Kenneth A. Browne

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

Abstract The resolution 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 1 H NMR spectroscopy and restrained molecular modeling. The exchangeable and nonexchangeable proton resonances of d(CGCA 3 T 3 GCG) 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 31 P NMR shows interaction of the Zn(II) with the phosphate backbone. Proton chemical shift differences between d(CGCA 3 T 3 GCG) 2 : 6b :Zn(II) and d(CGCA 3 T 3 GCG) 2 : 6b are in agreement with the polyamino substituent of 6b {-(CH 2 ) 4 N(CH 2 CH 2 )N-(CH 2 CH 2 NH 2 ) 2 } forming a four-coordinated Zn(II) complex similar to that found in the X-ray structure of ‘tren-chloride’:Zn(II). The P 9 and P 10 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° in the helical axis of d(CGCA 3 T 3 GCG) 2 : 6b :Zn(II) compared to that found in d(CGCA 3 T 3 GCG) 2 : 6b . Single stranded cleavage of linear DNA fragments was not observed in the presence of 6b and Fe(II), Co(II), Cu(II), Zn(II), La(II) or Ce(II); this is likely due to the metal ion being sequestered as in the structure of d(CGCA 3 T 3 GCG) 2 : 6b :Zn(II) complex. Supercoiled DNA was susceptible to cleavage by 6b :Cu(II) in the presence of O 2 and a reducing agent.

DESIGN, SYNTHESIS, AND CHARACTERIZATION OF A NOVEL HEXA-AZACYCLOPHANE AND INTERACTIONS WITH D(CGCA3T3GCG)2, CTDNA AND T4DNA

Abstract A novel polyazacyclophane hexa-amine (1) has been designed, synthesized and characterized by X-ray crystallography, 1H NMR and fluorescence spectroscopy. 1 has the structural shape and disposition of charges complementary to the major groove of B-DNA. Acid dissociation constants for the protonated 1 were pKa1(D) = 4.8 and pKa2(D) = 8.5. Equilibrium constants for the binding of 1 to ctDNA and T4 DNA were 1.2 × 105 and 1.8 × 106, respectively.