A series of mononuclear ruthenium(ii) complexes containing the tetradentate ligand bis[4(4'-methyl-2,2'-bipyridyl)]-1,7-heptane have been synthesised and their biological properties examined. In the synthesis of the [Ru(phen')(bb)] complexes (where phen' = 1,10-phenanthroline and its 5-nitro-, 4,7-dimethyl- and 3,4,7,8-tetramethyl- derivatives), both the symmetric cis-α and non-symmetric cis-β isomers were formed. However, upon standing for a number of days (or more quickly under harsh conditions) the cis-β isomer converted to the more thermodynamically stable cis-α isomer. 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 the [Ru(5-NOphen)(bb)] complex had little or no activity against any of the bacterial strains. By contrast, for the other cis-α-[Ru(phen')(bb)] complexes, the antimicrobial activity increased with the degree of methylation. In particular, the cis-α-[Ru(Mephen)(bb)] complex showed excellent and uniform MIC activity against all bacteria. By contrast, the MBC values for the cis-α-[Ru(Mephen)(bb)] complex varied considerably across the bacteria and even within S. aureus and E. coli strains. In order to gain an understanding of the relative antimicrobial activities, the DNA-binding affinity, cellular accumulation and water-octanol partition coefficients (log P) of the ruthenium complexes were determined. Interestingly, all the [Ru(phen')(bb)] complexes exhibited stronger DNA binding affinity (K ≈ 1 × 10 M) than the well-known DNA-intercalating complex [Ru(phen)(dppz)] (where dppz = dipyrido[3,2-a:2',3'-c]phenazine).

The extract of the strain Aspergillus flavipes DL‐11 exerted antibacterial activities against six Gram‐positive bacteria. During the following bioassay‐guided separation, ten diphenyl ethers (1–10), two benzophenones (11–12), together with two xanthones (13–14) were isolated. Among them, 4′‐chloroasterric acid (1) was a new chlorinated diphenyl ether. Their structures were elucidated by extensive spectroscopic data analysis, including IR, HR‐ESI‐MS, NMR experiments, and by comparison with the literature data. All compounds showed moderate to strong antibacterial effects on different Gram‐positive bacteria with MIC values that ranged from 3.13 to 50 μg/mL, but none of the compounds exhibited activity against Gram‐negative bacteria Vibrio parahaemolyticus ATCC17802 (MIC>100 μg/mL). In particular, the MICs of some compounds are at the level of positive control.

The cis‐α isomer of [Ru(bb7)(dppz)]2+ (dppz=dipyrido[3,2‐a:2′,3′‐c]phenazine; bb7=bis[4(4′‐methyl‐2,2′‐bipyridyl)]‐1,7‐alkane) has been synthesised. The minimum inhibitory concentrations and the minimum bactericidal concentrations of [Ru(bb7)(dppz)]2+ and its parent complex [Ru(phen)2(dppz)]2+ (phen=1,10‐phenanthroline) were determined against a range of bacteria. The results showed that both ruthenium complexes exhibited good activity against Gram‐positive bacteria, but [Ru(bb7)(dppz)]2+ showed at least eightfold better activity against the Gram‐negative bacteria than [Ru(phen)2(dppz)]2+. Luminescence assays demonstrated that [Ru(bb7)(dppz)]2+ accumulated in a Gram‐negative bacterium to the same degree as in a Gram‐positive species, and assays with liposomes showed that [Ru(bb7)(dppz)]2+ interacted more strongly with membranes than the parent [Ru(phen)2(dppz)]2+ complex. The DNA binding affinity for [Ru(bb7)(dppz)]2+ was determined to be 6.7 × 106 m−1. Although more toxic to eukaryotic cells than [Ru(phen)2(dppz)]2+, [Ru(bb7)(dppz)]2+ exhibited greater activity against bacteria than eukaryotic cells.

The non-linear polypyridylruthenium(ii) complex (Rubb7-TNL) exhibited good antimicrobial activity, but surprisingly was also highly active against cancer cells. The results suggest Rubb7-TNL may have potential as a new anticancer agent.

The toxicity (IC50) of a series of mononuclear ruthenium complexes containing bis[4(4′-methyl-2,2′-bipyridyl)]-1,n-alkane (bbn) as a tetradentate ligand against three eukaryotic cell lines—BHK (baby hamster kidney), Caco-2 (heterogeneous human epithelial colorectal adenocarcinoma) and Hep-G2 (liver carcinoma)—have been determined. The results demonstrate that cis-α-[Ru(Me4phen)(bb7)]2+ (designated as α-Me4phen-bb7, where Me4phen = 3,4,7,8-tetramethyl-1,10-phenanthroline) showed little toxicity toward the three cell lines, and was considerably less toxic than cis-α-[Ru(phen)(bb12)]2+ (α-phen-bb12) and the dinuclear complex [{Ru(phen)2}2{μ-bb12}]4+. Fluorescence spectroscopy was used to study the binding of the ruthenium complexes with human serum albumin (HSA). The binding of α-Me4phen-bb7 to the macrocyclic host molecule cucurbit[10]uril (Q[10]) was examined by NMR spectroscopy. Large upfield 1H NMR chemical shift changes observed for the methylene protons in the bb7 ligand upon addition of Q[10], coupled with the observation of several intermolecular ROEs in ROESY spectra, indicated that α-Me4phen-bb7 bound Q[10] with the bb7 methylene carbons within the cavity and the metal center positioned outside one of the portals. Simple molecular modeling confirmed the feasibility of the binding model. An α-Me4phen-bb7-Q[10] binding constant of 9.9 ± 0.2 × 106 M−1 was determined by luminescence spectroscopy. Q[10]-encapsulation decreased the toxicity of α-Me4phen-bb7 against the three eukaryotic cell lines and increased the binding affinity of the ruthenium complex for HSA. Confocal microscopy experiments indicated that the level of accumulation of α-Me4phen-7 in BHK cells is not significantly affected by Q[10]-encapsulation. Taken together, the combined results suggest that α-Me4phen-7 could be a good candidate as a new antimicrobial agent, and Q[10]-encapsulation could be a method to improve the pharmacokinetics of the ruthenium complex.

Fmoc-capped tetrapeptides bearing two lysines and two tyrosines show programmable enzymatic activity. Solvent accessible tyrosines determine the extent of reactivity with tyrosinase, and subsequent quinone formation drives polymerisation.

Phosphonopeptides are important phosphorus analogs of natural peptides and have been widely applied as enzyme inhibitors and antibacterial agents. A series of phosphonodipeptides containing C-terminal α-aminoalkylphosphonic acids was synthesized in satisfactory to good yields conveniently from 2-(N-benzyloxycarbonylamino)alkanamides, aldehydes, and phosphorus trichloride via Mannich-type reaction and subsequent sequential hydrolysis. The reaction mechanism was proposed and verified by (31)P NMR tracing experiments. The current method is an efficient and convenient method for preparation of phosphonopeptides containing C-terminal α-aminoalkylphosphonic acids.

The incorporation of polar amino acids into the Fmoc-FF motif yields tetrapeptide hydrogels whose biocompatibility in the gel state is inversely proportional to their biocompatibility in the solution state.