A simple validated RP‐HPLC bioanalytical method for the quantitative determination of a novel valproic acid arylamide derivative in rat hepatic microsomes

A simple and specific bioanalytical method based on reversed‐phase high‐performance liquid chromatography (RP‐HPLC) coupled with ultraviolet detection was developed and validated for the determination of a novel valproic acid arylamide, N‐(2‐hydroxyphenyl)‐2‐propylpentanamide (HO‐AAVPA) in rat hepatic microsomes (a subcellular fraction containing phase I enzymes, especially cytochrome P450). The chromatographic separation was achieved using a reversed‐phase Zorbax SB‐C₁₈ column and a mobile phase of acetic acid in water (0.2% v/v) and acetonitrile (40:60 v/v) with a flow rate of 0.5 mL/min. The calibration curve was linear over the range of 882–7060 ng/mL (r² = 0.9987), and the lower limit of quantification and the lower limit of determination were found to be 882 and 127.99 ng/mL, respectively. The method was validated with excellent sensitivity, and intra‐day accuracy and precision varied from 93.79 to 93.12%, and from 2.12 to 4.36%, respectively. The inter‐day accuracy and precision ranged from 93.29 to 97.30% and from 0.68 to 3.60%, respectively. The recovery of HO‐AAVPA was measured between 91.36 and 97.98%. The assay was successfully applied to the analysis of kinetic metabolism and pharmacokinetic parameters in vitro by a substrate depletion approach. Copyright © 2014 John Wiley & Sons, Ltd.     

One Step Syntheses of Heteropropellanes

The preparation of two new propellanes containing the oxazino-oxazine moiety is described. The structure of 2,7-dioxa-5,10-diaza[4.4.4] propellane was determined by X-ray crystallographic analysis     

A Non‐Invasive NMR Method Based on Histidine Imidazoles to Analyze the pH‐Modulation of Protein–Nucleic Acid Interfaces

A useful ²J(N?H) coupling‐based NMR spectroscopic approach is proposed to unveil, at the molecular level, the contribution of the imidazole groups of histidines from RNA/DNA‐binding proteins on the modulation of binding to nucleic acids by pH. Such protonation/deprotonation events have been monitored on the single His96 located at the second RNA/DNA recognition motif (RRM2) of T‐cell intracellular antigen‐1 (TIA‐1) protein. The pK_a values of the His96 ionizable groups were substantially higher in the complexes with short U‐rich RNA and T‐rich DNA oligonucleotides than those of the isolated TIA‐1 RRM2. Herein, the methodology applied to determine changes in pK_a of histidine side chains upon DNA/RNA binding, gives valuable information to understand the pH effect on multidomain DNA/RNA‐binding proteins that shuttle among different cellular compartments.     

Revisiting the European sovereign bonds with a permutation-information-theory approach

In this paper we study the evolution of the informational efficiency in its weak form for seventeen European sovereign bonds time series. We aim to assess the impact of two specific economic situations in the hypothetical random behavior of these time series: the establishment of a common currency and a wide and deep financial crisis. In order to evaluate the informational efficiency we use permutation quantifiers derived from information theory. Specifically, time series are ranked according to two metrics that measure the intrinsic structure of their correlations: permutation entropy and permutation statistical complexity. These measures provide the rectangular coordinates of the complexity-entropy causality plane; the planar location of the time series in this representation space reveals the degree of informational efficiency. According to our results, the currency union contributed to homogenize the stochastic characteristics of the time series and produced synchronization in the random behavior of them. Additionally, the 2008 financial crisis uncovered differences within the apparently homogeneous European sovereign markets and revealed country-specific characteristics that were partially hidden during the monetary union heyday.     

A novel nucleophilic attack to N-enoyl oxazolidinethiones

The oxazolidinethione synthon can act as a chiral auxiliary and nucleophile (S⁻) carrier molecule simultaneously. Surprisingly, the thiolate attacks N-enoyl oxazolidinethiones producing a new heterocycle, as established by X-ray analysis.     

Fokker-Planck equation and relevant Chapman-Cowling-Davydov expression modified for coulomb scattering

Summary TheP ₁ approximation to the Boltzmann equation in the case of slightly ionized gases leads to the usual Fokker-Planck equation whose solution in steady-state condition is the Chapman-Cowling-Davydov (CCD) expression. We have extended the same procedure to include electron-ion interactions when the corresponding collision frequency is of the same order of, or larger than, the electron-neutral molecule collision frequency. We have considered a case where, after an initial ionization of a column of gas, the majority of the electrons have diffused to, and have been captured by, the walls of the chamber so that we may neglect the electron-electron interactions. We have found a modified CCD expression. However, numerical calculations show that the differences between the modified expressions and the standard ones in which the electron-ion collision frequency for momentum transfer is added to the electron-neutral collision frequency are beyond the present experimental accuracy.