Assembly of ruthenium complexes on double stranded DNA using mismatch binding ligands

Area of Science:

• Chemical Biology
• DNA Nanotechnology
• Coordination Chemistry

Background:

• DNA mismatches are critical in genetic variation and disease.
• Developing precise methods for targeting specific DNA structures is essential for molecular diagnostics and therapeutics.
• Small molecules offer versatile platforms for interacting with nucleic acids.

Purpose of the Study:

• To introduce novel small molecules, NCD-RO and NCD-RC, for DNA binding.
• To demonstrate the selective assembly of ruthenium complexes on G-G mismatch DNA.
• To utilize a naphthyridine carbamate dimer (NCD) scaffold for controlled metal complexation on double-stranded DNA (dsDNA).

Main Methods:

• Synthesis and characterization of NCD-RO and NCD-RC small molecules.
• DNA binding assays to assess selectivity for G-G mismatch DNA.
• Spectroscopic and structural analyses to confirm ruthenium complex assembly on DNA.

Main Results:

• NCD-RO and NCD-RC exhibit specific binding to G-G mismatch DNA sequences.
• The naphthyridine carbamate dimer scaffold facilitates controlled ruthenium complexation at the mismatch site.
• Selective metal complex assembly on DNA was achieved through rational molecular design.

Conclusions:

• NCD-RO and NCD-RC are effective tools for targeting G-G mismatch DNA.
• The NCD scaffold provides a robust platform for developing DNA-targeted metallodrugs or probes.
• This work advances the field of DNA-templated synthesis and molecular recognition.