Abstract
Luminescence of monoclinic lithium metatitanate (Li
2
TiO
3
) powders activated with different quantities of Mn
4+
is studied in detail. Its strong deep‐red emission arising from the Mn
4+ 2
...E
g
→
4
A
2g
spin forbidden transition is centered at around 688 nm and is suitable for luminescence thermometry. Structural and electron paramagnetic resonance analyses show that Mn
4+
ions are equally distributed in two almost identical Ti
4+
sites in which they are octahedrally coordinated by six oxygen ions. Calculations based on the exchange charge model of the crystal field provided values of Racah parameters (B=760 cm
−1
, C= 2993 cm
−1
), crystal‐field splitting Dq= 2043 cm
−1
, and the nephelauxetic parameter β
1
=0.9775. The maximal quantum efficiency of 24.1% at room temperature is found for 0.126% Mn
4+
concentration. Temperature quenching of emission occurs by a cross‐over via
4
T
2
excited state of the Mn
4+
ions with
T
1/2
=262 K and is quite favorable for the application in the lifetime‐based luminescence thermometry since relative changes in emission decay values are exceptionally‐large (around 3.21% at room temperature). We derived theoretical expressions for the temperature dependence of the absolute and relative sensitivities and discuss the influence of host material properties on lifetime sensitivities.
Five silver(I) complexes with aromatic nitrogen-containing heterocycles, phthalazine (phtz) and quinazoline (qz), were synthesized, characterized and analyzed by single-crystal X-ray diffraction ...analysis. Although different AgX salts reacted with phtz, only dinuclear silver(I) complexes of the general formula {Ag(X-O)(phtz-N)2(μ-phtz-N,N′)2} were formed, X=NO3− (1), CF3SO3− (2) and ClO4− (3). However, reactions of qz with an equimolar amount of AgCF3SO3 and AgBF4 resulted in the formation of polynuclear complexes, {Ag(CF3SO3-O)(qz-N)2}n (4) and {Ag(qz-N)BF4}n (5). Complexes 1–5 were evaluated by in vitro antimicrobial studies against a panel of microbial strains that lead to many skin and soft tissue, respiratory, wound and nosocomial infections. The obtained results indicate that all tested silver(I) complexes have good antibacterial activity with MIC (minimum inhibitory concentration) values in the range from 2.9 to 48.0μM against the investigated strains. Among the investigated strains, these complexes were particularly efficient against pathogenic Pseudomonas aeruginosa (MIC=2.9–29μM) and had a marked ability to disrupt clinically relevant biofilms of strains with high inherent resistance to antibiotics. On the other hand, their activity against the fungus Candida albicans was moderate. In order to determine the therapeutic potential of silver(I) complexes 1–5, their antiproliferative effect on the human lung fibroblastic cell line MRC5, has been also evaluated. The binding of complexes 1–5 to the genomic DNA of P. aeruginosa was demonstrated by gel electrophoresis techniques and well supported by molecular docking into the DNA minor groove. All investigated complexes showed an improved cytotoxicity profile in comparison to the clinically used AgNO3.
Five new silver(I) complexes with aromatic N-heterocycles phthalazine and quinazoline show potent activity against pathogenic Pseudomonas aeruginosa and can be used to prevent infections due to P. aeruginosa biofilms. Display omitted
•Synthesis and characterization of silver(I) complexes with phthalazine and quinazoline•Biological activities of the silver(I) complexes•High activity of the silver(I) complexes against Pseudomonas aeruginosa strains•Binding of the silver(I) complexes to genomic DNA from Pseudomonas aeruginosa
Three new silver(I) complexes Ag(NO
)(tia)(H
O)
(
), Ag(CF
SO
)(1,8-naph)
(
) and Ag
(1,8-naph)
(H
O)
(PF
)
(
), where tia is thianthrene and 1,8-naph is 1,8-naphthyridine, were synthesized and ...structurally characterized by different spectroscopic and electrochemical methods and their crystal structures were determined by single-crystal X-ray diffraction analysis. Their antimicrobial potential was evaluated against four bacterial and three
species, and the obtained results revealed that these complexes showed significant activity toward the Gram-positive
Gram-negative
and the investigated
species with minimal inhibitory concentration (MIC) values in the range 1.56-7.81 μg/mL. On the other hand, tia and 1,8-naph ligands were not active against the investigated strains, suggesting that their complexation with Ag(I) ion results in the formation of antimicrobial compounds. Moreover, low toxicity of the complexes was detected by in vivo model
. The interaction of the complexes with calf thymus DNA (ct-DNA) and bovine serum albumin (BSA) was studied to evaluate their binding affinity towards these biomolecules for possible insights into the mode of antimicrobial activity. The binding affinity of
-
to BSA was higher than that for DNA, indicating that proteins could be more favorable binding sites for these complexes in comparison to the nucleic acids.
Five aromatic nitrogen-containing heterocycles, pyridazine (pydz, 1), pyrimidine (pm, 2), pyrazine (pz, 3), quinoxaline (qx, 4) and phenazine (phz, 5) have been used for the synthesis of gold(iii) ...and silver(i) complexes. In contrast to the mononuclear Au1-5 complexes all having square-planar geometry, the corresponding Ag1-5 complexes have been found to be polynuclear and of different geometries. Complexes Au1-5 and Ag1-5, along with KAuCl sub(4), AgNO sub(3) and N-heterocyclic ligands used for their synthesis, were evaluated by in vitro antimicrobial studies against a panel of microbial strains that lead to many skin and soft tissue, respiratory, wound and nosocomial infections. All tested complexes exhibited excellent to good antibacterial activity with minimal inhibitory (MIC) values in the range of 2.5 to 100 mu g mL super(-1) against the investigated strains. The complexes were particularly efficient against pathogenic Pseudomonas aeruginosa (MIC = 2.5-30 mu g mL super(-1)) and had a marked ability to disrupt clinically relevant biofilms of strains with high inherent resistance to antibiotics. Moreover, the Au1-4 and Ag1-5 complexes exhibited pronounced ability to competitively intercalate double stranded genomic DNA of P. aeruginosa, which was demonstrated by gel electrophoresis techniques and supported by molecular docking into the DNA major groove. Antiproliferative effect on the normal human lung fibroblast cell line MRC5 has also been evaluated in order to determine therapeutic potential of Au1-5 and Ag1-5 complexes. Since the investigated gold(iii) complexes showed much lower negative effects on the viability of the MRC5 cell line than their silver(i) analogues and slightly lower antimicrobial activity against the investigated strains, the combination approach to improve their pharmacological profiles was applied. Synergistic antimicrobial effect and the selectivity index of 10 were achieved for the selected gold(iii)/silver(i) complexes mixtures, as well as higher P. aeruginosa PAO1 biofilm disruption activity, and improved toxicity profile towards zebrafish embryos, in comparison to the single complexes. To the best of our knowledge, this is the first report on synergistic activity of gold(iii)/silver(i) complexes mixtures and it could have an impact on development of new combination therapy methods for the treatment of multi-resistant bacterial infections.
In a search for novel antimicrobial metal-based therapeutic agents, mononuclear gold(III) complexes 1-7 of the general formula AuCl
(azole), where azole stands for imidazole (im, 1), ...1-isopropylimidazole (ipim, 2), 1-phenylimidazole (phim, 3), clotrimazole (ctz, 4), econazole (ecz, 5), tioconazole (tcz, 6) and voriconazole (vcz, 7) were synthesized, characterized and biologically evaluated. In all complexes, the corresponding azole ligand is monodentately coordinated to the Au(III)
the imidazole or triazole nitrogen atom, while the remaining coordination sites are occupied by chloride anions leading to the square-planar arrangement.
antimicrobial assays showed that the complexation of inactive azoles, imidazole, 1-isopropylimidazole and 1-phenylimidazole, to the Au(III) ion led to complexes 1-3, respectively, with moderate activity against the investigated strains and low cytotoxicity on the human normal lung fibroblast cell line (MRC-5). Moreover, gold(III) complexes 4-7 with clinically used antifungal agents clotrimazole, econazole, tioconazole and voriconazole, respectively, have, in most cases, enhanced antimicrobial effectiveness relative to the corresponding azoles, with the best improvement achieved after complexation of tioconazole (6) and voriconazole (7). The complexes 4-7 and the corresponding antifungal azoles inhibited the growth of dermatophyte
at 50 and 25 μg mL
. Gold(III) complexes 1-3 significantly reduced the amount of ergosterol in the cell membrane of
at the subinhibitory concentration of 0.5 × MIC (minimal inhibitory concentration), while the corresponding imidazole ligands did not significantly affect the ergosterol content, indicating that the mechanism of action of the gold(III)-azole complexes is associated with inhibition of ergosterol biosynthesis. Finally, complexes 5 and 6 significantly reduced the production of pyocyanin, a virulence factor in
controlled by quorum sensing, and increased cell survival after exposure to this bacterium. These findings could be of importance for the development of novel gold(III)-based antivirulence therapeutic agents that attenuate virulence without pronounced effect on the growth of the pathogens, offering a lower risk for resistance development.
Infections of the cow udder leading to mastitis and lower milk quality are one of the biggest problems in the dairy industry worldwide. Unfortunately, therapeutic options for the treatment of cow ...mastitis are limited as a consequence of the development of pathogens that are resistant to conventionally used antibiotics. In the search for agents that will be active against cow mastitis associated pathogens, in the present study, five new silver(i) complexes with different chelating pyridine-4,5-dicarboxylate types of ligands, Ag(NO
)(py-2py)
(1), Ag(NO
)(py-2metz)
(2), Ag(CH
CN)(py-2py)BF
(3), Ag(py-2tz)
BF
(4) and Ag(py-2metz)
BF
(5), py-2py is dimethyl 2,2'-bipyridine-4,5-dicarboxylate, py-2metz is dimethyl 2-(4-methylthiazol-2-yl)pyridine-4,5-dicarboxylate and py-2tz is dimethyl 2-(thiazol-2-yl)pyridine-4,5-dicarboxylate, were synthesized, structurally characterized and assessed for in vitro antimicrobial activity using both standard bioassay and clinical isolates from a contaminated milk sample obtained from a cow with mastitis. These complexes showed remarkable activity against the standard panel of microorganisms and a selection of clinical isolates from the milk of the cow diagnosed with mastitis. With the aim of determining the therapeutic potential of silver(i) complexes, their toxicity in vivo against the model organism, Caenorhabditis elegans (C. elegans), was investigated. The complexes that had the best therapeutic profile, 2 and 5, induced bacterial membrane depolarization and the production of reactive oxygen species (ROS) in Candida albicans cells and inhibited the hyphae as well as the biofilm formation. Taken together, the presented data suggest that the silver(i) complexes with pyridine ligands could be considered for the treatment of microbial pathogens, which are causative agents of cow mastitis.
Two zinc(II) complexes with dimethyl 2,2′-bipyridine-4,5-dicarboxylate (py-2py) of the general formula Zn(py-2py)X2, X = Cl− (1) and Br− (2) were synthesized and characterized by NMR, IR and UV-Vis ...spectroscopy and single-crystal X-ray diffraction analysis. Complexes 1 and 2 are isostructural and adopt a slightly distorted tetrahedral geometry with values of tetrahedral indices τ4 and τ’4 in the range of 0.80–0.85. The complexes were evaluated for their in vitro antimicrobial activity against two bacterial (Pseudomonas aeruginosa and Staphylococcus aureus) and two fungal strains (Candida albicans and Candida parapsilosis), while their cytotoxicity was tested on the normal human lung fibroblast cell line (MRC-5) and the model organism Caenorhabditis elegans. Complex 1 showed moderate activity against both Candida strains. However, this complex was twofold more cytotoxic compared to complex 2. The complexes tested had no effect on the survival rate of C. elegans. Complex 2 showed the ability to inhibit filamentation of C. albicans, while complex 1 was more effective than complex 2 in inhibiting biofilm formation. The interactions of complexes 1 and 2 with calf thymus DNA (ct-DNA) and bovine serum albumin (BSA) were studied to evaluate their binding affinity toward these biomolecules.
The purification of pravastatin, simvastatin and lovastatin in the sodium salt or lactone form and of mevastatin in the lactone form by reversed-phase displacement chromatography is presented. The ...mobile phases consisted of water or mixtures of water–methanol and water–acetonitrile. Six different displacers were successfully used. Up to 0.14 g of raw sample per gram of stationary phase was loaded on a column packed with silica-based octadecyl phase. Crude substances from 85 to 88% chromatographic purity were purified and at least 99.5% purity was achieved.
Five aromatic nitrogen-containing heterocycles, pyridazine (pydz,
1
), pyrimidine (pm,
2
), pyrazine (pz,
3
), quinoxaline (qx,
4
) and phenazine (phz,
5
) have been used for the synthesis of gold(
...iii
) and silver(
i
) complexes. In contrast to the mononuclear
Au1-5
complexes all having square-planar geometry, the corresponding
Ag1-5
complexes have been found to be polynuclear and of different geometries. Complexes
Au1-5
and
Ag1-5
, along with KAuCl
4
, AgNO
3
and N-heterocyclic ligands used for their synthesis, were evaluated by
in vitro
antimicrobial studies against a panel of microbial strains that lead to many skin and soft tissue, respiratory, wound and nosocomial infections. All tested complexes exhibited excellent to good antibacterial activity with minimal inhibitory (MIC) values in the range of 2.5 to 100 μg mL
−1
against the investigated strains. The complexes were particularly efficient against pathogenic
Pseudomonas aeruginosa
(MIC = 2.5-30 μg mL
−1
) and had a marked ability to disrupt clinically relevant biofilms of strains with high inherent resistance to antibiotics. Moreover, the
Au1-4
and
Ag1-5
complexes exhibited pronounced ability to competitively intercalate double stranded genomic DNA of
P. aeruginosa
, which was demonstrated by gel electrophoresis techniques and supported by molecular docking into the DNA major groove. Antiproliferative effect on the normal human lung fibroblast cell line MRC5 has also been evaluated in order to determine therapeutic potential of
Au1-5
and
Ag1-5
complexes. Since the investigated gold(
iii
) complexes showed much lower negative effects on the viability of the MRC5 cell line than their silver(
i
) analogues and slightly lower antimicrobial activity against the investigated strains, the combination approach to improve their pharmacological profiles was applied. Synergistic antimicrobial effect and the selectivity index of 10 were achieved for the selected gold(
iii
)/silver(
i
) complexes mixtures, as well as higher
P. aeruginosa
PAO1 biofilm disruption activity, and improved toxicity profile towards zebrafish embryos, in comparison to the single complexes. To the best of our knowledge, this is the first report on synergistic activity of gold(
iii
)/silver(
i
) complexes mixtures and it could have an impact on development of new combination therapy methods for the treatment of multi-resistant bacterial infections.
Combination therapy may be applied in the case of gold(
iii
) and silver(
i
) complexes with aromatic nitrogen-containing heterocycles to improve their antimicrobial activity and reduce toxic-side effects.
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