CobaltIII polyamine complexes

Hydrolysis of the phosphodiester bond is of critical importance at several stages in a cell cycle (including DNA repair and excision, integration and signal transduction). Metal-containing enzyme-mediated nucleic acid hydrolysis is therefore a common catalytic pathway in nucleic acid biochemistry.76 Cobalt(III) polyamine complexes have long been known to be among the most effective catalysts for the hydrolysis of phosphate esters.77 79 Chin etal.80 have demonstrated the particular capabilities of 1,4,7,10-tetraazacyclododecane (cyclen) or tris(3-aminopropyl)amine (trpn) complexes (Figure 11.6), in which cobalt(III) complexes with an enforced cis-configuration at the labile coordination sites are proved as one of the most key elements for artificial nucleases. Recently Chin et al. have prepared a dimeric cobalt(III) complex and have proposed a mechanism in which the phosphate is doubly Lewis acid activated and subsequently cleaved by attack of a cobalt(III)-bound hydroxide ion.81

Vance and Czarnik have reported that the dinuclear cobalt(III) cyclen complexes based on both a very rigid anthracene spacer and a very flexible alkyl spacer promoted the hydrolysis of the phosphate diester BNPP (bis(nitro-phenyl)phosphate).82 The rigid complexes are more reactive than the flexible complexes, whereas no cooperativity between the metal ions is observed for the

Figure 11.6 Cobalt(III) complexes of cyclen or trpn

Figure 11.6 Cobalt(III) complexes of cyclen or trpn

BNPP hydrolysis. Hettich and Schneider etal. have increased the DNA affinity of dinuclear cyclen-Co(III) by modification with positively charged peralkyl-ammonium ions that can interact with the anionic phosphate ester linkages in DNA.83 The presence of additional positive charges has small effects on the hydrolysis rates of BNPP ester but leads to substantially enhanced cleavage of plasmid DNA. The highest activity was observed for a complex in which two cobalt(III) centers can act simultaneously on the DNA grooves.

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