Screening and rank ordering of reversible mechanism‐based inhibitors of Hepatitis C virus NS3 protease using electrospray ionization mass spectrometry

An affinity‐selection study using size exclusion chromatography (SEC) combined with off‐line electrospray ionization mass spectrometry (ESI‐MS) was performed on libraries of peptidic α‐ketoamide inhibitors directed against the hepatitis C virus (HCV) NS3 protease. A limiting amount of HCV NS3 protease (25 µM ) was incubated with equimolar amounts (100 µM ) of 49 reversible mechanism‐based ketoamide inhibitors, previously grouped into seven sets to ensure clearly distinguishable mass differences of the enzyme‐inhibitor complexes (>10 Da). The unbound compounds were separated rapidly from the protease and the protease‐inhibitor complexes by SEC spin columns. The eluate of the SEC was immediately analyzed by direct‐infusion ESI‐MS. An enzyme‐inhibitor complex, with a molecular mass corresponding to the NS3 protease binding to the preferred inhibitor, SCH212986, was the only molecular species detected. By increasing the molar ratio of HCV NS3 protease to inhibitors to 1:2 while keeping the inhibitors' concentration constant, the complex of the second most tightly bound inhibitor, SCH215426, was also identified. Although the potencies of these inhibitors were virtually un‐measurable by kinetic assays, a rank order of CVS4441 > SCH212986 > SCH215426 was deduced for their inhibition potencies by direct competition experiment with CVS4441 ( M ). As discussed in the article, through judicious application of this strategy, even large libraries of fairly weak, reversible and slow‐binding inhibitors could be rapidly screened and rank ordered to provide critical initial structure‐activity insights. Copyright © 2011 John Wiley & Sons, Ltd.     

Fabrication of multi-structure nanocarbons from carbon xerogel: a unique scaffold towards bio-imaging

A novel route has been developed to fabricate different carbon nanostructures having individual morphology of carbon nanoparticles: nanofullerene, nanocube, nanoleaf and porous nanorods, through the combustion of carbon xerogel with nitric acid. These fabricated nanostructures exhibited bright green fluorescence under the exposure of UV light.     

Self-assembling properties of lactic acid derivative with several ester linkages in the molecular core

The effect of several polar ester linkage groups incorporated in the molecular core of a chiral lactic acid derivative on self-assembling properties has been investigated by polarizing optical microscopy, small angle X-ray diffraction, differential scanning calorimetry, optical and electro--optical studies. The compound possesses the paraelectric smectic A* (SmA*) and ferroelectric smectic C* (SmC*) phases over a broad temperature range. Mesomorphic behaviour, spontaneous polarization, birefringence, optical transmission, dielectric anisotropy and structural properties of the self-assembled chiral material have been determined. The obtained results are discussed and compared with that of other liquid crystalline materials. Experimentally determined spontaneous polarization and tilt angle values are also used to elucidate the nature of SmC* to SmA* phase transition. The effect of polar ester linkages in the molecular core has also been discussed.     

A Systematic Study of Fluorescence‐Based Detection of Nitroexplosives and Other Aromatics in the Vapor Phase by Microporous Metal–Organic Frameworks

A systematic study is conducted on four microporous metal–organic framework compounds built on similar ligands but different structures, namely [Zn₃(bpdc)₃(bpy)] ? 4 DMF ? H₂O ( 1 ), [Zn₃(bpdc)₃(2,2′dmbpy)] ? 4 DMF ? H₂O ( 2 ), [Zn₂(bpdc)₂(bpe)] ? 2 DMF ( 3 ), and [Zn(bpdc)(bpe)] ? DMF ( 4 ) (bpdc=4,4′‐biphenyldicarboxylate; bpy=4,4′‐bipyridine; 2,2′dmbpy=2,2′‐dimethyl‐4,4′bipyridine; bpe=1,2‐bis(4‐pyridyl)ethane; DMF=N,N′‐dimethylformamide) to investigate their photoluminescence properties and sensing/detection behavior upon exposure to vapors of various aromatic molecules (analytes) including nitroaromatic explosives. The results show that all four compounds are capable of detecting these molecules in the vapor phase through fluorescence quenching or enhancement. Both electrochemical measurements and theoretical calculations are performed to analyze the analyte–MOF interactions, to explain the difference in signal response by different analytes, and to understand the mechanism of fluorescence quenching or enhancement observed in these systems. Interestingly, compound 3 also shows an emission frequency shift when exposed to benzene (BZ), chlorobenzene (ClBZ), and toluene (TO), which provides an additional variable for the identification of different analytes in the same category.     

Cu<Subscript><Emphasis Type="Italic">x</Emphasis></Subscript>Ni<Subscript>1−<Emphasis Type="Italic">x</Emphasis></Subscript> alloy nanoparticles embedded SiO<Subscript>2</Subscript> films: synthesis and structure

Cu–Ni fcc alloy nanoparticles (NPs) of tunable atomic ratios were generated in SiO₂ films. The films were prepared using the Cu(NO₃)₂ and Ni(NO₃)₂ co-doped inorganic–organic hybrid silica sols by single dipping. Transparent, crack-free, glassy SiO₂ films of 310 ± 10 nm in thickness embedded with high mol percent of Cu–Ni alloy NPs were yielded after annealing at 750 °C in 10% H₂-90% Ar atmosphere. Nominal compositions of the films were 20 mol% (Cu–Ni)-80 mol% SiO₂. Optical spectral study of the heat-treated films showed disappearance of Cu plasmon bands due to Cu–Ni alloy formation. Grazing incidence X-ray diffraction (GIXRD) studies revealed the formation of Cu–Ni alloy (2:1, 1:1 and 1:2) NPs inside the SiO₂ film. GIXRD showed a systematic shifting of the diffraction peaks with respect to the fcc Cu–Ni alloy composition, maintaining the nominal ratios. Transmission electron microscopy (TEM) studies of the representative Cu_0.5Ni_0.5-doped film showed existence of homogeneously dispersed Cu–Ni alloy NPs of average size 6.35 nm inside the SiO₂ matrix. The energy dispersive X-ray scattering (EDX) analysis of the individual NPs using the nano-probe (scanning TEM mode) confirmed the presence of both the Cu and Ni with the desired atomic ratio.     

Sonochemical synthesis and application of rhodium–graphene nanocomposite

Abstract  

Highly water dispersible rhodium–graphene nanocomposite have been successfully synthesized by the simple reduction of Rh³⁺ salt on poly(ethylene oxide)/poly(propylene oxide)/poly(ethylene oxide) (PEO/PPO/PEO) triblock copolymer or pluronic-stabilized graphene oxide (GO) nanosheets with borohydride. Rhodium nanoparticles, having average size of 1–3 nm, are homogeneously distributed through out the graphene sheets. Some porous structures of graphene sheets have also been observed after the reduction of pluronic-stabilized GO in the presence of metal ions. The material is very effective for hydrogenation of arenes, especially for benzene as the substrate material at the room temperature and 5 atm pressure of hydrogen.     

Information transfer using a single particle path-spin hybrid entangled state

The path-spin entangled state of a single spin-1/2 particle is considered which is generated by using a beam-spitter and a spin-flipper. Using this hybrid entanglement at the level of a single particle as a resource, we formulate a protocol for transferring of the state of an unknown qubit to a distant location. Our scheme is implemented by a sequence of unitary operations along with suitable spin-measurements, as well as by using classical communication between the two spatially separated parties. This protocol, thus, demonstrates the possibility of using intraparticle entanglement as a physical resource for performing information theoretic tasks.     

Potential Therapeutic Approach of Melatonin against Omicron and Some Other Variants of SARS-CoV-2

The Omicron variant (B.529) of COVID-19 caused disease outbreaks worldwide because of its contagious and diverse mutations. To reduce these outbreaks, therapeutic drugs and adjuvant vaccines have been applied for the treatment of the disease. However, these drugs have not shown high efficacy in reducing COVID-19 severity, and even antiviral drugs have not shown to be effective. Researchers thus continue to search for an effective adjuvant therapy with a combination of drugs or vaccines to treat COVID-19 disease. We were motivated to consider melatonin as a defensive agent against SARS-CoV-2 because of its various unique properties. Over 200 scientific publications have shown the significant effects of melatonin in treating diseases, with strong antioxidant, anti-inflammatory, and immunomodulatory effects. Melatonin has a high safety profile, but it needs further clinical trials and experiments for use as a therapeutic agent against the Omicron variant of COVID-19. It might immediately be able to prevent the development of severe symptoms caused by the coronavirus and can reduce the severity of the infection by improving immunity.     

Chemodosimetric Mechanistic Insight through Trapping Intermediate for Selective Detection of Picric Acid in Aqueous Medium by a Dinuclear CdII Complex

A fluorescent dinuclear cadmium(II) based discrete metal complex of composition [Cd^II₂L(μ-Cl)Cl₂]( 1 ) is used {HL=2,6-bis[2-(methylamino)ethyliminomethyl]-4-Ethylphenol} for the specific recognition of 2,4,6-trinitrophenol (picric acid; PA) via fluorescence quenching phenomenon among various nitroaromatic compounds through a chemodosimetric approach. It has been established that 1 is a chemodosimeter in pure water. We have successfully been able to isolate three compounds: chemodosimeter 1 ; an intermediate complex 2 of composition [Cd^II(LH₂)Cl₂](Picrate) and final association complex 3 of composition [NH₃(CH₂CH₂)NH₂CH₃](Picrate)₂. Compounds have been characterised by CHN elemental analyses, single crystal X-ray crystallography, PXRD, NMR and FTIR. Selective interaction of 1 with PA was evaluated by fluorescence, UV-Vis and life time measurements. Fluorescence quenching of 1 occurs definitely due to the formation of compound 3 via intermediate 2 involving partial decomplexation, hydrolysis and proton transfer phenomena in solution during the course of sensing. The quenching constant (K_sv), association constant (K_a) and detection limit (LOD) of the complex 1 for picric acid are ∼1.55×10⁵ M⁻¹, ∼1.8×10¹⁰ M⁻² and ∼0.47 μM (0.108 ppm), respectively. Mechanism of sensing is proposed and the very rare case of isolation and characterization of intermediate in picric acid sensing is discussed.