Radosław Starosta

Copper(I) iodide complexes containing new aliphatic aminophosphine ligands and diimines—luminescent properties and antibacterial activity

The new, water soluble, aminomethylphosphines were synthesized from P(CH2OH)3 and alkylpiperazines: P(CH2N(CH2CH2)2NCH3)3 (1) and P(CH2N(CH2CH2)2NCH2CH3)3 (2). Described already in literature P(CH2N(CH2CH2)2O)3 (3) were also obtained. The spectroscopic 1H, 31P and 13C NMR analyses and crystallographic studies of 1, 2 and 3 demonstrate that all these compounds have similar structures and spectroscopic properties, which almost do not depend on aliphatic rings in the molecules. Heteroleptic copper(I) iodide complexes with phosphines mentioned above and 2,2′-bipyridine (bpy): [CuI(bpy)P(CH2N(CH2CH2)2NCH3)3] (1B), [CuI(bpy)P(CH2N(CH2CH2)2NCH2CH3)3] (2B), [CuI(bpy)P(CH2N(CH2CH2)2O)3] (3B) or 1,10-phenanthroline (phen): [CuI(phen)P(CH2N(CH2CH2)2NCH3)3] (1P), [CuI(phen)P(CH2N(CH2CH2)NCH2CH3)3] (2P), [CuI(phen)P(CH2N(CH2CH2)2O)3] (3P) were also synthesized. All complexes were characterized by 1H, 31P and 13C NMR spectroscopy also. Molecular structures of 1P·PhCH3 and 3P·0.5Cu2I2(phen)2 were determined from single crystal X-ray diffraction studies. Upon excitation at 470 nm, all complexes in the solid state exhibit red photoluminescence due to charge transfer transition. The luminescence of phen complexes is higher than the luminescence of bpy ones. The presented phosphines and copper(I) complexes were screened for their in vitro antibacterial and antifungal activity against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus strains and Candida albicans. All the copper complexes exhibit significant antibacterial activity against Staphylococcus aureus strains. The activity of 1,10-phenanthroline complexes is higher than 2,2′-bipyridine complexes.

Biological activity and structure dependent properties of cuprous iodide complexes with phenanthrolines and water soluble tris (aminomethyl) phosphanes.

This paper presents the biological activity of copper(I) iodide complexes with 1,10-phenanthroline (phen) or 2,9-dimethyl-1,10-phenanthroline (dmp) and three tris (aminomethyl) phosphanes: P(CH2N(CH2CH2)2NCH3)3 (1), P(CH2N(CH2CH2)2O)3 (2) and P (CH2N(CH3)CH2CH2OH)3 (3). Crystallographic and DFT data indicate a significantly stronger binding ability of 3 in the complexes [CuI (phen) P (CH2N (CH3)CH2CH2OH)3] (3P) and [CuI(dmp)P(CH2N(CH3)CH2CH2OH)3] (3N) in comparison to the 1 or 2 ligands. Most probably, this is caused by the relatively small steric requirements of 3. The complexes with dmp exhibit a very high in vitro activity against the Staphylococcus aureus strain (MIC - minimal inhibitory concentration: 2.5-5 μg/mL) and Candida albicans diploid fungus (MIC: 1.25-2.5 μg/mL). All the tested complexes also show a strong in vitro antitumor activity against human ovarian carcinoma cell lines: MDAH 2774 (IC50: 7-2 μM) and cisplatin-resistant SCOV3 (IC50: 3-2 μM). Interestingly, the complexes with dmp of higher biological activity more weakly interact with bovine serum albumin (BSA) and less efficiently cleave the pBluescriptSK+ plasmid.

Copper(I) (pseudo)halide complexes with neocuproine and aminomethylphosphines derived from morpholine and thiomorpholine - in vitro cytotoxic and antimicrobial activity and the interactions with DNA and serum albumins.

Herein, a series of CuI or CuNCS complexes with neocuproine (2,9‐dimethyl‐1,10‐phenanthroline: dmp) and two tris(aminomethyl)phosphines derived from morpholine (P(CH2N(CH2CH2)2O)3) or thiomorpholine (P(CH2N(CH2CH2)2S)3) were tested as cytotoxic agents in vitro towards mouse colon carcinoma (CT26) and human lung adenocarcinoma (A549). The studies showed that the complexes exhibit potential antitumor properties, displayed by IC50 values below 10 μm towards the tested cell lines, in the case of 4‐h incubation time with the examined compounds. Moreover, a high antimicrobial activity of all the complexes was observed against Staphylococcus aureus and Candida albicans with minimal inhibitory concentrations equal to 1–2 μg/mL. To gain insight into the molecular mechanism of biological activity of the complexes, we investigated also their interactions with plasmid DNA (pUC18) and the human and bovine serum albumins. Gel electrophoresis experiments demonstrated that all the compounds were comparably efficient in DNA degradation process; however, luminescence quenching showed surprising dependence on the interactions strength of the used compounds with the albumins. Apart from exceptionally effective [CuI(dmp)P(CH2N(CH2CH2)2O)3], the complexes with P(CH2N(CH2CH2)2O)3 quenched more strongly luminescence of bovine serum albumin, while the complexes with P(CH2N(CH2CH2)2S)3 were more active in the quenching of human serum albumin luminescence.

Solid state luminescence of copper(I) (pseudo)halide complexes with neocuproine and aminomethylphosphanes derived from morpholine and thiomorpholine

The copper(I) iodide or copper(I) isothiocyanate complexes with 2,9-dimethyl-1,10-phenanthroline (dmp) and two interesting aminomethylphosphanes: P(CH2N(CH2CH2)2O)3 (1) and novel P(CH2N(CH2CH2)2S)3 (2): CuI(dmp)P(CH2N(CH2CH2)2O)3 (1I), which was presented in our previous papers, CuI(dmp)P(CH2N(CH2CH2)2S)3 (2I), CuNCS(dmp)P(CH2N(CH2CH2)2O)3 (1T) and CuNCS(dmp)P(CH2N(CH2CH2)2S)3 (2T) are discussed in this work. The chemical structures of three new complexes were determined in solution by means of NMR spectroscopy and in solid state using X-ray measurements. For all presented complexes the coordination geometry about the Cu(I) centre is pseudo-tetrahedral showing the small flattening and large rocking distortions. All compounds crystallize as the discrete dimers bound by π-stacking interactions between dmp rings, which strongly depend on the phosphane ligand. Investigated complexes exhibit orange photoluminescence in the solid state of highly diversified intensity, position of the luminescence band and the lifetimes. On the basis of TDDFT calculations, the CT bands observed in UV-Vis spectra are assigned to the two mixed transitions from the CuX (X = I or NCS) bond with a small admixture of the CuP bond to π* orbitals of the dmp ligand: (MX,MPR3)LCT. However, emission bands can be interpreted to be of (MX)LCT type.

Coordination versatility of phosphine derivatives of fluoroquinolones. New CuI and CuII complexes and their interactions with DNA

In this paper, new copper(I) and copper(II) complexes with phosphine derivatives of two fluoroquinolones (ciprofloxacin and norfloxacin) are presented. The synthesized compounds ([CuI-PCp], [CuI-PNr], [OPCp-CuII]+ and [OPNr-CuII]+) were characterized by elemental analysis and MS as well as by the NMR, EPR and IR spectroscopies. X-ray techniques were used to determine the crystal and molecular structures of [CuI-PCp]·CH2Cl2·CH3CN and OPCp-CuII]NO3·3H2O. For all the studied compounds, the ability to interact with DNA was determined using three different methods. The results of gel electrophoresis revealed that in the presence or absence of H2O2, the copper(I) complexes caused only single-stranded cleavage of the sugar–phosphate backbone of DNA. In turn, the copper(II) complexes damaged the plasmid exclusively in the presence of the oxidant. The addition of H2O2 caused distinct changes in the plasmid structure, resulting in a complete disappearance of its native form. Forms II and III arising from single- and double-strand cleavage were detected. Studies of the interactions with calf thymus DNA in the presence of ethidium bromide (EB) showed that the tested complexes and phosphines interact with DNA in a partial intercalation mode, contrary to unmodified antibiotic and oxide derivatives, which do not displace EB from the system. Molecular docking (AutoDock Vina program) was performed using the synthetic double-stranded hexadecanucleotide (sequence: ATATCGCGATATCGCG). Data analysis showed that a majority of the compounds preferably bound to the minor or major grooves, however most of them were also able to intercalate with the DNA double helix.

Phosphine derivatives of ciprofloxacin and norfloxacin, a new class of potential therapeutic agents

In this paper a new series of chalcogenides of diphenylmethylaminophosphine derived from ciprofloxacin (PPh2CH2Cp) and a new phosphine derived from norfloxacin (PPh2CH2Nr) are presented. The synthesized compounds were characterized by NMR, MS and X-ray techniques. Both phosphines exhibit antibacterial activity against: S. aureus, E. coli, K. pneumoniae and P. aeruginosa, similar to ciprofloxacin and norfloxacin. They inhibit the growth of microorganisms in relatively low concentrations. Chalcogenides are slightly less active than phosphines and unmodified antibiotics. All the derivatives were also tested in vitro as anticancer agents towards mouse colon carcinoma (CT26) and human lung adenocarcinoma (A549). Cytotoxicity studies revealed that phosphines and their chalcogenides are able to inhibit the proliferation of the cells at relatively low concentrations. Moreover, all the tested compounds are more active against tested cell lines than cisplatin – the main representative of antitumor drugs.

Ruthenium(II) piano stool coordination compounds with aminomethylphosphanes: Synthesis, characterisation and preliminary biological study in vitro

Reaction of {[Ru(η6-p-cymene)Cl]2(μ-Cl)2} (1) with aminomethylphosphane derived from morpholine (P{CH2N(CH2CH2)2O}3 (A), PPh2{CH2N(CH2CH2)2O} (B)) or piperazine (P{CH2N(CH2CH2)2NCH2CH3}3 (C), PPh2{CH2N(CH2CH2)2NCH2CH3} (D)) results in four new piano stool ruthenium(II) coordination compounds: [Ru(η6-p-cymene)Cl2(A)] (2A), [Ru(η6-p-cymene)Cl2(B)] (2B), [Ru(η6-p-cymene)Cl2(C)] (2C) and [Ru(η6-p-cymene)Cl2(D)] (2D). Every complex was fully characterized using spectroscopic methods (1H, 13C{1H}, 31P{1H} NMR and ESI-MS), elemental analysis, X-ray single crystal diffraction and DFT calculations. Preliminary studies of in vitro cytotoxicity on the A549 (human lung adenocarcinoma) and MCF7 (human breast adenocarcinoma) cell lines revealed 2A-2D activity in the same order of magnitude as in the case of cisplatin. Additionally, the study confirmed the ability of 2A-2D to interact with DNA helix and transferrin.

Infinite sheet structure of disodium tetra-μ-acetato- dichlorodirhodate(II) tetrahydrate

The binuclear rhodium(II) complex Na2[Rh2Cl2(OAc)4]· 4H2O has an infinite sheet structure. Binuclear anionic complexes [Rh2Cl2(OAc)4]2− are bound with cationic entities. The Na+ cation has pseudooctahedral coordination and is surrounded by two chloro ligands and two oxygen atoms of bridging acetato ligands of two [Rh2Cl2(OAc)4]2− anions and two water molecules. Both Cl and H2O are bridging ligands involved in formation of the Na+ chains. The remaining water molecules are located between sheets.

Molecular structure and properties of the rhodium(II) complexes with chemilabile ether–phosphine ligands P(2-MeOC6H4)3 and P(2,6-(MeO)2C6H3)3

Abstract Reactions of dirhodium tetraacetate [Rh2(O2CCH3)4] with tris(2-methoxyphenyl)phosphine (OMP) yield the oxygen-metallated complexes [Rh2(μ-OAc)3{μ-(2-OC6H4)P(2-MeOC6H4)2}(HOAc)] (1·HOAc) and [Rh2(μ-OAc)3{μ-(2-OC6H4)P(2-MeOC6H4)2}(NCMe)] (1·NCMe). In the case of tris(2,6-dimethoxyphenyl)phosphine (DOMP) analogous compound [Rh2(μ-OAc)3{μ-(2-O-(6-MeO)C6H3)P(2,6-(MeO)2C6H3)2}(HOAc)] (2·HOAc) was obtained. In both ligands the CH3+ cation of one of the methoxy substituents is split off and the phosphine replaces one of the acetato bridges to form the bridge with Rh24+ core closing the six-member ring via P and O atoms. The compounds have been characterized using UV–vis, IR, 1H-, 13C{1H}- and 31P{1H}-NMR spectroscopies. The crystal structure of compound 1·NCMe has been determined. The Rh(1)Rh(2) distance is distinctly longer than that in [Rh2(OAc)4(H2O)2] (3·2H2O). Axial sites of dirhodium core are occupied by a molecule of acetonitrile and a methoxy group of one of the nonmetallated phenyl rings. Detailed NMR studies reveal dynamic properties of complex 1 involving exchange between axial methoxy substituents and tilting of the metallated ring. The complexes 1 and 2 react with carbon monoxide giving complexes with a CO ligand coordinated in axial coordination sites.

Unexpected formation of [Ru(η5-C5H5)(PH{CH2N(CH2CH2)2O}2)(PPh3)2]BF4 – the first “piano-stool” ruthenium complex bearing a secondary aminomethylphosphane ligand

In this paper we report the reaction of [Ru(η5-C5H5)Cl(PPh3)2] with P{CH2N(CH2CH2)2O}3 in the presence of NaBF4, in which, apart from the Cl− substitution, an unexpected P–C bond cleavage in the tertiary phosphane is observed. It results in the formation of [Ru(η5-C5H5)(PH{CH2N(CH2CH2)2O}2)(PPh3)2]BF4 (1) – the first “piano-stool” ruthenium complex with a secondary aminomethylphosphane ligand.