Synthesis and DNA photocleavage by a pyridine-linked bis-acridine chromophore in the presence of copper(II): Ionic strength effects

Aminomethylanthracene Dyes as High‐Ionic‐Strength DNA‐Photocleaving Agents: Two Rings are Better than One

“…The use of excitation wavelengths that extend into the near‐infrared range is particularly important due to the greater tissue penetration depth afforded by low light absorption in this region by biogenic chromophores . Towards these ends, our group has been exploring the effects of elevated NaCl and KCl concentrations on the photodynamic action of various ultra‐violet, visible, and long‐wavelength absorbing DNA photosensitizing agents ,. As expected, the addition of salts inhibited DNA photocleavage in the case of most of the chromophores that we studied.…”

“…If the photosensitizer is positively charged, it can be displaced by a mass action effect in which the cations effectively compete for negatively charged binding sites on the DNA duplex . As exemplified by many DNA photosensitizers including those based on meso substituted porphyrins, cyanine dyes, 9,10‐bis(aminomethyl)anthracene, bis‐proflavine, and methylene blue, salt‐induced reductions in ligand binding affinity decrease levels of photosensitizer‐induced DNA damage.…”

“…As expected, the addition of salts inhibited DNA photocleavage in the case of most of the chromophores that we studied. Conversely, we were surprised to find that salt addition had markedly increased the cleavage generated by an ultra‐violet light absorbing pyridylpolyamine dye possessing a single 9‐aminomethylanthracene ring ( 5 in Scheme ) ,…”

To Loop or Not to Loop: Influence of Hinge Flexibility on Self‐Assembly Outcomes for Acridine‐Based Triazolylpyridine Chelates with Zinc(II), Iron(II), and Copper(II)

“…This then raises the question of whether L6 can access other coordination geometries with less flexible metal ions. One metal ion of particular interest due to its redox properties, and its contribution to acridine‐assisted photocleavage of biological targets is copper(II). In contrast to triazole–pyridine complexes self‐assembled with metal ions of tetrahedral or octahedral coordination geometries, in the presence of square‐planar metals such as copper(II), the strong preference of the triazole–pyridine chelate for a head‐to‐tail geometry (reinforced by hydrogen bonding between the pyridine H6 proton and the triazole N2 atom) provides access to a much more planar chelate orientation, thereby influencing the self‐assembly outcome as well as the topology of the selected assembly –…”

“…Acridine is an attractive aromatic rigid spacer element: i) it is a known privileged scaffold in medicinal chemistry, with action against cancer,– infections,, and neurological disorders,, likely induced by its propensity to associate with nucleic acids;– ii) its photophysical– and photochemical– properties make it a good candidate for sensing and acting on biological targets, with the option of taking advantage of its pyridine‐like “buried” nitrogen atom, which is known to be sensitive to pH and hydrogen‐bonding triggers but remains reasonably inaccessible for coordination to metal ions; and iii) its intrinsic chemical reactivity may prove beneficial for covalent attachment to potential biological targets …”