A molecular docking and dynamics study to screen phytochemicals that target mutant thymidine phosphorylase for colon cancer therapy

Thymidine phosphorylase (TYPH) is an enzyme involved in pyrimidine catabolism and its mutation is associated with chemoresistance of colon cancer to 5-fluorouracil (5-FU) treatment. Here we have analysed the most destabilized mutation of TYPH protein at glycosyltransferase domain where isoleucine alter to alanine at position 214(I214A) that linked to the onset of colon cancer. This study aims to conduct virtual screening of phytochemicals to find novel compounds against mutated TYPH protein. The in silico study aimed to predict the physicochemical properties of phytochemicals and their binding performance with mutated TYPH compared to 5-FU. From the screened phytochemicals, berbamine showed the best binding affinity (?7.2 kcal/mol) with mutant TYPH protein as compared to 5-FU. For further confirmations, the dynamics properties of native, mutant, and docked complex of I214A mutant with berbamine systems were studied through molecular dynamics simulations with a trajectory of 100ns. From root mean square fluctuation, radius of gyration, number of hydrogen bonds, principal component analysis, and free energy landscape, we predicted that the I214A mutant lost its compactness, however, on complex formation with berbamine it gained its compactness. MM/PBSA and molecular docking studies confirmed that berbamine could show potential inhibitory effects against the mutant model of TYPH. Our finding may open the door for its experimental validation and may take as a potential therapeutic against colon cancer treatment in near future.     

Thermal, structural, magnetic and photoluminescence studies on cobalt ferrite nanoparticles obtained by citrate precursor method

Magnetic nanoparticles of cobalt ferrite have been synthesized by citrate precursor method. TG-DSC studies have been made to get the idea of the optimum temperature of annealing that could lead to the formation of nanoparticles. Annealing the citrate precursor was done at 450, 650, and 973?°C. The X-ray diffraction (XRD) studies and the scanning electron microscopy (SEM) have been used for characterization. The data from vibrating sample magnetometer and photoluminescence spectrometer (PL) have been analyzed for exploring their applications. Using the Scherrer formula, the crystallite size was found to be 25, 32, and 43?nm, respectively, using the three temperatures. The particle size increased with annealing temperature. Rietveld refinements on the X-ray (XRD) data were done on the cobalt ferrite nanoparticles (monoclinic cells) obtained on annealing at 650?°C, selecting the space group P2/M. The values of coercivity (1574.4?G) and retentivity (18.705?emu g^?1) were found out in the sample annealed at 650?°C while magnetization (39.032?emu g^?1) was also found in the sample annealed at 973?°C. The photoluminescence (PL) property of these samples were studied using 225, 330, and 350?nm excitation wavelength radiation source. The PL intensity was found to be increasing with the particle size.     

Free Radical Initiated Polymerization of N-[4-N′ -{(4-chlorophenyl) amino-carbonyl} phenyl] Maleimide and Characterization of Homopolymer and Copolymers with MMA

N-[4-N′ -{(4-chlorophenyl) amino-carbonyl} phenyl] maleimide (N-CPACPMI) was prepared. It was homopolymerized and copolymerized with methyl methacrylate (MMA) in order to study the effect of imide ring in polymer backbone. The copolymer composition was determined by nitrogen element analysis. The monomer reactivity ratio was determined by the Fineman-Ross method. The molecular weight was determined by GPC. The thermal behavior was studied by thermogravimetric analysis. The initial decomposition temperature of polymers were in the 255 to 299°C range.     

Polytypic transformations during the thermal decomposition of cobalt hydroxide and cobalt hydroxynitrate

The isothermal decomposition of cobalt hydroxide and cobalt hydroxynitrate at different intervals of temperature leads to the formation of Co₃O₄. The phase evolution during the decomposition process was monitored using powder X-ray diffraction. The transformation of cobalt hydroxide to cobalt oxide occurs via three phase mixture while cobalt hydroxynitrate to cobalt oxide occurs through a two phase mixture. The nature of the sample and its preparation method controls the decomposition mechanism. The comparison of topotactical relationship between the precursors to the decomposed product has been reported in relation to polytypism.     

Photodissolution of ferrihydrite in the presence of oxalic acid: an in situ ATR-FTIR/DFT study

The photodissolution of the iron oxyhydroxide, ferrihydrite, in the presence of oxalic acid was investigated with vibrational spectroscopy, density functional theory (DFT) calculations, and batch geochemical techniques that determined the composition of the solution phase during the dissolution process. Specifically, in situ attenuated total reflection Fourier transform infrared spectroscopy (ATR- FTIR) was used to determine the structure of the adsorbed layer during the dissolution process at a solution pH of 4.5. DFT based computations were used to interpret the vibrational data associated with the surface monolayer in order to help determine the structure of the adsorbed complexes. Results showed that at pH 4.5, oxalate adsorbed on ferrihydrite adopted a mononuclear bidentate (MNBD) binding geometry. Photodissolution at pH 4.5 exhibited an induction period where the rate of Fe(II) release was limited by a low concentration of adsorbed oxalate due to the site-blocking of carbonate that was intrinsic to the surface of the ferrihydrite starting material. Oxalate displaced this initial carbonate over time, and the dissolution rate showed a corresponding increase. Irradiation of oxalate/ferrihydrite at pH 4.5 also ultimately led to the appearance of carbonate reaction product (distinct from carbonate intrinsic to the starting material) on the surface.     

Boron Atoms as Spin Carriers in Two‐ and Three‐Dimensional Systems

To “B” or not to “B” : The unusual bonding of boron in organoboranes or oligoboron clusters is not only apparent in diamagnetic molecules but also in paramagnetic systems, including mixed‐valent species and oligoborane/carborane cluster radicals. The picture shows the singly occupied molecular orbital of the radical ion [C₄B₈R₄H₈]^.?, determined by DFT calculations.