Preparation of a spermine conjugate of the bis-phenanthroline ligand Clip-Phen and evaluation of the corresponding copper complex

We described the synthesis of conjugates of N,N-diethylethylenediamine and spermine with Clip-Phen, a new ligand with two I,10-phenanthrolines linked by serinol. The ability of the copper complexes of these Clip-Phen conjugates to cleave Phi X174 DNA when activated by a reductant in the presence of air was compared to that of 1,10-phenanthroline copper complexes. The results indicated that Clip-Phen-spermine with copper was the most active DNA cleaver. Comparison with a conjugate having only one phenanthroline unit linked to spermine showed that the high activity of Clip-Phen-spermine-Cu was not only due to the presence of spermine, which increases the affinity of the Clip-Phen entity for the DNA, but was effectively due to the presence of the two bridged phenanthroline entities. The DNA cleavage activity of (Clip-Phen-spermine)CuCl2 was analyzed on a 167 bp restriction fragment and a 45-mer double-stranded oligonucleotide.