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).     

A simple one pot synthesis of novel tricyclic quinazolinones

Synthesis of a series of tricyclic quinazolinones have been accomplished starting from anthranilamide and 1,3-cyclic dione promoted by TsOH·H₂O The protocol presented herein based on retro-Dieckmann type reaction, leading to incorporation of dione as an acyclic unit into the product. Simple reaction conditions, broad scope, excellent yields are the advantages of this protocol. Further, this methodology is extended to the synthesis of pyridopyrimidinones and benzimidazopyridines.     

Influence of spin-polarized current on superconductivity and the realization of large magnetoresistance

The superconducting state can be influenced by injecting spin-polarized current in a controlled manner by properly tailoring the interfacial transmittivity between a ferromagnet (F) and a superconductor (S), resulting in a large magnetoresistance of over 1100% for a F/I/S/I/F multilayer system (I insulator). Because of the competition between ferromagnetism and superconductivity, the superconducting transition temperature (T(C)) in the spin-parallel configuration is shifted below that in the spin antiparallel configuration. The T(C) shift is attributed to ferromagnet-induced nonequilibrium spin carriers in the superconductors.     

Divalent N(I) compounds with two lone pairs on nitrogen

Carbon with the C(0) state has been reported recently, examples of which were known for the past decades. Silicon in the Si(0) state and phosphorus in the P(I) state are also known experimentally. This prompted us to search for divalent N(I) compounds, which resulted in the identification of ::N(←L)(2)(⊕) systems with bicoordinated nitrogen in the N(I) formal oxidation state. It was found that several biguanide derivatives (especially in their protonated state) belong to this class. Quantum chemical analysis provided the structural details, molecular orbitals, charge localization (vs delocalization) trends, etc. This class of compounds has been found to be characterized by two lone pairs on the central nitrogen, very similar to the central carbon in divalent C(0) compounds (::C(←L)(2)). The new bonding environment for nitrogen reported in this article, divalent nitrogen N(I), is clearly different from the nitrenium ions NR(2)(⊕). The electronic structure and reactivity of representative examples of this novel class of divalent nitrogen N(I) systems (::N(←L)(2)(⊕)) have been analyzed in detail, in terms of molecular orbitals, atomic charges, protonation energies, complexation energies with Lewis acids like BH(3), AlCl(3), and AuCl and compared with those of divalent C(0) systems.     

TiO2 derived by titanate route from electrospun nanostructures for high-performance dye-sensitized solar cells

We report the use of highly porous, dense, and anisotropic TiO(2) derived from electrospun TiO(2)-SiO(2) nanostructures through titanate route in dye-sensitized solar cells. The titanate-derived TiO(2) of high surface areas exhibited superior photovoltaic parameters (efficiency > 7%) in comparison to the respective electrospun TiO(2) nanomaterials and commercially available P-25.     

Conformational polymorphism in bicalutamide: a quantum chemical study

Bicalutamide is an anti-neoplastic drug widely used for the treatment of prostate cancer and it exhibits conformational polymorphism. Three crystal structures of bicalutamide are reported as racemic mixtures, two of which are polymorphs. In addition, three co-crystals are also reported—two with organic coformers and one with adrenoreceptor (the macromolecular target). All the reported structures show significant conformational differences. Quantum chemical B3LYP/6-31+G(d,p) analysis has been carried out to understand the interplay of intra- and intermolecular interactions leading to the conformational preferences in this molecule. The difference between the two polymorphic forms has been traced to the C5–S8–C11–C12 torsional angle. Inside the cavity of androgen receptor, a completely different conformation is found but it does not correspond to any local minima on the potential energy surface of the drug. A relatively rigid torsional angle C11–C12–C15–N17 is also expected due to a strong five-membered ring intramolecular hydrogen bond (H–O13–C12–C15–O16), which has been reported to be desirable; quantum chemical analysis revealed that this rigidity is of the order of 11 kcal/mol. Ab initio calculations demonstrate that polymorphs and polymorphic co-crystals differ in the extent of intra- and intermolecular hydrogen bonding interactions. The strength of the intermolecular interactions associated with these structures is analyzed in terms of energy release due to dimerization.     

Substrate temperature influenced physical properties of silicon MOS devices with TiO2 gate dielectric

DC reactive magnetron sputtering technique was employed for deposition of titanium dioxide (TiO₂) films. The films were formed on Corning glass and p‐Si (100) substrates by sputtering of titanium target in an oxygen partial pressure of 6×10^?2 Pa and at different substrate temperatures in the range 303 – 673 K. The films formed at 303 K were X‐ray amorphous whereas those deposited at substrate temperatures ≥ 473 K were transformed into polycrystalline nature with anatase phase of TiO₂. Fourier transform infrared spectroscopic studies confirmed the presence of characteristic bonding configuration of TiO₂. The surface morphology of the films was significantly influenced by the substrate temperature. MOS capacitor with Al/TiO₂/p‐Si sandwich structure was fabricated and performed current–voltage and capacitance–voltage characteristics. At an applied gate voltage of 1.5 V, the leakage current density of the device decreased from 1.8 × 10^?6 to 5.4 × 10^?8 A/cm² with the increase of substrate temperature from 303 to 673 K. The electrical conduction in the MOS structure was more predominant with Schottky emission and Fowler‐Nordheim conduction. The dielectric constant (at 1 MHz) of the films increased from 6 to 20 with increase of substrate temperature. The optical band gap of the films increased from 3.50 to 3.56 eV and refractive index from 2.20 to 2.37 with the increase of substrate temperature from 303 to 673 K. Copyright © 2012 John Wiley & Sons, Ltd.     

Chronic NMDA administration to rats increases brain pro-apoptotic factors while decreasing anti-Apoptotic factors and causes cell death

Background  

Chronic N-Methyl-D-aspartate (NMDA) administration to rats is reported to increase arachidonic acid signaling and upregulate neuroinflammatory markers in rat brain. These changes may damage brain cells. In this study, we determined if chronic NMDA administration (25 mg/kg i.p., 21 days) to rats would alter expression of pro- and anti-apoptotic factors in frontal cortex, compared with vehicle control.     

Real‐time homonuclear broadband and band‐selective decoupled pure‐shift ROESY

Unambiguous spectral assignments in ¹H solution‐state NMR are central, for accurate structural elucidation of complex molecules, which is often hampered by signal overlap, primarily because of scalar coupling multiplets, even at typical high magnetic fields. The recent advances in homodecoupling methods have shown powerful means of achieving high resolution pure‐shift ¹H spectra in 1D and also in 2D J‐correlated experiments, by effectively collapsing the multiplet structures. The present work extends these decoupling strategies to through‐space correlation experiments as well and describes two new pure‐shift ROESY pulse schemes with homodecoupling during acquisition, viz., homodecoupled broadband (HOBB)‐ROESY and homodecoupled band‐selective (HOBS)‐ROESY. Furthermore, the ROESY blocks suppress the undesired interferences of TOCSY cross peaks and other offsets. Despite the reduced signal sensitivity and prolonged experimental times, the HOBB‐ROESY is particularly useful for molecules that exhibit an extensive scalar coupling network spread over the entire ¹H chemical shift range, such as natural/synthetic organic molecules. On the other hand, the HOBS‐ROESY is useful for molecules that exhibit well‐separated chemical shift regions such as peptides (NH, Hα and side‐chain protons). The HOBS‐ROESY sensitivities are comparable with the conventional ROESY, thereby saves the experimental time significantly. The power of these pure‐shift ROESY sequences is demonstrated for two different organic molecules, wherein complex conventional ROE cross peaks are greatly simplified with high resolution and sensitivity. The enhanced resolution allows deriving possibly more numbers of ROEs with better accuracy, thereby facilitating superior means of structural characterization of medium‐size molecules. Copyright © 2014 John Wiley & Sons, Ltd.     

Preparation and structural studies of metal(II)-1,3,8,10,15,17,22,24- octanitrophthalocyanines

Summary An efficient method for preparing pure 1,3,8,10,15,17,22,24-octanitrophthalocyanine derivatives of copper(II) (CuPON), cobalt(II) (CoPON) and nickel(II) (NiPON) has been developed. Elemental analysis, electronic spectra, i.r. spectra, magnetic susceptibility measurements, thermogravimetry and powder X-ray diffraction studies were done in order to check the purity, structural integrity, thermal stability and crystallinity of these complexes. Susceptibility measurements showed a variation in the magnetic moments of the complexes with magnetic field strength, indicating the presence of intermolecular cooperative effects.