Journal article
Platinum(II) Complexes with Sterically Expansive Tetraarylethylene Ligands as Probes for Mismatched DNA
Inorganic chemistry, Vol.57(20), pp.12641-12649
10/15/2018
DOI: 10.1021/acs.inorgchem.8b01782
PMID: 30260643
Abstract
Deficiencies in DNA mismatch repair (MMR) machinery result in greater incidence of DNA base pair mismatches in many types of cancer cells relative to normal cells. Consequently, luminescent probes capable of signaling the presence of mismatched DNA hold promise as potential cancer diagnostic and therapeutic tools. In this study, a series of cyclometalated platinum(II) complexes with sterically expansive tetraarylethylene ligands were synthesized and examined for selective detection of mismatched DNA. Increased steric bulk of the tetraarylethylene ligands in these complexes was observed to correlate with greater preferential luminescence enhancement in the presence of hairpin DNA oligonucleotides containing a mismatched site compared to well-matched oligonucleotides, with the most effective complex displaying ∼14-fold higher emission upon binding CC mismatched oligonucleotides compared to well-matched oligonucleotides. The results indicate binding to mismatched sites in DNA oligonucleotides occurs through metalloinsertion, and the luminescence response increases as a function of thermodynamic destabilization of the mismatch. Luminescence quenching experiments with Cu(phen)
and NaI further indicate mismatch binding from the minor groove, consistent with metalloinsertion. Binding to CC mismatched oligonucleotides was also investigated by isothermal titration calorimetry and UV-melting studies. These results demonstrate the efficacy of tetraarylethylene-based platinum(II) complexes for detection of mismatched DNA and establish a new molecular platform for development of organometallic DNA binding agents.
Details
- Title: Subtitle
- Platinum(II) Complexes with Sterically Expansive Tetraarylethylene Ligands as Probes for Mismatched DNA
- Creators
- Moustafa T Gabr - Department of Chemistry , University of Iowa , Iowa City , Iowa 52242 , United StatesF Christopher Pigge - Department of Chemistry , University of Iowa , Iowa City , Iowa 52242 , United States
- Resource Type
- Journal article
- Publication Details
- Inorganic chemistry, Vol.57(20), pp.12641-12649
- DOI
- 10.1021/acs.inorgchem.8b01782
- PMID
- 30260643
- ISSN
- 0020-1669
- eISSN
- 1520-510X
- Grant note
- name: Department of Chemistry, University of Iowa; DOI: 10.13039/100012011, name: Graduate College, University of Iowa
- Language
- English
- Date published
- 10/15/2018
- Academic Unit
- Radiology; Chemistry
- Record Identifier
- 9984216567502771
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