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In this paper, we present the synthesis of four new complexes: the dimeric precursor [Ir(dmppz)2(µ-Cl)]2 (1) (Hdmppz - 3,5-dimethyl-1-phenyl-1H-pyrazole) and heteroleptic bis-cyclometalated complexes: [Ir(dmppz)2(Py2CO)]PF6·½CH2Cl2 (2), [Ir(dmppz)2(H2biim)]PF6·H2O (3), and [Ir(dmppz)2(PyBIm)]PF6 (4), with auxiliary N,N-donor ligands: 2-di(pyridyl)ketone (Py2CO), 2,2'-biimidazole (H2biim) and 2-(2'-pyridyl)benzimidazole (PyBIm). In the obtained complexes, SC-X-ray analysis revealed that Ir(III) has an octahedral coordination sphere with chromophores of the type {IrN2C2Cl2} (1) or {IrN4C2} (2-4). The complexes obtained, which have been fully characterised by physicochemical methods (CHN, TG, FTIR, UV-Vis, PL and 1H, 13C, 15N NMR), were used to continue our studies on the factors influencing the cytotoxic properties of potential chemotherapeutic agents (in vitro). To this end, the following studies are presented: (i) comparative analysis of the effects on the biological properties of N,N-donor ligands and C,N-donor ligands in the studied complexes, (ii) studies of the interactions of the compounds with the selected molecular target: DNA and BSA (UV-Vis, CD and PL methods), (iii) and the reactivity towards redox molecules: GSH, NADH (UV-Vis and/or ESI-MS methods), (iv) cytotoxic activity (IC50) of potential chemotherapeutics against MCF-7, K-562 and CCRF-CEM cell lines.
Assuntos
Antineoplásicos , Proliferação de Células , Complexos de Coordenação , Irídio , Pirazóis , Pirazóis/química , Pirazóis/farmacologia , Pirazóis/síntese química , Humanos , Ligantes , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Irídio/química , Irídio/farmacologia , Proliferação de Células/efeitos dos fármacos , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Teoria Quântica , DNA/química , DNA/metabolismo , Estrutura Molecular , Modelos Moleculares , Processos FotoquímicosRESUMO
A series of four Cd(II) complexes with 5-methyl-4-imidazolecarboxaldehyde (L) with different inorganic anions within or outside the coordination sphere of general formula: [CdCl2L2] (1), [CdBr2L2] (2), [CdI2L2] (3), and [CdL4](PF6)2·3H2O (4) was synthesized through one-step and two-step reactions, respectively. All complexes were obtained as colorless crystals without the need for recrystallization and exhibited solubility in aqueous solutions. Structural analysis revealed different coordination environments for each complex, with variations in bond lengths and angles. The crystal packing of the complexes was stabilized by hydrogen bonding and π-π stacking interactions. FT-IR analysis indicated coordination of the ligand to the metal ion, and UV-Vis studies confirmed the stability of the complexes in solution. Computational analysis has revealed the polar nature of the complexes and their favorable stability constants. Affinity studies with DNA using the switchSense technique demonstrated rapid association and dissociation processes for all complexes, with temperature-dependent binding constants. Thermodynamic analysis suggested spontaneous with positive entropy change and endothermic formation processes for the complexes. Overall, the study underscores the synthesis, examination, and interaction with DNA of Cd(II) complexes, demonstrating their promise within medicinal chemistry.
Assuntos
Cádmio , Complexos de Coordenação , DNA , DNA/química , Cádmio/química , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Termodinâmica , Imidazóis/química , Modelos Moleculares , Estrutura Molecular , Teoria da Densidade FuncionalRESUMO
Organometallic half-sandwich complexes [(η5-Cp)IrCl(L)]PF6 (1) and [(η5-Cp)RhCl(L)]PF6 (2) were prepared using pentamethylcyclopentadienyl chloride dimers of iridium(III) or rhodium(III) with the 4-amino-N-(2,2'-bipyridin-5-yl)benzenesulfonamide ligand (L) and ammonium hexafluorophosphate. The crystal structures of L, 1, and 2 were analyzed in detail. The coordination reactions of the ligand with the central ions were confirmed using various spectroscopic techniques. Additionally, the interactions between sulfaligand, Ir(III), and Rh(III) complexes with carbonic anhydrase (CA), human serum albumin (HSA), and CT-DNA were investigated. The iridium(III) complex (1) did not show any antiproliferative properties against four different cancer cell lines, i.e., nonsmall cell lung cancer A549, colon cancer HCT-116, breast cancer MCF7, lymphoblastic leukemia Nalm-6, and a nonmalignant human embryonic kidney cell line HEK293, due to high binding affinity to GSH. The sulfonamide ligand (L) and rhodium(III) complex (2) were further studied. L showed competitive inhibition toward CA, while complexes 1 and 2, uncompetitive. All compounds interacted with HSA, causing a conformational change in the protein's α-helical structure, suggesting the induction of a more open conformation in HSA, reducing its biological activity. Both L and 2 were found to induce cell death through a caspase-dependent pathway. These findings position L and 2 as potential starting compounds for pharmaceutical, therapeutic, or medicinal research.
Assuntos
Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Complexos de Coordenação , Neoplasias Pulmonares , Ródio , Humanos , Complexos de Coordenação/química , Ligantes , Irídio/farmacologia , Irídio/química , Ródio/farmacologia , Ródio/química , Células HEK293 , Antineoplásicos/química , Linhagem Celular TumoralRESUMO
Two dinuclear copper(II) complexes with macrocyclic Schiff bases K1 and K2 were prepared by the template reaction of (R)-(+)-1,1'-binaphthalene-2,2'-diamine and 2-hydroxy-5-methyl-1,3-benzenedicarboxaldehyde K1, or 4-tert-butyl-2,6-diformylphenol K2 with copper(II) chloride dihydrate. The compounds were characterized by spectroscopic methods. X-ray crystal structure determination and DFT calculations confirmed their geometry in solution and in the solid phase. Moreover, intermolecular interactions in the crystal structure of K2 were analyzed using 3D Hirshfeld surfaces and the related 2D fingerprint plots. The magnetic study revealed very strong antiferromagnetic CuII-CuII exchange interactions, which were supported by magneto-structural correlation and DFT calculations conducted within a broken symmetry (BS) framework. Complexes K1 and K2 exhibited luminescent properties that may be of great importance in the search for new OLEDs. Both K1 and K2 complexes showed emissions in the range of 392-424 nm in solutions at various polarities. Thin materials of the studied compounds were deposited on Si(111) by the spin-coating method or by thermal vapor deposition and studied by scanning electron microscopy (SEM/EDS), atomic force microscopy (AFM), and fluorescence spectroscopy. The thermally deposited K1 and K2 materials showed high fluorescence intensity in the range of 318-531 nm for K1/Si and 326-472 nm for the K2/Si material, indicating that they could be used in optical devices.
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Cobre , Magnetismo , Modelos Moleculares , Cobre/química , Bases de Schiff/química , Corantes , Fenômenos Magnéticos , Cristalografia por Raios XRESUMO
Herein, we present biological studies on 3,4-dihydropyrimidin-2(1H)-ones (DHPMs) obtained via Biginelli reaction catalyzed by NH4Cl under solvent-free conditions. Until now, DHPMs have not been tested for biological activity against pathogenic E. coli strains. We tested 16 newly synthesized DHPMs as antimicrobial agents on model E. coli strains (K12 and R2-R4). Preliminary cellular studies using MIC and MBC tests and digestion of Fpg after modification of bacterial DNA suggest that these compounds may have greater potential as antibacterial agents than typically used antibiotics, such as ciprofloxacin (ci), bleomycin (b) and cloxacillin (cl). The described compounds are highly specific for pathogenic E. coli strains based on the model strains used and may be engaged in the future as new substitutes for commonly used antibiotics in clinical and nosocomial infections in the pandemic era.
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To evaluate the antioxidant activity of potential synthetic enzyme mimetics, we prepared new five copper(II) complexes via a self-assembly method and named them [Cu(2-(HOCH2)py)3](ClO4)2 (1), [Cu(2-(HOCH2)py)2(H2O)2]SiF6 (2), [Cu2(2-(HOCH2CH2)py)2(2-(OCH2CH2)py)2](ClO4)2 (3), [Cu(pyBIm)3](BF4)2·1.5H2O (4) and [Cu(py2C(OH)2)2](ClO4)2 (5). The synthetic protocol involved N,O- or N,N-donors: 2-(hydroxymethyl)pyridine (2-(HOCH2)py), 2-(hydroxyethyl)pyridine (2-(HOCH2CH2)py), 2-(2-pyridyl)benzimidazole (pyBIm), di(2-pyridyl)ketone (py2CO). The obtained Cu(II) complexes were fully characterised by elemental analysis, FTIR, EPR, UV-Vis, single-crystal X-ray diffraction and Hirshfeld surface analysis. Crystallographic and spectroscopic analyses confirmed chromophores of both monomeric ({CuN3O3} (1), {CuN2O4} (2), {CuN6} (4), {CuN4O2} (5)) and dimeric complex ({CuN2O3} (3)). Most of the obtained species possessed a distorted octahedral environment, except dimer 3, which consisted of two copper centres with square pyramidal geometries. The water-soluble compounds (1, 3 and 5) were selected for biological testing. The results of the study revealed that complex 1 in solutions displayed better radical scavenging activity than complexes 3, 5 and free ligands. Therefore, complex 1 has been selected for further studies to test its activity as an enzyme mimetic. The chosen compound was tested on the erythrocyte lysate of two groups of patients after undergoing chemotherapy and chemoradiotherapy. The effect of the tested compound (1) on enzyme activity levels (TAS, SOD and CAT) suggests that the selected complex can be treated as a functional mimetic of the enzymes.
Assuntos
Cobre/química , Sequestradores de Radicais Livres/química , Metaloproteínas/química , Nitrogênio/química , Oxigênio/química , Benzimidazóis/química , Domínio Catalítico/fisiologia , Complexos de Coordenação/química , Cristalografia por Raios X/métodos , Ligantes , Estrutura Molecular , Piridinas/químicaRESUMO
Two novel coordination polymers, [Bi2(2,3pydc)2(2,3pydcH)2(H2O)]n (1) and {(Et3NH)2[Bi(2,3pydc)(2,3pydcH)Cl2]}n (2) were prepared using as a prolinker pyridine-2,3-dicarboxylic acid (2,3pydcH2). The obtained complexes were fully characterized by elemental analysis, TG/DTG, FT-IR, solid-state photoluminescence, DFT calculations and single-crystal X-ray diffraction. The obtained complexes crystallized in the triclinic P-1 space group (1) and comprise dimeric units with two crystallographically different Bi(III) centers (polyhedra: distorted pentagonal bipyramid and bicapped trigonal prism) and monoclinic P21/c space group (2) with a distorted monocapped pentagonal bipyramid of Bi(III) center. The various coordination modes of bridging carboxylate ligands are responsible for the formation of 1D chains with 4,5C10 (1) and 2C1 (2) topology. The photoluminescence quantum yield for polymer 2 is 8.36%, which makes it a good candidate for more specific studies towards Bi-based fluorescent materials. Moreover, it was detected that polymer 1 is more than twice as active against H. pylori as polymer 2. It can be concluded that there is an existing relationship between the structure and the antibacterial activity because the presence of chloride and triethylammonium ions in the structure of complex 2 reduces the antibacterial activity.
Assuntos
Antibacterianos , Bismuto/química , Complexos de Coordenação , Ácidos Dicarboxílicos/química , Corantes Fluorescentes , Helicobacter pylori/crescimento & desenvolvimento , Piridinas/química , Antibacterianos/química , Antibacterianos/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Corantes Fluorescentes/química , Corantes Fluorescentes/farmacologiaRESUMO
The oncological use of cisplatin is hindered by its severe side effects and a very important resistance problem. To overcome these problems, scientists have attempted to design new generation transition-metal anticancer complexes. In this study, we present new complexes, ruthenium(II) [(η6-p-cymene)RuCl(py2CO)]PF6 (1), iridium(III) [(η5-Cp)IrCl(py2CO)]PF6 (2), and NH4[IrCl4(py2CO)]·H2O (3), based on di-2-pyridylketone (py2CO). The prepared complexes were characterized by FTIR, 1H, 13C, 15N NMR, UV-Vis, PL and elemental analysis techniques. The single-crystal X-ray structure analysis and comparative data revealed pseudo-octahedral half-sandwich 1 and 2 complexes and octahedral tetrachloroiridate(III) 3 with a rare chelating κ2N,O coordination mode of py2CO. The compounds were tested in vitro against three cancer cell lines-colorectal adenoma (LoVo), myelomonocytic leukaemia (MV-4-11), breast adenocarcinoma (MCF-7), and normal fibroblasts (BALB/3T3). The most promising results were obtained for iridium(III) complex 3 against MV-4-11 (IC50 = 35.8 ± 13.9 µg/mL) without a toxic effect against normal BALB/3T3, which pointed towards its selectivity as a potential anticancer agent. Extensive research into their mode of binding with DNA confirmed for 1 and 2 complexes non-classical binding modes, while the 3D circular dichroism (CD) experiment (ΔTm) suggested that 3 induced the probable formation of covalent bonds with DNA. In addition, the obtained iridium complexes induce ROS, which, in synergy with hydrolysis promoting DNA bonding, may lead to cancer cell death.
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In this paper, we discussed the similarities and differences in d6 low-spin half-sandwich ruthenium, rhodium and iridium complexes containing 2,2'-biimidazole (H2biim). Three new complexes, {[RuCl(H2biim)(η6-p-cymene)]PF6}2·H2O (1), [(η5-Cp)RhCl(H2biim)]PF6 (2), and [(η5-Cp)IrCl(H2biim)]PF6 (3), were fully characterized by CHN, X-ray diffraction analysis, UV-Vis, FTIR, and 1H, 13C and 15N NMR spectroscopies. The complexes exhibit a typical pseudooctahedral piano-stool geometry, in which the aromatic arene ring (p-cymene or Cp) forms the seat, while the bidentate 2,2'-biimidazole and chloride ion form the three legs of the piano stool. Moreover, the cytotoxic activities of the compounds were examined in the LoVo, HL-60, MV-4-11, MCF-7 human cancer cell lines and BALB/3T3 normal mouse fibroblasts. Notably, the investigated complexes showed no cytotoxic effects towards the normal BALB/3T3 cell line compared to cisplatin, which has an IC50 value of 2.20 µg. Importantly, 1 displayed the highest activity against HL-60 (IC50 4.35 µg). To predict a binding mode, we explored the potential interactions of the metal complexes with CT-DNA and protein using UV absorption and circular dichroism. The obtained data suggest that the complexes could interact with CT-DNA via an outside binding mode. Moreover, binding of the complexes with the GSH via UV-Vis and ESI mass spectra was determined. Comparative studies have shown that the rhodium complex (2) is the most GSH reactive, which is probably responsible for its deactivation towards LoVo and MCF-7 tumour cells. The influence of the metal ion on the biological activity of isostructural Rh(III) and Ir(III) complexes was an important goal of the presented investigation.
Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Complexos de Coordenação/síntese química , Complexos de Coordenação/farmacologia , Irídio/química , Ródio/química , Rutênio/química , Células 3T3 , Animais , Antineoplásicos/química , Antineoplásicos/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Técnicas de Química Sintética , Complexos de Coordenação/química , Complexos de Coordenação/metabolismo , DNA/metabolismo , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Interações Hidrofóbicas e Hidrofílicas , Camundongos , Modelos Moleculares , Conformação Molecular , Albumina Sérica Humana/metabolismoRESUMO
BACKGROUND: Application of coordination chemistry in nanotechnology is a rapidly developing research field in medicine. Bismuth complexes have been widely used in biomedicine with satisfactory therapeutic effects, mostly in Helicobacter pylori eradication, but also as potential antimicrobial and anti-leishmanial agents. Additionally, in recent years, application of bismuth-based compounds as potent anticancer drugs has been studied extensively. METHODS: Search for data connected with recent trends on bismuth compounds in cancer chemo- and radiotherapy was carried out using web-based literature searching tools such as ScienceDirect, Springer, Royal Society of Chemistry, American Chemical Society and Wiley. Pertinent literature is covered up to 2016. RESULTS: In this review, based on 213 papers, we highlighted a number of current problems connected with: (i) characterization of bismuth complexes with selected thiosemicarbazone, hydrazone, and dithiocarbamate classes of ligands as potential chemotherapeutics. Literature results derived from 50 papers show that almost all bismuth compounds inhibit growth and proliferation of breast, colon, ovarian, lung, and other tumours; (ii) pioneering research on application of bismuth-based nanoparticles and nanodots for radiosensitization. Results show great promise for improvement in therapeutic efficacy of ionizing radiation in advanced radiotherapy (described in 36 papers); and (iii) research challenges in using bismuth radionuclides in targeted radioimmunotherapy, connected with choice of adequate radionuclide, targeting vector, proper bifunctional ligand and problems with 213Bi recoil daughters toxicity (derived from 92 papers). CONCLUSION: This review presents recent research trends on bismuth compounds in cancer chemo- and radiotherapy, suggesting directions for future research.
Assuntos
Antineoplásicos/química , Bismuto/química , Complexos de Coordenação/química , Antineoplásicos/farmacologia , Bismuto/farmacologia , Linhagem Celular Tumoral , Complexos de Coordenação/farmacologia , Descoberta de Drogas/métodos , Humanos , Hidrazonas/química , Ligantes , Estrutura Molecular , Nanopartículas/química , Radiossensibilizantes/química , Radioimunoterapia/métodos , Relação Estrutura-Atividade , Tiocarbamatos/química , Tiossemicarbazonas/químicaRESUMO
A dinuclear [Pb2(4-CHO-5-MeIm)6(NO3)2](NO3)2 (1) and a polynuclear [Pb(2-pzc)2(H2O)]n (2) complexes (where 5(4)-carbaldehyde-4(5)-methylimidazole (5(4)-CHO-4(5)-MeIm) and pyrazine-2-carboxylic acid (2-pzcH)) have been synthesized and characterized by elemental analysis, IR spectroscopy and X-ray crystallography. Structural determination for complex 1 reveals a cationic species [Pb(4-CHO-5-MeIm)3]2+ connected through bridging nitrate(V) ions. There are also an uncoordinated nitrate ions as counterions. Complex 2 is a three-dimensional architecture consisting of Pb6O12 building units. The pyrazine-2-carboxylato ligand behaves as a chelating agent and a bi-connective bridge. The coordination polyhedra around lead(II) ion could be described as a distorted docecahedron (1) or monocapped trigonal prism (2). The luminescent properties of 1 and 2 investigated in the solid state at room temperature indicate structure-dependent photoluminescent properties. The DFT calculations and the X-ray structural data point on rather hemidirected type of coordination around Pb(II) ions of 1 and 2.
Assuntos
Fenômenos Químicos , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Chumbo/química , Cristalografia por Raios X , Análise Diferencial Térmica , Ligação de Hidrogênio , Ligantes , Luminescência , Modelos Moleculares , Polímeros/química , Teoria Quântica , Espectrometria de Fluorescência , Espectroscopia de Infravermelho com Transformada de Fourier , TermogravimetriaRESUMO
A novel 3D coordination polymer [Cd2(L(1))(2)(SCN)(4)(MeOH)(2)](n) (1) and monomeric [Cd(NCS)(2)L(2)] (2) (L(1) = urotropine, L(2) = tris(1-(3,5-dimethylpyrazolylmethyl))amine) have been prepared in a one-pot synthesis using 1-hydroxymethyl-3,5-dimethylpyrazole as the starting ligand. The most prominent feature is the formation in situ of the organic compounds: urotropine and scorpionate-tripodal ligands.