Rapid reduction of pentavalent antimony by trypanothione: potential relevance to antimonial activation

The dithiol trypanothione can reduce an antiparasitic pentavalent antimony agent to trivalent rapidly; this reduction process is both pH and temperature dependent and trypanothione may therefore play an important role in the activation of the drug.     

Unusual conformations of 1,3‐dialk­oxy­thia­calix[4]arenes in the solid state

The structures of three syn‐1,3‐dialkoxy­thia­calix[4]arenes with unusual conformations in the solid state are reported. The pinched cone conformation of syn‐2²,4²‐dihydroxy‐1²,3²‐bis­(prop‐2‐enyl­oxy)thia­calix[4]arene, C₃₀H₂₄O₄S₄, (3a), is stabilized by two intra­molecular hydrogen bonds, remarkably formed from both OH groups to the same ether O atom. In syn‐2²,4²‐dihydroxy‐1⁵,2⁵,3⁵,4⁵‐tetra­nitro‐1²,3²‐bis­(prop‐2‐enyl­oxy)thia­calix[4]arene acetone disolvate, C₃₀H₂₀N₄O₁₂S₄·2C₃H₆O, (3b1), the mol­ecule is found in the 1,3‐alternate conformation. The crystallographic C2 symmetry is due to a twofold rotation axis running through the centre of the calixarene ring. The hydroxy groups cannot form intra­molecular hydrogen bonds as in (3a) and both are bonded to an acetone solvent mol­ecule. The mol­ecule of the pseudo‐polymorph of (3b1) in which the same compound crystallized without any solvent, viz. (3b2), is located on a crystallographic mirror plane. Only one of the two hydroxy groups forms a hydrogen bond, and this is with a nitro group of a neighbouring mol­ecule as acceptor. Mol­ecular mechanics calculations for syn‐1,3‐diethers suggest a preference of the 1,3‐alternate over the usual cone conformation for thia­calix[4]arene versus calix[4]arene and for para‐nitro versus para‐H derivatives.     

Templated metal catalysis for single nucleotide specific DNA sequence detection

A catalytic DNA-templated reaction of hydrolysis of an ester group in an N-modified peptide nucleic acid, which is activated by a Cu2+ complex-PNA, has been discovered and optimized. Both the ester-containing PNA and the metal complex PNA bind neighboring sites on a template DNA. This brings the reacting groups (the ester and the Cu2+ complex) in proximity to each other and accelerates the hydrolysis of the ester approximately 500 times in comparison with its hydrolysis in the absence of the template. The hydrolysis reaction provides >10(2)-fold kinetic discrimination between DNAs that are different from each other at a single nucleotide position. Natural enzyme T4 DNA ligase is slightly less selective. On the basis of this reaction a fully homogeneous and sensitive assay for sequence-specific DNA detection has been developed (10 fmol DNA). Identification of one of four DNAs (variation at one position) can be done in a single experiment. Since the Cu2+ ion is tightly bound in an associate containing the ester PNA, the metal complex PNA, and the template DNA, application of this method in buffers containing other Cu2+-binding ligands, e.g., PCR buffer and physiological buffer, is possible.     

New aurone epoxide and auronolignan from the heartwood of Cotinus coggygria Scop

New aurone epoxide, 2,10-oxy-10-methoxysulfuretin (14), and new auronolignan (15), named cotinignan A, were isolated by silica gel column and semipreparative HPLC chromatography from the methylene chloride/methanol extract of Cotinus coggygria Scop. heartwood. In addition, thirteen known secondary metabolites namely sulfuretin, 2,3-trans-fustin, fisetin, butin, butein, taxifolin, eriodictyol, 3',5,5',7–tetrahydroxyflavanone, 3',4',7-trihydroxyflavone, 3-O-methyl-2,3-trans-fustin, 3-O-galloyl-2,3-trans-fustin, β-resorcylic acid and 3-O-β-sitosterol glucoside were isolated as well. Their structures were elucidated by 1D and 2D NMR, HR-ESI-MS, IR and UV. Ten out of eleven isolated flavonoids possess 7, 3' and 4' hydroxy groups. These structural features could be considered as chemotaxonomic characteristic of flavonoids from C. coggygria. Cotinignan A (15) represents new subclass of secondary metabolites - auronolignans.

     

Structure/Odor Relationships of (&sminus 0;)- and (&splus 0;)-β-Vetivone,and Their Demethyl Derivatives

(−)-β-Vetivone ((−)- 3a ), one of the main constituents of vetiver oil, was submitted to a structure/odor relationship study. The influence of the Me groups at the cyclohexenone ring and of the configuration on the odor was examined. Detailed ¹H- and ¹³C-NMR-spectroscopic data were collected, and the absolute configurations were determined by CD methods.     

Poly(phenylsilsesquioxane)s: Structural and morphological characterization

Poly(phenylsilsesquioxane) (PPSQ) polymers that were obtained from different synthetic routes were comparatively studied. The polymers were characterized by infrared and solid‐state ²⁹Si NMR spectroscopies. According to the results of X‐ray diffraction and thermogravimetric analyses, the materials richest in silanol showed a less organized network and lower weight loss temperature. The morphology of the products was influenced by the preparation conditions. PPSQ, with a morphology rich in spherical particles, was achieved with an n‐hexadecyltrimethylammonium bromide template in the reaction medium, whereas the morphology of this polymer obtained in the absence of the template was featureless. Small‐angle X‐ray scattering analyses revealed that the PPSQ samples showed a predominance of surface‐fractal behavior. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 1580–1589, 2000     

Cytotoxicity of tantalum(V) and niobium(V) small carborane complexes and mode of action in P388 lymphocytic leukemia cells

The metallacarboranes (Et₂C₂B₄H₄)‐­TaCl₂(C₅H₅) ( 1 ), (Et₂C₂B₄H₄)NbCl₂(C₅H₅) ( 2 ), (Et₂C₂B₄H₄)TaCl₂(C₅Me₅) ( 3 ), [(Me₃Si)₂­C₂B₄H₄]TaCl₂(C₅H₅) ( 4 ) and (Me₂C₂B₄H₄)‐­TaCl₂(C₅H₅) ( 5 ) are potent cytotoxic agents against suspended tumors, producing cell death in several tissue culture lines; for example, all were effective against murine L1210 lymphoid leukemia, and all except 5 against murine P388 lymphocytic growth. Human leukemic growth is also retarded since 1–4 were effective against Tmolt₃ cell leukemia, all except 4 against Tmolt₄ leukemia, and 1, 2 , and 5 against HI‐60 leukemia. Cytotoxicity was found towards HuT‐8 lymphoma, THP‐1 acute monocytic leukemia and suspended HeLa‐S³ uterine carcinoma. Some but not all of the complexes were active against Sk‐2 melanoma and Mcf‐7 breast effusion growth. Mode‐of‐action studies in P388 lymphocytic leukemia cells showed that de novo purine synthesis was inhibited; this inhibition reduces DNA and RNA syntheses. Purine synthesis was reduced by compounds 3 and 4 at the regulatory enzymes, i.e. phosphoribosyl pyrophosphate (PRPP) amidotransferase and dihydrofolate reductase. The agents lowered d[ATP] and d[CTP] pools, further reducing DNA synthesis. The complexes afforded DNA fragmentation leading to apoptosis, but this was not by a mechanism of nucleoside alkylation, intercalation between base‐pairs or cross‐linking of the DNA strands. Copyright © 2000 John Wiley & Sons, Ltd.     

13C‐NMR spectra of santalol derivatives: a comparison of DFT‐based calculations and database‐oriented prediction techniques

A systematic investigation of a series of santalol and epi‐santalol derivatives by means of ab initio and density functional theory (DFT) calculations together with database‐oriented prediction methods leads to a configurational reassignment within this compound class. The DFT calculations as well as the HOSE‐code and neural network‐based predictions allow deriving a general rule set for unambiguous assignment within this compound class. The methyl group in position 2′ serves as an indication for the configuration at this stereocenter allowing easy differentiation between santalol derivatives and their diastereomers belonging to the epi‐santalol series. Copyright © 2009 John Wiley & Sons, Ltd.