Complexes between cobalt(III) and eight different 1,4,7,10-tetraazacyclododecane (cyclen) as well as two tris(3-aminopropyl)amine (trpn) derivatives are reported with varying numbers and structures of peralkylammonium groups in side chains of the ligands. The presence of additional positive charges has small effects on hydrolysis rates of nitrophenyl- and bis(nitrophenyl)phosphate esters but leads to substantially enhanced cleavage of plasmid DNA. Increasing the number of the charged side groups and/or their distance to the metal ion center provides for better binding to the DNA groove, as shown also by affinity measurements with calf-thymus DNA. In line with this, saturation kinetics of plasmid DNA cleavage yield a corresponding increase of efficiency in Michaelis−Menten-type K M values, with rather constant k cat parameters. A binuclear cobalt complex with two cyclen centers separated by a −(CH2)6-N+(CH3)2-(CH2)6-N+(CH3)2-(CH2)6− spacer shows, with only 5 × 10-5 M catalyst concentration, the largest known rate enhancement factor of >107 (corresponding to >1011 at 1 M) against DNA; incubation with 0.05 mM at 37 °C for only 2 h leads to almost complete cleavage without appearance of products typical for redox cleavage. These results are in contrast to experiments with corresponding copper(II) complexes with added hydrogen peroxide, which has no effect with corresponding Co, Zn, Cd, or Ni complexes.

Saturation kinetics are measured with all lanthanides and bis(nitrophenyl) phosphate BNPP as substrate. They show rather constant K M values; the k cat values, however, increase by up to 66 times for La3+ to Er3+ and decrease again for Yb3+ and Lu3+. With all lanthanides, hydrolysis of the intermediate mononitrophenyl phosphate NPP is 2−30 times faster than that of BNPP. The k cat values measured with BNPP correlate with the ion diameter of the lanthanides, in line with accepted mechanisms but with the notable exception of the higher lanthanides. A similar correlation holds for the cleavage rates with plasmid DNA, with striking differences again observed with the higher lanthanides, however. Thus, a concentration increase from 5 × 10-5 to 1 × 10-2 M leads to 64% and 84% more DNA cleavage with La3+ and Pr3+, respectively, but to up to 68% less DNA cleavage, respectively, but with Yb3+, Tm3+ or Lu3+. In contrast to the BNPP cleavage, saturation kinetics derived k cat values with DNA change little with the used cation, which on the other hand led to larger variations in the K M parameters. Preliminary UV and CD studies with plasmid DNA indicate lanthanide-induced conformational changes with pseudo-first-order rate constants 10−100 times higher than the cleavage rate under the same conditions. Again, Yb3+ shows different effects than Eu3+. The unusual behavior of the higher lanthanides is discussed on the basis of cation clustering, which, in contrast to earlier assumptions by Bamann et al., leads to diminished activities. Addition of salts such as of NaCl or MgCl2 leads to distinct decrease of catalytic effects of for instance Eu3+. The corresponding rates correlate well with Debye−Hückel ionic strength parameters. These as well as the effects of added amines are in line with a simple competition mechanism of the added cations for the anionic substrates.

The catalysis of plasmid ds-DNA cleavage by lanthanoid cations and their complexes is characterized by saturation kinetics; addition of polyamines or cryptand does not hinder catalysis, which can be enhanced to a total factor of 107 by alcoholic co-substrates such as glycerol, or by intercalating ligands.The hydrolytic cleavage of nucleic acids by lanthanides' is of considerable interest, in particular for possible biotechnological applications. The extremely long half-life time of DNA approaching more than 100 million years for total hydrolysis* makes the development of supramolecular catalysts a particular challenge. With few exceptions,3 the up to date available chemical nucleases cleave DNA by radical processes$ with the disadvantage of less discriminate reactions of e.g. highly reactive hydroxy radicals, and of concomitant partial destruc-Ln3+:

Complex 2a crystallizes from water at 25 C in the triclinic space group Pi (no. 2) with u = 685.1(2). h = 880.6(4), c =1108.4(3) pm. 2 =109.77(1). {j = 96.36(2). 7 = 93.45(2) . Z = 2. V = 622 x 10" pm'. p ',,, id = VCH ~~~/ (~g s g~~. s e / / . r~/~(~~i nihH. 0-69451 Wwn/i&ii, 1993

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