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Fully Reversible Photocontrol over DNA Intercalation with Visible Light
David E Grantz1, Christophe Lachance-Brais1, Giuseppe Giangreco1,2
1Stratingh Institute for Chemistry, Faculty for Science and Engineering, University of Groningen, Nijenborgh 3, 9747 AG Groningen, The Netherlands.
Journal of the American Chemical Society
|June 5, 2026
Summary
Researchers developed novel photoswitchable DNA intercalators that reversibly bind DNA. These diazocine compounds offer unprecedented light-controlled "on-off" binding, enabling precise photopharmacology applications.
Area of Science:
- Medicinal Chemistry
- Molecular Biology
- Photochemistry
Background:
- DNA intercalators are crucial in molecular biology and medicine.
- Developing controllable DNA-binding agents is a key challenge.
- Photoswitchable molecules offer potential for spatiotemporal control.
Purpose of the Study:
- To synthesize and characterize novel photoswitchable DNA intercalators.
- To investigate their DNA binding properties and light-responsive behavior.
- To evaluate their potential in photopharmacology.
Main Methods:
- Synthesis of diazocine-based photoswitchable compounds.
- B-DNA binding affinity measurements (KD) in trans and cis states.
- Reversibility and fatigue testing under visible light.
- Cytotoxicity assays (EC50) in HeLa cells with and without irradiation.
Main Results:
- Three novel photoswitchable DNA intercalators based on the diazocine scaffold were synthesized.
- Compounds exhibit reversible "on-off" DNA binding upon visible light irradiation.
- The trans state shows high affinity (KD ~10-4 M), with >1000-fold lower affinity in the cis state.
- Negligible dark toxicity for compound 3 (EC50 > 100 μM), with photo-induced toxicity upon 395 nm irradiation (EC50 = 45.4 μM).
Conclusions:
- The developed diazocine intercalators demonstrate efficient and reversible light-controlled DNA binding.
- This photoswitchable binding is superior to existing literature methods.
- The compounds show potential for spatiotemporal control in photopharmacology due to their tunable activity.
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