Reductive and oxidative DNA damage by photoactive platinum(II) intercalators

Area of Science:

• Coordination Chemistry
• Photochemistry
• Biophysical Chemistry

Background:

• Development of photoactive metal complexes for probing biological systems.
• Platinum(II) complexes as potential agents for DNA interaction studies.
• Need for tools to investigate DNA oxidation and reduction mechanisms.

Purpose of the Study:

• Synthesize and characterize novel photoactive platinum(II) alpha-diimine intercalators.
• Evaluate the redox properties of these complexes in their excited states.
• Investigate their potential as probes for DNA oxidation and reduction chemistry.

Main Methods:

• Synthesis of five water-soluble bis(N,N,N,3,5-pentamethylaniline)Pt(II) complexes with aromatic alpha-diimine ligands.
• X-ray crystallography for structural characterization of [(naphtha[2,3-f][1,omega]phenanthroline)Pt(mes')(2)]Cl(2).
• Electrochemical measurements to determine excited-state oxidation and reduction potentials.
• Photochemical studies using modified nucleosides (N(2)-cyclopropyldeoxyguanosine and N(4)-cyclopropylcytidine) and DNA.

Main Results:

• Successful synthesis of platinum(II) complexes with diverse alpha-diimine ligands.
• Structural analysis revealed steric hindrance by mes' ligands, preventing unwanted substitution.
• Complexes exhibited potent photoreductant (-0.6 to -1.0 V) and photooxidant (1.0 to 1.5 V) properties.
• Photoexcited complexes, particularly [(dipyridophenazine)Pt(mes')(2)](2+), efficiently induced photooxidation of d(Cp)G and photoreduction of (Cp)C.
• Intercalation of [(dppz)Pt(mes')(2)]Cl(2) into DNA promoted both reductive and oxidative damage.

Conclusions:

• The synthesized platinum(II) complexes are effective photoactive agents for DNA studies.
• The complexes can act as both photooxidants and photoreductants, allowing versatile applications.
• These compounds serve as valuable tools for comparing reductive and oxidative DNA damage mechanisms.