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1.
Dalton Trans ; 49(25): 8528-8539, 2020 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-32525156

RESUMO

The search for new antifungals is very important because the large genetic variation of pathogenic organisms has resulted in the development of increasingly effective defense mechanisms by microorganisms. Metal complexes as potential drugs are nowadays gaining interest, because they are characterized by accessible redox states of metal centers and a plethora of easily modifiable geometries. In this work we present two new copper(i) iodide or thiocyanide complexes with 2,9-dimethyl-1,10-phenanthroline (dmp) and a diphenylphosphane derivative of ketoconazole (KeP), where a ketoconazole acetyl group is replaced by the -CH2PPh2 unit, [CuI(dmp)KeP] (1-KeP) and [CuNCS(dmp)KeP] (2-KeP) - their synthesis and structural characteristics. The analysis of the intrinsic fluorescence of the ketoconazole moiety in the coordinated KeP molecule revealed that the copper(i) central atom does not act as a quencher and the observed decrease of fluorescence intensity is a result of a strong inner filter effect caused by the presence of the CuXdmp unit. Moreover, the complexes exhibit a remarkable MLCT (metal-ligand charge transfer) based phosphorescence with the emission maximum at 600-615 nm in aqueous media, which probably results from the formation of dimers and higher order oligomers in the most polar solutions. Both complexes proved to be promising antifungal agents towards Candida albicans, showing a relatively high efficiency towards the fluconazole resistant strains with -CDR1 and CDR2 or MDR1 efflux pump overexpression, which suggests that they overcome at least partially these defense mechanisms. Simulations of docking to the cytochrome P450 14α-demethylase (the azoles' primary molecular target) suggested that the compounds studied were rather incapable of competitively inhibiting this enzyme, unlike ketoconazole and the KeP ligand. On the other hand, the phosphorescence in aqueous solutions allowed recording the confocal micrographs of the complexes which showed that both of them are situated in spherical structures inside the cells, most likely in the vacuoles.


Assuntos
Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Complexos de Coordenação/farmacologia , Inibidores das Enzimas do Citocromo P-450/farmacologia , Sistema Enzimático do Citocromo P-450/metabolismo , Imagem Óptica , Adulto , Antifúngicos/síntese química , Antifúngicos/química , Candida albicans/citologia , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Cobre/química , Cobre/farmacologia , Inibidores das Enzimas do Citocromo P-450/síntese química , Inibidores das Enzimas do Citocromo P-450/química , Humanos , Cetoconazol/química , Cetoconazol/farmacologia , Medições Luminescentes , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Estrutura Molecular , Fenantrolinas/química , Fenantrolinas/farmacologia , Fosfinas/química , Fosfinas/farmacologia
2.
Sci Rep ; 9(1): 16214, 2019 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-31700024

RESUMO

Four new derivatives of ketoconazole (Ke) were synthesized: diphenylphosphane (KeP), and phosphane chalcogenides: oxide (KeOP), sulphide (KeSP) and selenide (KeSeP). These compounds proved to be promising antifungal compounds towards Saccharomyces cerevisiae and Candida albicans, especially in synergy with fluconazole. Simulations of docking to the cytochrome P450 14α-demethylase (azoles' primary molecular target) proved that the new Ke derivatives are capable of inhibiting this enzyme by binding to the active site. Cytotoxicity towards hACSs (human adipose-derived stromal cells) of the individual compounds was studied and the IC50 values were higher than the MIC50 for C. albicans and S. cerevisiae. KeP and KeOP increased the level of the p21 gene transcript but did not change the level of p53 gene transcript, a major regulator of apoptosis, and decreased the mitochondrial membrane potential. Taken together, the results advocate that the new ketoconazole derivatives have a similar mechanism of action and block the lanosterol 14α-demethylase and thus inhibit the production of ergosterol in C. albicans membranes.


Assuntos
Antifúngicos/química , Antifúngicos/farmacologia , Compostos de Bifenilo/química , Cetoconazol/química , Cetoconazol/farmacologia , Tecido Adiposo/citologia , Antifúngicos/toxicidade , Apoptose/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Sinergismo Farmacológico , Humanos , Cetoconazol/toxicidade , Saccharomyces cerevisiae/efeitos dos fármacos , Células-Tronco/citologia , Células-Tronco/efeitos dos fármacos
3.
J Inorg Biochem ; 189: 69-80, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30243120

RESUMO

Fusobacterium nucleatum is an anaerobic, Gram-negative bacteria linked to colon cancer. It is interesting to determine how metal ions interact with bacterial adhesin proteins. To this end, the coordination of ATDAAS-NH2 and MKKFL-NH2 fragments of Fusobacterium adhesin A (FadA) to copper(II) ions was studied by potentiometry, spectroscopic techniques (UV-Vis, CD, EPR and NMR) and the density functional theory (DFT) methods. At pH 6.8 (colon physiological pH), the metal ion in the first peptide (ATDAAS-NH2) is coordinated by one oxygen and three nitrogen donors while in the second one (MKKFL-NH2) - by sulfur and three nitrogen atoms. Both complexes form two five- and one six-membered stable chelate rings. Moreover, reactivity studies confirmed the production of reactive oxygen species such as hydroxyl radical, superoxide anion radical and singlet oxygen. Generation of reactive oxygen species (ROS) was observed during gel electrophoresis and spectroscopic assays with reporting molecules like NDMA (N,N-dimethyl-p-nitrosoaniline) and NBT (Nitrotetrazolium Blue Chloride). All reactions were conducted in the presence of hydrogen peroxide as endogenous oxidant.


Assuntos
Adesinas Bacterianas/química , Cobre/química , Fusobacterium nucleatum/química , Espectroscopia de Ressonância de Spin Eletrônica , Concentração de Íons de Hidrogênio , Potenciometria , Espécies Reativas de Oxigênio/química , Superóxidos/química
4.
J Inorg Biochem ; 186: 162-175, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29945023

RESUMO

The main disadvantage of conventional anticancer chemotherapy is the inability to deliver the correct amount of drug directly to cancer. Those molecular delivering systems are very important to destroy cancer cells selectively. Herein we report synthesis of phosphine-peptide conjugate (Ph2PCH2-Sar-Gly-OH, PSG) derived from SarGly (sarcosine-glycine), which can be easily exchanged to other peptide carriers, its oxide (OPh2PCH2-Sar-Gly-OH, OPSG) and the first copper(I) complex ([CuI(dmp)(P(Ph)2CH2-Sar-Gly-OH)], 1-PSG, where dmp stands for 2,9-dimethyl-1,10-phenanthroline). The compounds were characterized by elemental analysis, NMR (1D, 2D), UV-Vis spectroscopy and DFT (Density Functional Theory) methods. PSG and 1-PSG proved to be stable in biological medium in the presence of atmospheric oxygen for several days. The cytotoxicity of the compounds and cisplatin was tested against cancer cell lines: mouse colon carcinoma (CT26; 1-PSGIC50 = 3.12 ±â€¯0.1), human lung adenocarcinoma (A549; 1-PSGIC50 = 2.01 ±â€¯0.2) and human breast adenocarcinoma (MCF7; 1-PSGIC50 = 0.98 ±â€¯0.2) as well as against primary line of human pulmonary fibroblasts (MRC-5; 1-PSGIC50 = 78.56 ±â€¯1.1). Therapeutic index for 1-PSG (MCF7) equals 80. Intracellular accumulation of 1-PSG complex increased with time and was much higher (96%) inside MCF7 cancer cells than in normal MRC5 cells (20%). Attachment of SarGly to cytotoxic copper(I) complex via phosphine motif improved selectivity of copper(I) complex 1-PSG into the cancer cells. Precise mechanistic study revealed that the 1-PSG complex causes apoptotic cells MCF7 death with simultaneous decrease of mitochondrial membrane potential and increase of caspase-9 and -3 activities. Additionally, 1-PSG generated high level of reactive oxygen species that was the reason for oxidative damages to the sugar-phosphate backbone of plasmid DNA.


Assuntos
Antineoplásicos , Neoplasias da Mama/tratamento farmacológico , Complexos de Coordenação , Cobre , Peptídeos , Fosfinas , Células A549 , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Cobre/química , Cobre/farmacologia , Feminino , Humanos , Células MCF-7 , Peptídeos/química , Peptídeos/farmacologia , Fosfinas/química , Fosfinas/farmacologia
5.
J Inorg Biochem ; 170: 178-187, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28259056

RESUMO

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.


Assuntos
Complexos de Coordenação , Rutênio , Células A549 , Cisplatino/farmacologia , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Humanos , Células MCF-7 , Rutênio/química , Rutênio/farmacologia
6.
J Inorg Biochem ; 165: 25-35, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27764707

RESUMO

In this paper we present lomefloxacin's (HLm, 2nd generation fluoroquinolone antibiotic agent) organic and inorganic derivatives: aminomethyl(diphenyl)phosphine (PLm), its oxide as well as new copper(I) iodide or copper(I) thiocyanate complexes with PLm and 2,9-dimethyl-1,10-phenanthroline (dmp) or 2,2'-biquinoline (bq) as the auxiliary ligands. The synthesized compounds were fully characterised by NMR, UV-Vis and luminescence spectroscopies. Selected structures were analysed by theoretical DFT (density functional theory) methods. High stability of the complexes in aqueous solutions in the presence of atmosferic oxygen was proven. Cytotoxic activity of all compounds was tested towards three cancer cell lines (CT26 - mouse colon carcinoma, A549 - human lung adenocarcinoma, and MCF7 - human breast adenocarcinoma). All complexes are characterised by cytotoxic activity higher than the activity of the parent drug and its organic derivatives as well as cisplatin. Studied derivatives as well as parent drug do not intercalate to DNA, except Cu(I) complexes with bq ligand. All studied complexes caused single-stranded cleavage of the sugar-phosphate backbone of plasmid DNA. The addition of H2O2 caused distinct changes in the plasmid structure and led to single- and/or double-strain plasmid cleavage. Studied compounds interact with human serum albumin without affecting its secondary structure.


Assuntos
Cobre , Citotoxinas , DNA/química , Fluoroquinolonas , Albumina Sérica/química , Animais , Cobre/química , Cobre/farmacologia , Citotoxinas/síntese química , Citotoxinas/química , Citotoxinas/farmacologia , DNA/metabolismo , Feminino , Fluoroquinolonas/síntese química , Fluoroquinolonas/química , Fluoroquinolonas/farmacologia , Humanos , Células MCF-7 , Camundongos , Espectrofotometria
7.
Dalton Trans ; 44(31): 13969-78, 2015 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-26155929

RESUMO

Addition of aminomethylphosphane P{CH2N(CH2CH2)2O}3 (), PPh2{CH2N(CH2CH2)2O} () or PPh2{CH2N(CH2CH2)2NCH2CH3} () to a methanolic solution of RuCl3 results in reduction of ruthenium(iii) ions giving finally ttt-[RuCl2()2] (), ttt-[RuCl2()2] () and ttt-[RuCl2()2] (). The synthesized complexes are the first examples of ruthenium(ii) coordination compounds possessing aminomethylphosphanes chelating via phosphorus and nitrogen atoms. They were fully characterized (NMR, ESI-MS, IR, elemental analysis, X-ray crystallography). Preliminary studies of the in vitro cytotoxicity on the A549 cell line (human lung adenocarcinoma) and interactions with human serum proteins (albumin and apotransferrin) showed moderate activity of the complexes. Interestingly, the P,N-chelation leads to formation of strained 4-membered Ru-P-C-N-Ru rings, which in the case of and undergo opening in the presence of CH3CN, which results in rearrangement to ctc-[RuCl2()2(CH3CN)2] () and ctc-[RuCl2()2(CH3CN)2] ().


Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Complexos de Coordenação/síntese química , Complexos de Coordenação/farmacologia , Fosfinas/química , Rutênio/química , Antineoplásicos/química , Antineoplásicos/metabolismo , Apoproteínas/metabolismo , Linhagem Celular Tumoral , Técnicas de Química Sintética , Complexos de Coordenação/química , Complexos de Coordenação/metabolismo , Humanos , Ligantes , Modelos Moleculares , Conformação Molecular , Óxidos/química , Albumina Sérica/metabolismo , Transferrina/metabolismo
8.
Dalton Trans ; 44(28): 12688-99, 2015 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-26085118

RESUMO

In this paper we present new copper(i) iodide or copper(i) thiocyanate complexes with hydroxymethyldiphenylphosphine (PPh2(CH2OH)) or phosphine derivatives of sparfloxacin, a 3(rd) generation fluoroquinolone antibiotic agent (PPh2(CH2-Sf)) and 2,9-dimethyl-1,10-phenanthroline (dmp) or 2,2'-biquinoline (bq) auxiliary ligands. The synthesised complexes were fully characterised by NMR and UV-Vis spectroscopy as well as by mass spectrometry. Selected structures were additionally analysed using X-ray and DFT methods. All complexes proved to be stable in solution in the presence of water and atmospheric oxygen for several days. The cytotoxic activity of the complexes was tested against two cancer cell lines (CT26 - mouse colon carcinoma and A549 - human lung adenocarcinoma). Applying two different incubation times, the studies enabled a preliminary estimation of the dependence of the selectivity and the mechanism of action on the type of diimine and phosphine ligands. The results obtained showed that complexes with PPh2(CH2-Sf) are significantly more active than those with PPh2(CH2OH). On the other hand, the relative impact of diimine on cytotoxicity is less pronounced. However, the dmp complexes are characterised by strong inhibitory properties, while the bq ones are rather not. This confirms the interesting and promising biological properties of the investigated group of copper(i) complexes, which undoubtedly are worthy of further biological studies.


Assuntos
Complexos de Coordenação , Cobre , Iodetos , Fenantrolinas , Fosfinas , Quinolinas , Tiocianatos , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Cobre/química , Cobre/farmacologia , Cristalografia por Raios X , Fluoroquinolonas/química , Humanos , Iodetos/química , Iodetos/farmacologia , Ligantes , Espectroscopia de Ressonância Magnética , Camundongos , Fenantrolinas/química , Fenantrolinas/farmacologia , Fosfinas/química , Fosfinas/farmacologia , Quinolinas/química , Quinolinas/farmacologia , Espectrofotometria Ultravioleta , Tiocianatos/química , Tiocianatos/farmacologia
9.
J Inorg Biochem ; 142: 68-74, 2015 01.
Artigo em Inglês | MEDLINE | ID: mdl-25450020

RESUMO

We have studied processes of copper(II) ion binding by ribavirin, an antiviral agent used in treating hepatitis C, which is accompanied usually by an increased copper level in the serum and liver tissue. Protonation equilibria and Cu(II) binding were investigated using the UV-visible, EPR and NMR spectroscopic techniques as well as the DFT (density functional theory) calculations. The spectroscopic data suggest that the first complex is formed in the water solution at pH as low as 0.5. In this compound Cu(II) ion is bound to one of the nitrogen atoms from the triazole ring. Above pH6.0, the metal ion is surrounded by two nitrogen and two oxygen atoms from two ligand molecules. The DFT calculations allowed to determine the exact structure of this complex. We found that in the lowest energy isomer two molecules of the ligand coordinate via O and N4 atoms in trans positions. The hypothetical oxidative properties of the investigated system were also examined. It proved not to generate plasmid DNA scission products. However, the calf thymus (CT)-DNA binding studies showed that it reacts with ribavirin and its cupric complex. Moreover, the interaction with the complex is much more efficient.


Assuntos
Antivirais/química , Complexos de Coordenação/química , Cobre/química , DNA/química , Ribavirina/química
10.
Chem Biol Drug Des ; 82(5): 579-86, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23841542

RESUMO

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(CH2 N(CH2 CH2 )2 O)3 ) or thiomorpholine (P(CH2 N(CH2 CH2 )2 S)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(CH2 N(CH2 CH2 )2 O)3 ], the complexes with P(CH2 N(CH2 CH2 )2 O)3 quenched more strongly luminescence of bovine serum albumin, while the complexes with P(CH2 N(CH2 CH2 )2 S)3 were more active in the quenching of human serum albumin luminescence.


Assuntos
Anti-Infecciosos , Complexos de Coordenação , Cobre/química , DNA/metabolismo , Fenantrolinas/química , Fosfinas/química , Albumina Sérica/metabolismo , Animais , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Anti-Infecciosos/toxicidade , Candida albicans/efeitos dos fármacos , Bovinos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Complexos de Coordenação/toxicidade , DNA/química , Humanos , Camundongos , Testes de Sensibilidade Microbiana , Morfolinas/química , Albumina Sérica/química , Staphylococcus aureus/efeitos dos fármacos
11.
Acta Crystallogr Sect E Struct Rep Online ; 68(Pt 6): m756-7, 2012 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-22719316

RESUMO

In the centrosymmetric dinuclear title complex, [Cu(2)I(2)(C(22)H(16)N(2)O(4))(2)], the Cu(I) atom is coordinated in a distorted tetra-hedral geometry by an N,N'-bidentate dimethyl 2,2'-biquinoline-4,4'-dicarboxyl-ate ligand and two symmetry-related I atoms, which act as bridges to a symmetry-related Cu(I) atom. The distance between the Cu(I) atoms within the dinuclear unit is 2.6723 (11) Å.

12.
J Inorg Biochem ; 108: 62-8, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22266462

RESUMO

The ability of four stable hemiaminals differently substituted in the phenyl ring and their complexes with Cu(2+) ions to inhibit catalytic cleavage of the antigenomic delta ribozyme was compared. The hemiaminals were novel chiral derivatives of 1,2,4-triazole [i.e. (2,4-dinitrophenyl)(4H-1,2,4-triazol-4-ylamino) methanol (2,4-dnbald), (2-nitrophenyl)(4H-1,2,4-triazol-4-ylamino) methanol (2-nbald), (3-nitrophenyl)(4H-1,2,4-triazol-4-ylamino) methanol (3-nbald) and (4-nitrophenyl)(4H-1,2,4-triazol-4-ylamino) methanol (4-nbald)]. The complexes of nbalds with Cu(2+) were characterized using UV and EPR methods and additionally, the formation of 2,4-dnbald-Cu(2+) complex with CuL(2) stoichiometry was confirmed by mass spectrometry. The data suggest that there are two ways in which nbalds and their Cu(2+) complexes can influence catalytic cleavage of antigenomic delta ribozyme. The coordinated Cu(2+) ions may play the role of new cationic ligands increasing the affinity of the complexes to the ribozyme. Such situation occurs in the case of 2- and 2,4-nbald. Their Cu(2+) complexes decrease ribozyme cleavage rates twice more efficiently than uncomplexed compounds. Moreover, the Cu(2+) complexes displace the catalytic divalent metal ions from their strong binding sites located in the ribozyme J4/2 region as shown by the Pb(2+)-induced cleavage approach. On the other hand, 3- and 4-nbald inhibit catalysis more strongly as compared to 2-nbald and 2,4-dnbald but the ribozyme cleavage rates are changed only slightly upon Cu(2+) complexation. The mechanism of ribozyme inhibition by interfering with the formation of a correct ribozyme tertiary structure seems to operate in this case.


Assuntos
Cobre/química , Metais/química , RNA Catalítico/química , Triazóis/química , Catálise , Conformação de Ácido Nucleico
13.
J Inorg Biochem ; 106(1): 23-31, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22112836

RESUMO

Protonation equilibria and Cu(II) binding processes by an antifungal agent fluconazole, α-(2,4-difluorophenyl)-α-(1H-1,2,4-triazol-1-yl-methyl)-1H-1,2,4-triazole-1-ethanol, were studied using the UV-Vis, EPR and NMR spectroscopic techniques. The protonation constant of fluconazole was determined from NMR titration and attributed to N4' nitrogen atoms using the DFT methods. The spectroscopic data suggest that at pH as low as 0.4 the first complex is formed, in which one or two Cu(II) ions are bound to one of the nitrogen atoms (N4') from triazole rings. Above pH 1.5 each Cu(II) ion is surrounded by two nitrogen atoms (also N4') from two different ligand molecules, forming primary monomeric complexes and above pH=5, both dimeric or oligomeric species occur, which is well registered by the EPR technique. The mixture of Cu(NO(3))(2) with fluconazole in a 1:1 molar ratio in a water (pH=4.5)/ethanol solution gave crystals of [Cu(2)(H(2)O){(C(6)H(3)-2,4-F(2))(CH(2)N(3)C(2)H(2))(2)C-OH}{(C(6)H(3)-2,4-F(2))(CH(2)N(3)C(2)H(2))(2)C-O}(NO(3))](NO(3))(2)·9(H(2)O). This complex is the first example of a cupric 3D polymeric structure with a fluconazole ligand coordinated via both N2' and N4' atoms from the same triazole rings. At higher pH values, we obtained a binuclear complex [Cu(2)(L)(2)(H(2)O)(2)(NO(3))(2)], in which the copper(II) atoms were bridged by the oxygen atoms of the deprotonated OH group of fluconazole. The hypothetical oxidative properties of this system were also examined, however it failed to generate either reactive oxygen species or DNA scission products.


Assuntos
Cobre/química , Fluconazol/química , Compostos Organometálicos/química , Sítios de Ligação , Cobre/metabolismo , Cristalografia por Raios X , Espectroscopia de Ressonância de Spin Eletrônica , Fluconazol/metabolismo , Cinética , Espectroscopia de Ressonância Magnética , Modelos Químicos , Modelos Moleculares , Estrutura Molecular , Oxirredução , Espectrofotometria , Água/química
14.
J Inorg Biochem ; 105(8): 1102-8, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21726774

RESUMO

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.


Assuntos
Antibacterianos/química , Antifúngicos/química , Antineoplásicos/química , Cobre/química , Iodetos/química , Fosfinas/química , Antibacterianos/farmacologia , Antifúngicos/farmacologia , Antineoplásicos/farmacologia , Candida albicans/efeitos dos fármacos , Linhagem Celular Tumoral , Cobre/farmacologia , Humanos , Iodetos/farmacologia , Ligantes , Fenantrolinas/química , Fenantrolinas/farmacologia , Fosfinas/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Relação Estrutura-Atividade , Água
15.
Dalton Trans ; 40(11): 2459-68, 2011 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-21286606

RESUMO

The luminescent complexes of triphenylphosphine and two interesting aminomethylphosphines: P(CH(2)N(CH(2)CH(2))(2)NCH(3))(3) and P(CH(2)N(CH(2)CH(2))(2)O)(3) with copper(I) iodide and 2,9-dimethyl-1,10-phenanthroline (dmp): [CuI(dmp)PPh(3)], [CuI(dmp)P(CH(2)N(CH(2)CH(2))(2)NCH(3))(3)] and [CuI(phen)P(CH(2)N(CH(2)CH(2))(2)O)(3)] are presented in this work. These complexes were characterized in solution by means of NMR spectroscopy and their structures were crystallographically determined in the solid state. All complexes crystallize as the discrete dimers bound by π-stacking interactions between dmp rings. The coordination geometry about the Cu(I) centre is pseudo-tetrahedral showing small flattening and large rocking distortions. The investigated compounds exhibit intense orange photoluminescence in the solid state (emission peaks at r.t.: λ(max) = 588-592 nm; τ = 1.7-2.2 and 6.4-10.0 µs; at 77 K: λ(max) = 605-612 nm; τ = 4.8-6.5 and 32-47 µs), which is several orders higher than the luminescence of the analogous complexes with 1,10-phenanthroline (phen). Electronic and structural properties of the [CuI(dmp/phen)PR(3)] complexes were characterized using DFT methods to interpret their photophysics. On the basis of TDDFT calculations the broad CT bands observed in UV-Vis spectra are interpreted as the two mixed transitions from σ(CuI) bond with a small admixture of σ(CuP) bond to π* phen or dmp ligand: (MX,MPR(3))LCT, while the emissions most probably occur from two triplet states which are in thermal equilibrium.

16.
Dalton Trans ; 39(32): 7547-55, 2010 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-20617235

RESUMO

Chalcogenide derivatives of three aminomethylphosphines: P(CH2N(CH2CH2)2NCH3)3 (1), P(CH2N(CH2CH2)2NCH2CH3)3 (2) and P(CH2N(CH2CH2)2O)3 (3) were prepared: oxides--OP(CH2N(CH2CH2)2NCH3)3 (4), OP(CH2N(CH2CH2)2NCH2CH3)3 (5), OP(CH2N(CH2CH2)2O)3 (6), sulfides--SP(CH2N(CH2CH2)2NCH3)3 (7), SP(CH2N(CH2CH2)2NCH2CH3)3 (8), SP(CH2N(CH2CH2)2O)3 (9) and selenides--SeP(CH2N(CH2CH2)2NCH3)3 (10), SeP(CH2N(CH2CH2)2NCH2CH3)3 (11), SeP(CH2N(CH2CH2)2O)3 (12). The spectroscopic NMR analyses, DFT (B3LYP/6-31G**) calculations together with crystallographic studies of compounds 5, 6, 9 and 12 demonstrate that the structures and spectroscopic properties are strongly influenced by the chalcogen atom and not entirely contingent on aliphatic rings in the molecules. TEPs (Tolman's electronic parameters), estimated with DFT methods equal 2059.7 cm(-1) for 1, 2059.8 cm(-1) for 2 and 2061.2 cm(-1) for 3. These values are similar to TEPs estimated experimentally for other aminomethylphosphines. Phosphines 1, 2 and 3, despite very large Tolman cone angles show rather low influence of molecular geometry on their electronic properties: S4' (symmetric deformation coordinate) (59.8-64.8) and S4 (63.4-63.7) parameters are moderate. Suresh's steric effect (S(eff)) parameters for phosphines 1, 2 and 3 (2.70, 2.73 and 2.66, respectively) indicate minor electron-donating effect. Electronic effect (E(eff)) parameters (4.92, 5.21 and -0.40, respectively) can be easily modified by changing the substituents. 1J(SeP) coupling constants in the selenides are low (10: 707.5 11: 707.5 12: 709.8 Hz), but do not correlate with the TEP values in a way typical for aliphatic phosphines. The examined compounds do not show mutagenic properties and their potential toxicity is low, which is relevant in the context of their possible medical applications.


Assuntos
Morfolinas/química , Fosfinas/química , Piperazinas/química , Animais , Calcogênios/química , Chlorocebus aethiops , Cristalografia por Raios X , Elétrons , Espectroscopia de Ressonância Magnética , Conformação Molecular , Fosfinas/toxicidade , Células Vero
17.
Dalton Trans ; (17): 3348-53, 2009 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-19421639

RESUMO

The new compounds 2,2'-bipyridine-3,3',6,6'-tetracarboxylic acid (bptcH(4)) () and iron(II) [Fe(2)(bptcH(2))(2)(H(2)O)(4)].4.74H(2)O () and [Co(2)(bptcH(2))(2)(H(2)O)(4)].4.5H(2)O () have been prepared and characterized using (1)H NMR, IR and UV-Vis spectroscopic methods. X-Ray structures of these compounds have been determined. Acid crystallizes in the space group Aba2 and complexes and in P2(1)/c. The metal atoms are coordinated with N and O atoms of 6,6' carboxylate groups of the bridging ligands and two aqua ligands. The crystals are stabilized by intra- and intermolecular O-HN and OHO hydrogen bonds. Magnetic moments of complexes and at room temperature are characteristic of the high spin Fe(II) and Co(II) compounds. The 1/chi(M) dependences on temperature show weak antiferromagnetic interactions of and .

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