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Published on: May 21, 2019
One-Pot Conversion of Acridines Into Phototherapeutic Near-Infrared Spirocyanines
Zhaobin Wang1, Tianyang Zhang2, Xia Wang1
1Key Laboratory of High Performance Polymer Materials and Technology of Ministry of Education, Department of Polymer Science & Engineering, School of Chemistry, Nanjing University, Nanjing, Jiangsu, People's Republic of China.
Abstract:
As near-infrared (NIR) bio-imaging and phototherapeutic agents, polymethine cyanines have disadvantages in optical properties due to the fast nonradiative transition. Herein, we reported a small-sized and spirocycle-fused trimethine acridinocyanine (SpiroCY) via one-pot oxidative trimerization using oxygen as the oxidant. Theoretical calculations using the Automated Design of Chemical Reaction (ADCR) program elucidate the formation of the O2-derived hydroperoxyl radical (HO2 •) and demonstrate a radical cascade reaction (RCR) mechanism for spirocyanine synthesis. The spiro-functionalization effect greatly reshapes the photophysical properties of the parent acridinocyanine by improving brightness and suppressing H-aggregation due to the three-dimensional architecture and enhanced rigidity, which allows for mitochondria-targeted NIR-I and NIR-II cell imaging at a very low dose (10-100 nM); and switches the parent acridinocyanine into a potential antitumor drug and Type-I photosensitizer generating superoxide anion radical (O2 •-) and hydroxyl radical (•OH) under 808 nm light irradiation for efficient photodynamic therapy. This work provides a new insight for dye functionalization, adds mechanistic understandings of the spirocyclic effect, and paves a way for developing spiro dyes as unique NIR-I and NIR-II imaging and phototherapeutic agents.
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