Jian Dai

Stoichiometric preference in copper-promoted oxidative DNA damage by ochratoxin A.

The ability of the fungal carcinogen, ochratoxin A (OTA, 1), to facilitate copper-promoted oxidative DNA damage has been assessed using supercoiled plasmid DNA (Form I)-agarose gel electrophoresis and gas chromatography-mass spectrometry with selected-ion monitoring (GC-MS-SIM). OTA is shown to promote oxidative cleavage of Form I DNA with optimal cleavage efficiency occurring under excess Cu(II) conditions. As the concentration of OTA was increased and present in excess of Cu(II) the cleavage was less effective. Parallel findings were found for the ability of the OTA-Cu mixture to facilitate oxidative base damage. Yields (lesions per 10(6) DNA bases) of modified bases upon exposure of calf-thymus DNA (CT-DNA) to OTA-H(2)O(2)-Cu(II) were diminished when the OTA:Cu ratio was increased to 5:1. Electrochemical studies carried out in methanol implicate a ligand-centered 2e oxidation of OTA in the presence of excess Cu(II), while product analyses utilizing electrospray mass spectrometry support the intermediacy of the quinone, OTQ (3), in Cu-promoted oxidation of OTA. The implications of these findings with regard to the mutagenicity of OTA are discussed.

Photochemically Catalyzed Reaction of Ochratoxin A with d- and l-cysteine¶

The photolysis (>300 nm) of ochratoxin A (OTA, N‐{[(3R)‐5‐chloro‐8‐hydroxy‐3‐methyl‐1‐oxo‐7‐isochromanyl]carbonyl}‐3‐phenyl‐l‐alanine, 1) in the presence of excess (2 and 12 molar equiv) cysteine (CySH) has been investigated and found to yield sulfur adducts 5 and 6 that are characterized by liquid chromatography–mass spectrometry and 1H‐NMR spectroscopy. The adduct 5 was ascribed to the Michael addition conjugate resulting from covalent attachment of CySH to the ochratoxin quinone ( 4 ) generated by photooxidation of OTA. This species was also formed by photolysis of a synthetic sample of the hydroquinone of OTA (ochratoxin hydroquinone, 3) in the presence of 12 equiv l‐CySH. The conjugate 5 derived from photolysis of 3 with l‐CySH was used for 1H‐NMR analysis. The sulfur adduct 6 was the major species detected from covalent attachment of CySH to photoactivated OTA, and it resulted from direct displacement of the OTA Cl atom by CySH. The implications of the cysteinyl adducts to the in vivo toxicity of OTA are discussed, with particular emphasis given to conjugate 5, as products from the photooxidative pathway may be of relevance to the nephrotoxic properties of OTA.

An efficient method for the synthesis of 3-alkylthiophenes bearing functional groups on the side chain: imides and amides

A method utilizing Rieke® zinc reagents is described for the synthesis of 5-(3-thienyl)pentanenitrile from which 5-(3-thienyl)-N-acetylpentanamide and 5-(3-thienyl)-N-(4-trifluoromethyl)benzoylpentaneamine have been prepared. A study of the effect of different catalysts on the product composition and extent of conversion has been carried out. The method should be widely applicable to the synthesis of 3-alkylthiophenes bearing functional groups on the side chain which have been rather difficult to prepare previously. The characterization and oxidative polymerization/oligomerization of the new compounds is described.