Mono- and dinuclear copper(II) complexes of pendant-arm macrocyclic polyamines: synthesis, characterization and investigation as hydrolytic cleavage agents for DNA

Based on the 10-methyl-1,4,8,12-tetraazacyclopentadecane-10-amine (1) parent, macrocycles 10-benzylamine-10-methyl-1,4,8,12-tetraazacyclopentadecane (2), 10-(2'-pyridinylmethanamino)- 10-methyl-1,4,8,12-tetraazacyclopentadecane (3) and 5- (hydroxymethyl)-5'-(10''-methyl-1'',4'',8'',12''-tetraazacyclopentadecane-10''-amino)-(2,2'-dipyridine) (4), as well as the p-xylene-linked dinucleating macrocycle 1,4-bis(10'-methyl- 1',4',8',12'-tetraazacyclopentacecane-10'-aminomethyl)benzene (5) and its o-xylene analogue (6), have been synthesized as free ligands and or copper(II) complexes and characterized spectroscopically. Cyclic voltammetry of the Cu(II) complexes of 2 – 6 are also reported, with involvement of the pendant groups in complexation influencing voltammetric behaviour. Potentiometric titrations of 1, 2, 5 and 6 and their Cu(II) complexes yielded pKa values. Both dimers 5 and 6, as well as their mononuclear close analogues 1 and 2, have proven to be inefficient as hydrolytic cleavage agents for DNA, as was also the case for mononuclear Cu(II) complexes of N4 -macrocycles with a range of N-pendant groups based on the 3,7,11,17-tetraazabicyclo[11.3.1]heptadeca-1(17),13,15- triene framework (7). Mononuclear triazamacrocyclic Cu(II) complexes show greater activity. Of other dinuclear systems examined, dicopper(II) complexes of the relatively rigid compartment ligands 3,13-dimethyl-3,13-dinitro-1,5,11,15-tetraazacycloeicosane-8,18- diol and -dithiol are also inactive. Whereas the 1:1 Cu(II):L complexes of cyclam and its N,N´,N´´,N´´´-tetrakis(methylbenzyl) substituted analogue are inactive, the tetrakis(2-methylpyridine)-substituted analogue as a 2:1 Cu(II):L