Synthesis, structure and interactions with DNA of novel tetranuclear, [Mn4(II/II/II/IV)] mixed valence complexes

Reaction of Mn(II) with phenoxyalkanoic acids and di-2-pyridyl ketone oxime (Hpko) leads to neutral tetranuclear complexes of the general formula Mn4(O)(pko)4(phenoxyalkanoato)4 (phenoxyalkanoic acids: H-mcpa = 2-methyl-4-chloro-phenoxy-acetic acid, H-2,4,5-T = 2,4,5-trichloro-phenoxy-acetic acid or H3,4-D = 3,4-dichloro-phenoxy-acetic acid). The compounds were synthesized by adding di-2-pyridyl ketone oxime to MnCl2 in the presence of the sodium salts of the alkanoic acids in methanol. The crystal structure of Mn4(II/II/II/IV)(O)(pko)4(2,4,5-T)4 · 2.5CH3OH · 0.25H2O 1 shows that the complex consists of a [Mn4(μ4-O)]8+ core with a Mn(IV) and 3 Mn(II) ions in octahedral environment and a μ4-O atom bridging the four manganese ions. Spectroscopic studies of the interaction of these tetranuclear clusters with DNA showed that these compounds bind to dsDNA. The binding strength of the Mn4(II/II/II/IV)(O)(pko)4(2,4,5-T)4 complex for calf thymus DNA is equal to 1.1 × 104 M−1. Among the deoxyribonucleotides they bind preferentially to deoxyguanylic acid (dGMP). Competitive studies with ethidium bromide (EthBr) showed that the Mn4(II/II/II/IV)(O)(pko)4(2,4,5-T)4 complex exhibited the ability to displace the DNA-bound EthBr indicating that the complex binds to DNA via intercalation in strong competition with EthBr for the intercalative binding site. Additionally, DNA electrophoretic mobility experiments showed that all three complexes, at low cluster concentration, are obviously capable of binding to pDNA causing its cleavage (relaxation) at physiological pH and temperature. At higher cluster concentration, catenated dimer forms of pDNA was formed.