Urszula Kalinowska-Lis

Synthesis, Characterization, and Antimicrobial Activity of Silver(I) and Copper(II) Complexes of Phosphate Derivatives of Pyridine And Benzimidazole

Two silver(I) complexes—{[Ag(4‐pmOpe)]NO3}n and [Ag(2‐bimOpe)2]NO3—and three copper(II) complexes—[Cu4Cl6O(2‐bimOpe)4], [CuCl2(4‐pmOpe)2], and [CuCl2(2‐bis(pm)Ope]—were synthesized by reaction of silver(I) nitrate or copper(II) chloride with phosphate derivatives of pyridine and benzimidazole, namely diethyl (pyridin‐4‐ylmethyl)phosphate (4‐pmOpe), 1H‐benzimidazol‐2‐ylmethyl diethyl phosphate (2‐bimOpe), and ethyl bis(pyridin‐2‐ylmethyl)phosphate (2‐bis(pm)Ope). These compounds were characterized by 1H, 13C, and 31Pu2005NMR as well as IR spectroscopy, elemental analysis, and ESIMS spectrometry. Additionally, molecular and crystal structures of {[Ag(4‐pmOpe)]NO3}n and [Cu4Cl6O(2‐bimOpe)4] were determined by single‐crystal X‐ray diffraction analysis. The antimicrobial profiles of synthesized complexes and free ligands against test organisms from the ATCC and clinical sources were determined. Silver(I) complexes showed good antimicrobial activities against Candida albicans strains (MIC values of ∼19u2005μM). [Ag(2‐bimOpe)2]NO3 was particularly active against Pseudomonas aeruginosa and methicillin‐resistant Staphylococcus epidermidis, with MIC values of ∼5 and ∼10u2005μM, respectively. Neither copper(II) complexes nor the free ligands inhibited the growth of test organisms at concentrations below 500u2005μgu2009mL−1.

Antibacterial Activity and Cytotoxicity of Silver(I) Complexes of Pyridine and (Benz)Imidazole Derivatives. X-ray Crystal Structure of [Ag(2,6-di(CH2OH)py)2]NO3

Selected aspects of the biological activity of a series of six nitrate silver(I) complexes with pyridine and (benz)imidazole derivatives were investigated. The present study evaluated the antibacterial activities of the complexes against three Gram-negative strains: Pseudomonas aeruginosa ATCC 15442, Escherichia coli ATCC 25922 and Proteus hauseri ATCC 13315. The results were compared with those of silver nitrate, a silver sulfadiazine drug and appropriate ligands. The most significant antibacterial properties were exerted by silver(I) complexes containing benzimidazole derivatives. The cytotoxic activity of the complexes was examined against B16 (murine melanoma) and 10T1/2 (murine fibroblasts) cells. All of the tested silver(I) compounds were not toxic to fibroblast cells in concentration inhibited cancer cell (B16) viability by 50%, which ranged between 2.44–28.65 µM. The molecular and crystal structure of silver(I) complex of 2,6-di(hydroxymethyl)pyridine was determined by single-crystal X-ray diffraction analysis. The most important features of the crystal packing and intermolecular non-covalent interactions in the Ag(I) complex were quantified via Hirshfeld surface analysis.

Cytotoxic activity and chemical reactivity of cis-platinum(II) and trans-palladium(II) complexes with diethyl (pyridinylmethyl)phosphates.

A series of square-planar platinum(II) and palladium(II) complexes of the formula cis-[PtCl2L2] and trans-[PdCl2L2] [L stands for diethyl (pyridin-2-ylmethyl)phosphate (2-pmOpe) or diethyl (pyridin-3-ylmethyl)phosphate (3-pmOpe) or diethyl (pyridin-4-ylmethyl)phosphate (4-pmOpe)] have been synthesized and tested in vitro for their cytotoxicity against mouse leukemia L1210 cells. The results indicated that the cis-platinum complexes showed superior activity than trans-palladium complexes, but lower in comparison to cisplatin. The chemical reactivity of the tested complexes has been determined in an in vitro NBP test. The platinum complexes exhibited very high chemical reactivity in NBP test, higher than cisplatin. The results showed no correlation between cytotoxicity and chemical reactivity for platinum complexes. Two platinum(II) complexes {cis-[PtCl2(2-pmOpe)2], cis-[PtCl2(3-pmOpe)2]} have been synthesized and characterized by IR, 1H NMR, 31P NMR, and elemental analysis.

Genotoxic effects of irinotecan combined with the novel platinum(II) complexes in human cancer cells.

Combination chemotherapy has become increasingly important as synergistic drugs enable to achieve therapeutic effects at substantially lower doses and limited spectrum of side effects. Irinotecan as a one of the camptothecin analogues has shown a broad spectrum of antitumor activity against various malignancies. It is commonly used in treatment of gastrointestinal and pulmonary cancer. In this study were measured the effect of the novel platinum(II) complexes: cis-[PtCl(2)(4-pmOpe)(2)] and trans-[PtCl(2)(4-pmOpe)(2)], with diethyl (pyridine-4-ylmethyl)phosphates (4-pmOpe) as non-leaving ligands, on genotoxicity of irinotecan in human cancer cells. Irinotecan showed genotoxic activity in combination with the new platinum(II) derivatives in cancer cells. Combination of irinotecan with cis-[PtCl(2)(4-pmOpe)(2)] or trans-[PtCl(2)(4-pmOpe)(2)] resulted in significant increase in DNA damage in A549 and HT29 cells when compared to effects of irinotecan or platinum(II) complexes used separately. The highest degree of DNA migration in the comet tails was found after the cancer cells were treated with irinotecan and trans-[PtCl(2)(4-pmOpe)(2)]. In addition, the analysis of DNA repair revealed that irinotecan in combination with trans-[PtCl(2)(4-pmOpe)(2)] induced unrepairable DNA damage suggesting the poor recognition of the damage by HMG proteins and other repair mechanisms. Thus, genotoxicity of irinotecan was modulated by the structurally different DNA-platinum adducts formed by novel platinum(II) complexes. These data suggest that the use of irinotecan with novel platinum(II) complexes may represent a new strategy for pharmacotherapy in cancer.

Influence of selected inorganic counter-ions on the structure and antimicrobial properties of silver(I) complexes with imidazole-containing ligands

Water-soluble silver(I) complexes containing the 4(5)-(hydroxymethyl)imidazole ligand with the formula [Ag(4-CH2OHimH)2]X (where X = NO3−, ClO4−, CF3COO−, BF4− and SO3CH3−) were synthesized. The complexes were characterized by NMR (1H and 13C) and IR spectroscopy, ESI-MS spectrometry and EA. The molecular structures of three complexes were confirmed by X-ray crystallography. The antimicrobial activity of the silver(I) complexes were evaluated against six strains of microorganisms: Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Pseudomonas aeruginosa, Proteus hauseri and Candida albicans. All tested silver complexes displayed excellent antibacterial properties against Gram-positive bacteria. Among them, the complex containing the trifluoroacetate counter-ion exhibited the highest antibacterial activity, with MIC values 2 to 3-fold lower than that required by silver sulfadiazine.

Complexing Properties of Pyridine-4-methylene Derivatives: Diethyl(pyridine-4-ylmethyl)phosphate, 4-Pyridylmethylphosphonic Acid and 4-Hydroxymethylpyridine with Cu(II) in Aqueous Solution

The coordinating properties in aqueous solution of two novel pyridine-4-methylene derivatives, diethyl(pyridine-4-ylmethyl)phosphate (4-PO(Oet)2CH2-pyxa0=xa04-pmOpe) and 4-pyridylmethylphos phonic acid (4-PO(OH)2CH2-pyxa0=xa04-pmpa), towards Cu(II) are compared with those of 4-hydroxymethyl-pyridine (4-OHCH2-pyxa0=xa04-pmOH). The two new derivatives were chosen due to their expected interesting biological activity that is observed for related solid complexes of several metals with various pyridine-methylene derivatives. The studies were carried out using pH potentiometry, UV–Vis spectrophotometry and EPR spectroscopy. The results show that 4-pmOpe and 4-pmpa, similarly to 4-OHCH2-py, form mononuclear L:Mxa0=xa01:1 and 2:1 complexes with Cu(II). However, in the case of 4-pmpa, complexation occurs both via oxygen atoms of the R-

Spectroscopic studies and crystal structure of a dimeric Zn(II) complex with diethyl (pyridin-2-ylmethyl)phosphate

{text{PO}}_{3}^{2 - }

Synthesis, characterization and antimicrobial activity of water-soluble silver(I) complexes of metronidazole drug and selected counter-ions

PO32- group (ML and ML2 species) and the N(1) nitrogen (protonated MLH and ML2H2 complexes). The possible attendance of the third ligand in the coordination sphere was indicated for 4-OHCH2-py by EPR spectroscopy.