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Published on: April 3, 2014
Ternary nickel(II) complexes as hydrolytic DNA-cleavage agents
Pulimamidi R Reddy1, Kandibanda S Rao
1Department of Chemistry, Osmania University, Hyderabad-500 007, India. rabi_pr@rediffmail.com
Chemistry & Biodiversity
|December 29, 2006
Summary
Nickel(II) complexes with ethylenediamine, histamine, and histidylleucine were synthesized and tested. These complexes show potential as DNA-cleavage agents, intercalating with DNA and cleaving it at physiological pH.
Area of Science:
- Coordination Chemistry
- Bioinorganic Chemistry
- Biophysical Chemistry
Background:
- Metal complexes are investigated for their potential in DNA manipulation.
- Understanding the interaction of metal complexes with DNA is crucial for developing novel therapeutic and diagnostic agents.
Purpose of the Study:
- To synthesize and characterize novel Nickel(II) complexes with ethylenediamine, histamine, and histidylleucine.
- To evaluate the DNA-binding and DNA-cleavage activities of these complexes at physiological pH.
Main Methods:
- Synthesis and characterization of Ni(II) complexes.
- Spectroscopic studies (UV/VIS, fluorescence titration) to determine DNA binding.
- Thermal denaturation assays to assess DNA intercalation.
- Electrophoresis to confirm DNA cleavage.
- ESI-MS for species identification.
- Molecular dynamics simulations for structural analysis.
Main Results:
- Formation of stable 1:1:1 ternary complexes [Ni(II)(en)(HisLeu)] and [Ni(II)(hist)(HisLeu)] at physiological pH.
- Both complexes intercalate into DNA with significant binding constants (150 and 290).
- Efficient cleavage of supercoiled DNA to nicked-circular DNA by both complexes at physiological pH (rate constants 0.64 and 0.75 h⁻¹).
Conclusions:
- The studied Ni(II) ternary complexes exhibit promising DNA-binding and hydrolytic DNA-cleavage properties.
- These complexes represent potential candidates for developing novel DNA-targeting agents.
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