Imaging of a clickable anticancer iridium catalyst

Xiuxiu Wang; Mingli Zhu; Fei Gao; Wei Wei; Yong Qian; Hong-Ke Liu; Jing Zhao

doi:10.1016/j.jinorgbio.2017.12.019

Imaging of a clickable anticancer iridium catalyst

J Inorg Biochem. 2018 Mar:180:179-185. doi: 10.1016/j.jinorgbio.2017.12.019. Epub 2017 Dec 29.

Authors

Xiuxiu Wang¹, Mingli Zhu¹, Fei Gao¹, Wei Wei¹, Yong Qian², Hong-Ke Liu³, Jing Zhao⁴

Affiliations

¹ State Key Laboratory of Coordination Chemistry, Institute of Chemistry and BioMedical Sciences, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, China.
² Jiangsu Collaborative Innovation Center of Biomedical Functional Materials, Jiangsu Key Laboratory of Biofunctional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210023, China.
³ Jiangsu Collaborative Innovation Center of Biomedical Functional Materials, Jiangsu Key Laboratory of Biofunctional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210023, China. Electronic address: liuhongke@njnu.edu.cn.
⁴ State Key Laboratory of Coordination Chemistry, Institute of Chemistry and BioMedical Sciences, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, China. Electronic address: jingzhao@nju.edu.cn.

PMID: 29306719
DOI: 10.1016/j.jinorgbio.2017.12.019

Abstract

Iridium-based anticancer reagents are receiving increasing attention for their high cytotoxicity. Herein, by activating CH bonds in the well-known antioxidant α-phenyl-N-tert-butylnitrone (PBN), we synthesized and characterized a series of new iridium complexes. Complex 1-AMP exhibited the best antiproliferation activity towards human ovarian cancer A2780 cells. The azide group in complex 1-AMP underwent the Cu(I)-catalysed azide-alkyne cycloaddition (CuAAC) reaction and the resulting fluorescent imaging in cells suggested it mainly accumulated in mitochondria. In comparison, to eliminate cytotoxicity of Cu(I) catalyst, we conducted a reaction between complex 1-AMP and a commercialized dye via strain-promoted alkyne-azide cycloaddition (SPAAC) reaction in live cells, confirming its targeting mainly in the mitochondria. Iridium-based anticancer complexes containing a nitrone ligand and azide group may offer a useful tool to probe the mechanism of metallodrugs.

Keywords: Anticancer; CH activation; Imaging; Iridium; Location.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alkynes / chemistry
Antineoplastic Agents / chemistry*
Antineoplastic Agents / metabolism
Antineoplastic Agents / pharmacology
Azides / chemistry
Catalysis
Cell Line, Tumor
Cell Proliferation / drug effects
Click Chemistry*
Coloring Agents / chemistry
Cycloaddition Reaction
Female
Humans
Iridium / chemistry*
Iridium / metabolism
Microscopy, Fluorescence
Mitochondria / metabolism
Molecular Probes
Ovarian Neoplasms / pathology

Substances

Alkynes
Antineoplastic Agents
Azides
Coloring Agents
Molecular Probes
Iridium