Complex DNA binding kinetics resolved by combined circular dichroism and luminescence analysis

Area of Science:

• Coordination Chemistry
• Biophysical Chemistry
• Materials Science

Background:

• Ruthenium complexes demonstrate kinetic selectivity for AT-rich DNA sequences.
• Luminescence studies reveal complex, multiphasic binding kinetics for these complexes.
• Understanding intercalation mechanisms is crucial for developing novel DNA-targeting agents.

Purpose of the Study:

• To elucidate the factors governing the complex luminescence kinetics of ruthenium-DNA interactions.
• To investigate the influence of complex structure, flexibility, and ligand size on DNA intercalation.
• To correlate binding kinetics with DNA sequence and conformation.

Main Methods:

• Synthesis and characterization of novel ruthenium complexes with varying structural features.
• Monitoring DNA intercalation kinetics using luminescence spectroscopy and circular dichroism (CD).
• Comparative studies on homogeneous (poly(dAdT)2) and heterogeneous (ct-DNA) DNA sequences.

Main Results:

• Luminescence kinetics complexity arises from environmental sensitivity and binding geometry variations.
• DNA threading is monoexponential for B and P on poly(dAdT)2, but multiphasic on ct-DNA.
• Complex flexibility and ancillary ligand size significantly affect intercalation rates and kinetics.
• A rigid complex (F) shows slower threading than a flexible analogue (P).
• A complex with nonaromatic ligands (S) exhibits surprisingly slow and biphasic binding kinetics.

Conclusions:

• The observed complex luminescence trajectories are attributed to slow relaxations in binding geometry and environment.
• Flexibility of the bridging ligand and steric bulk of ancillary ligands are critical determinants of intercalation rates.
• The energy landscape of the threading pathway, influenced by ligand properties, governs DNA binding kinetics.