Search

Half-sandwich Ru(II) complexes belong to group of biologically active metallo-compounds with promising antimicrobial and anticancer activity. Herein, we report the synthesis and characterization of arene ruthenium complexes containing benzimidazole moiety, namely, [(η6-p-cymene)RuCl(bimCOO)] (1) and [(η6-p-cymene)RuCl2(bim)] (2) (where bimCOO = benzimidazole-2-carboxylate and bim = 1-H-benzimidazole). The compounds were characterized by 1H NMR, 13C NMR, IR, UV–vis and CV. Molecular structures of the complexes were determined by SC-XRD analysis, and the results indicated the presence of a pseudo-tetrahedral (piano stool) geometry. Interactions in the crystals of the Ru complexes using the Hirshfeld surface analysis were also examined. In addition, the biological studies of the complexes, such as antimicrobial assays (against planktonic and adherent microbes), cytotoxicity and lipophilicity, were performed. Antibacterial activity of the complexes was evaluated against S. aureus, E. coli, P. aeruginosa PAO1 and LES B58. Cytotoxic activity was tested against primary human fibroblasts and adenocarcinoma human alveolar basal epithelial cells. Obtained biological results show that the ruthenium compounds have bacteriostatic activity toward Pseudomonas aeruginosa PAO1 strain and are not toxic to normal cells. A molecular docking study was applied as a predictive source of information about the plausibility of examined structures binding with HSA as a transporting system.

Antimicrobial resistance is a growing public health concern that requires urgent action. Biofilm-associated resistance to antimicrobials begins at the attachment phase and increases as the biofilms maturate. Hence, interrupting the initial binding process of bacteria to surfaces is essential to effectively prevent biofilm-associated problems. Herein, we have evaluated the antibacterial and anti-biofilm activities of three ruthenium complexes in different oxidation states with 2-pyridin-2-yl-1H-benzimidazole (L1 = 2,2′-PyBIm): [(η6-p-cymene)RuIIClL1]PF6 (Ru(II) complex), mer-[RuIIICl3(CH3CN)L1]·L1·3H2O (Ru(III) complex), (H2L1)2[RuIIICl4(CH3CN)2]2[RuIVCl4(CH3CN)2]·2Cl·6H2O (Ru(III/IV) complex). The biological activity of the compounds was screened against Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa strains. The results indicated that the anti-biofilm activity of the Ru complexes at concentration of 1 mM was better than that of the ligand alone against the P. aeruginosa PAO1. It means that ligand, in combination with ruthenium ion, shows a synergistic effect. The effect of the Ru complexes on cell surface properties was determined by the contact angle and zeta potential values. The electric and physical properties of the microbial surface are useful tools for the examined aggregation phenomenon and disruption of the adhesion. Considering that intermolecular interactions are important and largely define the functions of compounds, we examined interactions in the crystals of the Ru complexes using the Hirshfeld surface analysis.

The constantly growing resistance of bacteria to antibiotics and other antibacterial substances has led us to an era in which alternative antimicrobial therapies are urgently required. One promising approach is to target bacterial pathogens using metal complexes. Therefore, we investigated the possibility of utilizing series of manganese(II) complexes with heteroaromatic ligands: Alcohol, aldehyde, ketone, and carboxylic acid as inhibitors for biofilm formation of Pseudomonas aeruginosa. To complete the series mentioned above, Mn-dipyCO-NO3 with dipyridin-2-ylmethanone (dipyCO) was isolated, and then structurally (single-crystal X-ray analysis) and physicochemically characterized (FT-IR, TG, CV, magnetic susceptibility). The antibacterial activity of the compounds against representative Gram-negative and Gram-positive bacteria was also evaluated. It is worth highlighting that the results of the cytotoxicity assays performed (MTT, DHI HoloMonitorM4) indicate high cell viability of the human fibroblast (VH10) in the presence of the Mn(II) complexes. Additionally, the inhibition effect of catalase activity by the complexes was studied. This paper focused on such aspects as studying different types of intermolecular interactions in the crystals of the Mn(II) complexes as well as their possible effect on anti-biofilm activity, the structure–activity relationship of the Mn(II) complexes, and regularity between the electrochemical properties of the Mn(II) complexes and anti-biofilm activity.

With increasing antimicrobial resistance there is an urgent need for new strategies to control harmful biofilms. In this study, we have investigated the possibility of utilizing ruthenium(IV) complexes (H3O)2(HL1)2[RuCl6]&middot, 2Cl&middot, 2EtOH (1) and [RuCl4(CH3CN)2](L32)&middot, H2O (2) (where L1-2-hydroxymethylbenzimadazole, L32-1,4-dihydroquinoxaline-2,3-dione) as effective inhibitors for biofilms formation. The biological activities of the compounds were explored using E. coli, S. aureus, P. aeruginosa PAO1, and P. aeruginosa LES B58. The new chloride ruthenium complexes were characterized by single-crystal X-ray diffraction analysis, Hirshfeld surface analysis, FT-IR, UV-Vis, magnetic and electrochemical (CV, DPV) measurements, and solution conductivity. In the obtained complexes, the ruthenium(IV) ions possess an octahedral environment. The intermolecular classical and rare weak hydrogen bonds, and &pi, &middot, &pi, stacking interactions significantly contribute to structure stabilization, leading to the formation of a supramolecular assembly. The microbiological tests have shown complex 1 exhibited a slightly higher anti-biofilm activity than that of compound 2. Interestingly, electrochemical studies have allowed us to determine the relationship between the oxidizing properties of complexes and their biological activity. Probably the mechanism of action of 1 and 2 is associated with generating a cellular response similar to oxidative stress in bacterial cells.

Pseudomonas aeruginosa biofilm-associated infections are a serious medical problem, and new compounds and therapies acting through novel mechanisms are much needed. Herein, the authors report a ruthenium(IV) complex that reduces P. aeruginosa PAO1 biofilm formation by 84%, and alters biofilm morphology and the living-to-dead cell ratio at 1 mM concentration. Including the compound in the culture medium altered the pigments secreted by PAO1, and fluorescence spectra revealed a decrease in pyoverdine. Scanning electron microscopy showed that the ruthenium complex did not penetrate the bacterial cell wall, but accumulated on external cell structures. Fluorescence quenching experiments indicated strong binding of the ruthenium complex to both plasmid DNA and bovine serum albumin. Formamidopyrimidine DNA N-glycosylase (Fpg) protein digestion of plasmid DNA isolated after ruthenium(IV) complex treatment revealed the generation of oxidative stress, which was further proved by the observed upregulation of catalase and superoxide dismutase gene expression.

The antibacterial and antibiofilm activities of two new ruthenium complexes against E. coli, S. aureus, P. aeruginosa PAO1 (laboratory strain) and P. aeruginosa LES B58 (clinical strain) were evaluated. Complexes, mer-[RuIII (2-bimc)3 ] ⋅ H2 O (1) and cis-[RuIV Cl2 (2,3-pydcH)2 ] ⋅ 4H2 O (2), were obtained using aromatic carboxylic acid ligands, namely, 1H-benzimidazole-2-carboxylic acid (2-bimcH) and pyridine-2,3-dicarboxylic acid (2,3-pydcH2 ). Compounds were physicochemically characterized using X-ray diffraction, Hirshfeld surface analysis, IR and UV/VIS spectroscopies, as well as magnetic and electrochemical measurements. Structural characterization revealed that Ru(III) and Ru(IV) ions in the complexes adopt a distorted octahedral geometry. The intermolecular classical and weak hydrogen bonds, and π⋅⋅⋅π contacts significantly contribute to structure stabilization, leading to the formation of a supramolecular assembly. Biological studies have shown that the Ru complexes inhibit the growth of bacteria and biofilm formation by the tested strains and the complexes seem to be a potential as antimicrobial agents.

A mononuclear compound of the general formula [(η6-p-cymene)RuIICl(2,2′-PyBIm)]PF6 has been synthesized from a bidentate N,N-donor ligand, viz. 2,-(2′-pyridyl)benzimidazole (2,2′-PyBIm) and the corresponding chloro-complex [(η6-p-cymene)Ru(μ-Cl)Cl]2 (precursor). The isolated coordination compound was characterized by IR, UV–vis and 1H, 13C NMR spectroscopies. The single crystal X-ray analysis of the complex reveals that the asymmetric part of the unit cell consists of two symmetrically independent, [(η6-p-cymene)RuCl(2,2′-PyBIm)]+ cationic complexes. Each cation exhibits a pseudo-octahedral three-legged piano-stool geometry, in which three “legs” are occupied by one chloride ion and two nitrogen donor atoms of the chelating ligand 2,2′-PyBIm. The Hirshfeld surface analysis of obtained complex was determined, too. The ionic nature of the compound is identified by a strong band at around 830 cm−1 due to the νP−F stretching mode of the PF6− counter ion. The electronic spectrum of this monomeric complex displays high intensity bands in the ultraviolet region assignable to π→π*/n→π* transitions, as well as a band attributable to the metal-to-ligand charge transfer (MLCT) dπ(Ru)→π*(L) transition. Additionally, the complex has been screened for its cytotoxicity against three human cancer lines: non-small cell lung carcinoma (A549), colon adenocarcinoma (HT29) and breast adenocarcinoma (MCF-7) as well as normal mice fibroblast cells (BALB/3T3). The complex demonstrated a moderate antiproliferative activity against the cell lines tested.

This review is focused on the use of nitrogen-containing heteroaromatic alcohols as ligands with increasing significance in diverse areas of chemistry. The application of such ligands ranges from structural chemistry, catalysis, and biomimetic modelling to molecular magnetism of polynuclear transition metal clusters as single-molecule magnets (SMMs). The efficiency of these ligands for the assembly of polynuclear complexes is due to their simultaneous N,O-chelating and O-bridging capabilities. For these reasons, to investigate the coordination chemistry of N-donor heteroaromatic alcohols presented in our earlier review, in this study, we paid special attention to (i) general approaches to formulate new SMMs based on 3d and 3d–4f central ions of polynuclear species and their structural and magnetic properties and (ii) synthesis of functional mimetics of metaloenzymes, such as catalase, and complexes with cytotoxic and antimicrobial properties. We also present an interesting group of coordination complexes with new multipodal ligands obtained in situ using 1-hydroxymethyl-3,5-dimethylpyrazole as a proligand.

Proteus mirabilis is a pathogenic gram-negative bacterium that frequently causes kidney infections, typically established by ascending colonization of the urinary tract. The present study is focused on ureolytic activity and urease inhibition in biofilms generated by P. mirabilis O18 cells. Confocal microscopy revealed morphological alterations in biofilms treated with urea and a urease inhibitor (acetohydroxamic acid, AHA), as some swarmer cells were found to protrude from the biofilm. The presence of a quorum-sensing molecule (N-butanoyl homoserine lactone, BHL) increased biofilm thickness and its ureolytic activity. Laser interferometric determination of diffusion showed that urea easily diffuses through P. mirabilis biofilm, while AHA is blocked. This may suggest that the use of urease inhibitors in CAUTIs may by less effective than in other urease-associated infections. Spectroscopic studies revealed differences between biofilm and planktonic cells indicating that polysaccharides and nucleic acids are involved in extracellular matrix and biofilm formation.

To compare thermal stability of Co(II), Zn(II), and Cd(II) complexes with 4-CHO-5-MeIm, the two compounds of formula [MnL2(NO3)2] and [NiL3](NO3)2 have been prepared and structurally characterized. Elemental analysis and spectroscopic studies have confirmed a bidentate fashion of coordination of the ligand to Mn(II) and Ni(II) ions. IR and Raman spectra indicate that there are different coordination modes of the NO3− in compounds: non-coordinated and coordinated. The decomposition process of the studied complexes in nitrogen and argon (Ni(II) complex) atmosphere proceeds in three main stages, except Zn(II) complex, in temperature range 353–1163 K. The final products of decomposition are CoO, MnO, Cd, ZnN4, NiN3. In addition, we have to admit that the different coordination mode of the NO3− ions in complexes: non-coordinated (in the (1), (4), and (5)) and coordinated (in the (2) and (3)) correlate with its thermal behavior. Thus, temperature ranges of its decompositions are observed: below 533 K and above 533 K, respectively. In Co(II), Mn(II), and Cd(II) complexes the fragments of N-donor atom-containing ligands decompose in the last stages, contrary to Zn(II) and Ni(II) compounds, in which metal ion surrounded by N atoms remains until the end. The course of pyrolysis and molecular structure of the complexes lead to the same conclusion about the strength of metal–ligand bonds. On the basis of obtained results, it is concluded that the thermal stability of the studied compounds follows the order: (1) < (5) < (2) < (3) < (4).

In this study, we analyzed influence of the type of the syntheses used: hydrothermal and non-hydrothermal on pyridine-2,3-dicarboxylic acid (2,3pydcH2) coordination fashion. Two manganese(II) complexes: [Mn(H2O)3(2,3pydc)] n (1) and [Mn(H2O)6][Mn(2,3pydcH)3]2 (2) were successfully synthesized from the non-hydrothermal reaction system containing organic ligand and different Mn(II) salts. The received complexes have been prepared and characterized by spectroscopic (IR, Raman), structural (X-ray single crystal), and thermogravimetric methods. The results of the crystal study give some evidence that ligand exhibits various topological structures and interesting properties. Pyridine-2,3-dicarboxylic acid acts as monodicarboxylate N,O-chelating anion (complex 2) or a doubly deprotonated three-dentate-N,O,O′ dicarboxylate ion (complex 1). In the [Mn(H2O)6][Mn(2,3pydcH)3]2 the coordination geometry around Mn(1) ion can be considered as being distorted octahedron {MnN3O3}. The Mn(2) cation possesses the same coordination polyhedron (octahedral). We have also analyzed influence of furnace atmosphere on the thermal behavior and the kind of final product. The sample of (1) decomposes in four stages in N2 (368–1073 K) and the final residue is MnO2. The thermogram of (2) exhibits three main distinct decomposition steps (383–973 K). A residue of MnO is remained. In both air and nitrogen atmosphere, Mn(II) complexes (1) and (2) keep unchanged over all steps of decomposition. Only the final residues are different (Mn2O3 are formed). The course of pyrolysis and molecular structure of the complexes lead to the same conclusion about the strength of metal–ligand bonds. On the basis of the above results, it is concluded that the thermal stability of the manganese(II) compounds is slightly different.

The reaction of zinc salts with heterocyclic ether (1-ethoxymethyl-2-methylimidazole (1-ExMe-2-MeIm)), acid (pyridine-2,3-dicarboxylic acid (2,3-pydcH2)) and amide (3,5-dimethylpyrazole-1-carboxamide (3,5-DMePzCONH2)) yielded three new zinc complexes formulated as [Zn(1-ExMe-2-MeIm)2Cl2] 1, fac-[Zn(H2O)6][Zn(2,3-pydcH)3]2 2 and [Zn(3,5-DMePz)2(NCO)2] 3. Complexes of 1 and 3 are four-coordinated with a tetrahedron as coordination polyhedron. However, compound 2 forms an octahedral cation–anion complex. The complex 3 was prepared by eliminating of the carboxamide group from the ligand and then the 3,5-dimethylpyrazole (3,5-DMePz) and isocyanates formed were employed as new ligands. The IR and X-ray studies have confirmed a bidentate fashion of coordination of the 2,3-pydcH and monodentate fashion of coordination of the 1-ExMe-2-MeIm and 3,5-DMePz to the Zn(II) ions. The crystal packing of Zn(II) complexes are stabilized by intermolecular classical hydrogen bonds of O–H⋯O and N–H⋯O types. The most interesting feature of the supramolecular architecture of complexes is the existence of C–H⋯O, C–H⋯Cl and C–H⋯π interactions and π⋯π stacking, which also contributes to structural stabilisation. The correlation between crystal structure and thermal stability of zinc complexes is observed. In all compounds the fragments of ligands donor-atom containing go in the last steps. Additionally, antimicrobial activities of compounds were carried out against certain Gram-positive and Gram-negative bacteria and counts of CFU (colony forming units) were also determined. The achieved results confirmed a significant antibacterial activity of some tested zinc complexes. On the basis of the Δ log CFU values the antibacterial activity of zinc complexes follows the order: 3 > 2 > 1. Influence a number of N-donor atoms in zinc environment on antibacterial activity is also observed.

The reactions of a mother solution of RuCl 3 with benzimidazole derivatives 2-(2 ’ -pyridyl)benzimidazole (2,2 ’ -PyBIm, L 1 ) and 2-hydroxymethylbenzimidazole (2-CH 2 OHBIm, L 2 ) yielded three novel ruthenium complexes: (H 2 L 1 ) 2 [Ru III Cl 4 (CH 3 CN) 2 ] 2 [Ru IV Cl 4 (CH 3 CN) 2 ]·2Cl·6H 2 O( 1 ), mer -[Ru III Cl 3 L 1 (CH 3 CN)]·L 1 ·3H 2 O( 2 ), and (HL 2 ) 4 [Ru IV Cl 6 ]·2Cl·4H 2 O( 3 ). The isolated compounds were characterised by elemental analyses, UV-Vis and IR spectroscopy, and magnetic measurements. The nature of the ligands bound to the metal ions of these compounds and the experimental conditions signi fi cantly in fl uenced the ruthenium com- plexes in di ff erent oxidation states. The N,N-donor ligand bound to the metal centre is a recognised stabiliser of the +III state of ruthenium, whereas the lack of ligand coordination promotes the formation of a mixed (Ru III /Ru IV ) complex. In the case of complex 3 , the absence of a N,O-donor ligand in the co- ordinate sphere facilitates the formation of the compound in a higher oxidation state. X-ray single crystal analyses revealed an octahedral geometry in each of the complexes. The crystal structure of ruthenium complexes is formed by a network of intermolecular classical and unconventional (C – H ⋯ π ) hydrogen bonds. The most interesting feature of the supramolecular architecture of complexes is the existence of a very rare Cl − ⋯ π interaction and π ⋯ π stacking, which also contribute to structural stabilisation. Ruthenium compounds 2 and 3 behave as paramagnets with an octahedral geometry, corresponding to the pres- ence of one or two unpaired electrons, respectively. The cyclic voltammetric data of complex 2 show three one-electron redox processes. The fi rst redox couple is reversible, whereas the two other couples have a quasi-reversible nature. In the case of complex 3 , two redox couples are reversible and the elec- trode processes are connected with exchange of one electron.