gram-scale capability, and substrate versatility. A diverse range of spirocyclic cyclopropanes was synthesized extensively with both mediators, and the supported pyridine was reused in subsequent cycles. Density functional theory calculations confirmed the formation of spirocyclopropane as the lower energy pathway.

Previously we identified a non-nucleotide agonist BDW568 that selectively activates the human STING A230 allele. Here, we further characterized the mechanism of BDW568 and highlighted its potential use for selectively controlling the activation of engineered macrophages that constitutively express STING A230 as a genetic adjuvant. We obtained the crystal structure of the C-terminal domain of STING A230 complexed with BDW-OH (active metabolite) at 1.95 Å resolution. Structure-activity relationship studies revealed that all three heterocycles in BDW568 and the S-acetate side chain are critical for retaining activity. We demonstrated that BDW568 could robustly activate type I interferon signaling in purified human primary macrophages that were transduced with lentivirus expressing STING A230 . In contrast, BDW568 could not stimulate innate immune responses in human primary peripheral blood mononuclear cells in healthy donors in the absence of a STING A230 allele. This high STING variant specificity suggested a promising application of STING A230 agonists in macrophage-based therapeutic approaches., Competing Interests: The authors declare no competing financial interest., (© 2024 American Chemical Society.)

Molecular electronics promises the ultimate level of miniaturization of computers and other machines as organic molecules are the smallest known physical objects with nontrivial structure and function. But despite the plethora of molecular switches, memories, and motors developed during the almost 50-years long history of molecular electronics, mass production of molecular computers is still an elusive goal. This is mostly due to the lack of scalable nanofabrication methods capable of rapidly producing complex structures (similar to silicon chips or living cells) with atomic precision and a small number of defects. Living nature solves this problem by using linear polymer templates encoding large volumes of structural information into sequence of hydrogen bonded end groups which can be efficiently replicated and which can drive assembly of other molecular components into complex supramolecular structures. In this paper, we propose a nanofabrication method based on a class of photosensitive polymers inspired by these natural principles, which can operate in concert with UV photolithography used for fabrication of current microelectronic processors. We believe that such a method will enable a smooth transition from silicon toward molecular nanoelectronics and photonics. To demonstrate its feasibility, we performed a computational screening of candidate molecules that can selectively bind and therefore allow the deterministic assembly of molecular components. In the process, we unearthed trends and design principles applicable beyond the immediate scope of our proposed nanofabrication method, e.g., to biologically relevant DNA analogues and molecular recognition within hydrogen-bonded systems.

Detection of molecular anions in interstellar media implies that negatively charged species play a prominent role in astrochemical reactions. Among the observed species, carbon chain anions are important, as they can be precursors for the production of complex organic molecules. These anions can form either via direct electron attachment to the corresponding neutral species or through chain growth reactions of smaller anions, resulting in longer chains. In a recent study, crossed beam experiments coupled with velocity map imaging techniques were used to investigate the carbon chain growth reaction C 2 n - + C 2 H 2 → C 2 n +2 H m - + H 2- m ( n = 1-3, m = 0,1). Products and branching ratios were established from experimental data. In the present work, electronic structure calculations and on-the-fly direct dynamics simulations were used to study these reactions. Energy profiles were investigated by using different density functional methods. Direct trajectory simulations were performed at the experimental collision energies using the B3LYP/6-31+G* level of theory. Trajectory analysis showed a variety of reaction pathways, and detailed atomic-level reaction mechanisms are presented.

Chlorogenic acids (CHLs) are known to competitively bind to translocase-I (T1) of the glucose-6-phosphatase (G6 Pase) system, thereby inhibiting the transport of glucose-6-phosphate (G6P). This competitive binding results in a consequential reduction in blood sugar levels. In this study, steered molecular dynamics (SMD) simulation is employed to investigate the interaction between T1 and G6P, aiming to gain insights into the binding dynamics and diffusion process of G6P through T1. A database comprising 41 CHLs sourced from various plants was developed, subjected to minimization, and screened against T1 through conventional docking methods. The docked conformations were fed into a newly developed customized scoring method incorporating contact-based weights to assess the binding affinities that systematically rank and identify the most effective competitive inhibitors. Among the screened CHLs, 1-methoxy 3,5-dicaffeoylquinic acid, 3,4 dicaffeoyl quinic acid, and 3,4,5-tricaffeoylquinic acid stood out as the top three inhibitors, showcasing crucial atomic interactions with key residues within the binding pocket of T1, and these CHLs are sourced from readily available plants, diminishing reliance on coffee as the predominant CHL source. Along with the devised scoring function, which serves as a valuable tool for virtual screening and lead optimization in drug development, this study also marks a pioneering effort as it involves the modeling of the human translocase and unravels the mechanism of binding and diffusion of G6P within human T1, providing valuable insights into the structural prerequisites for successfully inhibiting the G6P system, laying the foundation for a rational approach to drug design. This research contributes to the progress of drug discovery strategies focused on the G6P system, presenting potential therapeutic avenues for addressing metabolic disorders linked to an impaired glucose metabolism., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

In this study, an eco-friendly strategy was used to prepare a novel SrTiO 3 /Ag/rGO composite. A SrTiO 3 /Ag/rGO composite-modified screen-printed carbon electrode (SPCE) was applied for the electrochemical detection of 4-nitrophenol. A simple ultrasonic method with an ultrasonic frequency of 20 kHz was used for the synthesis of SrTiO 3 /Ag/rGO composite material. The obtained SrTiO 3 /Ag/rGO composite was characterized by X-ray diffraction, Fourier transform infrared, Raman spectroscopy, field emission electron microscopy, and UV-visible spectroscopy. Electrochemical impedance spectroscopy was used to determine the electrical conductivity of the SrTiO 3 /Ag/rGO composite. The electrochemical properties of the modified electrode were studied using cyclic voltammetry as well as linear sweep voltammetry techniques. In comparison to SrTiO 3 /SPCE, SrTiO 3 /Ag/SPCE, and SrTiO 3 /rGO/SPCE electrodes, SrTiO 3 /Ag/rGO/SPCE demonstrates a considerable increase in 4-nitrophenol redox peak current. At optimum conditions, a large linear response range of 0.1-1000 M, with a relatively low limit of detection (0.03 M), outperforms the previously published modified electrode for 4-nitrophenol. Moreover, the SrTiO 3 /Ag/rGO/SPCE electrode-based 4-nitrophenol sensor is distinguished by good selectivity, high stability, and repeatability. Furthermore, SrTiO 3 /Ag/rGO/SPCE contributed to the detection of 4-nitrophenol in river water and drinking water with the recovery range from 97.5 to 98.7%. The experimental finding was supported by density functional theory calculation., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

While the phenomenal clinical success of blockbuster platinum (Pt) drugs is highly encouraging, the inherent and acquired resistance and dose-limiting side effects severely limit their clinical application. To find a better alternative with translational potential, we synthesized a library of six organo-Ir III half-sandwich [(η 5 -Cp X )Ir(N∧N)Cl] + -type complexes. In vitro screening identified two lead candidates [(η 5 -Cp XPh )Ir(Ph 2 Phen)Cl] + ( 5 , Cp XPh = tetramethyl-phenyl-cyclopentadienyl and Ph 2 Phen = 4,7-diphenyl-1,10-phenanthroline) and [(η 5 -Cp XBiPh )Ir(Ph 2 Phen)Cl] + ( 6 , Cp XBiPh = tetramethyl-biphenyl-cyclopentadienyl) with nanomolar IC 50 values. Both 5 and 6 efficiently overcame Pt resistance and presented excellent cancer cell selectivity in vitro . Potent antiangiogenic properties of 6 were demonstrated in the zebrafish model. Satisfyingly, 6 and its nanoliposome Lipo-6 presented considerably higher in vivo antitumor efficacy as compared to cisplatin, as well as earlier reported Ir III half-sandwich complexes in mice bearing the A549 non-small lung cancer xenograft. In particular, complex 6 is the first example of this class that exerted dual in vivo antiangiogenic and antitumor properties.

Merrifield resin-anchored pyridines were prepared and applied as reusable mediators for trans -selective cascade synthesis of 2,3-dihydroindoles. The developed approach relied on in situ N -ylide formation followed by Michael substitution reactions. The cascade reaction was also carried out efficiently with simple pyridine. The products were further transformed into synthetically valuable compounds, and supported pyridine was reused for multiple cycles. Density functional theory calculations confirmed the trans -selectivity as the lower-energy pathway.

One of the most common diseases in women is breast cancer, which has the highest death globally. Surgery, chemotherapy, hormone treatments, and radiation are the current treatment options for breast cancer. However, these options have several adverse side effects. Recently, peptide-based drugs have gained attention as anticancer therapy. Studies report that peptides from biological toxins such as venom and virulent pathogenic molecules have potential therapeutic effects against multiple diseases, including cancers. This study reports on the in vitro anticancer effect of a short peptide, PS9, derived from a virulent protein, glycosyl hydrolase, of an aquatic fungus, Aphanomyces invadans . This peptide arrests MCF-7 proliferation by regulating intercellular reactive oxygen species (ROS) and apoptotic pathways. Based on the potential for the anticancer effect of PS9, from the in silico analysis, in vitro analyses using MCF-7 cells were executed. PS9 showed a dose-dependent activity; its IC 50 value was 25.27-43.28 μM at 24 h. The acridine orange/ethidium bromide (AO/EtBr) staining, to establish the status of apoptosis in MCF-7 cells, showed morphologies for early and late apoptosis and necrotic cell death. The 2,7-dichlorodihydrofluorescein diacetate (DCFDA) staining and biochemical analyses showed a significant increase in reactive oxygen species (ROS). Besides, PS9 has been shown to regulate the caspase-mediated apoptotic pathway. PS9 is nontoxic, in vitro , and in vivo zebrafish larvae. Together, PS9 may have an anticancer effect in vitro ., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Controlling π-conjugated polymer-acceptor complex interaction, including the interaction strength and location along the polymer backbone, is central to organic electronics and energy applications. Straps in the strapped π-conjugated polymers mask the π-face of the polymer backbone and hence are useful to control the interactions of the π-face of the polymer backbone with other polymer chains and small molecules compared to the conventional pendant solubilizing chains. Herein, we have synthesized a series of strapped π-conjugated copolymers containing a mixture of strapped and nonstrapped comonomers to control the polymer-acceptor interactions. Simulations confirmed that the acceptor is directed toward the nonstrapped repeat unit. More importantly, strapped copolymers overcome a major drawback of homopolymers and display higher photoinduced photoluminescence (PL) quenching, which is a measure of electron transfer from the polymer to acceptor, compared to that of both the strapped homopolymer and the conventional polymer with pendant solubilizing chains. We have also shown that this strategy applies not only to strapped polymers, but also to the conventional polymers with pendant solubilizing chains. The increase in PL quenching is attributed to the absence of a steric sheath around the comonomers and their random location along the polymer backbone, which enhances the probability of non-neighbor acceptor binding events along the polymer backbone. Thus, by mixing insulated and noninsulated monomers along the polymer backbone, the location of the acceptor along the polymer backbone, polymer-acceptor interaction strength, and the efficiency of photoinduced charge transfer are controllable compared to the homopolymers., Competing Interests: The authors declare no competing financial interest., (© 2023 American Chemical Society.)

Two important methods for enhancing gas sensing performance are vacancy/defect and interlayer engineering. Tin sulfide (SnS 2 ) has recently attracted much attention for sensing of the NO 2 gas due to its active surface sites and tunable electronic structure. Herein, SnS 2 has been synthesized by the chemical vapor deposition (CVD) method followed by nitrogen plasma treatment with different exposure times for fast detection of NO 2 molecules. Plasma treatment created a substantial number of surface vacancies on SnS 2 flakes, which were controlled by the exposure period to modify the surface of flakes. After 12 min of nitrogen plasma treatment, SnS 2 nanoflakes show considerable improvement in NO 2 sensing characteristics, including a high sensing response of ∼264% toward 100 ppm NO 2 at 120°C. The enhancement in the relative response of the sensor is due to the electronic interaction between NO 2 molecules and the S vacancies on the surface of SnS 2 . Density functional theory (DFT) computations indicate that the S-vacancy defects on the surface dominate the effective NO 2 detection and the NO 2 adsorption mechanism transition from physisorption to chemisorption. Adsorption kinetics of the NO 2 gas over SnS 2 nanoflake-based chemiresistor sensors were studied using the Lee and Strano model [ Langmuir 2005, 21(11), 5192-5196]. The irreversible rate of the reaction for various NO 2 concentrations exposed to the gas sensor is extracted using this model, which also appropriately describes the response curves. The forward rate constant of the irreversible gas sensor increased with the increase of the N 2 plasma treatment time and reached the maximum in the 12 min plasma-treated sample. Through defect engineering, this research may open up new vistas for the design and synthesis of 2D materials with enhanced sensing properties.

A family of first-generation dendrimers containing 3,5-bis(carbazolyl)phenyl dendrons attached to a green emissive fac -tris(2-phenylpyridyl)iridium(III) core were prepared. The solubility of the dendrimers was imparted by the attachment of tert -butyl surface groups to the carbazole moieties. The dendrimers differed in the number of dendrons attached to each ligand (one or two dendrons) as well as the degree of rotational restriction within the dendrons. The densities of the films containing the doubly dendronized materials were higher than those of their mono-dendronized counterparts, with the dendrimer containing two rotationally constrained dendrons per ligand having the highest density at 1.12 ± 0.04 g cm -3 . The dendrimers were found to have high photoluminescence quantum yields (PLQYs) in solution of between 80 and 90%, with the doubly dendronized materials having the lower values and a red-shifted emission. The neat film PLQY values of the dendrimers were less than those measured in solution although the relative decrease was smaller for the doubly dendronized materials. The dendrimers were incorporated into solution-processed bilayer organic light-emitting diodes (OLEDs) composed of neat or blend emissive layers and an electron transport layer. The best-performing devices had the dendrimers blended with a host material and external quantum efficiencies as high as 14.0%, which is higher than previously reported results for carbazole-incorporating emissive dendrimers. A feature of the devices containing blends of the doubly dendronized materials was that the maximum efficiency was relatively insensitive to the concentration in the host between 1 and 7 mol %.

Synthesizing a material with the desired polymorphic phase in a chemical vapor deposition (CVD) process requires a delicate balance among various thermodynamic variables. Here, we present a methodology to synthesize rhombohedral (3 R )-phase MoS 2 in a well-defined sword-like geometry having lengths up to 120 μm, uniform width of 2-3 μm and thickness of 3-7 nm by controlling the carrier gas flow dynamics from continuous mode to pulsed mode during the CVD growth process. Characteristic signatures such as high degree of circular dichroism (∼58% at 100 K), distinct evolution of low-frequency Raman peaks and increasing intensity of second harmonic signals with increasing number of layers conclusively establish the 3 R -phase of the material. A high value (∼844 pm/V) of second-order susceptibility for few-layer-thick MoS 2 swords signifies the potential of MoS 2 to serve as an atomically thin nonlinear medium. A field effect mobility of 40 cm 2 /V-s and I on / I off ratio of ∼10 6 further confirm the electronic-grade standard of this 3 R -phase MoS 2 . These findings are significant for the development of emerging quantum electronic devices utilizing valley-based physics and nonlinear optical phenomena in layered materials.

Emergence of resistance in cancer cells and dose-limiting side effects severely limit the widespread use of platinum (Pt) anticancer drugs. Multi-action hybrid anticancer agents that are constructed by merging two or more pharmacophores offer the prospect of circumventing issues of Pt drugs. Herein, we report the design, synthesis, and in-depth biological evaluation of a ruthenium-ferrocene (Ru-Fc) bimetallic agent [(η 6 - p -cymene)Ru(1,1,1-trifluoro-4-oxo-4-ferrocenyl-but-2-en-2-olate)Cl] and its five analogues. Along with aquation/anation chemistry, we evaluated the in vitro antitumor potency, Pt cross-resistance profile, and in vivo antiangiogenic properties. A structure activity analysis was performed to understand the impact of Fc, CF 3 , and p -cymene groups on the anticancer potency of the Ru-Fc hybrid. Finally, in addition to assessing cellular uptake and intracellular distribution, we demonstrated that the Ru-Fc hybrid binds to nucleophilic biomolecules and produces reactive oxygen species, which causes mitochondrial dysfunction and induces ER stress, leading to poly(ADP-ribose) polymerase-mediated necroptotic cell death.

Bacopa monnieri is reported as a potent Indian medicinal plant that possesses numerous pharmacological activities due to the presence of various bioactive compounds. These pharmacological activities were used in the ancient medicine system to cure inflammatory conditions. Bacopa has the ability to reduce acute pain and inflammation by inhibiting the enzyme cyclo-oxygenase-2 ( COX-2 ) and reducing COX-2 -arbitrated prostanoid mediators. Moreover, the anti-inflammatory property may also be associated with the neuroprotective activity of Bacopa. Considering this importance, the current pilot study focused on the anti-inflammatory potential of various phytocompounds of bacopa and their interaction with inflammation responsible genes such as COX2 , iNOS , LOX , STAT3 , CCR1 , and MMP9 through pharmacology analysis of its systems. Docking results revealed that, quercetin (QR) showed significant binding energies with inflammatory genes. Hence, we selected QR as a potential phytocompound for further in vitro experiments. This existing study aimed to evaluate the efficacy of QR as a potent anti-inflammatory compound against lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. The in vitro analysis concludes that QR effectively reduces the production of nitric oxide (NO) in LPS-induced RAW264.7 cells and downregulates the expression of COX-2 and iNOS genes due to the inhibitory potential of QR on LPS-stimulated NO production., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Aminohydroxymethylene (H 2 N-C̈-OH) is the simplest aminooxycarbene which is a heteroatom stabilized carbene. This highly reactive molecule was prepared in an Ar matrix in a recent experimental work. Unimolecular reactivity of this astrochemically important molecule was investigated and only fragmentations were identified contrary to the observations of both fragmentations and intramolecular rearrangements in other hydroxycarbenes. These rearrangement reactions form the corresponding imine and carbonyl compounds. In the present work, direct chemical dynamics simulations of unimolecular chemistry of aminohydroxymethylene were performed in the gas phase to study atomic level dissociation mechanisms. Classical trajectories were generated on-the-fly using potentials and gradients computed at the density functional B3LYP/6-31+G* level of electronic structure theory. Simulation results showed that intramolecular rearrangements accompany fragmentations during the unimolecular decay process of aminohydroxymethylene. However, the average lifetime of the intermediate isomers were found to be only few picoseconds which might not have been long enough for detection in the experiments.

Wearable skin-inspired electronic skins present remarkable outgrowth in recent years because their promising comfort device integration, lightweight, and mechanically robust durable characteristics led to significant progresses in wearable sensors and optoelectronics. Wearable electronic devices demand real-time applicability and factors such as complex fabrication steps, manufacturing cost, and reliable and durable performances, severely limiting the utilization. Herein, we nominate a scalable solution-processable electrospun patterned candidate capable of forming ultralong mechanically robust nano-microdimensional fibers with higher uniformity. Nanofibrous patterned substrates present surface energy and silver nanoparticle crystallization shifts, contributing to strain-sensitive and -insensitive conductive electrodes (10 000 cycles of 50% strain). Synergistic robust stress releasing and durable electromechanical behavior engenders stretchable durable health sensors, strain-insensitive pressure sensors (sensitivity of ∼83 kPa -1 and 5000 durable cycles), robust alternating current electroluminescent displays, and flexible organic light-emitting diodes (20% improved luminescence and 300 flex endurance of 2 mm bend radius).

Polyimide-Al 2 O 3 membranes are developed as a direct alternative to current polyolefin separators by the electrospinning technique and their chemical structures confirm the carbonyl group with the presence of asymmetric and symmetric stretching and bending vibrations at 1778, 1720, and 720 cm -1 and stretching vibration at 1373 cm -1 for the imide group. Porous nanofiber architecture morphology is realized with a nanofiber thickness of ∼200 nm and shows an ultrasmooth surface and >1 μm pore size in the architecture, built with the chemical constituents of carbon, nitrogen, aluminum, and oxygen elements. The galvanostatic cycling study of the Li/PI-Al 2 O 3 /LiFePO 4 lithium cell delivers stable charge-discharge capacities of 144/143 mAh g -1 at 0.2 C and 110/100 mAh g -1 at 1 C for 1-100 cycles. The fabricated MCMB/PI-Al 2 O 3 /LiFePO 4 lithium-ion full-cell reveals less charge transfer resistance of R ct ∼ 25 Ω and yields stable charge-discharge capacities of 125/119 mAh g -1 . The thermogravimetric curve for the PI-Al 2 O 3 separator discloses thermal stability up to 525 °C, and the differential scanning calorimetric curve shows a straight line until 300 °C and depicts high thermal stability than the PP separator. In situ multimode calorimetry analysis of the MCMB/PP/LiFePO 4 full-cell showed a pronounced exothermic peak at 225 °C with a higher released heat energy of 211 J g -1 at the thermal runaway event, while the MCMB/PI-Al 2 O 3 /LiFePO 4 full-cell revealed an almost 8-fold less exothermic released heat energy of 25 J g -1 than the Celgard polypropylene separator, which was because the MCMB anode and LiFePO 4 cathode can be mechanically isolated without any additional separator's melting and burning reactions, as a fire-suppressant separator for lithium-ion batteries.

Red-light-emitting silver nanoclusters (AgNCs) are recently emerged as a promising nanoprobe in the field of biomedical applications, because of their attractive properties, including brightness, luminescence stability, and better biocompatibility. In this report, we have developed highly water-soluble red-light-emitting AgNCs by using N -cholyl d-penicilamine (NCPA) as a biosurfactant at above the critical micelle concentration (CMC) at room temperature. Moreover, the NCPA was initially synthesized by demonstrating the reaction between cholic acid and d-penicilamine via a simple coupling reaction strategy. The primary and secondary critical micellar concentration (CMC) of NCPA surfactant was measured using pyrene (1 × 10 -6 M) as a fluorescent probe, and the values were found to be 3.18 and 10.6 mM, respectively. Steady-state fluorescence measurements reveal that the prepared AgNCs shows the excitation and emission maxima at 365 and 672 nm, respectively, with a large Stokes shift (307 nm). The average lifetime measurements and quantum yield of the AgNCs were calculated to be 143.43 ns and 16.34%, respectively. Also, the red luminescent NCPA-templated AgNCs was synthesized in various protic and aprotic polar solvents, among which DMF and DMSO exhibit bright emission at longer wavelength as synthesized in aqueous medium. At higher concentration of AgNO 3 , bright luminescent and highly stable solid AgNCs was obtained with excitation and emission maxima at 607 and 711 nm, respectively. Furthermore, the synthesized AgNCs has been successfully utilized as a fluorescent probe for selective and sensitive detection of S 2- ions at nanomolar level in water samples, showing its potential applicability for the detection of S 2- ions in drinking, river, and tap water samples. Finally, toxicity and bioimaging studies of NCPA-templated AgNCs was demonstrated using zebrafish as in vivo model, showing no significant toxicity up to 200 μL/mL. The AgNCs-stained embryos exhibited red fluorescence with high intensity, which shows that AgNCs are stable in a living system.

Three-dimensional (3D) shape morphism observed in nature inspires the development of stimuli-responsive soft actuators. Vapor-responsive actuators are promising among the different stimuli-responsive materials due to their capability to produce macroscale movements in response to a minuscule amount of specific chemical vapor. Here, we report unusual multiple vapor-responsive bidirectional macroscale actuation behaviors of single-layer regenerated silk fibroin films. The vapor-responsive silk fibroin actuator exhibits antagonistic actuation characteristics in a reversible manner to both water and ethanol vapors. For instance, it produces an upward bending in the presence of water vapor and downward bending in ethanol vapor, which demonstrates the chemical vapor-specific actuation. However, the actuation characteristics remain largely invariant upon changing the polarity of alcohol molecules. The silk fibroin actuators effectively utilize the vapor-induced minuscule expansion and contraction of the film surface to produce large-scale actuation, which is fully reversible. The intrinsic water content of the films and the vapor pressure of the stimulants are exploited to control the actuation performance. Further, we demonstrated the 3D shape morphing ability of the actuator by generating an undulating wavelike motion via preprogrammed water and ethanol vapor exposure conditions. The change in the actuation direction is instantaneous, which ensures the sensitivity and rapid response of the fabricated actuators.

In this study, we report about the preparation of nickel cobalt telluride nanorods (NiCoTe NRs) by the hydrothermal method using ascorbic acid and cetyltrimethylammonium bromide as reducing agents. The NiCoTe NRs (NCT 1 NRs) were characterized through use of different methods. The nonlinear optical measurements were carried out using Z-scan techniques. The results give the nonlinear absorption that arises from the combined two photon absorption and free carrier absorption. NCT 1 has an excellent electrocatalytic activity toward hydrogen peroxide with a sensitivity of 3464 μA mM -1 cm -2 , a wide linear range of 0.002-1835 μM, and the lower detection limit of 0.02 μM, and the prepared electrode was strong in sensing in vivo H 2 O 2 free from raw 264.7 cells. Therefore, the binary transition metal chalcogenide based nanostructures have promising potential in live cell biosensing applications., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

A set of meta -substituted 3-arylisoquinolinones have been identified that show substantial cytotoxicity in breast, liver, lung and colon cancer cell lines; these are up to 700-fold more active than the corresponding para analogues. These compounds were initially proposed as inhibitors of N -ribosyl dihydronicotinamide (NRH): quinone oxidoreductase 2 (NQO2) but were found to be inactive against the enzyme. Instead, COMPARE analysis suggested that 6-fluoro-3-( meta -fluorophenyl)isoquinolin-1(2 H )-one ( 4 ) could mimic colchicine and interact with microtubules, a recognized target for cancer therapy. Subsequent docking, molecular dynamics simulations, and free energy analysis further suggested that compound 4 bound well into the colchicine-binding pocket of tubulin. Indeed, 4 suppressed tubulin polymerization, caused G 2 / M cell cycle arrest, and induced apoptosis. Also, 4 inhibited the formation of endothelial cell capillary-like tubes and further disrupted the structure of preestablished tubes; the effects were not observed with para analogue 5 . In accordance with this, the computed free energy of binding of 5 to tubulin was lower in magnitude than that for 4 and appeared to arise in part from the inability of the para substituent to occupy a tubulin subpocket, which is possible in the meta orientation. In conclusion, the antiproliferative potential of the novel 3-arylisoquinolinones is markedly influenced by a subtle change in the structure ( meta versus para ). The meta -substituted isoquinolinone 4 is a microtubule-destabilizing agent with potential tumor-selectivity and antiangiogenic and vascular disrupting features.

Advanced wave-shape non-graphitizable carbon sheets are derived, comprising mesoporous weaved turbostratic micropore enabled stable Na + ion storage. The non-graphitizable amorphous characteristics are determined from the obtained two broad diffraction peaks at 22.7° and 43.8°. The observed D-band at 1325 cm -1 and G-band at 1586 cm -1 confirm the disordered graphitic structure, attributed to the measured specific surface area of 54 m 2 g -1 . Mesoporous weaved wave-shape carbon sheet architecture is confirmed by surface morphological studies, showing lattice fringes of disordered graphitic structures and dispersed ring patterns for the non-crystalline characteristics. The predominant stable redox peak at 0.014 V/0.185 V and the broader rectangular shape between 0.9 and 0.15 V depict the adsorption-micropore filling mechanism. The mesoporous hard carbon sheet delivers discharge-charge capacities of 450/311 mAh g -1 (1st cycle) and 263/267 mAh g -1 (250th cycle) at 25 mA g -1 , exhibiting a superior anode for sodium-ion batteries. Besides, in situ multimode calorimetry results disclose that the micropore filling Na + ion storage shows a higher released total heat energy of 721 J g -1 than the adsorption (471 J g -1 ). Ultimately, differential scanning calorimetry analysis of micropore filling Na + ion storage (discharged state at 0.01 V) has revealed a predominant exothermic peak at 156 °C with the highest released total heat energy of 2183 J g -1 compared to adsorption (553 J g -1 ) and deintercalation (85 J g -1 ), indicating that micropore filling status is more unsafe than the adsorption and deintercalation for SIBs.

We present the water vapor-induced swelling and the emergence of a penetrant-induced glass-like transition in the substrate-supported glassy chitosan thin films. The time evolution of the film thickness under different levels of relative humidity conditions is measured in real-time using a spectroscopic ellipsometer equipped with a humidity cell. In a dry film, the network of chitosan chains is in a glassy state, and upon exposure to water vapor, initially, the film swells by Fickian diffusion of water molecules, which triggers the structural relaxations of the chains. Under higher humidity conditions, a relatively slower evolution of thickness succeeds the initial rapid swelling due to the non-Fickian sorption of water molecules. The swelling characteristics of the polymer films are accounted for by considering the diffusion-relaxation mechanism of chains in the presence of smaller penetrant molecules. The penetrant-induced glass-like transition ( P g ), where the polymer film isothermally transits from a glassy to a rubbery state, is determined for pristine and cross-linked chitosan films. P g is determined from the abrupt change in the rate of swelling observed upon increasing the relative humidity. Chemical crosslinking has an evident influence on the penetrant-induced glass-like transition of the chitosan films. P g was found to rise sharply for stiffer films with higher cross-linking density.

A sol-gel process followed by heat treatment derived a layered P2-type NaCoO 2 cathode, which depicted unit cell parameters values of a = 2.8389 Å, c = 10.9899 Å, and V = 76.71 Å 3 in powder X-ray diffraction pattern. The synthesized cathode exhibited hexagonal, 2D platelets with an ∼300 nm thickness. During the anodic and cathodic sweeps, the cyclic voltammograms revealed multiple redox peaks with the same current densities, shapes, and peak positions, associated with the highly reversible phase transition mechanism of the layered P2-type NaCoO 2 cathode. The sodium cells yielded the capacities of 93/92 mAh g -1 at 0.5 C and 87/87 mAh g -1 at 1 C for the 50th charge-discharge cycles. The in situ multimode calorimetry (MMC) studies of sodium cells demonstrated a thermal explosion event, which occurred by sodium melting, short-circuit, electrode decomposition reaction, gas generation, exothermic reaction, released heat energy ,and cell gasket melting. Ultimately, the calculated released total heat energies of ∼550/740 J g -1 for in situ MMC studies and ∼312/594 J g -1 for ex situ DSC analyses (charge state at 4 V and discharge state at 2 V) show that the discharged state of sodiated layered P2-type NaCoO 2 cathode material is more unsafe than the charge state. Furthermore, the ex situ differential scanning calorimetry (DSC) spectrum of a discharge state at 2 V of layered P2-type NaCoO 2 revealed a decreased onset temperature (DOT) at 141 °C with two pronounced exothermic peaks at 197 and 266 °C with a released higher total heat energy of 594 J g -1 than the charge state heat energy at 312 J g -1 , attributed to the higher charge onset temperature (COT) at 191 °C. Thus, the observed higher heat energy and decreased onset temperature for the discharge state at 2 V is associated with the higher Na + ion in the discharge state of the layered P2-type Na x CoO 2 cathode than that of the pristine cathode, showcasing that the layered P2-type NaCoO 2 cathode is unsafe at the discharged condition for sodium-ion batteries.

The latest progress in alkaline anion-exchange membranes has led to the expectation that less costly catalysts than those of the platinum-group metals may be used in anion-exchange membrane fuel cell devices. In this work, we compare structural properties and the catalytic activity for the hydrogen-oxidation reaction (HOR) for carbon-supported nanoparticles of Ni, Ni 3 Co, Ni 3 Cu, and Ni 3 Fe, synthesized by chemical and solvothermal reduction of metal precursors. The catalysts are well dispersed on the carbon support, with particle diameter in the order of 10 nm, and covered by a layer of oxides and hydroxides. The activity for the HOR was assessed by voltammetry in hydrogen-saturated aqueous solutions of 0.1 mol dm -1 KOH. A substantial activation by potential cycling of the pristine catalysts synthesized by solvothermal reduction is necessary before these become active for the HOR; in situ Raman spectroscopy shows that after activation the surface of the Ni/C, Ni 3 Fe, and Ni 3 Co catalysts is fully reduced at 0 V, whereas the surface of the Ni 3 Cu catalyst is not. The activation procedure had a smaller but negative impact on the catalysts synthesized by chemical reduction. After activation, the exchange-current densities normalized with respect to the ECSA (electrochemically active surface area) were approximately independent of composition but relatively high compared to catalysts of larger particle diameter., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

An omnipresent pathogenic bacterium, Pseudomonas aeruginosa ( P. aeruginosa PAO1), is easy to contaminate environmental water or foods, causing daily food spoilage and infections. The biofilm-forming ability and bacterial resistance of P. aeruginosa PAO1 make it difficult to be eradicated by traditional bacteriostatic agents. In this work, we designed and synthesized a pyridinium-based pillar[5]arene (PP5), while trimethylammonium-based pillar[5]arene (TP5) was used as a control compound. After clear characterization, the antibacterial and antibiofilm activities as well as the microbial resistance of TP5 and PP5 against P. aeruginosa PAO1 were extensively examined. It was revealed that PP5 exhibited good inhibition activity with the minimum inhibitory concentration (MIC) of 0.051 mmol/L, while no significant antibacterial and biofilm formation activity for TP5 against P. aeruginosa PAO1 was observed. More importantly, PP5 had negligible antimicrobial resistance even after 18th passages. A transmission electron microscope (TEM) showed that PP5 could physically disrupt the cell membranes, causing the leakage of internal constituents, which is possibly ascribed to the synergistic penetrability and π-π interactions of strain, thus greatly reduced the development of bacterial resistance. Overall, the presented studies indicated that pyridinium moieties could facilitate the cationic pillar[5]arene to generate surprising antibacterial and antibiofilm formation ability against P. aeruginosa PAO1.

Nimbolide, a major limonoid constituent of Azadirachta indica , commonly known as neem, has attracted increasing research attention owing to its wide spectrum of pharmacological properties, predominantly anticancer activity. Nimbolide is reported to exert potent antiproliferative effects on a myriad cancer cell lines and chemotherapeutic efficacy in preclinical animal tumor models. The potentiality of nimbolide to circumvent multidrug resistance and aid in targeted protein degradation broaden its utility in enhancing therapeutic modalities and outcome. Accumulating evidence indicates that nimbolide prevents the acquisition of cancer hallmarks such as sustained proliferation, apoptosis evasion, invasion, angiogenesis, metastasis, and inflammation by modulating kinase-driven oncogenic signaling networks. Nimbolide has been demonstrated to abrogate aberrant activation of cellular signaling by influencing the subcellular localization of transcription factors and phosphorylation of kinases in addition to influencing the epigenome. Nimbolide, with its ever-expanding repertoire of molecular targets, is a valuable addition to the anticancer drug arsenal.

Carvacrol is an essential oil traditionally used in culinary processes as spice due to its aromatic nature and also known for various biological activities. In the present study, the antivirulence efficacy of carvacrol against methicillin-resistant Staphylococcus aureus (MRSA) is explored. MRSA is an opportunistic pathogen capable of causing various superficial and systemic infections in humans. Biofilm formation and virulence factors of MRSA are responsible for its pathogenesis and resistance. Hence, the aim of this study was to explore the antibiofilm and antivirulence efficacy of carvacrol against MRSA. Carvacrol at 75 μg/mL inhibited MRSA biofilm by 93%, and it also decreased the biofilm formation on polystyrene and glass surfaces. Further, microscopic analyses revealed the reduction in microcolony formation and collapsed structure of biofilm upon carvacrol treatment. The growth curve analysis and the Alamar blue assay showed the nonfatal effect of carvacrol on MRSA. Further, carvacrol significantly reduced the production of MRSA biofilm-associated slime and extracellular polysaccharide. In addition, carvacrol strongly inhibited the antioxidant pigment staphyloxanthin and its intermediates' synthesis in MRSA. Inhibition of biofilm and staphyloxanthin by carvacrol enhanced the susceptibility of MRSA to oxidants and healthy human blood. Quantitative polymerase chain reaction (qPCR) analysis unveiled the downregulation of sarA -mediated biofilm gene expression and staphyloxanthin-associated crtM gene expression. The sarA -dependent antibiofilm potential of carvacrol was validated using S. aureus Newman wild-type and isogenic Δ sarA strains. In silico molecular docking analysis showed the high binding efficacy of carvacrol with staphylococcal accessory regulator A (SarA) and 4,4'-diapophytoene synthase (CrtM) when compared to positive controls. Furthermore, the in vivo efficacy of carvacrol against MRSA infection was demonstrated using the model organism Galleria mellonella . The results revealed the nontoxic nature of carvacrol to the larvae and the rescuing potential of carvacrol against MRSA infection. Finally, the current study reveals the potential of carvacrol in inhibiting the biofilm formation and staphyloxanthin synthesis of MRSA by targeting the global regulator SarA and a novel antivirulence target CrtM., Competing Interests: The authors declare no competing financial interest., (© 2020 American Chemical Society.)

TRAF2 and NCK-interacting kinase (TNIK) is a critical factor in colorectal cancer (CRC) proliferation mediated by Wnt signaling. We attempted to identify efficient TNIK inhibitors using computational high-throughput virtual screening (HTVS) from various drug banks and databases. By performing/on performing e-pharmacophore screening and molecular docking methods, from ∼700 000 molecules, compounds LC_222150, LC_112060, and LC_64796 were identified as potential leads, through molecular dynamics (MD) simulations and density functional theory (DFT). These top 3 structures were commercially procured, and their inhibitory activity was assessed in vitro. Significant TNIK inhibition was observed, with an average IC 50 of 18.33 ± 0.75 nM. In terms of anticancer activity, the observed average relative % activity (RPA) of 90.28 ± 1.04 for these compounds compared well with doxorubicin (86.75 ± 1.45) as a standard. Compounds LC_222150, LC_112060, and LC_64796, therefore, warrant further evaluation in vivo to assess their CRC therapeutic effects.

γ-Ketohydroperoxide [3-(hydroperoxy)propanal] is an important reagent in synthetic chemistry and, in particular, oxidation reactions. It is considered to be a precursor for secondary organic aerosol formation in the troposphere. Due to enhanced reactivity and limitations associated with analytical techniques, theoretical methods have been employed to study the unimolecular reactivity of hydroperoxides. A number of automated reaction discovery techniques have been used to study the reactivity of γ-ketohydroperoxide, and a large number of reactions have been reported in such studies. In the present work, we have investigated the unimolecular reaction dynamics of this molecule using electronic structure theory calculations and direct chemical dynamics simulations to assess the relevance of different reaction pathways. Classical trajectories were launched from the reactant well with fixed amounts of total energies and integrated on-the-fly using density functional B3LYP/6-31+G* model chemistry. Three dissociation channels among the previously reported reactions were identified as important. Korcek decomposition, which was proposed earlier as a source of carbonyl compounds from thermal decomposition of γ-ketohydroperoxide, was not observed in the present high-temperature simulations. However, trajectories showed the formation of carbonyl compounds such as aldehydes via other pathways. Results are compared with previous studies, and detailed atomic-level reaction mechanisms are presented.

Curtius rearrangement is the elimination of N 2 from carbonyl azides RC(O)N 3 to form isocyanates RNCO. Two mechanisms, viz., stepwise and concerted have been proposed in the literature for this reaction. The stepwise mechanism involves the formation of a nitrene RC(O)N by elimination of N 2 followed by an intramolecular rearrangement of the nitrene to form the isocyanate. The concerted mechanism is a single-step pathway forming the N 2 + RNCO products directly. Previous experimental and theoretical studies have indicated that the mechanism is usually concerted for thermal reactions and both stepwise and concerted are preferred under photochemical conditions. In the present work, we investigated the mechanism of Curtius rearrangement of two carbonyl azides with different substituents (R = CH 3 and F). Atomic level reaction mechanisms were studied using chemical dynamics simulations under thermal reaction conditions. Classical trajectories were generated on-the-fly at the density functional B3LYP/6-31+G* level of electronic structure theory with similar initial conditions for both the molecules. Simulation results showed a dominant concerted mechanism for CH 3 C(O)N 3 and the operation of both the mechanisms for FC(O)N 3 . The fluorocarbonyl nitrene FC(O)N had an appreciable lifetime before undergoing intramolecular rearrangement to form the isocyanate. In a small number of trajectories, the product isocyanate produced via the concerted dissociation of FC(O)N 3 , isomerized back to the nitrene form.

Two new classes of heteroarene-fused [1,2,4]thiadiazole and [1,2,4]selenadiazole are synthesized through the iodine-mediated [3 + 2] oxidative cyclization of 2-aminoheteroarenes and isothiocyanates/isoselenocyanates. This oxidative [3 + 2] annulation strategy is highly regiospecific to proceed a selective C-N bond formation at the endo-nitrogen of 2-aminoheteroarenes followed by an intramolecular oxidative N-S/N-Se bond formation. It is the first example of an I 2 -mediated oxidative nitrogen-selenium (N-Se) bond formation.

A one-pot, three-component synthesis of benzimidazole-linked thiazolidines from 2-cyanomethyl benzimidazole, iso-, isothio-, or isoselenocyanates and 1,2-dichloroethane is reported. Isolation of the key intermediate formed during the course of the reaction validates its mechanistic pathway. Under the same reaction conditions, benzimidazole-linked/fused thiazinanes were obtained when 1,3-dichloropropane or diiodomethane was used.

A great deal of attention has been given to the decomposition chemistry of halons (halomethanes) due to their role in stratospheric ozone depletion. Knowledge of certain aspects of dissociation of halons such as the competition between radical and molecular pathways and their mechanistic details is limited. Halon molecules can isomerize to an iso form containing a halogen-halogen bond and such iso-halon forms have been identified as intermediates in condensed phase chemistry. Recently, a quantum chemistry study of role of iso-halons in the gas phase decomposition of halomethanes has been reported. In the present work, we have investigated the ground state dissociation chemistry of select halon molecules - CF 2 Cl 2 , CF 2 Br 2 , CHBr 3 , and CH 2 BrCl using electronic structure theory calculations and direct chemical dynamics simulations. Classical trajectories were generated on-the-fly using density functional PBE0/6-31G* level of theory at a fixed total energy. Simulation results showed that molecular products, in general, were dominant for all the four molecules at the chosen energy. A variety of mechanisms such as direct dissociation via multicenter transition states, decomposition via isomerization, radical recombinations, and roaming pathways contributed to the formation of molecular products. Atomic level mechanisms are presented, and the role of iso-halons in the gas phase chemistry of halomethanes is clearly established.

Design and development of multifunctional materials have drawn incredible attraction in recent years. Herein, we report the design and construction of versatile star-shaped intramolecular charge transfer (ICT)-coupled excited-state intramolecular proton transfer (ESIPT)-active mechanoresponsive and aggregation-induced emissive (AIE) luminogen triaminoguanidine-diethylaminophenol ( LH 3 ) conjugate from simple precursors triaminoguanidine hydrochloride and 4-( N , N -diethylamino)salicylaldehyde. Solvent-dependent dual emission in nonpolar to polar protic solvents implies the presence of ICT-coupled ESIPT features in the excited state. Aggregation-enhanced emissive feature of LH 3 was established in the CH 3 CN/water mixture. Furthermore, this compound exhibits mechanochromic fluorescence behavior upon external grinding. Fluorescence microscopy images of pristine, crystal, and crushed crystals confirm the naked-eye mechanoresponsive characteristics of LH 3 . In addition, LH 3 selectively sensed a Cu 2+ ion through a colorimetric and fluorescence "turn-off" route, and subsequently, the LH 3 -Cu 2+ ensemble could act as a selective and sensitive sensor for S 2- in a "turn-on" fluorescence manner via a metal displacement approach. Reversible "turn-off-turn-on" features of LH 3 with Cu 2+ /S 2- ions were efficiently demonstrated to construct the IMPLICATION logic gate function. The Cu 2+ /S 2- -responsive sensing behavior of LH 3 was established in the paper strip experiment also, which can easily be characterized by the naked eye under daylight as well as a UV lamp (λ = 365 nm)., Competing Interests: The authors declare no competing financial interest.

The proton transfer reaction H 3 + + CO → HCO + /HOC + + H 2 has gained considerable attention in the literature due to its importance in interstellar chemistry. The reaction products-formyl cation (HCO + ) and isoformyl cation (HOC + )-are known to initiate multiple chemical reaction networks, resulting in complex molecules found in space. Several experimental and theoretical studies probing the structure and energetics of the [H 3 CO] + system, HCO + /HOC + product branching ratios, reaction mechanisms, etc., have been reported in the literature. In the present work, we investigated the H 3 + + CO bimolecular reaction in the gas phase using direct dynamics methodology. The simulation conditions were chosen to mimic recently reported velocity map imaging experiments on the same reaction. The calculations were performed using the density functional PBE0/aug-cc-pVDZ level of electronic structure theory. Internal energy and scattering angle distributions of reaction products found from the simulations are in qualitative agreement with the experiment. However, the product branching ratios at low collision energies were in contrast with the experimental predictions. Interesting dynamical features were observed in the simulations, and detailed atomic level mechanisms are presented.

Oxidative stress during sepsis pathogenesis remains the most-important factor creating imbalance and dysregulation in immune-cell function, usually observed following initial infection. Hydrogen peroxide (H 2 O 2 ), a potentially toxic reactive oxygen species (ROS), is excessively produced by pro-inflammatory immune cells during the initial phases of sepsis and plays a dominant role in regulating the pathways associated with systemic inflammatory immune activation. In the present study, we constructed a peroxide scavenger mannosylated polymeric albumin manganese dioxide (mSPAM) nanoassembly to catalyze the decomposition of H 2 O 2 responsible for the hyper-activation of pro-inflammatory immune cells. In a detailed manner, we investigated the role of mSPAM nanoassembly in modulating the expression and secretion of pro-inflammatory markers elevated in bacterial lipopolysaccharide (LPS)-mediated endotoxemia during sepsis. Through a facile one-step solution-phase approach, hydrophilic bovine serum albumin reduced manganese dioxide (BM) nanoparticles were synthesized and subsequently self-assembled with cationic mannosylated disulfide cross-linked polyethylenimine (mSP) to formulate mSPAM nanoassembly. In particular, we observed that the highly stable mSPAM nanoassembly suppressed HIF1α expression by scavenging H 2 O 2 in LPS-induced macrophage cells. Initial investigation revealed that a significant reduction of free radicals by the treatment of mSPAM nanoassembly has reduced the infiltration of neutrophils and other leukocytes in a local endotoxemia animal model. Furthermore, therapeutic studies in a systemic endotoxemia model demonstrated that mSPAM treatment reduced TNF-α and IL-6 inflammatory cytokines in serum, in turn circumventing organ damage done by the inflammatory macrophages. Interestingly, we also observed that the reduction of these inflammatory cytokines by mSPAM nanoassembly further prevented IBA-1 immuno-positive microglial cell activation in the brain and consequently improved the cognitive function of the animals. Altogether, the administration of mSPAM nanoassembly scavenged H 2 O 2 and suppressed HIF1α expression in LPS-stimulated macrophages and thereby inhibited the progression of local and systemic inflammation as well as neuroinflammation in an LPS-induced endotoxemia model. This mSPAM nanoassembly system could serve as a potent anti-inflammatory agent, and we further anticipate its successful application in treating various inflammation-related diseases.

A novel and efficient method for the one-pot synthesis of 2 H-indazole from readily available building blocks is reported. The reaction of 2-nitrobenzylamines with zinc and ammonium formate underwent partial reduction to nitroso-benzylamine followed by an intramolecular cyclization to afford 2 H-indazole via N-N bond formation. The carboxylic acid moiety of indazole was proceeded to regioselective alkyne insertion under ruthenium catalysis to form pyranone-fused indazoles. The regioselectivity is influenced by the weak coordination of indazole ring nitrogen to the metal center.

3-Oxetanone is a strained cyclic molecule which plays an important role in synthetic chemistry. A few studies exist in the literature about the equilibrium properties of this molecule and the dissociation patterns of substituted 3-oxetanones. For the unsubstituted 3-oxetanone, formation of ketene (CH 2 CO) and formaldehyde (HCHO) was considered to be the major dissociation pathway. In a recent work, pyrolysis products of 3-oxetanone molecule in the gas phase were investigated by Fourier transform infrared spectroscopy and photoionization mass spectrometry. In this study, an additional dissociation channel forming ethylene oxide (c-C 2 H 4 O) and carbon monoxide CO was reported. In the present work, gas phase dissociation chemistry of 3-oxetanone was investigated by electronic structure theory, ab initio classical chemical dynamics simulations, and Rice-Ramsperger-Kassel-Marcus (RRKM) rate constant calculations. The barrier height for the ethylene oxide channel was found to be much higher than the ketene pathway. The dynamics simulations were performed at three different total energies, viz., 150, 200, and 300 kcal/mol, and multiple reaction pathways and varying branching ratios observed. A new dissociation channel involving a ring-opened isomer of ethylene oxide was identified in the simulations. This pathway has a lower energy barrier and was dominant in our dynamics simulations.

A three-component cascade reaction of 2-aminobenzimidazole, aldehyde, and terminal alkyne has been explored for an efficient synthesis of benzimidazole-linked tetrasubstituted pyrroles. The reaction sequence involves the formation of propargylamine, insertion of a terminal alkyne, and a ring opening reaction followed by an intramolecular carbonylative cyclization under aerobic conditions. It represents a novel strategy to the construction of C═N, C═C, C═O bonds and a new five-membered 2-ketopyrrole ring. In this process, the reaction conditions are crucial and an attempt to elucidate the novel reaction pathway is well supported by X-ray crystallography.

Gas phase decomposition of protonated amino acids are of great interest due to their role in understanding protein and peptide chemistry. Several experimental and theoretical studies have been reported in the literature on this subject. In the present work, decomposition of the aromatic amino acid protonated tryptophan was studied by on-the-fly classical chemical dynamics simulations using density functional theory. Mass spectrometry and electronic structure theory studies have shown multiple dissociation pathways for this biologically relevant molecule. Unlike aliphatic amino acids, protonated tryptophan dissociates via NH 3 elimination rather than the usual iminium ion formation by combined removal of H 2 O and CO molecules. Also, a major fragmentation pathway in the present work involves C α -C β bond fission. Results of the chemical dynamics simulations reported here are in overall agreement with experiments, and detailed atomic level mechanisms are presented.

A mild and transition-metal-free synthesis of β-keto arylthioethers has been developed by the aryne triggered [2,3] Stevens rearrangement of allylthioethers. The key sulfur ylide intermediate for the rearrangement was formed by the S-arylation of allylthioethers with arynes generated from 2-(trimethylsilyl)aryl triflates using CsF. Later, the reaction products are converted into valuable heterocycles in two steps.

The prime focus of the present study is to employ NMR relaxation measurement to address the intermolecular interactions, as well as motional dynamics, of drugs, viz., paracetamol and aspirin, encapsulated within the β-cyclodextrin (β-CD) cavity. In this report, we have attempted to demonstrate the applicability of nonselective (R 1 ns ), selective (R 1 se ), and bi-selective (R 1 bs ) spin-lattice relaxation rates to infer dynamical parameters, for example, the molecular rotational correlation times (τ c ) and cross-relaxation rates (σ ij ) of the encapsulated drugs. Molecular rotational correlation times of the free drugs were calculated using the selective relaxation rate in the fast molecular motion time regime (ω H 2 τ c 2 ≪ 1 and R 1 ns /R 1 se ≈ 1.500), whereas that of the 1:1 complexed drugs were found from the ratio of R 1 ns /R 1 se in the intermediate motion time regime (ω H 2 τ c 2 ∼ 1 and R 1 ns /R 1 se ≈ 1.054), and these values were compared with each other to confirm the formation of inclusion complexes. Furthermore, the cross-relaxation rates were used to evaluate the intermolecular proton distances. Also, density functional theory calculations were performed to determine the minimum energy geometry of the inclusion complexes and the results compared with those from experiments. The report, thus, presents the possibility of utilizing NMR relaxation data, a more cost-effective experiment, to calculate internuclear distances in the case of drug-supramolecule complexes that are generally obtained by extremely time consuming two-dimensional nuclear Overhauser enhancement-based methods. A plausible mode of insertion of the drug molecules into the β-CD cavity has also been described based on experimental NMR relaxation data analysis.

Sodium-ion batteries are now close to replacing lithium-ion batteries because they provide superior alternative energy storage solutions that are in great demand, particularly for large-scale applications. To that end, the present study is focused on the properties of a new type of dual-electrode material, Na 0.5 Ni 0.25 Mn 0.75 O 2 , synthesized using a mixed hydroxy-carbonate route. Cyclic voltammetry confirms that redox couples, at high and low voltage ranges, are facilitated by the unique features and properties of this dual-electrode, through sodium ion deintercalation/intercalation into the layered Na 0.5 Ni 0.25 Mn 0.75 O 2 material. This material provides superior performance for Na-ion batteries, as evidenced by the fabricated sodium cell that yielded initial charge-discharge capacities of 125/218 mAh g -1 in the voltage range of 1.5-4.4 V at 0.5 C. At a low voltage range (1.5-2.6 V), the anode cell delivered discharge-charge capacities of 100/99 mAh g -1 with 99% capacity retention, which corresponds to highly reversible redox reaction of the Mn 4+/3+ reduction and the Mn 3+/4+ oxidation observed at 1.85 and 2.06 V, respectively. The symmetric Na-ion cell, fabricated using Na 0.5 Ni 0.25 Mn 0.75 O 2 , yielded initial charge-discharge capacities of 196/187 μAh at 107 μA. These results encourage the further development of new types of futuristic sodium-ion-battery-based energy storage systems.

The yellow fluorescent protein (YFP) is frequently used in a protein complementation assay called bimolecular fluorescence complementation (BiFC), and is employed to visualize protein-protein interactions. In this analysis, two different, nonfluorescent fragments of YFP are genetically attached to proteins of interest. Upon interaction of these proteins, the YFP fragments are brought into proximity close enough to reconstitute their original structure, enabling fluorescence. BiFC allows for a straightforward readout of protein-protein interactions and furthermore facilitates their functional investigation by in vivo imaging. Furthermore, it has been observed that the available color range in BiFC can be extended upon complementing fragments of different proteins that are, like YFP, derived from the Aequorea victoria green fluorescent protein, thereby allowing for a multiplexed investigation of protein-protein interactions. Some spectral characteristics of "multicolor" BiFC (mcBiFC) complexes have been reported before; however, no in-depth analysis has been performed yet. Therefore, little is known about the photophysical characteristics of these mcBiFC complexes because a proper characterization essentially relies on in vitro data. This is particularly difficult for fragments of autofluorescent proteins (AFPs) because they show a very strong tendency to form supramolecular aggregates which precipitate ex vivo. In this study, this intrinsic difficulty is overcome by directly fusing the coding DNA of different AFP fragments. Translation of the genetic sequence in Escherichia coli leads to fully functional, highly soluble fluorescent proteins with distinct properties. On the basis of their construction, they are designated chimeric AFPs, or BiFC chimeras, here. Comparison of their spectral characteristics with experimental in vivo BiFC data confirmed the utility of the chimeric proteins as a BiFC model system. In this study, nine different chimeras were thoroughly analyzed at both the ensemble and the single-molecular level. The data indicates that mutations believed to be photophysically silent significantly alter the properties of AFPs.

Arynes are employed in the transition-metal-free and mild [2,3] Stevens rearrangement of tertiary allylic amines for the synthesis of functionalized homoallylic amines in moderate to good yield with a broad substrate scope. The key nitrogen ylide intermediate was generated by the N-arylation of allyl amines using arynes. Moreover, the reaction of chiral allyl amines with arynes resulted in the enantiospecific synthesis of homoallylic amines. In addition, preliminary studies on the [1,2] Stevens rearrangement is also presented.

A divergent reaction of 2-aminobenzimidazole with isothiocyanates and dihalomethanes has been developed for the selective synthesis of benzoimidazothiazetidine and benzoimidazothiadiazine. A single-pot reaction of 2-aminobenzimidazole in the presence of sodium hydride delivers benzoimidazothiazetidine, whereas triethylamine promotes the formation of benzoimidazothiadiazine via a sequential stepwise fashion. The reaction sequence involves the initial formation of thiourea followed by regioselective nucleophilic addition and intramolecular ring-closing with dihalo electrophiles. The observed regioselectivity of this reaction is governed by the nature of bases and the reaction sequence.

The transition-metal-free and temperature-dependent highly selective reaction of arynes with 2H-azirines allowing the synthesis of either N-unsubstituted or N-arylindoles has been developed. At 60 °C, arynes generated from 2-(trimethylsilyl)aryl triflates smoothly insert into 2H-azirines to form 2,3-diarylindoles with high selectivity. Interestingly, when the reaction was performed at -10 °C, the selectivity was switched to the formation of 1,2,3-triarylindoles in good yields.