Core-valence correlation potentials based on density functional theory. Applications to valence-electron-only calculations on Na and K diatomics

The core-valence correlation potential has been derived for Na and K employing atomic calculations which make use of the density functional formula worked out by Lee, Yang and Parr based on Colle-Salvetti approach. The numerical potential is fitted with a small number of Gaussians leading to a very simple expression for an one-electron corevalence correlation operator? _cv . The core-valence correlation corrections can be computed by applying? _cv on a quite general class of wavefunctions. Applications of the? _cv operator within the framework of valence-electron-only calculations using effective Hamiltonians are presented for Na and K atoms, for Na₂, K₂, NaK and their cations. Almost all the corrections calculated for the physical properties due to the core-valence correlation lead to results which are in good agreement with those obtained from much more sophisticated treatments and experimental data.     

Efficient three-step sequence for the deamination of α-aminoesters. Application to the synthesis of CysLT1 antagonists

A practical and efficient three-step sequence for the deamination of α-aminoesters is reported. This method is based on the NaBH₄-mediated selective reduction of α-diazoesters to α-hydrazonoesters and has been successfully applied to the deamination of several representative α-aminoesters including some l-cysteine ethyl ester derivatives, key intermediates in the synthesis of a series of CysLT1 antagonists.     

Development and validation of a GC-MS method for rapid determination of galanthamine in Leucojum aestivum and Narcissus ssp.: a metabolomic approach

Galanthamine, an acetylcholinesterase inhibitor marketed as a hydrobromide salt for the treatment of Alzheimer's disease, is obtained from some Amaryllidaceae plants. A new method was developed and validated for its quantification by GC-MS in different plant sources: bulbs and leaves from Narcissus confusus; bulbs from N. pseudonarcissus cv. Carlton; and leaves and in vitro cultures from L. aestivum. Samples (50 mg) were extracted with methanol (1 mL) for 2 h, then aliquots of the extracts were silylated and analyzed by GC-MS. The calibration line was linear over a range of 15-800 μg galanthamine/sample, ensuring an analysis of samples with a content of 0.03-1.54% analyte referred to dry weight. The recovery was generally more than 95%. Good inter- and intra assay precision was observed (RSD < 3%). Principal component analysis of GC-MS chromatograms allowed discrimination of the plant raw material with respect to species, organs and geographical regions. The analytical method developed in this study proved to be simple, sensitive and far more informative than the routine analytical methods (GC, HPLC, CE and NMR), so it may be useful for quality control of plant raw materials in the pharmaceutical industry.     

Synthesis and Characterization of Acetone Hydrazones

1‐Isopropylidene‐2‐methylhydrazine ( 1 ), 1‐isopropylidene‐2‐hydroxyethylhydrazine ( 2 ) and 1‐isopropylidene‐2‐formylhydrazine ( 3 ) were synthesized by reaction of the corresponding hydrazine with an excess of acetone in the presence of a drying agent (anhydrous sodium sulfate or barium oxide). All compounds 1 – 3 were characterized by elemental analysis, coupled gas chromatography‐mass spectrometry (GC–MS), multinuclear NMR spectroscopy (¹H, ¹³C and ¹⁵N) and vibrational spectroscopy (infrared and Raman). Compounds 1 and 2 are liquid at room conditions and their density was measured by means of a picnometer, however, (at room conditions) compound 3 is a solid and its crystal density and structure were determined by low temperature X‐ray diffraction techniques (monoclinic, P2₁/n, Z = 4, a = 5.666(1) Å, b = 6.254(1) Å, c = 15.277(4) Å, β = 91.30(2)°, V = 541.2(2) ų). The structure of hydrazone 3 is discussed in detail and compared to that of monoformylhydrazine. Finally, the (gas phase) structure of compound 3 was optimized using DFT calculations (B3LYP/6‐31+G(d, p)) and its NBO charges are reported.     

Probing the acceptor substrate binding site of Trypanosoma cruzi trans-sialidase with systematically modified substrates and glycoside libraries

Systematically modified octyl galactosides and octyl N-acetyllactosamines were assessed as inhibitors of, and substrates for, T. cruzi trans-sialidase (TcTS) in the context of exploring its acceptor substrate binding site. These studies show that TcTS, which catalyses the α-(2→3)-sialylation of non-reducing terminal β-galactose residues, is largely intolerant of substitution of the galactose 2 and 4 positions whereas substitution of the galactose 6 position is well tolerated. Further studies show that even the addition of a bulky sugar residue (glucose, galactose) does not impact negatively on TcTS binding and turnover, which highlights the potential of 'internal' 6-substituted galactose residues to serve as TcTS acceptor substrates. Results from screening a 93-membered thiogalactoside library highlight a number of structural features (notably imidazoles and indoles) that are worthy of further investigation in the context of TcTS inhibitor development.