Regio- and stereoselective synthesis of spiro-pyrrolidine/pyrrolizidine/thiazolidine-grafted macrocycles through intramolecular 1,3-dipolar cycloaddition reaction

Regioselective synthesis of spiropyrrolidine-grafted 11-membered macrocycle was accomplished through an intramolecular [3+2] cycloaddition of azomethine ylides. The key precursor alkenyl diketone (4a–b) was obtained from simple starting materials. The dipole generated from isatin tethered to O-alkyl enone (4a–b) was reacted intramolecularly to yield the spiropyrrolidine-grafted macrocycles (6a–b). The structures of the cycloadducts were assigned by 2D NMR and confirmed by single crystal analysis.     

Nickel and Tungsten Bimetallic Nanoparticles Modified Pencil Graphite Electrode: A High-performance Electrochemical Sensor for Detection of Endocrine Disruptor Bisphenol A

In this work, an economically viable, very low cost, indigenous, ubiquitously available electrochemical sensor based on bimetallic nickel and tungsten nanoparticles modified pencil graphite electrode (NiNP-WNP@PGE) was fabricated for the sensitive and selective detection of bisphenol A (BPA). The NiNP-WNP@PGE sensor was prepared by a facile electrochemical one step co-deposition method. The prepared nanocomposite was morphologically characterized by scanning electron microscopy (SEM), energy dispersive X-ray (EDX), X-ray diffraction (XRD), electrochemically by cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS). The proposed sensor displayed high electrocatalytic activity towards electro-oxidation of BPA with one irreversible peak. The fabricated sensor displayed a wide detection window between 0.025 μM and 250 μM with a limit of detection of 0.012 μM. PGE sensor was successfully engaged for the detection of BPA in bottled water, biological, and baby glass samples.     

Development of Pen-type Portable Electrochemical Sensor Based on Au-W Bimetallic Nanoparticles Decorated Graphene-chitosan Nanocomposite Film for the Detection of Nitrite in Water,Milk and Fruit Juices

The development and fabrication of a simple, portable, and sensitive detection tool to precisely monitor nitrite level is of growing importance in electrochemistry research, given the strong interest in the protection of drinking water quality, treatment of wastewater, food production, and control of remediation processes. This work describes the fabrication of a simple, cost-effective, pen-type electrochemical sensor based on bimetallic gold and tungsten nanoparticles electrochemically decorated on graphene-chitosan modified pencil graphite electrode (PGE) for the trace detection of nitrite in real samples. The prepared nanocomposite was characterized using XRD, SEM, and EDS. The electrochemical behavior of the sensor was evaluated by cyclic voltammetry (CV) and impedance electrochemical spectroscopy (EIS). Results revealed that the proposed sensor displayed excellent electrocatalytic activity towards electro-oxidation of nitrite with an irreversible redox reaction. The AuNPs-WNPs@Gr-Chi/PGE sensor exhibited excellent analytical performance with a wide linear range from 10 to 250 μM towards nitrite. The LOD and LOQ were calculated to be 0.12 μM and 0.44 μM, respectively. The designed electrochemical sensor was successfully applied for the detection of nitrite in water, milk, and natural fruit juice samples.     

Design,synthesis, molecular docking,and spectral studies of new class of carbazolyl polyhydroquinoline derivatives as promising antibacterial agents with noncytotoxicity towards human mononuclear cells from peripheral blood

In the present study, we report the design and eco-benign synthesis of new class of carbazolyl-1,4-dihydropyridine (1,4-CDHP) and carbazolyl-1,8-dioxodecahydroacridine (CAD) derivatives via a three-component coupling reaction of substituted carbazole aldehydes, ethyl acetoacetate/dimedone, and ammonium acetate under solvent-free conditions at 112°C to 115°C. We also report an efficient one-pot synthesis of new class of carbazolyl polyhydroquinoline (CPQ) derivatives via a four-component coupling reaction of substituted ethyl acetoacetate, dimedone, ammonium acetate, and carbazole aldehydes in acetonitrile/water medium (3:1) at 73°C to 75°C in moderate yields. All the products were thoroughly characterized by ¹H NMR, ¹³C NMR, Fourier transform infrared (FTIR), mass spectral, and CHN analysis. The synthesized heterocyclic compounds were evaluated for their in vitro antibacterial activity against pathogenic strains of both Gram-negative and Gram-positive bacteria. Minimum inhibitory concentration (MIC) of the active compounds was evaluated by macrodilution method. The CPQ derivative ( 8a ) displayed superior antibacterial activity against Escherichia coli, Pseudomonas aeruginosa, and Salmonella typhi with the MIC values of 16.0 to 32.0 μg/mL in comparison with the reference drug. The mechanism of antibacterial action of the CPQ derivatives was investigated via scanning electron microscope (SEM) studies. The molecular docking studies indicate that the CPQ derivative ( 8a ) binds to the cell wall protein of E coli and P aeruginosa by formation of hydrogen bonds with amino acid residues (TYR328 and GLU249) of the bacterial cell wall protein. The 1,4-CDHP, CAD, and CPQ derivatives were either noncytotoxic or exhibited minimal cytotoxicity towards human mononuclear cells from peripheral blood. All the products were evaluated for Lipinski rule of five (RO5) and were found to have good oral bioavailability.     

Mobility of a single alkali metal atom on fullerene C60: first principles molecular dynamical study

The dynamical behavior of a single K or Na alkali metal atom on the surface of a C(60) molecule is investigated via Car-Parrinello molecular dynamics simulations in a temperature range up to 300 K. These provide direct evidence for the heteroatom motion, postulated earlier in pioneering experiments, and show that an alkali metal atom can move both on the surface and radially outward from the surface, resulting in a dynamics ranging from diffusive to free orbital motion, on time-scales of up to a few picoseconds.     

Synthesis of a New Class of Sulfonamido Bis Heterocycles—Pyrrolyl/Pyrazolyl‐1,3,4‐oxadiazoles, 1,3,4‐Thiadiazoles,and 1,2,4‐Triazoles

A new class of sulfonamido bis heterocycles—pyrrolyl/pyrazolyl‐oxadiazoles, thiadiazoles, and triazoles—were prepared from arylaminosulfonylacetic acid hydrazide and E‐aroylethenesulfonylacetic acid adopting simple and versatile synthetic methodologies.     

3′-Hydroxy-4-methoxychalcone as a potential antibacterial coating on polymeric biomaterials

Antimicrobial property of chalcone coated high density polyethylene (HDPE), low density polyethylene (LDPE), polypropylene (PP) and polyurethane (PU) against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa is reported here. The presence of chalcone on the surface was confirmed from fourier transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS). Bacterial adhesion decreased considerably on all the coated surfaces. Bacterial adhesion was highest on PU surface (most hydrophobic) and lowest on HDPE (most hydrophilic) surface. Chalcone seems to damage the membrane of the bacteria as well as exhibit slimicidal activity. Reasonably good correlation was observed between the CFU (Colony Forming Units) ratio (it is defined as the ratio of CFU on coated surface to the chalcone uncoated surface) at the 24th hour against both hydrophobicity of the microorganism and roughness of the coated polymeric surfaces. Increasing roughness of the polymer and hydrophobicity of the microorganisms were positively and negatively correlated respectively with CFU ratio. Hence, the chalcone coated polymers can be used in the development of newer biomaterials.     

The charge-transfer properties of the S2 state of fucoxanthin in solution and in fucoxanthin chlorophyll-a/c2 protein (FCP) based on stark spectroscopy and molecular-orbital theory

Fucoxanthin chlorophyll-a/c 2 protein (FCP), the membrane-intrinsic light harvesting complex from the diatom Cyclotella meneghiniana, is characterized by Stark spectroscopy to obtain a quantitative measure of the excited-state dipolar properties of the constituent pigments. The electro-optical properties of the carotenoid fucoxanthin (Fx), the primary light harvester in FCP, were determined from the Stark spectrum measured in a MeTHF glass (77 K) and compared to the results from electronic-structure calculations. On photon absorption by Fx, a 17 D change in the static dipole moment (|Delta mu|exp), and a somewhat larger |Delta mu|exp at the red edge, are measured for the S 0 --> S 2 (1 (1)A g (-)-like -->1 (1)B u *+-like) transition. The large change in dipole moment indicates that Fx undergoes photoinduced charge transfer (CT), and underscores the influence of the S 2 state on the polarity-dependent excited-state dynamics of Fx that has so far been attributed to, and discussed in terms of, the S 0 and the S 1/ICT states. MNDO-PSDCI and SACCI-CISD calculations indicate that the 1 (1)B u (*+)-like state intrinsically possesses a dipole moment much smaller than the 2 (1)A g (*-)-like state, suggesting that solvent fields promote the mixing of these two states and could account for the large dipole moments measured here for the S 0 --> S 2 transition. These CT properties of the 1 (1)B u (*+)-like state of Fx are further enhanced in the protein and underpin its photosynthetic capabilities for light harvesting and energy transfer (ET). In FCP, the CT properties of the Fx's vary according to the energetic position: between 450 and 500 nm there appear to be two sets of Fx's that exhibit |Delta mu| exp values on the order of 5 and 15 D, whereas the red-most Fx's, that are very efficient in ET to chlorophyll-a (Chl-a), exhibit strikingly large |Delta mu| exp values on the order of 40 D. Such magnitudes of |Delta mu| exp suggest a mechanism that enhances Coulombic coupling to promote ET from the S 2 state of Fx to Chl-a. These three sets of Fx's, including a fourth red Fx, are identified by fitting the Stark spectrum of FCP with the Stark spectrum of Fx in MeTHF. In contrast to the Fx's in the protein, the electrostatic properties of the Chl's in FCP are comparatively much smaller. Notably, for the Q y band of Chl-a, a |Delta mu| exp of 0.92 D and a change in polarizability ( Delta alpha exp) of 20 A (3), indicate that the Chl-a's are monomeric in nature and decoupled from each other.     

Additional synthesis on thiophene-containing trisubstituted methanes (TRSMs) as inhibitors of M. tuberculosis and 3D-QSAR studies

Abstract

We earlier reported thiophene-containing trisubstituted methanes (TRSMs) as novel cores carrying anti-tubercular activity, and identified S006-830 as the phenotypic lead with potent bactericidal activity against single- and multi-drug resistant clinical isolates of Mycobacterium tuberculosis (M. tb). In this work, we carried out additional synthesis of several TRSMs. The reaction scheme essentially followed the Grignard reaction and Friedel–Crafts alkylation, followed by insertion of a dialkylaminoethyl chain. We also performed microbiological evaluations including in vitro screening against the virulent strain M. tb H37Rv, cytotoxicity assessment in the Vero C-1008 cell line, and 3D-QSAR studies with comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA). CoMFA and CoMSIA models yielded good statistical results in terms of q² and r² values, suggesting the validity of the models. It was concluded that a para-substituted benzene ring with bulkier electron-donating groups and aminoalkyl chains are required for higher inhibitory capacity against M. tuberculosis. We believe that these insights will rationally guide the design of newer, optimal, TRSMs.