Importance of cytochromes in cyclization reactions: Quantum chemical study on a model reaction of proguanil to cycloguanil

Proguanil, an anti‐malarial prodrug, undergoes cytochrome P450 catalyzed biotransformation to the pharmacologically active triazine metabolite (cycloguanil), which inhibits plasmodial dihydrofolate reductase. This cyclization is catalyzed by CYP2C19 and many anti‐malarial lead compounds are being designed and synthesized to exploit this pathway. Quantum chemical calculations were performed using the model species (Cpd I for active species of cytochrome and N4‐isopropyl‐N6‐methylbiguanide for proguanil) to elucidate the mechanism of the cyclization pathway. The overall reaction involves the loss of a water molecule, and is exothermic by approximately 55 kcal/mol, and involves a barrier of approximately 17 kcal/mol. The plausible reaction pathway involves the initial H‐radical abstraction from the isopropyl group by Cpd I, followed by two alternative paths‐ (i) oxygen rebound to provide hydroxyl derivative and (ii) loss of additional H‐radical to yield 1,3,5‐triazatriene, which undergoes cyclization. This study helped in understanding the role of the active species of cytochromes in this important cyclization reaction. © 2014 Wiley Periodicals, Inc.     

Reverse saturable absorption in nano colloidal Ge28Sb12Se60 chalcogenide glass

We report the preparation and investigation of nano colloidal solutions of Ge₂₈Sb₁₂Se₆₀ chalcogenide glass based on nonlinear optical transmission by the open-aperture Z-scan technique, using nanosecond laser pulses, at the excitation wavelengths of 532 nm. The Z scan spectra reveal a strong non linear absorption (reverse saturable absorption) for the nano colloid Ge₂₈Se₆₀Sb₁₂ solutions. Observation of optical limiting at excitation wavelength suggests the potential of these materials to be used as optical limiters.     

Electronic structure and conformational analysis of P218: An antimalarial drug candidate

P218 is one of the very important and recent lead compounds for antimalarial research. The 3D structural and electronic details of P218 are not available. In this article, quantum chemical studies to understand the possible 3D structures of P218 are reported and compared with 3D structures from the active site cavities of hDHFR and PfDHFR. The neutral P218, can adopt open chain as well as cyclic arrangements. Under implicit solvent condition a zwitterionic‐cyclic conformer is found to be quite possible. Microsolvation studies using explicit water molecules indicate that one water molecule may bridge the two ends of zwitterionic‐cyclic P218. It was observed that the protonation occurs preferentially at N¹ position of the 2,4‐diaminopyrimidine ring, with a proton affinity of 274.49 kcal/mol (implicit solvent phase) and 236.35 kcal/mol (gas phase). A dimer of P218 may be zwitterionic dimer, the dimer formation can release upto ～28.60 kcal/mol (implicit solvent phase).     

LiFe5O8 prepared by sol–gel synthesis: microstructural and morphological effects by organic and inorganic templates

Lithium ferrite was prepared using a sol–gel growth process using different fuels and inorganic templates. The aim of this study is to evaluate the influence of inorganic template agent like KCl, KBr and KI as well as the effect of different fuels like urea, glycine and citric acid on the morphology change of lithium ferrite. The structure, morphology and magnetic properties of the ferrite were investigated using powder X-ray diffraction (XRD), Infrared red spectroscopy and vibrating sample magnetometer. Thermal decomposition studies reveal the formation of lithium ferrite at a low temperature ~440 °C. Powder XRD pattern has shown the formation of a single α-phase lithium ferrite except the sample with inorganic template KBr, in which the presence of hematite as a secondary phase was observed. Scanning electron microscopy studies show that the structural morphology is highly sensitive to the inorganic template as well as on the fuel. The rod shaped nanoparticles are observed with the inorganic template KCl and KBr. The decrease in grain size is observed for LiFe₅O₈/glycine as compared to LiFe₅O₈/citric acid and flake shaped dense particles are observed for LiFe₅O₈/urea. The magnetic properties of the ferrite have also been investigated.     

Photoinduced changes in optical properties of Ga-Sb-Ge-Se glasses

The kinetics of photoinduced effects on Ga₅Sb₁₀Ge₂₅Se₆₀ thin film exposed to continuous wave laser radiations are studied as a function of exposure time and laser intensity. The transmission and reflection spectra of thin films before and after exposure are investigated. The optical band gap and the refractive index are derived from the above spectra. Generalized Miller's rule and linear refractive index are used to find the nonlinear susceptibility and nonlinear refractive index of the thin films. The studies show a red shift in the band gap with increase in exposure time and laser power which is attributed to the photoinduced darkening in the films.