Synthesis and Characterization of the Adducts of Bis(<Emphasis Type="Italic">O</Emphasis>-butyldithiocarbonato)nickel(II) with Substituted Heterocyclic Amines and X-ray Structure of Bis(<Emphasis Type="Italic">O</Emphasis>-butyldithiocarbonato)bis(4-cyanopyridine)nickel(II)

Abstract  

We report the synthesis and study of a new series of the adducts of Bis(O-butyldithiocarbonato)nickel(II) with substituted heterocyclic amines such as amino and cyanopyridines. Analytical results show that the adducts have 1:2 stoichiometry with general formula M(Xan)₂ L ₂ (M = Ni(II), Xan = O-butyldithiocarbonate, L = 2-, 3- and 4-aminopyridines, 3- and 4-cyanopyridines). The complexes have been characterized by analytical, magnetic susceptibility measurements, molar conductivity measurements, IR, electronic spectral data and X-ray diffraction analysis. One of the adducts, bis(O-butyldithiocarbonato)bis(4-cyanopyridine)nickel(II), crystallizes in the monoclinic space group P2₁/c with unit cell parameters : a = 12.546(4), b = 11.495(3), c = 9.351(3) ?, β = 102.73(3)o, Z = 2. Crystal structure was solved by direct methods and refined by full matrix least squares procedures to a final R-value of 0.0299 for 2,788 observed reflections. The packing of layers of molecules is stabilized by weak C–H···N and C–H···π hydrogen bonds.     

LC‐MS/MS‐ESI method for simultaneous quantitation of metformin and repaglinidie in rat plasma and its application to pharmacokinetic study in rats

A highly sensitive and specific LC‐MS/MS‐ESI method has been developed for simultaneous quantification of metformin (MFN) and repaglinide (RGN) in rat plasma (50 μL) using phenacetin as an internal standard (IS). Simple protein precipitation was used to extract MFN and RGN from rat plasma. The chromatographic resolution of MFN, RGN and IS was achieved with a mobile phase consisting of 0.2% formic acid in water–acetonitrile (1:1, v/v) with a time program flow gradient on a Chromolith RP‐18e column. The total chromatographic run time was 3.5 min and the elution of MFN, RGN and IS occurred at 1.64, 2.21 and 2.15 min, respectively. A linear response function was established for the range of concentrations 0.855–394 and 0.021–21.7 ng/mL for MFN and RGN, respectively. The intra‐ and inter‐day precision values for MFN and RGN met the acceptance as per FDA guidelines. MFN and RGN were stable in battery of stability studies viz., bench‐top, auto‐sampler and freeze–thaw cycles. The developed assay was applied to a pharmacokinetic study in rats. Copyright © 2012 John Wiley & Sons, Ltd.     

Force prediction equation using distorted model as an analog device

The force versus speed response of a distorted model of a soil-engaging tool operating in a soil and at a depth where the performance evaluation of the prototype is required to be determined, is used to compute analog values. A prediction equation relating draft force with tool width, depth of cut, soil specific weight, tool velocity and analog values has been developed. A comparison between the forces predicted by the equation and that measured on flat rectangular blades and angled tools operating at a speed of 2–8.5 km/hr is presented. The closeness in prediction accuracies points that the distorted model itself can be used as a fairly good analog device.     

Diffusion of Au and Cu in amorphous Fe80B20 and Fe82B18 alloys

Diffusion rates (D) of Au in two amorphous alloys, Fe₈₀B₂₀ and Fe₈₂B₁₈, and of Cu in amorphous Fe₈₂B₁₈ alloy were measured in the temperature range 546–645 K by using the technique of Rutherford backscattering spectrometry (RBS) and Auger electron spectroscopy (AES), respectively. The diffusion of Au was found to be 3 to 6 times faster in Fe₈₀B₂₀ than in Fe₈₂B₁₈, though both the alloys had almost similar crystallization temperatures. The observed differences in the diffusion rates corroborate the fact that Fe₈₀B₂₀ has a more open structure than Fe₈₂B₁₈ as revealed from the reported values of the metal packing fractions of these two alloys. Also, the diffusivities of smaller sized Cu atoms (radius: 0.128 nm) were found to be higher by more than an order of magnitude than those of larger sized Au atoms (radius: 0.146 nm), suggesting a dependence ofD on the size of the diffusing species.     

Synthesis and Infrared Spectral Study of Neodymium Furfuroxides and Tetrahydrofurfuroxides

Nd(OR')₃, Nd(OR)(OR')₂ and Nd(OR)₂(OR') are prepared from neodymium isopropoxide and furfurylalcohol and tetrahydrofurfuryl alcohol in different stoichiometric ratios under reflux where OR=OPrⁱ or OBu'; OR'=deprotonated furfuryl and tetrahydrofurfuryl alcohol. Neodymium tertiary butoxide derivatives were prepared by alcohol exchange technique from the corresponding isopropoxide derivatives. The i.r. spectra of the alkoxy derivatives are discussed.     

N-Substituted Amido Derivatives of Lanthanides

The synthesis of lanthanide amido complexes of the type Ln(CH₃CONR)₃ (I), (OPrⁱ)Ln(C₆H₅CONC₆H₅)₂ (II), and (OBu^t)Ln(C₆H₅CONC₆H₅)₂ (III) [where Ln = La, Pr, Nd; R = C₆H₅, p-NO₂C₆H₄, p-BrC₆H₄] are described. Infrared spectra indicate deprotonation of the secondary amide (anilide). Anion coordination is proposed as chelating bidenate ligands.     

Integration-mediated prediction enrichment of quantitative model for Hsp90 inhibitors as anti-cancer agents: 3D-QSAR study

The present study describes a systematic 3D-QSAR study consisting of pharmacophore modeling, docking, and integration of ligand-based and structure-based drug design approaches, applied on a dataset of 72 Hsp90 inhibitors as anti-cancer agents. The best pharmacophore model, with one H-bond donor (HBD), one H-bond acceptor (HBA), one hydrophobic_aromatic (Hy_Ar), and two hydrophobic_aliphatic (Hy_Al) features, was developed using the Catalyst/HypoGen algorithm on a training set of 35 compounds. The model was further validated using test set, external set, Fisher’s randomization method, and ability of the pharmacophoric features to complement the active site amino acids. Docking analysis was performed using Hsp90 chaperone (PDB-Id: 1uyf) along with water molecules reported to be crucial for binding and catalysis (Sgobba et al. ChemMedChem 4:1399–1409, 2009). Furthermore, an integration of the ligand-based as well as structure-based drug design approaches was done leading to the integrated model, which was found to be superior over the best pharmacophore model in terms of its predictive ability on internal [integrated model 2: R _(train) = 0.954, R _(test) = 0.888; Hypo-01: R _(train) = 0.912 and R _(test) = 0.819] as well as on external data set [integrated model 2: R _(ext.set) = 0.801; Hypo-01: R _(ext.set) = 0.604].     

Profiling the structural determinants for the selectivity of representative factor-Xa and thrombin inhibitors using combined ligand-based and structure-based approaches

The current study deciphers the combined ligand- and structure-based computational insights to profile structural determinants for the selectivity of representative diverse classes of FXa-selective and thrombin-selective as well as dual FXa-thrombin high affinity inhibitors. The thrombin-exclusive insertion 60-loop (D-pocket) was observed to be one of the most notable recognition sites for the known thrombin-selective inhibitors. Based on the topological comparison of four common active-site pockets (S1-S4) of FXa and thrombin, the greater structural disparity was observed in the S4-pocket, which was more symmetrical (U-shaped) in FXa as compared to thrombin mainly due to the presence of L99 and I174 residues in latter in place of Y99 and F174 respectively in former protease. The S2 pocket forming partial roof at the entry of 12 ? deep S1-pocket, with two extended β-sheets running antiparallel to each other by undergoing U-turn (～180?), has two conserved glycine residues forming H-bonds with the bound ligand for governing ligand binding affinity. The docking, scoring, and binding pose comparison of the representative high-affinity and selective inhibitors into the active sites of FXa and thrombin revealed critical residues (S214, Y99, W60D) mediating selectivity through direct- and long-range electrostatic interactions. Interestingly, most of the thrombin-selective inhibitors attained S-shaped conformation in thrombin, while FXa-selective inhibitors attained L-shaped conformations in FXa. The role of residue at 99th position of FXa and thrombin toward governing protease selectivity was further substantiated using molecular dynamics simulations on the wild-type and mutated Y99L FXa bound to thrombin-selective inhibitor 2. Furthermore, predictive CoMFA (FXa q2 = 0.814; thrombin q2 = 0.667) and CoMSIA (FXa q2 = 0.807; thrombin q2 = 0.624) models were developed and validated (FXa r2(test) = 0.823; thrombin r(2)(test) = 0.816) to feature molecular determinants of ligand binding affinity using the docking-based conformational alignments (DBCA) of 141 (88(train)+53(test)) and 39 (27(train)+11(test)) nonamidine class of potent FXa (0.004 ≤ K(i) (nM) ≤ 4700) and thrombin (0.001 ≤ K(i) (nM) ≤ 940) inhibitors, respectively. Interestingly, the ligand-based insights well corroborated with the structure-based insights in terms of the role of steric, electrostatic, and hydrophobic parameters for governing the selectivity for the two proteases. The new computational insights presented in this study are expected to be valuable for understanding and designing potent and selective antithrombotic agents.     

Comparison of urinary iodide determination in female thyroid patients by two techniques

Iodine deficiency affects a substantial portion of the world’s population, provoking severe health problems as well as important economic losses to the region in which this condition is found. In present study, evaluated the levels of urinary iodide (UI) and thyroid hormone status in female hypothyroid patients (HPs) and control subjects of same age group 16–30 years. The UI in HPs was measured by means of a Potentiometric method after microwave-assisted acid digestion, and compared the results with those obtained by the Sandell-Kolthoff method. The validity and accuracy was checked by using certified reference materials. The significantly lower concentration of iodide in the urine samples of the female goiter patients were observed as compared to control/referents subjects (p < 0.001). Serum thyroid status thyroid stimulating hormone, free triiodothyronine and free thyroxin were significantly lower in female patients as compared to control females (p < 0.003). The proposed method was relatively rapid, precise, accurate, efficient, as well as cost effective by using inexpensive equipment.