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Group transfer polymerization (GTP) is an important ambient-temperature living polymerization method using silyl ketene acetal (SKA) or related initiators. Although several different GTP systems have been developed for polymerizing acrylic monomers, they all require the use of a catalyst to activate the SKA initiator, commonly believed to be ineffective on its own. Now, this work shows that, in fact, the neutral SKA alone mediates either controlled or extremely rapid polymerization of acrylic monomers such as methyl methacrylate (MMA) in polar donor solvents such as DMF, depending on the nuclearity of the SKA and the chelating pendant group on Si. In the case of a mono-SKA such as Me2CC(OMe)OSiMe3, the GTP of MMA in DMF is relatively slow (several hours to completion) but is controlled and remarkably efficient, producing PMMA with Mn values close to those predicted on the basis of the [M]/[I] ratio, low Đ values (≤1.2), and high initiation efficiencies (≥80%). In sharp contrast, the di-SKAs linked by an oxo, ferrocenyl, or binaphthyl bridge, as well as the mono-SKA with a donor chelating methoxy pendant group on Si, mediate extremely rapid polymerization (a few seconds to completion), affording an extremely high turnover frequency up to 1.92 × 105 h-1, but the polymerization is uncontrolled. Several lines of evidence obtained through mechanistic studies indicate that the polymerization by the mono-SKA and di-SKA in DMF proceeds through a dissociative pathway with the released enolate anion being the highly active species and the polymerization characteristics are highly dependent on the amount of free enolate anions in solution. In this mechanism, the donor ability of the solvent plays a critical role in promoting the activity through activation of the Si site of the neutral SKA by forming the pentacoordinate Si intermediate. [ABSTRACT FROM AUTHOR]

This contribution reports the first chemoselective, stereospecific, and living polymerization of polar divinyl monomers, enabled by chiral ansa-zirconocenium catalysts through an enantiomorphic-site controlled coordination-addition polymerization mechanism. Silyl-bridged-ansa-zirconocenium ester enolate 2 has been synthesized and structurally characterized, but it exhibits low to negligible activity and stereospecificity in the polymerization of polar divinyl monomers including vinyl methacrylate (VMA), allyl methacrylate (AMA), 4-vinylbenzyl methacrylate (VBMA), and N,N-diallyl acrylamide (DAA). In contrast, ethylene-bridged-ansa-zirconocenium ester enolate 1 is highly active and stereospecific in the polymerization of such monomers including AMA, VBMA, and DAA. The polymerization by 1 is perfectly chemoselective for all four polar divinyl monomers, proceeding exclusively through conjugate addition across the methacrylic C═C bond, while leaving the pendant C═C bonds intact. The polymerization of DAA is most stereospecific and controlled, producing essentially stereoperfect isotactic PDAA with [mmmm] > 99%, Mn matching the theoretical value (thus a quantitative initiation efficiency), and a narrow molecular weight distribution (Đ = 1.06-1.16). The stereospecificity is slightly lower for the AMA polymerization but still leading to highly isotactic poly(allyl methacrylate) (PAMA) with 95-97% [mm]. The polymerization of VBMA is further less stereospecific, affording PVBMA with 90-94% [mm], while the polymerization VMA is least stereospecific. Several lines of evidence from both homo- and block copolymerization results have demonstrated living characteristics of the AMA polymerization by 1. Mechanistic studies of this polymerization have yielded a monometallic coordination-addition polymerization mechanism involving the eight-membered chelating intermediate. Post-functionalization of isotactic polymers bearing the pendant vinyl group on every repeating unit via the thiol-ene "click" reaction achieves a full conversion of all the pendant double bonds to the corresponding thioether bonds. Photocuring of such isotactic polymers is also successful, producing an elastic material readily characterizable by dynamic mechanical analysis. [ABSTRACT FROM AUTHOR]

Group 4 tetrabenzyl compounds MBn4(M = Zr, Ti), uponprotonolysis with an equimolar amount of the tetradentate amine-tris(phenol)ligand N[(2,4-tBu2C6H2(CH2)OH]3in toluene from −30to 25 °C, unexpectedly lead to amine-bis(phenoxy) dibenzyl complexes,BnCH2N[(2,4-tBu2C6H2(CH2)O]2MBn2(M = Zr (1), Ti (2)) in 80% (1) and 75% (2) yields. This reaction involves an apparentcleavage of the >NCH2–ArOH bond (loss of thephenolin the ligand) and formation of the >NCH2–CH2Bn bond (gain of the benzyl group in the ligand). Structuralcharacterization of 1by X-ray diffraction analysis confirmsthat the complex formed is a bis(benzyl) complex of Zr coordinatedby a newly derived tridentate amine-bis(phenoxy) ligand arranged ina mer configuration in the solid state. The abstractiveactivation of 1and 2with B(C6F5)3·THF in CD2Cl2at room temperature generates the corresponding benzyl cations {BnCH2N[(2,4-tBu2C6H2(CH2)O]2MBn(THF)}+[BnB(C6F5)3]−(M = Zr (3), Ti, (4)). These cationic complexes, alongwith their analogues derived from (imino)phenoxy tri- and dibenzylcomplexes, [(2,6-iPr2C6H3)NC(3,5-tBu2C6H2)O]ZrBn3(5) and [2,4-Br2C6H2(O)(6-CH2(NC5H9))CH2NCH(2-adamantyl-4-MeC6H2O)]ZrBn2(6), have beenfound to effectively polymerize the biomass-derived renewable β-methyl-α-methylene-γ-butyrolactone(βMMBL) at room temperature into the highly stereoregularpolymer PβMMBL with an isotacticity up to 99% mm. A combined experimental and DFT study has yielded amechanistic pathway for the observed unusual C–C bond cleavagein the present protonolysis reaction between ZrBn4andN[(2,4-tBu2C6H2(CH2)OH]3for the formation of complex 1, which involves the benzyl radical and the Zr(III) species,resulting from thermal and photochemical decomposition of ZrBn4, followed by a series of reaction sequences consisting ofprotonolysis, tautomerization, H-transfer, oxidation, elimination,and radical coupling. [ABSTRACT FROM AUTHOR]

Recent advancements in near-field flexible microwave sensor technology have significantly enhanced their capabilities in wearables for noninvasive sensing. This paper aims to evaluate chronic wounds, specifically bone cracks, and their healing processes utilizing near-field microwave sensors for various designs and substrates, as the near-field effect is challenging in assessing chronic bone cracks. The proposed polyamide- and polydimethylsiloxane-based microwave sensor displays novelty in terms of resonating and electromagnetic band gap structures in the FR1 band. The sharp resonance and gain of the sensor make it suitable for wearable bandages in detecting and assessing the percentage of bone cracks. The analysis involves the utilization of tetrad cell electromagnetic band gap structures for crack detection with multiple resonance frequencies at 2.286, 2.35, 3.04, and 3.616 GHz, in which the crack analysis is varied between 0 and 100% noninvasively. The corresponding results are obtained and interpreted through simulations of various resonator use cases for comprehensive chronic bone analysis., Competing Interests: The authors declare no competing financial interest., (© 2025 The Authors. Published by American Chemical Society.)

Dried Matrix Spot (DMS) is a cost-effective and stable sampling technique used in population-based studies, clinical research, and noninvasive chemical and biomarker screening. DMS is especially useful in developing countries like India, where collaborative initiatives are required for its improved applications.

Semen liquefaction is a postejaculation process that transforms semen from a gel-like (coagulated) form to a water-like consistency (liquefied). This process is primarily regulated by serine proteases from the prostate gland, most prominently, prostate-specific antigen (PSA; KLK3). Inhibiting PSA activity has the potential to impede liquefaction of human semen, presenting a promising target for nonhormonal contraception in the female reproductive tract. This study employed triazole B1 as a starting compound. Through systematic design, synthesis, and optimization, we identified compound 20 (CDD-3290) as a 216 nM inhibitor of PSA with better stability in media than triazole B1. Further, we also evaluated the selectivity profile of compound 20 (CDD-3290) by testing against closely related proteases and demonstrated excellent inhibition of PSA versus α-chymotrypsin and elastase and similar potency versus thrombin. Thus, compound 20 is an improved PSA inhibitor that can be tested for efficacy in vitro or in the female reproductive tract., Competing Interests: The authors declare no competing financial interest., (© 2024 American Chemical Society.)

Heavy metal ions (HMIs) are very harmful to the ecosystem when they are present in excess of the recommended limits. They are carcinogenic in nature and can cause serious health issues. So, it is important to detect the metal ions quickly and accurately. The metal ions arsenic (As 3+ ), cadmium (Cd 2+ ), chromium (Cr 3+ ), lead (Pb 2+ ), and mercury (Hg 2+ ) are considered to be very toxic among other metal ions. Standard analytical methods like atomic absorption spectroscopy, atomic fluorescence spectroscopy, and X-ray fluorescence spectroscopy are used to detect HMIs. But these methods necessitate highly technical equipment and lengthy procedures with skilled personnel. So, electrochemical sensing methods are considered to be more advantageous because of their quick analysis with precision and simplicity to operate. They can detect a wide range of heavy metals providing real-time monitoring and are cost-effective and enable multiparametric detection. Various sensing applications necessitate severe regulation regarding the modification of electrode surfaces. Numerous nanomaterials such as graphene, carbon nanotubes, and metal nanoparticles have been extensively explored as interface materials in electrode modifiers. These nanoparticles offer excellent electrical conductivity, distinctive catalytic properties, and high surface area resulting in enhanced electrochemical performance. This review examines different HMI detection methods in an aqueous medium by an electrochemical sensing approach and studies the recent developments in interface materials for altering the electrodes., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Thorium (Th) and uranium (U) are important strategic resources in nuclear energy-based heavy industries such as energy and defense sectors that also generate significant radioactive waste in the process. The management of nuclear waste is therefore of paramount importance. Contamination of groundwater/surface water by Th/U is increasing at an alarming rate in certain geographical locations. This necessitates the development of strategic adsorbent materials with improved performance for capturing Th/U species from radioactive waste and groundwater. This report describes the design of a unique, robust, and radiation-resistant porous organic polymer (POP: TP-POP-SO 3 NH 4 ), which demonstrates ultrafast removal of Th(IV) (<30 s)/U(VI) (<60 s) species present in simulated radioactive wastewater/groundwater samples. Thermal, chemical, and radiation stabilities of these POPs were studied in detail. The synthesized ammoniated POP revealed exceptional capture efficiency for trace-level Th (<4 ppb) and U (<3 ppb) metal ions through the cation-exchange mechanism. TP-POP-SO 3 NH 4 shows a significant sorption capacity [Th (787 mg/g) and U (854 mg/g)] with an exceptionally high distribution coefficient ( K d ) of 10 7 mL/g for Th. This work also demonstrates a facile protocol to convert a nonperforming POP, by simple chemical modifications, into a superfast adsorbent for efficient uptake/removal of U/Th.

Polyethoxylated tallow amine (POEA) surfactants in glyphosate formulations are understudied. They may constitute greater health risks than glyphosate itself. Lack of validated biomarkers of exposure and metabolism, as well as analytical methods for measuring POEA, limit the study of a formulation's toxicity and associated risk.

The number of newly synthesized and produced organic chemicals has increased extremely quickly. However, the measurements of their physical properties, including their vapor-liquid equilibrium (VLE) data, are time-consuming. It so happens that there is no physical property data about a brand-new chemical. Therefore, the importance of calculating their physicochemical properties has been playing a more and more important role. 4,6-Dichloropyrimidine (DCP) is also a relatively new molecule of high industrial importance with little existing data. Therefore, their measurements and the comparison with the calculated data are of paramount concern. DCP is a widespread heterocyclic moiety that is present in synthetic pharmacophores with biological activities as well as in numerous natural products. Isobaric VLE for the binary system of 4,6-dichloropyrimidine and its main solvent monochlorobenzene (MCB) was measured using a vapor condensate and liquid circulation VLE apparatus for the first time in the literature. Density functional-based VLE was calculated using the COSMO-SAC protocol to verify the laboratory results. The COSMO-SAC calculation was found to be capable of representing the VLE data with high accuracy. Adequate agreement between the experimental and calculated VLE data was acquired with a minimal deviation of 3.0 × 10 -3 , which allows for broader use of the results., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Pseudomonas aeruginosa (P.A.) is a human pathogen belonging to the top priorities for the discovery of new therapeutic solutions. Its propensity to generate biofilms strongly complicates the treatments required to cure P.A. infections. Herein, we describe the synthesis of a series of novel rotaxanes composed of a central galactosylated pillar[5]arene, a tetrafucosylated dendron, and a tetraguanidinium subunit. Besides the high affinity of the final glycorotaxanes for the two P.A. lectins LecA and LecB, potent inhibition levels of biofilm growth were evidenced, showing that their three subunits work synergistically. An antibiofilm assay using a double Δ lecA Δ lecB mutant compared to the wild type demonstrated that the antibiofilm activity of the best glycorotaxane is lectin-mediated. Such antibiofilm potency had rarely been reached in the literature. Importantly, none of the final rotaxanes was bactericidal, showing that their antibiofilm activity does not depend on bacteria killing, which is a rare feature for antibiofilm agents.

The interfacial electrochemistry of reversible redox molecules is central to state-of-the-art flow batteries, outer-sphere redox species-based fuel cells, and electrochemical biosensors. At electrochemical interfaces, because mass transport and interfacial electron transport are consecutive processes, the reaction velocity in reversible species is predominantly mass-transport-controlled because of their fast electron-transfer events. Spatial structuring of the solution near the electrode surface forces diffusion to dominate the transport phenomena even under convective fluid-flow, which in turn poses unique challenges to utilizing the maximum potential of reversible species by either electrode or fluid characteristics. We show Coulombic force gated molecular flux at the interface to target the transport velocity of reversible species; that in turn triggers a directional electrostatic current over the diffusion current within the reaction zone. In an iron-based redox flow battery, this gated molecular transport almost doubles the volumetric energy density without compromising the power capability.

Engineering cellular microenvironment on a functional platform using various biophysical cues to modulate stem cell fate has been the central theme in regenerative engineering. Among the various biophysical cues to direct stem cell differentiation, the critical role of physiologically relevant electric field (EF) stimulation was established in the recent past. The present study is the first to report the strategy to switch EF-mediated differentiation of human mesenchymal stem cells (hMSCs) between neuronal and glial pathways, using tailored functional properties of the biomaterial substrate. We have examined the combinatorial effect of substrate functionalities (conductivity, electroactivity, and topography) on the EF-mediated stem cell differentiation on polyvinylidene-difluoride (PVDF) nanocomposites in vitro , without any biochemical inducers. The functionalities of PVDF have been tailored using conducting nanofiller (multiwall-carbon nanotube, MWNT) and piezoceramic (BaTiO 3 , BT) by an optimized processing approach (melt mixing-compression molding-rolling). The DC conductivity of PVDF nanocomposites was tuned from ∼10 -11 to ∼10 -4 S/cm and the dielectric constant from ∼10 to ∼300. The phenotypical changes and genotypical expression of hMSCs revealed the signatures of early differentiation toward neuronal pathway on rolled-PVDF/MWNT and late differentiation toward glial lineage on rolled-PVDF/BT/MWNT. Moreover, we were able to distinguish the physiological properties of differentiated neuron-like and glial-like cells using membrane depolarization and mechanical stimulation. The excitability of the EF-stimulated hMSCs was also determined using whole-cell patch-clamp recordings. Mechanistically, the roles of intracellular reactive oxygen species (ROS), Ca 2+ oscillations, and synaptic and gap junction proteins in directing the cellular fate have been established. Therefore, the present work critically unveils complex yet synergistic interaction of substrate functional properties to direct EF-mediated differentiation toward neuron-like and glial-like cells, with distinguishable electrophysiological responses.

We report the independent role of isomerism of secondary sphere substituents over their nature, a factor often overlooked in molecular electrocatalysis pertaining to electrochemical sensing, by establishing that isomerism redefines the electronic structure at the catalytic reaction center via geometrical factors. UV-vis spectroscopy and X-ray photoelectron spectroscopy suggest that a substituent's isomerism in molecular catalysts conjoins molecular planarity and catalytic activation through competing field effects and resonance effects. As a classical example, we demonstrate the influence of isomerism of the -NO 2 substituents for the electrocatalytic multi electron oxidation of As(III), a potentially important electrochemical pathway for water remediation and arsenic detection. The isomerism dependent oxidative activation of catalytic center leads to a nonprecious molecular catalyst capable for direct As(III) oxidation with an experimental detection limit close to WHO guidelines. This work opens up an unusual approach in analytical chemistry for developing various sensing platforms for challenging chemical and electrochemical reactions.

The overall goal of this study is to elucidate the potential effect(s) of arsenic on a variety of human brain cells. Arsenic is the most pervasive Group A human environmental carcinogen. Long-term exposure to arsenic is associated with human diseases including cancer, cardiovascular disease, and diabetes. More immediate are the health effects on neurological development and associated disorders in infants and children exposed to arsenic in utero . Arsenic is metabolized in various organs and tissues into more toxic methylated species, including methylarsenite (MAs(III)), so the question arises whether the methylate species are responsible for the neurological effects of arsenic. Arsenic enters the brain through the blood-brain barrier and produces toxicity in the brain microvascular endothelial cells, glia (astrocytes and microglia), and neurons. In this study, we first assessed the toxicity in different types of brain cells exposed to either inorganic trivalent As(III) or MAs(III) using both morphological and cytotoxicity cell-based analysis. Second, we determined the methylation of arsenicals and the expression levels of the methylation enzyme, As(III) S-adenosylmethionine (SAM) methyltransferase (AS3MT), in several types of brain cells. We showed that the toxicity to neurons of MAs(III) was significantly higher than that of As(III). Interestingly, the differences in cytotoxicity between cell types was not due to expression of AS3MT, as this was expressed in neurons and glia but not in endothelial cells. These results support our hypothesis that MAs(III) is the likely physiological neurotoxin rather than inorganic arsenic species.

The role of electrocatalysts in energy storage/conversion, biomedical and environmental sectors, green chemistry, and much more has generated enormous interest in comprehending their structure-activity relations. While targeting the surface-to-volume ratio, exposing reactive crystal planes and interfacial modifications are time-tested considerations for activating metallic catalysts; it is primarily by substitution in molecular electrocatalysts. This account draws the distinction between a substituent's chemical identity and isomerism, when regioisomerism of the -NO 2 substituent is conferred at the "α" and "β" positions on the macrocycle of cobalt phthalocyanines. Spectroscopic analysis and theoretical calculations establish that the β isomer accumulates catalytically active intermediates via a cumulative influence of inductive and resonance effects. However, the field effect in the α isomer restricts this activation due to a vanishing resonance effect. The demonstration of the distinct role of isomerism in substituted molecular electrocatalysts for reactions ranging from energy conversion to biosensing highlights that isomerism of the substituents makes an independent contribution to electrocatalysis over its chemical identity.

The human body is endowed with an uncanny ability to distinguish self from foreign. The implantation of a foreign object inside a mammalian host activates complex signaling cascades, which lead to biological encapsulation of the implant. This reaction by the host system to a foreign object is known as foreign body response (FBR). Over the last few decades, it has been increasingly important to have a deeper insight into the mechanisms of FBR is needed to develop biomaterials for better integration with living systems. In the light of recent advances in tissue engineering and regenerative medicine, particularly in the field of biosensors and biodegradable tissue engineering scaffolds, the classical concepts related to the FBR have acquired new dimensions. The aim of this review is to provide a holistic view of the FBR, while critically analyzing the challenges, which need to be addressed in the future to overcome this innate response. In particular, this review discusses the relevant experimental methodology to assess the host response. The role of erosion and degradation behavior on FBR with biodegradable polymers is largely explored. Apart from the discussion on temporal progression of FBR, an emphasis has been given to the design of next-generation biomaterials with favorable host response.

We illustrate that the extent of hydration and consequently the heat of hydration of alkali metal ions can be utilized to control their insertion/deinsertion chemistry in a redox active metal coordination polymer framework (CPF) electrode. The formal redox potential of CPF electrode for cation intercalation is inversely correlated to hydrated ionic radii, with clear distinction between the intercalation of ions across alkali metal series. This leads to noninvasive identification and differentiation of cations in the alkali metal series by utilizing a single sensing platform.

The oxysilicate apatite host CaLa 4 (SiO 4 ) 3 O has been explored for immobilization of radioactive nuclides. Divalent ion, trivalent rare earth ion, and combined ionic substitutions in the silicate oxyapatite were carried out to optimize the simulated wasteform composition. The phases were characterized by powder X-ray diffraction, FT-IR, TGA, SEM-EDS, and HT-XRD techniques. The results revealed the effect of ionic substitutions on the structure and thermal expansion behavior. The investigation resulted in the formulation of simulated wasteforms such as La 3.4 Ce 0.1 Pr 0.1 Nd 0.1 Sm 0.1 Gd 0.1 Y 0.1 (SiO 4 ) 3 O (WF-1) and Ca 0.8 Sr 0.1 Pb 0.1 La 3.4 Ce 0.1 Pr 0.1 Nd 0.1 Sm 0.1 Gd 0.1 Y 0.1 (SiO 4 ) 3 O (WF-2). In comparison to the average axial thermal expansion coefficients of the hexagonal unit cell of the parent CaLa 4 (SiO 4 ) 3 O measured in the temperature range 298-1073 K (α' a = 9.74 × 10 -6 K -1 and α' c = 10.10 × 10 -6 K -1 ), rare earth ion substitution decreases the thermal expansion coefficients, as in the case of La 3.4 Ce 0.1 Pr 0.1 Nd 0.1 Sm 0.1 Gd 0.1 Y 0.1 (SiO 4 ) 3 O (α' a = 8.67 × 10 -6 K -1 and α' c = 7.94 × 10 -6 K -1 ). However, the phase Ca 0.8 Sr 0.1 Pb 0.1 La 3.4 Ce 0.1 Pr 0.1 Nd 0.1 Sm 0.1 Gd 0.1 Y 0.1 (SiO 4 ) 3 O shows an increase in the values of thermal expansion coefficients: α' a = 11.74 × 10 -6 K -1 and α' c = 11.70 × 10 -6 K -1 .

We utilize proton-coupled electron transfer in hydrogen storage molecules to unlock a rechargeable battery chemistry based on the cleanest chemical energy carrier molecule, hydrogen. Electrochemical, spectroscopic, and spectroelectrochemical analyses evidence the participation of protons during charge-discharge chemistry and extended cycling. In an era of anthropogenic global climate change and paramount pollution, a battery concept based on a virtually nonpolluting energy carrier molecule demonstrates distinct progress in the sustainable energy landscape.

Electrochemical interfaces invariably generate unipolar electromotive force because of the unidirectional nature of electrochemical double layers. Herein we show an unprecedented generation of a time varying bipolar electric field between identical half-cell electrodes induced by tailored interfacial migration of magnetic particles. The periodic oscillation of a bipolar electric field is monotonically correlated with velocity-dependent torque, opening new electrochemical pathways targeting velocity monitoring systems.

State-of-the-art proton exchange membrane fuel cells (PEMFCs) anodically inhale H 2 fuel and cathodically expel water molecules. We show an unprecedented fuel cell concept exhibiting cathodic fuel exhalation capability of anodically inhaled fuel, driven by the neutralization energy on decoupling the direct acid-base chemistry. The fuel exhaling fuel cell delivered a peak power density of 70 mW/cm 2 at a peak current density of 160 mA/cm 2 with a cathodic H 2 output of ∼80 mL in 1 h. We illustrate that the energy benefits from the same fuel stream can at least be doubled by directing it through proposed neutralization electrochemical cell prior to PEMFC in a tandem configuration.

Molecular oxygen, the conventional electron acceptor in fuel cells poses challenges specific to direct alcohol fuel cells (DAFCs). Due to the coupling of alcohol dehydrogenation with the scission of oxygen on the positive electrode during the alcohol crossover, the benchmark Pt-based air cathode experiences severe competition and depolarization losses. The necessity of heavy precious metal loading with domains for alcohol tolerance in the state of the art DAFC cathode is a direct consequence of this. Although efforts are dedicated to selectively cleave oxygen, the root of the problem being the inner sphere nature of either half-cell chemistry is often overlooked. Using an outer sphere electron acceptor that does not form a bond with the cathode during redox energy transformation, we effectively decoupled the interfacial chemistry from parasitic chemistry leading to a DAFC driven by alcohol passive carbon nanoparticles, with performance metrics ∼8 times higher than Pt-based DAFC-O 2 .

Bipolar junction transistors are at the frontiers of modern electronics owing to their discrete voltage regulated operational levels. Here we report a redox active binary logic gate (RLG) which can store a "0" and "1" with distinct operational levels, albeit without an external voltage stimuli. In the RLG, a shorted configuration of half-cell electrodes provided the logic low level and decoupled configuration relaxed the system to the logic high level due to self-charge injection into the redox active polymeric system. Galvanostatic intermittent titration and electrochemical quartz crystal microbalance studies indicate the kinetics of self-charge injection are quite faster and sustainable in polypyrrole based RLG, recovering more than 70% signal in just 14 s with minor signal reduction at the end of 10000 cycles. These remarkable properties of RLGs are extended to design a security sensor which can detect and count intruders in a locality with decent precision and switching speed.

Mycobacterium tuberculosis, the causative agent of tuberculosis, accounts for 1.5 million human deaths annually worldwide. Despite efforts to eradicate tuberculosis, it still remains a deadly disease. The two best characterized strains of M. tuberculosis, virulent H37Rv and avirulent H37Ra, provide a unique platform to investigate biochemical and signaling pathways associated with pathogenicity. To delineate the biomolecular dynamics that may account for pathogenicity and attenuation of virulence in M. tuberculosis, we compared the proteome and phosphoproteome profiles of H37Rv and H37Ra strains. Quantitative phosphoproteomic analysis was performed using high-resolution Fourier transform mass spectrometry. Analysis of exponential and stationary phases of these strains resulted in identification and quantitation of 2709 proteins along with 512 phosphorylation sites derived from 257 proteins. In addition to confirming the presence of previously described M. tuberculosis phosphorylated proteins, we identified 265 novel phosphorylation sites. Quantitative proteomic analysis revealed more than five-fold upregulation of proteins belonging to virulence associated type VII bacterial secretion system in H37Rv when compared to those in H37Ra. We also identified 84 proteins, which exhibited changes in phosphorylation levels between the virulent and avirulent strains. Bioinformatics analysis of the proteins altered in their level of expression or phosphorylation revealed enrichment of pathways involved in fatty acid biosynthesis and two-component regulatory system. Our data provides a resource for further exploration of functional differences at molecular level between H37Rv and H37Ra, which will ultimately explain the molecular underpinnings that determine virulence in tuberculosis.

Altered gravity conditions, such as experienced by organisms during spaceflight, are known to cause transcriptomic and proteomic changes. We describe the proteomic changes in whole adult Drosophila melanogaster (fruit fly) but focus specifically on the localized changes in the adult head in response to chronic hypergravity (3 g) treatment. Canton S adult female flies (2 to 3 days old) were exposed to chronic hypergravity for 9 days and compared with 1 g controls. After hypergravity treatment, either whole flies (body + head) or fly-head-only samples were isolated and evaluated for quantitative comparison of the two gravity conditions using an isobaric tagging liquid chromatography-tandem mass spectrometry approach. A total of 1948 proteins from whole flies and 1480 proteins from fly heads were differentially present in hypergravity-treated flies. Gene Ontology analysis of head-specific proteomics revealed host immune response, and humoral stress proteins were significantly upregulated. Proteins related to calcium regulation, ion transport, and ATPase were decreased. Increased expression of cuticular proteins may suggest an alteration in chitin metabolism and in chitin-based cuticle development. We therefore present a comprehensive quantitative survey of proteomic changes in response to chronic hypergravity in Drosophila, which will help elucidate the underlying molecular mechanism(s) associated with altered gravity environments.

Achieving complete chemoselectivity in the polymerization of multivinyl polar monomers is an important yet challenging task, currently achievable only by metal- or metalloid-mediated polymerization processes but in a noncatalytic fashion. Now this work shows that organic N -heterocyclic carbene (NHC) catalysts effect rapid, chemoselective, and catalytic polymerization of multivinyl-functionalized γ-butyrolactones, particularly γ-vinyl-α-methylene-γ-butyrolactone (VMBL). Thus, the NHC-catalyzed polymerization of VMBL not only is quantitatively chemoselective, proceeding exclusively via polyaddition across the conjugated α-methylene double bond while leaving the γ-vinyl double bond intact, but also requires only an exceptionally low catalyst loading of 50 ppm, thus, exhibiting a remarkably high catalyst turnover frequency of 80000 h -1 and producing on average 33.6 polymer chains of M n = 73.8 kg/mol per NHC molecule. The resulting PVMBL can be either thermally cured into cross-linked materials or postfunctionalized with the thiol-ene "click" reaction to achieve complete conversion of the pendant vinyl group on every repeat unit into the corresponding thioether.

Graphene oxide (GO) is impermeable to H2 and O2 fuels while permitting H(+) shuttling, making it a potential candidate for proton exchange membrane fuel cells (PEMFC), albeit with a large anisotropy in their proton transport having a dominant in plane (σIP) contribution over the through plane (σTP). If GO-based membranes are ever to succeed in PEMFC, it inevitably should have a dominant through-plane proton shuttling capability (σTP), as it is the direction in which proton gets transported in a real fuel-cell configuration. Here we show that anisotropy in proton conduction in GO-based fuel cell membranes can be brought down by selectively tuning the geometric arrangement of functional groups around the dopant molecules. The results show that cis isomer causes a selective amplification of through-plane proton transport, σTP, pointing to a very strong geometry angle in ionic conduction. Intercalation of cis isomer causes significant expansion of GO (001) planes involved in σTP transport due to their mutual H-bonding interaction and efficient bridging of individual GO planes, bringing down the activation energy required for σTP, suggesting the dominance of a Grotthuss-type mechanism. This isomer-governed amplification of through-plane proton shuttling resulted in the overall boosting of fuel-cell performance, and it underlines that geometrical factors should be given prime consideration while selecting dopant molecules for bringing down the anisotropy in proton conduction and enhancing the fuel-cell performance in GO-based PEMFC.

Here we report the first potentiometric sensor for soil moisture analysis by bringing in the concept of Galvanic cells wherein the redox energies of Al and conducting polyaniline are exploited to design a battery type sensor. The sensor consists of only simple architectural components, and as such they are inexpensive and lightweight, making it suitable for on-site analysis. The sensing mechanism is proved to be identical to a battery type discharge reaction wherein polyaniline redox energy changes from the conducting to the nonconducting state with a resulting voltage shift in the presence of soil moisture. Unlike the state of the art soil moisture sensors, a signal derived from the proposed moisture sensor is probe size independent, as it is potentiometric in nature and, hence, can be fabricated in any shape or size and can provide a consistent output signal under the strong aberration conditions often encountered in soil moisture analysis. The sensor is regenerable by treating with 1 M HCl and can be used for multiple analysis with little read out hysteresis. Further, a portable sensor is fabricated which can provide warning signals to the end user when the moisture levels in the soil go below critically low levels, thereby functioning as a smart device. As the sensor is inexpensive, portable, and potentiometric, it opens up avenues for developing effective and energy efficient irrigation strategies, understanding the heat and water transfer at the atmosphere-land interface, understanding soil mechanics, forecasting the risk of natural calamities, and so on.

The methionine aminopeptidase (MetAP) family is responsible for the cleavage of the initiator methionine from newly synthesized proteins. Currently, there are no small molecule inhibitors that show selectivity toward the bacterial MetAPs compared to the human enzyme. In our current study, we have screened 20 α-aminophosphonate derivatives and identified a molecule (compound 15) that selectively inhibits the S. pneumonia MetAP in low micromolar range but not the human enzyme. Further bioinformatics, biochemical, and structural analyses suggested that phenylalanine (F309) in the human enzyme and methionine (M205) in the S. pneumonia MetAP at the analogous position render them with different susceptibilities against the identified inhibitor. X-ray crystal structures of various inhibitors in complex with wild type and F309M enzyme further established the molecular basis for the inhibitor selectivity.

A practical stereoselective synthesis to obtain the substituted furan ring as the substructure of eribulin is developed. An asymmetric syn-aldol and intramolecular oxy-Michael were two key steps in our approach. The functionalized furan derivatives were then utilized further to build the 14- and 12-membered macrocyclic diversity as trans- and cis-fused (C-29 and C-30) compounds. This is the first report of building a chemical toolbox with macrocyclic small molecules having trans- or cis-fused 14- or 12-membered rings containing the substructure of eribulin and its diastereomer.

A stereoselective synthesis of a rapamycin fragment is developed and further utilized toward building a macrocyclic chemical toolbox. The amino alcohol moiety embedded in the 22-membered macrocyclic ring allowed for the addition of a variation in the chiral side chain. The key reactions leading to the synthesis of the rapamycin-derived pyran fragment include the following: (i) Paterson aldol, (ii) stereoselective β-OH carbonyl reduction, and (iii) regio- and stereoselective intramolecular oxy-Michael reaction. The other piece needed for building the macrocyclic diversity was obtained from the coupling of various amino alcohol moieties with S-pipecolic acid.

We report that the oxygen binding energy of alloy-core@Pt nanoparticles can be linearly tuned by varying the alloy-core composition. Using this tuning mechanism, we are able to predict optimal compositions for different alloy-core@Pt nanoparticles. Subsequent electrochemical measurements of ORR activities of AuPd@Pt dendrimer-encapsulated nanoparticles (DENs) are in a good agreement with the theoretical prediction that the peak of activity is achieved for a 28% Au/72% Pd alloy core supporting a Pt shell. Importantly, these findings represent an unusual case of first-principles theory leading to nearly perfect agreement with experimental results.

Methionine aminopeptidases (MetAPs) are essential enzymes that make them good drug targets in cancer and microbial infections. MetAPs remove the initiator methionine from newly synthesized peptides in every living cell. MetAPs are broadly divided into type I and type II classes. Both prokaryotes and eukaryotes contain type I MetAPs, while eukaryotes have additional type II MetAP enzyme. Although several inhibitors have been reported against type I enzymes, subclass specificity is scarce. Here, using the fine differences in the entrance of the active sites of MetAPs from Mycobacterium tuberculosis , Enterococcus faecalis , and human, three hotspots have been identified and pyridinylpyrimidine-based molecules were selected from a commercial source to target these hotspots. In the biochemical evaluation, many of the 38 compounds displayed differential behavior against these three enzymes. Crystal structures of four selected inhibitors in complex with human MetAP1b and molecular modeling studies provided the basis for the binding specificity.

We report electrocatalytic oxidation of formic acid using monometallic and bimetallic dendrimer-encapsulated nanoparticles (DENs). The results indicate that the Au147@Pt DENs exhibit better electrocatalytic activity and low CO formation. Theoretical calculations attribute the observed activity to the deformation of nanoparticle structure, slow dehydration of formic acid, and weak binding of CO on Au147@Pt surface. Subsequent experiments confirmed the theoretical predictions.

Candida glabrata is a common opportunistic human pathogen leading to significant mortality in immunosuppressed and immunodeficient individuals. We carried out proteomic analysis of C. glabrata using high resolution Fourier transform mass spectrometry with MS resolution of 60,000 and MS/MS resolution of 7500. On the basis of 32,453 unique peptides identified from 118,815 peptide-spectrum matches, we validated 4421 of the 5283 predicted protein-coding genes (83%) in the C. glabrata genome. Further, searching the tandem mass spectra against a six frame translated genome database of C. glabrata resulted in identification of 11 novel protein coding genes and correction of gene boundaries for 14 predicted gene models. A subset of novel protein-coding genes and corrected gene models were validated at the transcript level by RT-PCR and sequencing. Our study illustrates how proteogenomic analysis enabled by high resolution mass spectrometry can enrich genome annotation and should be an integral part of ongoing genome sequencing and annotation efforts.

MAPKAPK2, a substrate of p38 MAPKs, plays central role in p38-mediated signal transduction, and its inhibitors are promisingly useful in the treatment of inflammatory diseases. The computational approaches comprising both ligand-based drug design and structure-based drug design were used as virtual screening strategies for the discovery of novel MK2 inhibitors. Two quantitative pharmacophore models were generated with a training set of 27 MK2 inhibitors using HypoGen module of CATALYST. The two models suggested that two hydrogen bond acceptors, one hydrogen bond donor, and one hydrophobic feature are essential for ligand binding. Further, 3D QSAR model with comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) was constructed using a training set of 42 inhibitors. The predictive CoMFA and CoMSIA models have cross-validated coefficients (q2) of 0.804 and 0.765 and regression coefficients (r2) of 0.984 and 0.986, respectively. The structure-based studies were carried out by docking 77 known MAPKAPK2 inhibitors into the active site of receptor using Glide and analyzing the "hotspots" of the active site. Docking studies revealed that Met138, Leu141, Asp207, Lys93, Cys140, Leu70, Thr206, and Gly143 are showing interactions with highly active compounds. The structure activity relationships elucidated here for carboline derivatives combined with their binding information will provide an integrated approach to explore the chemical space further for improving the potency of MAPKAPK2 inhibitors.

Consensus virtual screening models were generated and validated utilizing a set of known human epidermal growth factor receptor-2 (HER2) inhibitors and modeled HER2 active and inactive state structures. The virtual screening models were successfully employed to discover a set of structurally diverse compounds with growth inhibitory activity against HER2-overexpressing SKBR3 breast cancer cell line. A search of a 3D database containing 350000 small-molecules using the consensus models retrieved 531 potential hits. Of the 531 hits, 57 were selected for testing in SKBR3 cells on the basis of structural novelty and desirable drug-like properties. Seven compounds inhibited growth of SKBR3 cells with IC50 values <10 microM. These lead compounds have desirable physicochemical properties and are excellent candidates for further optimization.

To obtain thermodynamic information about interactions between transmembrane helices in integral membrane proteins, partial unfolding of bacterioopsin in ethanol/water mixtures was studied by Förster-type resonance energy transfer (FRET) from tryptophan to a dansyl group on Lys 41. Tryptophan to dansyl FRET was detected by measuring sensitized emission at 490-500 nm from 285 nm excitation. FRET was observed in dansylbacterioopsin in apomembranes and in detergent micelles but not in 90% ethanol/water or in the chymotrypsin fragment C2 (residues 1-71). The main fluorescence donors are Trp 86 and Trp 182. Increase of FRET from C2 with added chymotrypsin fragment C1 (residues 72-248) provides an estimate of the C1-C2 association constant as 7.7 x 10(6) M(-1). With increasing ethanol concentration, the FRET signal from dansylbacterioopsin in detergent micelles disappeared with a sharp transition above 60% ethanol. No transition occurred in Trp fluorescence from bacterioopsin lacking the dansyl acceptor, nor did dansyl model compounds undergo a similar transition. Light scattering measurements show that the detergent micelles dissipate below 50% ethanol. Thus the observed transition is likely to be a partial unfolding of bacterioopsin. Assuming a two-state unfolding model, the free energy of unfolding was obtained by extrapolation as 9.0 kcal/mol. The slope of the transition (m-value) was -0.8 kcal mol(-1) M(-1). The unfolding process probably involves dissociation of several helices. The rate of association was measured by stopped-flow fluorometry. Two first-order kinetic processes were observed, having approximately equal weights, with rate constants of 2.32 s (-1) and 0.185 s(-1).