Vesicles and Micelles from Amphiphilic Zinc(II)−Cyclen Complexes as Highly Potent Promoters of Hydrolytic DNA Cleavage

Phosphate esters are essential to any living organism and their specific hydrolysis plays an important role in many metabolic processes. As phosphodiester bonds can be extraordinary stable, as in DNA, great effort has been put into mimicking the active sites of hydrolytic enzymes which can easily cleave these linkages and were often found to contain one or more coordinated metal ions. With this in mind, we report micellar and vesicular Zn(II)–cyclen complexes which considerably promote the hydrolytic cleavage of native DNA and the activated model substrate bis(4-nitrophenyl)phosphate (BNPP). They are formed by self-assembly from amphiphilic derivatives of previously employed complexes in aqueous solution and therefore allow a simple and rapid connection of multiple active metal sites without great synthetic effort. Considering the hydrolytic cleavage of BNPP at 25 °C and pH 8, the micellar and vesicular metal catalysts show an increase of second-order rate constants (k2) by 4–7 orders of magnitude compared to the unimolecular complexes under identical conditions. At neutral pH, they produce the highest k2 values reported so far. For pBR322 plasmid DNA, both a conversion of the supercoiled to the relaxed and linear form, and also a further degradation into smaller fragments by double strand cleavages could be observed after incubation with the vesicular Zn(II)–complexes. Finally, even the cleavage of nonactivated single-stranded oligonucleotides could be considerably promoted compared to background reaction.