Fully Reversible Photocontrolover DNA Intercalationwith Visible Light

作者：David E. Grantz, Christophe Lachance‐Brais, Giuseppe Giangreco, Edoardo J. Mattioli, Sina Katharina Götzfried, Matteo Calvaresi (1359069), Ben L. Feringa (1429174) · 发表于：Figshare · 年份：2026 · DOI：10.1021/jacs.6c00879.s001 · 研究领域：Photochromic and Fluorescence Chemistry、DNA and Nucleic Acid Chemistry、Molecular Sensors and Ion Detection

Here we present three novel photoswitchable DNA intercalators based on the diazocine scaffold. These compounds bind B-DNA in the trans state ( K D , trans = (4.14 ± 1.25)–(7.84 ± 3.41) × 10 –4 M) and show fully reversible “on”–“off” behavior upon visible-light irradiation without any sign of fatigue over six cycles. The affinity of the trans state is at least 1000-fold higher than of the cis state. The ability to reversibly turn off all observable binding with in situ visible light irradiation is so far unmatched in the literature. Preliminary cytotoxicity studies of 3,3′-dimethanamine-diazocine ( 3 ) show negligible dark toxicity (EC 50 > 100 μM) with a significant increase upon irradiation (395 nm, EC 50 = 45.4 μM, PI > 2) in HeLa cells, allowing for spatiotemporal control of activity in photopharmacology applications.