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Three new complexes Na[Ln(pic)4]ּ⋅2.5H2O (Ln = Tb, Eu or Gd; pic = picolinate) were synthesized and characterized by infrared spectroscopy, powder X-ray diffraction and thermogravimetric analyses. The molecular structures of the complexes have been determined by single-crystal X-ray diffraction. The three isostructural lanthanide complexes crystalize in the hexagonal system with space group P6122 to Eu complex and Gd complex and space group P6522 to Tb complex. In each of the complexes, the picolinate ligands are bonded to Ln3+ and Na+ ions by different coordination modes promoting polymeric structures. The photoluminescent properties of complexes were studied and combined with theoretical studies using the density functional theory (DFT: B3LYP, PBE1PBE) and the semiempirical method AM1/Sparkle from the single crystal X-ray diffraction structures to assign a suitable model for describing the system. The B3LYP DFT functional was considered the most adequate for providing structural properties of the compounds and for describing luminescence properties. The excited triplet states (T1) and excited singlet states (S1) of the ligand were determined theoretically using Time-dependent DFT calculations (TD-DFT: B3LYP, CAM-B3LYP and LC-wPBE) and INDO/S-CIS, with the best agreement with experimental values obtained from the LC-wPBE DFT functional. The photoluminescent spectra of the complexes and their lifetime measurements were determined indicating that the Eu complex and Tb complex display different intramolecular energy transfer mechanisms with higher efficiency to ligand-to-terbium energy transfer. In addition, the experimental and theorical Judd-Ofelt intensity parameters and quantum yields of the complexes were also determined and discussed besides to a proposed 9-state diagram to describe the luminescence properties of the Eu complex. The low value of emission quantum efficiency of 5D0 emitting level of Eu(III) ion was explained by the presence of the ligand-to-metal charge transfer state (LMCT) evidenced experimentally and theoretically. A good agreement was obtained between the proposed kinetic model and experimental results showing the consistency of the set of rate equations assumed and the intramolecular pathways proposed.

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Leishmaniases are neglected diseases with limited therapeutic options. Diffuse cutaneous leishmaniasis can occur in Brazil due to Leishmania amazonensis. This study details the antileishmanial activity and cytotoxicity of complexes of sodium usnate (SAU) with lanthanide ions ([LnL3 (H2O)x] (Ln = La(III), Nd(III), Gd(III), Tb(III), Eu(III) and Sm(III); L = SAU). All lanthanide complexes were highly active and more potent than SAU against L. amazonensis promastigotes and intracellular amastigotes (Pro: IC50 < 1.50 µM; Ama: IC50 < 7.52 µM). EuL3·3H2O and NdL3·3H2O were the most selective and effective on intracellular amastigotes, with a selectivity index of approximately 7.0. In silico predictions showed no evidence of mutagenicity, tumorigenicity or irritation for all complexes. Treatment with EuL3·3H2O triggered NO release even at the lowest concentration, indicating NO production as a mechanism of action against the parasite. Incubating promastigotes with the lanthanide complexes, particularly with SmL3·4H2O and GdL3·3H2O, led to a change in the mitochondrial membrane potential, indicating the ability of these complexes to target this essential organelle. The same complexes caused cell death through cell membrane disruption, but their relationship with early or late apoptotic processes remains unclear. Thus, the inclusion of lanthanide ions in SAU improves selectivity with a promising mechanism of action targeting the mitochondria.

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Metal-based drugs, including lanthanide complexes, have been extremely effective in clinical treatments against various diseases and have raised major interest in recent decades. Hence, in this work, a series of lanthanum (III) and cerium (III) complexes, including Schiff base ligands derived from (1H-benzimidazol-2-yl)aniline, salicylaldehyde, and 2,4-dihydroxybenzaldehyde were synthesized and characterized using different spectroscopic methods. Besides their cytotoxic activities, they were examined in human U-937 cells, primate kidney non-cancerous COS-7, and six other, different human tumor cell lines: U251, PC-3, K562, HCT-15, MCF-7, and SK-LU-1. In addition, the synthesized compounds were screened for in vitro antiparasitic activity against Leishmania braziliensis, Plasmodium falciparum, and Trypanosoma cruzi. Additionally, antibacterial activities were examined against two Gram-positive strains (S. aureus ATCC® 25923, L. monocytogenes ATCC® 19115) and two Gram-negative strains (E. coli ATCC® 25922, P. aeruginosa ATCC® 27583) using the microdilution method. The lanthanide complexes generally exhibited increased biological activity compared with the free Schiff base ligands. Interactions between the tested compounds and model membranes were examined using differential scanning calorimetry (DSC), and interactions with calf thymus DNA (CT-DNA) were investigated by ultraviolet (UV) absorption. Molecular docking studies were performed using leishmanin (1LML), cruzain (4PI3), P. falciparum alpha-tubulin (GenBank sequence CAA34101 [453 aa]), and S.aureus penicillin-binding protein 2a (PBP2A; 5M18) as the protein receptors. The results lead to the conclusion that the synthesized compounds exhibited a notable effect on model membranes imitating mammalian and bacterial membranes and rolled along DNA strands through groove interactions. Interactions between the compounds and studied receptors depended primarily on ligand structures in the molecular docking study.

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The synthesis of 1-benzyl-2-((2-Aminoethyl) amino)-5-oxopyrrolidine-3,4-diyl diacetate (boad), an oxopyrrolidine type ligand; designed to coordinate lanthanides (Eu3+ and Tb3+) to get luminescent material. The target complexes showed good photoluminescence properties, which indicate that this type of compound can be used as sensitizers having luminescence for the green (Tb3+) and red (Eu3+) emission. The obtained results revealed that sensitizer efficiency can be improved by adding ligands like acac (Eu(acac)3, which has also enhanced the luminescence quantum output and period for Eu3+ ions. The ground state geometries were developed by using density functional theory at B3LYP/6-31G** level. The charge transfer analysis and electronic properties were performed. The Europium and Terbium complexes formation with boad ligand was explored based on molecular electrostatic potential, MDC-q charges, and frontier molecular orbitals (FMOs) analysis.

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Novel lanthanide (Ln) compounds [Ln(L)2]Cl.xH2O (Ln = La3+, Ce3+, Sm3+) containing aromatic N,O-chelate ligands [HL1 = 4-amino-2-(1H-benzimidazol-2-yl)phenol; HL2 = 5-amino-2-(1H-benzimidazol-2-yl)phenol] have been synthesized and structurally characterized by elemental analysis, NMR and IR spectroscopy, molar conductance measurements, and mass spectrometry (MS). The spectroscopic data suggested that the benzimidazolyl-phenol ligands act as N,O-chelate ligands through the iminic nitrogen and phenolic oxygen atoms. Elemental analysis indicated that lanthanide compounds were formed in a 1:2 stoichiometry (metal:ligand). In vitro biological evaluation was carried out using these complexes, exhibiting moderate cytotoxicity against six different human tumor cell lines (U251, human glioblastoma; HCT-15, colorectal carcinoma; MCF-7, breast epithelial adenocarcinoma; PC-3, prostate cancer; K562, myelogenous leukemia; SKLU-1, lung carcinoma) and lower toxicity against a non-cancerous cell line (COS-7, primate kidney). In addition, the antibacterial activity of the compounds was assessed against two gram-positive strains (Staphylococcus aureus ATCC 25923, Listeria monocytogenes ATCC 19115) and two gram-negative strains (Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27583) using the microdilution method. The results obtained show that the metal complexes exhibit higher biological activity than the free ligands, confirming a synergistic effect. Further benzimidazolyl-phenol derivatives were explored for the detection of bacteria using fluorescence imaging studies. Interestingly, the fluorescent properties of these compounds make them potential candidates to monitor the morphology of bacteria at different compound concentrations. Hence, the interaction of the ligand and complexes with model membranes mimicking those of bacteria was studied by using differential scanning calorimetry (DSC) and molecular dynamics (MD), showing that both compounds decreased the enthalpy of transition in two model membranes as the concentration of the compounds increased. In addition, the main transition temperature was slightly reduced as a result of these interactions.

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RESUMEN Este documento reporta la síntesis y caracterización detallada de complejos lantánidos La(III), Ce(III), Nd(III) y Sm(III), con ligandos tridentados derivados de híbridos heteroaromáticos. Los ligandos y sus respectivos complejos metálicos fueron caracterizados mediante diferentes técnicas fisicoquímicas, incluyendo análisis elemental y termogravimétrico; espectroscopias UV-Vis, IR, 1H-NMR y 13C-NMR; mediciones de conductancia molar y espectrometría de masas. Los datos espectrales mostraron que el ligando híbrido se comporta como un ligando tridentado NOO a través de los átomos de nitrógeno y oxígeno de los anillos benzimidazol y oxadiazol, así como del átomo de oxígeno del grupo carbonilo. El análisis elemental y térmico mostró que los complejos metálicos obtenidos tienen una estequiometria 1:2 (metal:ligando). Se evaluó la capacidad antioxidante de los compuestos mediante los ensayos DPPH y medidas electroquímicas (voltametría cíclica y voltametría de onda cuadrada). Los resultados mostraron que los complejos metálicos tienen mayor actividad antioxidante que los ligandos libres. Finalmente, la actividad antibacteriana de los ligandos y sus complejos se determinaron mediante pruebas in vitro contra cepas bacterianas Gram positivas y cepas bacterianas Gram negativas utilizando el método de microdilución en caldo. Los complejos metálicos mostraron mayores actividades antimicrobianas que los ligandos precursores contra algunos de los microorganismos.

SUMMARY This paper reports the synthesis and detailed characterization of lanthanide complexes La(III), Ce(III), Nd(III) y Sm(III) with tridentate ligands derived from heteroaromatic hybrids. The ligands and their metal complexes were characterized by different physicochemical techniques, including elemental and thermogravimetric analysis; UV-Vis, IR, 1H-NMR and 13C-NMR spectroscopy; molar conductance measurements; and mass spectrometry. The spectral data showed that the hybrid ligand behaves as a NOO tridentate ligand through the nitrogen and oxygen atoms of the benzimidazole and oxadiazole rings and the oxygen atom of the carbonyl group. Elemental and thermal analyses indicated that the obtained metal complexes were formed in 1:2 stoichiometry (metal-ligand). The antioxidant capacity of these compounds was evaluated by both DPPH assay and electrochemical measurements (cyclic voltammetry and square wave voltammetry). The results showed that the metal complexes have higher antioxidant activity compare to the free ligands. Finally, the antibacterial activities of the ligands and their complexes were determined by in vitro tests against Gram-positive bacterial strains and Gram-negative bacterial strains using the broth microdilution method. The metal complexes showed greater antimicrobial activities than the precursor ligands against some of the microorganisms.

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Abstract This paper reports the synthesis and detailed characterization of six novel lanthanide complexes of La(III), Eu(III) and Nd(III) with N(4)-substituted thiosemicarbazones derived from the 2-carboxybenzaldehyde. The IR, 1H-NMR and 13C-NMR spectroscopic studies confirmed the coordination of the thiocarbonyl (C=S), azomethine (C=N) and carboxylate (COO-) groups to the metal centers, and the carboxylate was coordinated in a bidentate manner. The elemental and thermal analyses suggest that lanthanide complexes were formed in 1:2 molar ratios (metal:ligand). The molar conductivity values confirmed the non-electrolytic nature of the complexes. The interaction of these complexes with calf thymus DNA (CT-DNA) was investigated by UV absorption and viscosity measurements. It was found that the Eu(HI) and Nd(nI) complexes could roll along the DNA strands through groove interactions. Furthermore, lanthanide complexes could promote the oxidative cleavage of plasmid pBR322 in a high-oxidative stress environment. Finally, the Schiff base ligands (L) and their complexes were evaluated for their antibacterial activities against gram-positive and gram-negative bacteria using a microdilution procedure. The results indicate that the lanthanide complexes exhibit more potent antibacterial activity than the free ligands.

Resumen Este articulo reporta la síntesis y caracterización detallada de seis nuevos complejos lantánidos de La(III), Eu(III) y Nd(III) con tiosemicarbazonas N(4)-sustituidas derivadas del 2-carboxibenzaldehído. Los estudios espectroscópicos de IR, 1H-NMR y 13C-NMR confirmaron la coordinación de los grupos tiocarbonilo (C=S), azometina (C=N) y carboxilato (COO-) a los centros metálicos, y el carboxilato se coordinó de forma bidentada. Los análisis elemental y térmico sugieren que los complejos lantánidos se formaron en proporciones molares 1:2 (metal:ligando). Los valores de conductividad molar confirmaron la naturaleza no eléctrica de los complejos. Por medio de medidas de absorción UV y de viscosidad se investigó la interacción entre estos complejos con DNA de timo de ternera (CT-DNA). Se encontró que los complejos Eu(III) y Nd(III) podrían correr a lo largo de cadenas de DNA a través de interacciones en el surco. Además, los complejos lantánidos podrían promover el clivaje oxidativo del plásmido pBR322 en un ambiente de alto estrés oxidativo. Finalmente, se evaluaron las actividades antibacteriales de las bases de Schiff como ligandos (L) y sus complejos contra bacterias gram-positivas y gram-negativas usando un procedimiento de microdilución. Los resultados indican que los complejos lantánidos exhiben una actividad antibacterial más potente que los ligandos libres.

Resumo Este artigo reporta a síntese e caracterização detalhada de seis novos complexos lantanídeos de La(III), Eu(III) e Nd(III) com tiosemicarbazonas N(4)-substituídas derivadas do 2-carboxibenzaldeído. Os estudos espectroscópicos de IR, 1H-RMN e 13C-RMN confirmaram a coordenação dos grupos tiocarbonilos (C = S), azometina (C=N) e carboxilato (COO-) com os centros metálicos, e o carboxilato se coordenou de forma bidentada. As análises elementares e térmicas sugerem que os complexos lantanídeos se formaram em proporções molares 1:2 (metal:ligante). Os valores de condutividades molar confirmaram a natureza não-elétrica dos complexos. Se avaliou a interação entre estes complexos com DNA de vitela (CT-DNA) por meio de medidas de absorção UV e de viscosidade. Se observou que os complexos Eu(III) e Nd(III) poderiam deslocar-se ao longo da cadeia de DNA através de interações no sulco. Adicionalmente, os complexos lantanídeos poderiam promover a clivagem oxidativa do plasmídeo pBR322 em um ambiente de alto estresse oxidativo. Finalmente, se avaliaram as atividades antibacterianas das bases de Schiff como ligantes (L) e seus complexos contra bactérias gram-positivas e gram- negativas, usando o método de microdiluição. Os resultados indicam que os complexos lantanídeos exibem uma atividade antibacteriana mais potente que os ligantes livres.

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Solid-state compounds of the general formulae [ML3] (M=Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu, Y; L=ketoprofen) were synthesized and characterized using infrared, diffuse reflectance and luminescence spectroscopies. IR data suggested that the carboxylate group in ketoprofen is coordinated to the metals as a bidentate ligand. The triplet state energy level was determined using the Gd(3+) complex, which exhibited a ketoprofen blue luminescence when excited in the UV region. The compound containing Tb(3+) ion was sensitized by the ligand and emitted in the green region of the visible spectrum. On the other hand, for the analogous species containing the dysprosium ion, a competition for luminescence between the Dy(3+) and the ligand levels was observed. Finally, Tm(3+) complex exhibits only ligand luminescence. These optical behaviors are discussed based on rare earth energy diagrams. In addition, the compounds were evaluated for their anti-inflammatory activities. All the compounds showed a higher production of H2O2 and IL-10 than the ketoprofen, suggesting that the compounds exhibited an immunomodulatory effect and this opens up new perspectives for immunotherapeutic approaches.

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Herein we report the synthesis of the 6-(hydroxymethyl)pyridine-2-carboxaldehyde[2-methyl-pyrimidine-4,6-diyl]bis-hydrazone by a condensation reaction between 6-(hydroxymethyl)picolinaldehyde with 4,6-(bis-hydrazino)-2-methylpyrimidine. This bis-hydrazone can be visualized as a two-arm system which exhibits photochemical induced [E,E]/[E,Z]/[Z,Z’] isomerizations and double coordination to metal centers. Configurational changes, upon UV light irradiation, were followed over time by ¹H NMR, establishing that isomerization, in both arms, is a consecutive reaction that follows first-order kinetics (k1= 4.06 x 10-4 s-1 and k2= 2.80 x 10-4 s-1). Furthermore, the synthesis of bis-hydrazone metal complexes with La and Sm (III) ions was achieved; subsequently, the absorption and emission properties of these complexes were studied, determining the fluorescence quantum yields, ΦLa= 0.2024 and ΦSm= 0.1413. Electrochemical studies of the complexes were conducted by square wave voltammetry, demonstrating that the bis-hydrazone and its complexes are electroactive species between +1.5 and -2.5 V.

Se reporta la síntesis de la 6-(hidroximetil)piridin-2-carboxaldehído[2-metilpirimidina-4,6-diil]bishidrazona mediante la reacción de condensación entre el 6-(hidroximetil)piconaldehído con la 4,6-(bishidracino)-2-metilpirimidina. Esta bishidrazona puede ser visualizada como un sistema de dos brazos los cuales exhiben isomerizaciones [E,E]/[E,Z]/[Z,Z’] fotoquímicamente inducidas y coordinación a centros metálicos. Los cambios configuracionales, después de irradiación UV, fueron seguidos en el tiempo mediante RMN ¹H estableciendo que la isomerización, en ambos brazos del sistema, corresponde a una reacción consecutiva que sigue una cinética de primer orden (k1= 4,06 x 10-4 s-1 and k2= 2,80 x 10-4 s-1). Además se prepararon complejos metálicos de La y Sm(III), seguidamente, las propiedades de absorción y emisión de dichos complejos fueron estudiadas calculando rendimientos cuánticos de fluorescencia de ΦLa= 0,2024 y ΦSm= 0,1413. Estudios electroquímicos de los complejos se llevaron a cabo a través de voltametría de onda cuadrada indicando que los compuestos preparados poseen potenciales redox dentro del rango de trabajo del solvente.

Reporta-se a síntese da 6-(hidroximetil)piridin-2-carboxaldeído[2-metilpirimidina-4,6-diil]bis-hidrazona mediante a reação de condensação entre o 6-(hidroximetil)piconaldeído e a 4,6-(bis-hidrazino)-2-metilpirimidina. Esta bis-hidrazona pode ser visualizada como um sistema de dois braços os quais exibem isomerizações [E,E]/[E,Z]/[Z,Z’] fotoquimicamente induzidas e coordenação com íons metálicos (dupla coordenação a íons metálicos). Após a irradiação UV, as mudanças configuracionais foram monitoradas com o tempo por RMN 1H. Essas medidas estabeleceram que a isomerização em ambos braços do sistema corresponde a uma reação consecutiva apresentando uma cinética de primeira ordem (k1= 4.06 x 10-4 s-1 e k2= 2.80 x 10-4 s-1). Além disso, os complexos metálicos de La e Sm(III) foram preparados e suas propriedades de absorção e de emissão foram estudadas, calculando os rendimentos quânticos de fluorescência de ΦLa= 0.2024 e de ΦSm= 0.1413. Estudos eletroquímicos dos complexos foram feitos através de voltametria de onda quadrada indicando que os compostos preparados possuem potenciais redox dentro da faixa de trabalho do solvente.