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The Synthesis, Characterization and Reactivity of a Series of Ruthenium N-triphosPh Complexes
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The Antimicrobial Activity of Mononuclear Ruthenium(II) Complexes Containing the dppz Ligand
Xuewen Liu1,2, Biyun Sun1, Ruby E M Kell3
1School of Physical, Environmental and Mathematical Sciences, University of New South Wales, Australian Defence Force Academy, Canberra, ACT, 2600, Australia.
Chempluschem
|January 18, 2020
Summary
A novel ruthenium complex, [Ru(bb7)(dppz)]2+, shows enhanced antibacterial activity, particularly against Gram-negative bacteria. This new compound demonstrates improved membrane interaction and accumulation, offering potential as a new antibacterial agent.
Area of Science:
- Coordination Chemistry
- Medicinal Chemistry
- Antimicrobial Research
Background:
- Ruthenium complexes are explored for their potential antimicrobial properties.
- The dipyrido[3,2-a:2',3'-c]phenazine (dppz) ligand is known to facilitate DNA intercalation.
- Modifications to bipyridyl ligands can influence complex activity and cellular uptake.
Purpose of the Study:
- To synthesize and characterize the cis-α isomer of [Ru(bb7)(dppz)]2+.
- To evaluate the antibacterial activity of [Ru(bb7)(dppz)]2+ and compare it with [Ru(phen)2(dppz)]2+.
- To investigate the mechanism of action, including cellular accumulation and membrane interaction.
Main Methods:
- Synthesis of ruthenium complexes: cis-α-[Ru(bb7)(dppz)]2+ and [Ru(phen)2(dppz)]2+.
- Determination of minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC) against various bacteria.
- Luminescence assays for cellular accumulation studies.
- Liposome interaction assays to assess membrane affinity.
- DNA binding affinity measurements.
Main Results:
- [Ru(bb7)(dppz)]2+ exhibits significantly enhanced activity against Gram-negative bacteria (at least eightfold) compared to [Ru(phen)2(dppz)]2+.
- Both complexes show good activity against Gram-positive bacteria.
- [Ru(bb7)(dppz)]2+ accumulates similarly in Gram-negative and Gram-positive bacteria.
- The novel complex demonstrates stronger interaction with liposomal membranes.
- DNA binding affinity of [Ru(bb7)(dppz)]2+ is 6.7 × 10^6 M^-1.
- [Ru(bb7)(dppz)]2+ is more toxic to eukaryotic cells but shows greater selectivity for bacterial cells.
Conclusions:
- The bb7 ligand enhances the antibacterial efficacy of the dppz-based ruthenium complex, especially against Gram-negative bacteria.
- Increased membrane interaction and cellular accumulation contribute to the improved activity of [Ru(bb7)(dppz)]2+.
- This complex shows promise as a selective antibacterial agent with potential applications in combating bacterial infections.
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