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Published on: May 24, 2017
Luminescent platinum(II) complexes with functionalized N-heterocyclic carbene or diphosphine selectively probe
Sin Ki Fung1, Taotao Zou1,2, Bei Cao1
1State Key Laboratory of Synthetic Chemistry, Institute of Molecular Functional Materials, Chemical Biology Centre, and Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, China.
Abstract:
The selective targeting of mismatched DNA overexpressed in cancer cells is an appealing strategy in designing cancer diagnosis and therapy protocols. Few luminescent probes that specifically detect intracellular mismatched DNA have been reported. Here we used Pt(II) complexes with luminescence sensitive to subtle changes in the local environment and report several Pt(II) complexes that selectively bind to and identify DNA mismatches. We evaluated the complexes' DNA-binding characteristics by ultraviolet/visible absorption titration, isothermal titration calorimetry, nuclear magnetic resonance and quantum mechanics/molecular mechanics calculations. These Pt(II) complexes show up to 15-fold higher emission intensities upon binding to mismatched DNA over matched DNA and can be utilized for both detecting DNA abasic sites and identifying cancer cells and human tissue samples with different levels of mismatch repair. Our work highlights the potential of luminescent Pt(II) complexes to differentiate between normal cells and cancer cells which generally possess more aberrant DNA structures.
Insights
New luminescent platinum(II) complexes selectively detect DNA mismatches, offering a promising tool for cancer diagnosis. These probes can differentiate between normal and cancer cells based on DNA structure abnormalities.
Area of Science:
- Biochemistry
- Chemical Biology
- Oncology
Background:
- Targeting mismatched DNA in cancer cells is a key strategy for diagnosis and therapy.
- Few luminescent probes exist for specific intracellular mismatched DNA detection.
Purpose of the Study:
- To develop and evaluate novel platinum(II) complexes for selective detection of DNA mismatches.
- To assess the potential of these complexes in identifying cancer cells and human tissues.
Main Methods:
- Synthesis and characterization of platinum(II) complexes.
- Evaluation of DNA-binding using UV-Vis titration, ITC, and NMR.
- Computational studies using QM/MM.
Main Results:
- Platinum(II) complexes exhibited selective binding to mismatched DNA over matched DNA.
- Emission intensities increased up to 15-fold upon binding to mismatched DNA.
- Complexes detected DNA abasic sites and differentiated cancer cells from normal cells.
Conclusions:
- Luminescent platinum(II) complexes show potential for detecting DNA mismatches and abasic sites.
- These complexes can distinguish between normal and cancerous cells based on DNA structure.
- The findings highlight a novel approach for cancer cell identification and diagnosis.
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