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

• Published in: ChemistrySelect (Weinheim) 2018-05, Vol.3 (17), p.4897-4910
• Main Authors: Safiarian, Mohammad S., Sawoo, Sudeshna, Mapp, Carla T., Williams, Dominique E., Gude, Lourdes, Fernández, María‐José, Lorente, Antonio, Grant, Kathryn B.
• Format: Article
• Language: English
• Subjects: anthracene; bioorganic chemistry; DNA cleavage; ionic strength; photodynamic therapy
• ISSN: 2365-6549; 2365-6549
• DOI: 10.1002/slct.201703019

This paper compares the DNA interactions of a bis 9‐aminomethylanthracene dye (2) vs. a mono‐anthracene (4) under high ionic strength conditions similar to those in the cell nucleus (∼150 mM NaCl and 260 mM KCl). The chloride salts triggered an enhancement in anthracene‐sensitized DNA photocleavage, where bis‐anthracene 2 exhibited superior DNA binding affinity, faster reaction kinetics, and higher levels of DNA damage at low‐ to sub‐micro molar dye concentrations (350 nm hν, pH 7.0). While spectroscopic and viscometric data suggested that the chloride salts reduced DNA intercalation in favor of a non‐intercalative binding mode in which 2 and 4 were better able to generate hydroxyl radicals, there was evidence of persistent intercalation of the second anthracene ring of 2. We propose that such an interaction anchored the bis‐anthracene to DNA under the high ionic strength conditions, increasing its binding affinity and photocleaving capabilities relative to the mono analog (4). Salt‐selective photocleavage: Under high ionic strength conditions similar to those that exist in the cell nucleus, low micromolar concentrations of a chromophore equipped with two 9‐aminomethyl‐anthracene rings photosensitize extremely high levels of DNA damage.