Natural and synthetic double-stranded DNA binding studies of macrocyclic tetraamine zinc(II) complexes appended with polyaromatic groups

Abstract

The characteristic binding mode of zinc(II) complexes of macrocyclic tetraamines (1,4,7,10-tetraazacyclododecane, cyclen) appended with one or two arylmethyl group(s) [(4-quinolyl)methyl-, 1,7-bis(4-quinolyl)methyl-, (1-naphthyl)methyl-, 1,7-bis(1-naphthyl)methyl-, and (9-acridinyl)methyl-cyclen] to double-stranded calf thymus DNA and synthetic DNAs [poly(dA)-poly(dT), poly(dA-dT)2, poly(dI).poly(dC), poly(dI-dC)2, poly(dG) poly(dC), and poly(dG-dC)2] has been examined by spectrophotometric methods, Tm measurement, and inhibition of these DNA-directed transcriptions in vitro. Various hypochromic and bathochromic effects on the pendant aromatic absorption spectra of the complexes were observed in titration with the native and synthetic DNA. The binding constants Kapp (=[bound cyclen derivatives]/[unbound cyclen derivatives][DNA phosphates] M(-1)), at 25 degrees C in 10 mM EPPS (pH 8.0) containing 0.1 M Na+, were determined and compared with those of the corresponding Zn2+ -free ligands. The results showed that the Zn2+ -cyclen complexes interact with the DNA more strongly than the corresponding diprotonated ligands, leading to a stronger stacking of the pendant aromatic rings. The binding of Zn2+ -(9-acridinyl)methyl-cyclen to calf thymus DNA was competed by an AT-selective, minor groove binder, distamycin, but not by a major groove binder, methyl green. In an unusual interaction of excess Zn2+ -(9-acridinyl)methyl-cyclen with poly(dA).poly(dT), the Zn2+ -cyclen moiety went into the minor groove to make coordination bonds with the deprotonated imides of the thymines, resulting in disruption of the poly(dA).poly(dT) duplex. Thymine-containing DNA-directed transcription with Escherichia coli RNA polymerase in vitro was inhibited by the Zn2+ -(9-acridinyl)methyl-cyclen. The 50% inhibition concentrations of the transcription (IC50) were 22-45 microM with poly(dA).poly(dT) or poly(dA-dT)2 as templates, while with poly(dG-dC)2 as a template the IC50 value was 110 microM.

Effect of Ring Methylation on the Photophysical, Photochemical and Photobiological Properties of cis-Dichlorobis(1,10-Phenanthroline)Rhodium(III)Chloride†

“…The apparent binding constant, Kappr was determined using (Eq. the order of lo4 or greater (58)(59)(60)(61). Clearly, Kapp for OCTBP is below that level, consistent with the ample evidence in the literature that phenanthroline rings are not effective intercalators (62).…”

“…By comparison, BISPHEN shows only minimal association with CT‐DNA (100 M ‐1 ) and even this value is observed only in a solution of very low ionic strength (3). The intercalation of small molecules with DNA is generally characterized by association constants of the order of 10 4 or greater (58–61). Clearly, K app for OCTBP is below that level, consistent with the ample evidence in the literature that phenanthroline rings are not effective intercalators (62).…”

Synthesis and characterization of water‐soluble copper(II), cobalt(II) and zinc(II) complexes derived from 8‐hydroxyquinoline‐5‐sulphonic acid: DNA binding and cleavage studies

“…The hypochromism in the MLCT band reaches 24.5% for complex 1 when the [DNA]/[Cu] ratio equals 1.0 and the value of K b is 2.1 × 10 4 M −1 . The K b values observed here are lower than those observed for typical classical intercalators (ethidium–DNA, 7.0 × 10 7 M −1 in 40 mM Tris–HCl buffer, pH = 7.9; and proflavin– Escherichia coli DNA, 1.4 × 10 6 M −1 in 40 mM NaCl–25 mM Tris–HCl) with a proven DNA binding mode involving the complete insertion of the planar molecules between the base pairs . This is indicative of binding of complexes 1 – 3 with DNA host with lower affinity than the classical intercalators.…”

Cleavage of an RNA analog by Zn(II) macrocyclic catalysts appended with a methyl or an acridine group

“…As shown by Kimura and co-workers, an acridine group appended to a Zn(II) cyclen complex through a short one carbon tether increases the binding strength and specificity of interaction of the complex with oligonucleotides [30,49,50]. This complex exhibits enhanced binding to di or trinucleotides containing uridine or guanosine [30] in a binding interaction that is enhanced by stacking of the nucleobase on the acridine in conjunction with Zn(II) binding to uridine N3 or guanosine N7 [50].…”