Table 1.
Activities of selected ruthenium complexes against bacteria, toxicity to healthy mammalian cells, and mode of action.
| Complex [Reference] |
Activity Strain: MIC Values (µg/mL) |
Toxicity to Healthy Mammalian Cells (IC50, µg/mL, 24 h, unless Stated Otherwise) |
Modes of Action | |
|---|---|---|---|---|
| Gram-Positive Strains | Gram-Negative Strains | |||
| Polypyridylruthenium (II) complexes | ||||
| [Ru(2,9-Me2phen)2(dppz)]2+ [40] |
S. aureus MRSA252: 2, MRSA41: 4, MSSA160: 8, B. subtilis 168: 4 |
Not active on E. coli MC4100 | - | bactericidal; DNA intercalation |
| R-825 [41] |
S. pneumoniae D39 WT: 27.5 piuA mutant: 55 |
- | Not toxic to human alveolar epithelial A549 cells up to 480 µM |
interference with iron acquisition systems in S. pneumoniae cells |
| X-03 [42] |
S. pneumoniae D39: 25, Streptococcus suis 05ZYH33: 100, S. pyogenes MGAS5005: 25, Listeria monocytogenes 19,117: 25, S. aureus 29,213: 50 |
E. coli K12: > 200, Vibrio alginolyticus V12G01: > 200, Vibrio parahaemolyticus RIMD 2,210,633: > 200, A. baumanii 19,606: > 200 |
Not toxic to human alveolar A549 and bronchial HBE epithelial cells up to 100 µg/mL |
interference with iron acquisition systems in S. pneumoniae cells; oxidative stress, membrane damage |
| [Ru(bpy)2Cl(clbzpy)]+ [43] |
S. aureus ATCC 25,923: 500, S. epidermidis ATCC 12,228: 250 |
P. aeruginosa ATCC 10,145: not active | - | membrane damage |
| [Ru(bpy)2(methionine)]2+ [44] |
upon blue LED irradiation S. aureus ATCC 25,923: 62.5, S. epidermidis ATCC 12,228: 125 |
P. aeruginosa ATCC 10,145: not active E. coli ATCC 11,303: 500 |
- | DNA photodamage |
| [Ru(dmb)2(ETPIP)]2+ [45] |
S. aureus Newman: 50 | - | - | - |
| [Ru(phen)2(ETPIP)]2+ [45] |
S. aureus Newman: 25 | - | - | inhibits biofilm formation; interacts with intracellular thiols |
| [Ru(bpy)2(BTPIP)]2+ [46] |
S. aureus Newman: 16 | - | - | inhibits biofilm formation |
| [Ru(bpy)2curcumin]+ [47] |
S. aureus ATCC 29,213: 1 |
A. baumanii BAA-1605: > 64, E. coli ATCC 25,922: > 64, K. pneumoniae BAA-1705: > 64, P. aeruginosa ATCC 27,853: > 64 |
Vero (African green monkey kidney epithelial) cells: > 80 | bactericidal; inhibits biofilm formation |
| [Ru(phen)2curcumin]+ [47] |
S. aureus ATCC 29,213: 1 |
A. baumanii BAA-1605: 8–16, E. coli ATCC 25,922: > 64, K. pneumoniae BAA-1705: > 64, P. aeruginosa ATCC 27,853: > 64 |
Vero (African green monkey kidney epithelial) cells: > 80 | - |
| Mono-bb7 [38] |
S. aureus MSSA ATCC 25,923: 4 MRSA (JCU culture collection): 16 |
E. coli ATCC 25,922: 16 P. aeruginosa ATCC 27,853: > 128 |
- | bactericidal; membrane damage |
| Mono-bb10 [37,38] |
S. aureus MSSA ATCC 25,923: 4 MRSA (JCU culture collection): 16 |
E. coli ATCC 25,922: 16 P. aeruginosa ATCC 27,853: 32 |
- | bactericidal |
| Mono-bb16 [37] |
S. aureus MSSA ATCC 25,923: 16 MRSA (JCU culture collection): 16 |
E. coli ATCC 25,922: 64 P. aeruginosa ATCC 27,853: 64 |
- | - |
|
cis-α-[Ru(phen)bb12]2+ [48] |
S. aureus MSSA ATCC 25,923: 0.5 MRSA (JCU culture collection): 4 |
E. coli ATCC 25,922: 8 P. aeruginosa ATCC 27,853: 8 |
- | DNA binding |
|
cis-β-[Ru(phen)(bb12)]2+ [48] |
S. aureus MSSA ATCC 25,923: 0.5 MRSA (JCU culture collection): 4 |
E. coli ATCC 25,922: 16 P. aeruginosa ATCC 27,853: 32 |
- | DNA binding |
| [Ru(bb7)(dppz)]2+ [49] |
S. aureus SH 1000: 2 MRSA USA 300 LAC JE2: 2 |
E. coli avian pathogenic: 8 uropathogenic: 8 E. coli MG1655: 8 P. aeruginosa PAO1: 16 |
human embryonic kidney HEK-293 cells: 27 (48 h), human fetal hepatocyte L02 cells: 64 (48 h) |
bactericidal, DNA binding |
| [Ru(Me4phen)2(dppz)]2+ [50] |
S. aureus SH1000: 9.7, E. faecalis V583: 38.8 |
E. coli MG1655: 4.9, EC958: 4.9, P. aeruginosa PA2017: 9.7 A. baumannii AB184: 9.7 |
- | bactericidal, chromosomal DNA binding |
| SCAR4 [51] |
M. tuberculosis H37Rv ATCC 27,294 (neither G+, nor G-): 0.63 | - | Mouse monocyte macrophage J774A.1 cell line: 19.5 |
covalent binding to DNA |
| SCAR5 [51] |
M. tuberculosis H37Rv ATCC 27,294 (neither G+, nor G-): 0.26 | - | J774A.1: 3.9 |
covalent binding to DNA |
| SCAR6 [51] |
M. tuberculosis H37Rv ATCC 27,294 (neither G+, nor G-): 3.90 | - | J774A.1: 78.2 | covalent binding to DNA |
| RuNN [52] |
S. aureus ATCC 25,923: 15.6, S. aureus ATCC 700,698 (MRSA): 62.5 S. epidermidis ATCC 12,228: 31.2, S. epidermidis ATCC 358,983: 62.5 |
- | no cytotoxic effect against human erythrocytes |
bactericidal; inhibits biofilm formation |
| [Ru(hexpytri)3](PF6)2
[53] |
S. aureus MSSA ATCC 25,923: 8, S. aureus MSSA NZRM 9653: 1, S. aureus MRSA MR 9519: 4, S. pyogenes: 4 |
E. coli ATCC 25,922: non-active | Vero cells: IC50 > 128 (48h) |
cell wall/cytoplasmic membrane damage |
| [Ru(hexyltripy) (heptyltripy)]Cl2 [54] |
S. aureus ATCC 25,923: 2 | E. coli ATCC 25,922: 8 | HDFa (skin cells): 16.4 |
abnormal cellular division |
| ΔΔ-Rubb7 [37,38] |
S. aureus MSSA ATCC 25,923: 16 MRSA (JCU culture collection): 16 |
E. coli ATCC 25,922: 16 P. aeruginosa ATCC 27853: 128 |
Red blood cells: > 1024 | bactericidal; membrane damage, interaction with ribosomal RNA |
| ΔΔ-Rubb12 [55,56] |
S. aureus MSSA ATCC 25,923: 1 MRSA (JCU culture collection): 1 |
E. coli ATCC 25,922: 2 P. aeruginosa ATCC 27,853: 16 |
Baby hamster kidney (BHK): 113.9, HEK-293: 82.2 |
bactericidal; membrane damage, interaction with ribosomal RNA |
| ΔΔ-Rubb16 [56] |
S. aureus MSSA ATCC 25,923: 1 MRSA (JCU culture collection): 1 |
E. coli ATCC 25,922: 4 P. aeruginosa ATCC 27,853: 8 |
Red blood cells: 22, BHK: 49.8, HEK-293: 35.1 |
bactericidal; membrane damage, interaction with ribosomal RNA |
| [Ru2(Me4phen)2(tpphz)]4+ [57,58,59] |
S. aureus MSSA SH1000: 86, Enterococcus faecalis V583: 1 |
E. coli WT G1655: 2.5, EC958 ST131 (multi-drug-resistant, clinical isolate): 3.5, P. aeruginosa (clinical isolate): 4, K. pneumoniae (clinical isolate): 3.5, A. baumannii (clinical isolate): 3.5 |
HEK-293: 270 | membrane and DNA damage |
| Cl-Rubb7-Cl [55,60] |
S. aureus MSSA ATCC 25,923: 8 MRSA (JCU culture collection): 8 |
E. coli ATCC 25,922: 8 P. aeruginosa ATCC 27,853: 32 |
- | bactericidal |
| Cl-Rubb12-Cl [55,60] |
S. aureus MSSA ATCC 25,923: 1 MRSA (JCU culture collection): 1 |
E. coli ATCC 25,922: 2 P. aeruginosa ATCC 27,853: 8 |
- | bactericidal |
| Cl-Rubb16-Cl [55,60] |
S. aureus MSSA ATCC 25,923: 8 MRSA (JCU culture collection): 8 |
E. coli ATCC 25,922: 8 P. aeruginosa ATCC 27,853: > 128 |
- | bactericidal |
| Rubb7-Cl [56] |
S. aureus MSSA ATCC 25,923: 8 MRSA (JCU culture collection): 16 |
E. coli ATCC 25,922: 1 P. aeruginosa ATCC 27,853: 16 |
BHK: 337.5, HEK-293: 98 |
interaction with chromosomal DNA and ribosomal RNA |
| Rubb12-Cl [56] |
S. aureus MSSA ATCC 25,923: 1 MRSA (JCU culture collection): 1 |
E. coli ATCC 25,922: 1 P. aeruginosa ATCC 27,853: 16 |
BHK: 70.6, HEK-293: 87.3 |
interaction with chromosomal DNA and ribosomal RNA |
| Rubb16-Cl [56] |
S. aureus MSSA ATCC 25,923: 1 MRSA (JCU culture collection): 2 |
E. coli ATCC 25,922: 4 P. aeruginosa ATCC 27,853: 64 |
BHK: 34.9, HEK-293: 63.5 |
interaction with chromosomal DNA and ribosomal RNA |
| Rubb7-tri [37,61] |
S. aureus MSSA ATCC 25,923: 4 MRSA (JCU culture collection): 4 |
E. coli ATCC 25,922: 16 P. aeruginosa ATCC 27,853: 2 |
- | interaction with DNA |
| Rubb7-tetra (Rubb7-TL) [62] |
S. aureus MSSA ATCC 25,923: 8 MRSA (JCU culture collection): 16 |
E. coli avian pathogenic: 16 uropathogenic: 16 E. coli MG1655: 16 P. aeruginosa PAO1: 32 |
BHK: 176 (24 h) BHK: 36.4 (72 h) |
interaction with proteins |
| Rubb7-TNL [62] |
S. aureus MSSA ATCC 25,923: 4 MRSA (JCU culture collection): 8 |
E. coli avian pathogenic: 16 uropathogenic: 16 E. coli MG1655: 8 P. aeruginosa PAO1: 16 |
BHK: 276 (24 h) BHK: 81.6 (72 h) |
interaction with proteins |
| Rubb12-tri [37,55,61] |
S. aureus: 1 MRSA (JCU culture collection): 1 |
E. coli: 4 P. aeruginosa: 32 |
BHK: 50.9 (72 h), HEK-293: 21.8 (72 h) |
bactericidal, interaction with DNA |
| Rubb12-tetra [37,55,61] |
S. aureus: 2 MRSA (JCU culture collection): 2 |
E. coli: 2 P. aeruginosa: 16 |
BHK: 43.7 (72 h), HEK-293: 21.3 (72 h) |
bactericidal, interaction with DNA |
| Rubb16-tri [37,55,61] |
S. aureus: 2 MRSA (JCU culture collection): 2 |
E. coli: 8 P. aeruginosa: 32 |
BHK: 25.1 (72 h), HEK-293: 20.2 (72 h) |
bactericidal, interaction with DNA |
| Rubb16-tetra [37,55,61] |
S. aureus: 2 MRSA (JCU culture collection): 2 |
E. coli: 8 P. aeruginosa: 32 |
BHK: 19.8 (72 h), HEK-293: 15.8 (72 h) |
bactericidal, interaction with DNA |
| Ruthenium-based CORMs | ||||
| CORM-2 [63,64,65] |
Growth inhibitory effects on S. aureus (MIC value not reported) |
E. coli avian pathogenic: 250, uropathogenic: 250, E. coli MG1655: 250, P. aeruginosa PAO1: 3.8 H. pylori strains (including antibiotic resistant): 100–200 |
Murine RAW264.7 monocyte macrophages: > 50 (DMEM culture medium) |
Bactericidal, inhibition of aerobic respiration, inhibition of biofilm formation and disruption of mature biofilms, ROS generation, interaction with chromosomal DNA and intracellular proteins, interference with iron homeostasis |
| CORM-3 [64,66,67] |
Growth inhibitory effects on S. aureus, Lactobacillus lactis (MIC value not reported) |
E. coli MG1655: 4 (minimal GDMM medium) and > 512 (in rich MH-II medium) H. pylori 26,695: 420 (antibiotic resistant strains) |
L929 murine fibroblast cells: 63 (RPMI culture medium), RAW264.7: > 30 (DMEM culture medium) |
|
| Ruthenium complexes in Antimicrobial Photodynamic Therapy | ||||
| [Ru(dmob)3]2+ [68] |
S. aureus NCTC 10788: 12.5 | P. aeruginosa NCTC 8626: 50 | - | Light activation |
|
cis-[Ru(bpy)2(INH)2]2+ [69] |
Mycobacterium smegmatis: 4 | human lung fibroblast MRC-5 cell line: > 200 |
465 nm blue light activation | |
| [Ru(Ph2phen)2(dpp) PtCl2]2+ [70] |
- | E. coli JM109: 8 | - | visible light activation, binding to chromosomal DNA |
| [Ru(CO)2Cl2]n [71] |
S. aureus CETC 240, coincident with ATCC 6538 P: 0.033 | E. coli CET 516, coincident with ATCC 8739: 0.0066 | human dermal fibroblasts hDF: > 3.33 | 365 nm UV light activation, ROS generation, biofilm inhibition |