NMR structure of d(CGCA3T3GCG)2:tren-microgonotropen-b:Zn(II) complex and solution studies of metal ion complexes of tren-microgonotropen-b interacting with DNA.

The solution structure of a 1:1 complex of zinc tren-microgonotropen-b [6b:Zn(II)] with d(CGCAAATTTGCG)2 has been determined by 2D nuclear Overhauser effect 1H NMR spectroscopy and restrained molecular modeling. The exchangeable and nonexchangeable proton resonances of d(CGCA3T3GCG)2:6b:Zn(II) indicate that the Zn(II) is interacting in the A+T-rich region of the dsDNA and the tren region of 6b, while 31P NMR shows interaction of the Zn(II) with the phosphate backbone. Proton chemical shift differences between d(CGCA3T3GCG)2:6b:Zn(II) and d(CGCA3T3GCG)2:6b are in agreement with the polyamino substituent of 6b [-(CH2)4N(CH2CH2)N-(CH2CH2NH2)2] forming a four-coordinated Zn(II) complex similar to that found in the X-ray structure of 'tren-chloride':Zn(II). The P9 and P10 phosphate oxygens that are held by hydrogen bonding to the tren substituent of 6b in the DNA:6b complex become ligands to the tren-complexed Zn(II) in DNA:6b:Zn(II). To do so there is a 2 A decrease in the adjacent phosphate-to-phosphate distance at the Zn(II) binding site. This motion brings about an increased bend of 14.6 degrees in the helical axis of d(CGCA3T3GCG)2:6b:Zn(II) compared to that found in d(CGCA3T3GCG)2:6b. Single stranded cleavage of linear DNA fragments was not observed in the presence of 6b and Fe(II), Co(II), Ni(II), Cu(II), Zn(II), La(III) or Ce(III); this is likely due to the metal ion being sequestered as in the structure of d(CGCA3T3GCG)2:6b:Zn(II) complex. Supercoiled DNA was susceptible to cleavage by 6b:Cu(II) in the presence of O2 and a reducing agent.