In vitro plasmid DNA cleavage by chromium(V) and -(IV) 2-hydroxycarboxylato complexes.

The ability of relatively stable Cr(V) and Cr(IV) complexes with 2-hydroxycarboxylato ligands [2-ethyl-2-hydroxybutanoate(2-) = ehba; (1R,3R,4R,5R)-1,3,4,5-tetrahydroxycyclohexanecarboxylate(2-) = quinate = qa] to induce single-strand breaks in plasmid DNA has been studied under a wide range of reaction conditions. The Cr(V) complex, Na[CrVO(ehba)2], causes substantial DNA cleavage at pH 4.0-8.0 [[Cr(V)]0 = 0.010-0.75 mM, phosphate buffer, and 37 degrees C]. The DNA cleavage is inhibited by the presence of excess ligand, by exclusion of O2, or by addition of organic compounds, such as alcohols, carboxylic acids, or DMSO, but it is not affected by traces of catalytic metals [Fe(III) or Cu(II)] or by addition of catalase. The Cr(IV)-qa complexes, unlike the Cr(V) complexes, are able to cleave DNA in the presence of the ligand in a large excess [[Cr(IV)]0 = 0.50 mM, [qa] = 20-100 mM, pH 3.5-6.0, and 37 degrees C]. This is the first direct evidence for DNA cleavage induced by well-characterized Cr(IV) complexes. The proposed mechanism for DNA cleavage includes the following: (i) partial aquation of the bis-chelated Cr(V) and -(IV) complexes with the formation of reactive monochelated forms, (ii) binding of the Cr(V) and -(IV) monochelates to the phosphate backbone of DNA, (iii) one- or two-electron oxidations at the deoxyribose moieties of DNA by Cr(V) and -(IV), and (iv) cleavage of the resulting DNA radicals or cations with or without participation of O2. The patterns of DNA damage by Cr(V) and -(IV) can include strand breaks, generation of abasic sites, and the formation of Cr(III)-DNA complexes.

The binding of a complex cobalt ruthenium polyamine by deoxyribonucleic acid and a lipopolysaccharide: a model for a novel class of drugs.

In this paper we discuss the following: 1. Synthesis of [Co(H3CsarNHCH2pyRu(NH3)5)] (PF6)5, (CoRu). 2. Interaction of CoRu with calf thymus DNA and with lipopolysaccharide from Escherichia coli C (LPS) has been estimated using the absorption of the complex at 242 and 420 nm. 3. DNA and LPS increase the rate of fall of absorption at 420 nm due to autooxidation of the complex. 4. The fall in absorption of CoRu(II) at 420 nm can be used to give an approximate measure of binding to DNA and to LPS. 5. Both macromolecules are aggregated by CoRu at high concentrations and the cation and macromolecule complex can be removed by low speed centrifugation. 6. The DNA-CoRu complex can also be removed by high speed centrifugation when the cation concentration is too low to cause aggregation (20 microM CoRu/155 microM DNA-P). Absorption of redissolved complex at 420 nm is restored by reduction with ascorbic acid. 7. At saturation the ratio of mole CoRu bound/mole DNA-P is 0.16.