Synthesis and biological properties of tetranuclear ruthenium complexes containing the bis[4(4′-methyl-2,2′-bipyridyl)]-1,7-heptane ligand

Linear and non-linear tetranuclear ruthenium( ii ) complexes containing the bridging ligand bis[4(4′-methyl-2,2′-bipyridyl)]-1,7-heptane have been synthesised and their biological properties examined. The minimum inhibitory concentrations (MIC) and the minimum bactericidal concentrations (MBC) of th...

Full description

Saved in:
Bibliographic Details
Published in:Dalton transactions : an international journal of inorganic chemistry 2019-10, Vol.48 (38), p.1455-14515
Main Authors: Sun, Biyun, Sundaraneedi, Madhu K, Southam, Hannah M, Poole, Robert K, Musgrave, Ian F, Keene, F. Richard, Collins, J. Grant
Format: Article
Language:English
Subjects:
2,2'-Dipyridyl - chemistry
2,2'-Dipyridyl - pharmacology
Anti-Bacterial Agents - chemical synthesis
Anti-Bacterial Agents - chemistry
Anti-Bacterial Agents - pharmacology
Antiinfectives and antibacterials
Antimicrobial agents
Antineoplastic Agents - chemical synthesis
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Bacteria
Binding
Biological properties
Caco-2 Cells
Cell Proliferation - drug effects
Coordination Complexes - chemical synthesis
Coordination Complexes - chemistry
Coordination Complexes - pharmacology
Coordination compounds
Cytoplasm
Drug Screening Assays, Antitumor
E coli
Fluorescence
Gram-Negative Bacteria - drug effects
Gram-Positive Bacteria - drug effects
Hep G2 Cells
Heptanes
Heptanes - chemistry
Heptanes - pharmacology
Humans
Ligands
Mitochondria
Pseudomonas aeruginosa
Pyridines - chemistry
Ruthenium - chemistry
Ruthenium - pharmacology
Ruthenium compounds
Serum albumin
Toxicity
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Linear and non-linear tetranuclear ruthenium( ii ) complexes containing the bridging ligand bis[4(4′-methyl-2,2′-bipyridyl)]-1,7-heptane have been synthesised and their biological properties examined. The minimum inhibitory concentrations (MIC) and the minimum bactericidal concentrations (MBC) of the ruthenium( ii ) complexes were determined against six strains of bacteria: Gram-positive Staphylococcus aureus ( S. aureus ) and methicillin-resistant S. aureus (MRSA); and the Gram-negative Escherichia coli ( E. coli ) strains MG1655, APEC, UPEC and Pseudomonas aeruginosa ( P. aeruginosa ). The results showed that both tetranuclear complexes had significant antimicrobial activity, with the non-linear (branched) species ( Rubb 7 -TNL ) having slightly higher activity than the corresponding linear analogue ( Rubb 7 -TL ). The corresponding toxicity against three eukaryotic cell lines - BHK (baby hamster kidney), Caco-2 (heterogeneous human epithelial colorectal adenocarcinoma) and Hep-G2 (liver carcinoma) - have also been determined. Interestingly, both Rubb 7 -TNL and Rubb 7 -TL were as toxic to the eukaryotic cells as they were to the bacteria, a rarity for kinetically-inert cationic polypyridylruthenium( ii ) complexes, and exhibited lower IC 50 values than cisplatin over 24-, 48- or 72-hour incubation times. Fluorescence spectroscopy was used to study the binding of the ruthenium complexes with human serum albumin (HSA). Rubb 7 -TNL and Rubb 7 -TL exhibited strong HSA binding, with equilibrium binding constants in the order of 10 7 M −1 . Confocal microscopy was used to examine the cellular localisation of Rubb 7 -TNL in BHK cells. The results indicated that the ruthenium complex localised in the nucleolus. Significant accumulation was also observed in the cytoplasm, but not in the mitochondria. Taken together, the results of this study suggest that Rubb 7 -TNL is an unlikely candidate as an antimicrobial agent, but may have potential as an anticancer drug. The non-linear polypyridylruthenium( ii ) complex ( Rubb 7 -TNL ) exhibited good antimicrobial activity, but surprisingly was also highly active against cancer cells. The results suggest Rubb 7 -TNL may have potential as a new anticancer agent.
ISSN:1477-9226
1477-9234
DOI:10.1039/c9dt03221e