Christopher L Rector | PubMed Health

PubMed2006

Peroxyl radical clocks.

A series of peroxyl radical clocks has been developed and calibrated based on the competition between the unimolecular beta-fragmentation (k(beta)) of a peroxyl radical and its bimolecular reaction with a hydrogen atom donor (k(H)). These clocks are based on either methyl linoleate or allylbenzene and were calibrated directly with alpha-tocopherol or methyl linoleate, which have well-established rate constants for reaction with peroxyl radicals (k(H-tocopherol) = 3.5 x 10(6) M(-1) s(-1), k(H-linoleate) = 62 M(-1) s(-1)). This peroxyl radical clock methodology has been successfully applied to determine inhibition and propagation rate constants ranging from 10(0) to 10(7) M(-1) s(-1).

Calibration↗

PubMed2005

Peroxidation of polyunsaturated fatty acid methyl esters catalyzed by N-methyl benzohydroxamic acid: a new and convenient method for selective synthesis of hydroperoxides and alcohols.

A new catalytic system, based on N-methyl benzohydroxamic acid (NMBHA), was developed for the selective synthesis of lipid hydroperoxides and alcohols by aerobic oxidation of lipid precursors. The reactions were carried out under mild conditions with air at atmospheric pressure and 37 degrees C. The products were isolated in much better yields (50-60%) as compared to previously reported procedures. NMBHA can be recovered at the end of the reaction and recycled. The putative reactive intermediate, a nitroxyl radical, readily abstracts a hydrogen atom from polyunsaturated lipid precursors such as linoleate esters, and NMBHA itself is an excellent hydrogen atom donor, thus conferring high selectivity to oxidations catalyzed by this reagent.

Alcohols↗

PubMed2002

Mechanism of action of non-cisplatin type DNA-targeted platinum anticancer agents: DNA interactions of novel acridinylthioureas and their platinum conjugates.

The DNA binding of two novel acridinylthioureas, ACR-NH-(CH(2))(2)-C(S)-NHCH(3) (1) and ACR-N(CH(3))-C(S)-NHCH(3) (3), and their platinum conjugates 4 and 5-derived from [PtCl(2)(en)]-was studied in cell-free model systems using various physico-chemical and biophysical methods. These included: spectrophotometric drug-DNA titrations, ethidium-DNA fluorescence quenching, competitive drug displacement, high-resolution NMR spectroscopy, and unwinding of plasmid DNA monitored by agarose gel electrophoresis. The acridinium cation of 1 showed strong binding to native DNA with K(i)=1.5 x 10(6)M(-1) and an excluded site size (n) of 2bp (McGhee-von Hippel fits of absorbance data). Compound 3 showed no measurable association with DNA. Binding of 1 was an order of magnitude stronger than that of simple 9-methylaminoacridine (2). In alternating copolymers, 1 exhibited slight AT preference. In poly(dA-dT)(2), enhanced association was accompanied by an increased binding site (approximately 3bp), while parameters in poly(dG-dC)(2) were consistent with classical intercalation. Displacement of 1 by distamycin from calf thymus DNA was suggestive of non-intercalating thiourea in 1 being located in the minor groove of the duplex. 1H NMR data of d(GGAGCTCC)(2) modified with 1 indicated intercalative binding of planar acridine, based on upfield shifts of aromatic proton signals relative to those in unbound 1 (Deltadelta approximately equal to -0.5 to -1ppm). Finally, 4 and 5 were found to unwind negatively supercoiled pUC19 plasmid by 21 degrees and 7 degrees per adduct, respectively (electrophoretic gel mobility assays). The difference in DNA binding modes of 4 and 5 is discussed as the ultimate source of the distinctly different biological activities of the conjugates.

Acridines↗