A novel amino acid racemization in vitamin b6-amino acid schiff base copper complexes: crystal structures of aquo (5'-phosphopyridoxylidene-dl-tyrosinato) copper(II) 3.5H2O and aquo (5'-phosphopyridoxylidene-dl-phenylalaninato) copper(II) 2.5H2O

A novel racemization observed in the Vitamin B6-amino acid Schiff base complexes, aquo (5'-phosphopyridoxylidene-l-tyrosinato) copper(II) and aquo (5'-phosphopyridoxylidene-l-phenylalaninato) copper(II) is described. The racemization taking place in solution under mild acidic conditions (pH 5-6) was confirmed by CD studies and the products were characterized by single crystal X-ray diffraction. The structures of both complexes show almost parallel orientation of the aromatic side chain and the pyridoxal II-system. The activation of the αCsingle bondH group due to the intermolecular II- interaction is probably the reason for the unusual racemization observed.

Interactions of methoxyamine with pyridoxal-5'-phosphate-Schiff's base at the active site of sheep liver serine hydroxymethyltransferase

The mechanism of interaction of methoxyamine with sheep liver serine hydroxymethyltransferase (EC 2.1.2.1) (SHMT) was established by measuring changes in enzyme activity, visible absorption spectra, circular dichroism and fluorescence, and by evaluating the rate constant by stopped-flow spectrophotometry. Methoxyamine can be considered as the smallest substituted aminooxy derivative of hydroxylamine. It was a reversible noncompetitive inhibitor (Ki = 25 microM) of SHMT similar to O-amino-D-serine. Like in the interaction of O-amino-D-serine and aminooxyacetic acid, the first step in the reaction was very fast. This was evident by the rapid disappearance of the enzyme-Schiff base absorbance at 425 nm with a rate constant of 1.3 x 10(3) M-1 sec-1 and CD intensity at 430 nm. Concomitantly, there was an increase in absorbance at 388 nm (intermediate I). The next step in the reaction was the unimolecular conversion (1.1 x 10(-3) sec-1) of this intermediate to the final oxime absorbing at 325 nm. The identity of the oxime was established by its characteristic fluorescence emission at 460 nm when excited at 360 nm and by high performance liquid chromatography. These results highlight the specificity in interactions of aminooxy compounds with sheep liver serine hydroxymethyltransferase and that the carboxyl group of the inhibitors enhances the rate of the initial interaction with the enzyme.

The Reaction of N4P4Cl8 with Dibenzylamine: Formation of an Unusual Bicyclic Phosphazene, N4P4[N(CH2Ph)2]6(NCH2Ph), by Dealkylation

The reactions of halogenocyclotetraphosphazatetraenes N4P4X8, with nucleophiles have received little attention and only the reactions of the octachloride, N4P4Cl8, with amines have been investigated in any detail.1 Millington and Sowerby2 studied the reaction of N4P4Cl8 with dimethylamine and isolated the derivatives, N4P4Cl8-n (NMe2)n, n = 2,3,4,5,6,8;several N-methylanilino derivatives

Preparation and characterization of Cd(0.75)PS(3)A(0.5)(H2O)(y) [A = Na, K and Cs]

Cd(0.75)PS(3)A(0.5)(H2O)(y) [A = Na, K and Cs], synthesized by the ion-exchange intercalation reaction of the insulating layered CdPS3, exhibits interesting electrical properties. The electrical properties are strongly dependent on the extent of hydration of the alkali ion which resides in the interlamellar space. In the potassium and caesium ion-exchanged compounds, y = I, the lattice expansion is similar to 3 Angstrom and the electric response characteristic of a dielectric. In the as prepared A = Na compound, y = 2, the lattice expansion is 5.6 Angstrom, the compound is conducting with a DC conductance of 3 x 10(-5) S cm(-1) at 300 K. Cd0.75PS3Na0.5(H2O)(y), y = 2, on evacuation or on heating looses water, reversibly, to form a y = 1 phase with electrical properties similar to that of the K and Cs ion exchange intercalation compounds.

[n]peristylanes and [n]oxa[n]peristylanes (n = 3-6): A theoretical study

Theoretical studies at the HF and Becke3LYP levels using 6-31G* basis sets were carried out on a series of [n]peristylanes and [n]oxa[n]peristylanes (n = 3-6) to understand their structure and energetics. The structures of the [3]- and [4]peristylanes (1, 2) and their era-derivatives (5, 6) were calculated to have the anticipated high symmetry, C-nv. In contrast, a C-s structure (9) at HF/6-31G* and another (25) at the Becke3LYP/6-31G* level were calculated for the [5]oxa[5]peristylane. The energy difference between them is extremely small even though there are major differences in the structures indicating every soft potential energy surface: On the other hand, the potential energy surface of [6]oxa[6]peristylane is not as soft. Similar structures were also calculated for the top rings. Calculations on the seco-compounds 11-14 and 15-19 (Table 4) indicate that there is no unusual strain involved in the formation of 27 from 19. The Li+ interaction energies of the [n]oxa[n]peristylanes are 61.7 (n = 3), 72.8 (n = 4), 84.2 (n = 5) and 91.7 (n = 6) kcal mol(-1) at the Becke3LYP/6-3IG* level. Dramatic differences between the C-C bond lengths obtained from the solid state X-ray diffraction studies and those from the calculations for the [n]oxa[n]peristylanes were also observed.

Copper-Catalyzed Oxidative Transformation of Secondary Alcohols to 1,5-Disubstituted Tetrazoles

A mild and convenient oxidative transformation of secondary alcohols to 1,5-disubstituted tetrazoles is uncovered by employing trimethylsilyl azide (TMSN3) as a nitrogen source in the presence of a catalytic amount of copper(II) perchlorate hexahydrate Cu(ClO4)(2)(.)6H(2)O] (5mol%) and 2,3-dichloro-5,6-dicyano-para-benzoquinone (DDQ) (1.2equiv.) as an oxidant. This reaction is performed under ambient conditions and proceeds through CC bond cleavage.

Estimation of the 2.0(5) helix type i -> i hydrogen bond energy at Aib*-Oxa motif: an isodesmic approach

Bending at the valence angle N-C-alpha-C' (tau) is a known control feature for attenuating the stability of the rare intramolecular hydrogen bonded pseudo five-membered ring C-5 structures, the so called 2.0(5) helices, at Aib. The competitive 3(10)-helical structures still predominate over the C5 structures at Aib for most values of tau. However at Aib*, a mimic of Aib where the carbonyl 0 of Aib is replaced with an imidate N (in 5,6-dihydro-4H-1,3-oxazine = Oxa), in the peptidomimic Piv-Pro-Aib*-Oxa (1), the C(5)i structure is persistent in both crystals and in solution. Here we show that the i -> i hydrogen bond energy is a more determinant control for the relative stability of the C5 structure and estimate its value to be 18.5 +/- 0.7 kJ/mol at Aib* in 1, through the computational isodesmic reaction approach, using two independent sets of theoretical isodesmic reactions. (C) 2014 Elsevier Ltd. All rights reserved.

2-(4-Chlorobenzyl)-6-arylimidazo2,1-b]1,3,4]thiadiazoles: Synthesis, cytotoxic activity and mechanism of action

The cytotoxic activity of a new series of 2-(4'-chlorobenzyl)-5,6-disubstituted imidazo2,1-b]1,3,4]wthiadiazoles against different human and murine cancer cell lines is reported. Among the tested compounds, two derivatives namely 2-(4-chlorobenzyl)-6-(2-oxo-2H-chromen-3-yl)imidazo2,1-1)]1,3,4]th iadiazole-5-carbaldehyde 4i and 2-(4-chlorobenzyl)-6-(2-oxo-2H-chromen-3-ypimidazo2,1-1)]1,3,4]thi adiazol-5-yl thiocyanate 5i emerged as the most potent against all the cell lines. To investigate the mechanism of action, we selected compounds 4i for cell cycle study, analysis of mitochondrial membrane potential and Annexin V-FITC flow cytometric analysis and DNA fragmentation assay. Results showed that 4i induced cytotoxicity by inducing apoptosis without arresting the cell cycle. (C) 2014 Elsevier Masson SAS. All rights reserved.