Synthesis, antibacterial activity and interaction of DNA with lanthanide-β-cyclodextrin inclusion complexes

1 recurso en línea (páginas 99-117).En este trabajo se han sintetizado complejos de lantánidos a partir de los cloruros de La(III), Ce(III), Sm (III) e Yb(III) con ligandos cinamato, presentando coordinación bidentada entre el grupo carboxilo del ligando y el metal lantánido. Estos compuestos se utilizaron como huéspedes de la β-ciclodextrina con el fin de obtener nuevos complejos de inclusión mediante el método de co-precipitación, utilizando N,N-dimetilformamida como disolvente. Los productos de inclusión obtenidos fueron caracterizados mediante espectroscopía IR-ATR, Raman, UV-vis, RMN 1H y 13C, DRX, TGA, DSC, análisis elemental y complexometría con EDTA. Se realizaron pruebas de actividad antibacteriana empleando 6 cepas ATTC (S. aureus ATCC 25923, S. aureus ATCC 29213, E. coli ATCC 25922, P. aeruginosa ATCC 27853, S. Typhimurium ATCC 14028 y K. pneumoniae ATCC BAA-2146) mediante el método de microdilución con caldo Mueller-Hinton; los resultados de actividad biológica para los complejos lantánidos permitieron evidenciar el efecto sinérgico entre el catión lantánido y el ligando cinamato. Igualmente, para los complejos de inclusión se observó una disminución de la concentración mínima inhibitoria (CMI) respecto a los complejos lantánidos iniciales. Los resultados obtenidos con el ADN de timo de ternera y el ADN plasmídico pBR322 permiten proponer una interacción electrostática entre los complejos evaluados y la estructura molécular del ADN.In this work, lanthanide complexes were synthesized starting from the corresponding La (III), Ce (III), Sm (III) and Yb (III) chlorides and cinnamate ligands which present bidentate coordination between the carboxyl group of the ligand and the lanthanide metal. These compounds were used as hosts of β-cyclodextrin to obtain new inclusion complexes by a co-precipitation method using N,N-dimethylformamide as solvent. The inclusion products were characterized by IR-ATR spectroscopy, Raman, UV-vis, 1H and 13C NMR,XRD, TGA-DSC, elemental analysis and EDTA complexometry. Antibacterial activity tests were performed using six ATTC strains (S. aureus ATCC 25923, S. aureus ATCC 29213, E. coli ATCC 25922, P. aeruginosa ATCC 27853, S. Typhimurium ATCC 14028 and K. pneumoniae ATCC BAA-2146) by the microdilution method with Mueller-Hinton broth. The results of the biological activity for the lanthanide complexes showed the synergistic effect between the lanthanide cation and the cinnamate ligand. For the inclusion complexes, a decrease of the minimum inhibitory concentration (MIC) was observed with respect to the initial lanthanide complexes. The results obtained with the bovine thymus DNA and the plasmid pBR322 DNA allow to propose an electrostatic interaction between the evaluated complexes and the molécular structure of the DNA.Bibliografía y webgrafía: páginas 114-117

Actividad catalítica de complejos p-R-cinamato de Ce(III), Nd(III) y Sm(III) en la oxidación de β-pineno y canfeno

Se realizó la síntesis de nueve complejos lantánidos de cerio, neodimio y samario con ligandos trans-cinamato (L1), trans-p-clorocinamato (L2) y trans-p-metoxicinamato (L3). La caracterización se realizó mediante espectroscopia FT-IR, análisis térmicos (TGA y DSC) y análisis elemental. Los compuestos obtenidos se utilizaron como catalizadores para la oxidación de canfeno y β-pineno, usando peróxido de hidrógeno (30 %) y ácido peracético (12 %) como agentes oxidantes. En la oxidación de canfeno, el complejo [Nd(L2)3] presentó la conversión más alta (97.99 %) con una selectividad del 84.05 % hacia el ácido 3-canfenilocarboxílico, mientras que en la oxidación de β-pineno, el complejo [Ce(L3)3 . 2H2O] presentó la conversión más alta (82.62 %) con una selectividad hacia la nopinona del 70.52 %

Synthesis, antibacterial activity and DNA interactions of lanthanide(III) complexes of N(4)-substituted thiosemicarbazones

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(III) and Nd(III) 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.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

Synthesis, antibacterial activity and DNA interactions of lanthanide(III) complexes of N(4)-substituted thiosemicarbazones

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(III) and Nd(III) 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.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

Photochemical and electrochemical studies on lanthanide complexes of 6-(hydroxymethyl)pyridine- 2-carboxaldehyde[2- methyl-pyrimidine-4,6-diyl] bis-hydrazone

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 1 H 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 (III) and Sm (III) ions was achieved; subsequently, the absorption and emission properties of these complexes were studied, determining the fluorescence quantum yields, La= 0.2024 and Sm= 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

Steric control of the reduction of carbodiimides by samarium(II) and the synthesis of very crowded samarium(III) complexes

Reduction of N,N′-di(2,6-diisopropylphenyl)carbodiimide (DippNCNDipp) by [SmL2(thf)2] (1) (L = N,N′-bis(2,6-diisopropylphenyl)formamidinate, DippNC(H)NDipp) in PhMe gave [Sm(L)3] (2) in good yield. An analogous reaction of 1 with N,N′-dimesitylcarbodiimide (MesNCNMes) gave [SmL2(MesNC(H)NMes)] (3). In contrast, reduction of N,N′-dicyclohexylcarbodiimide (CyNCNCy) by 1 in PhMe gave mixture of products from which [SmL2(CyNC(CH2Ph)NCy)] (4) and [SmL2(CyNC(H)NCy)] (5) were isolated by fractional crystallisation. Using thf as the reaction solvent, solely compound 5 was crystallised. Reactions of [Sm(L)2(C[triple bond, length as m-dash]CPh)(thf)] (6) with the carbodiimides RNCNR (R = Cy, Mes) gave [Sm(L)2(RNC(C[triple bond, length as m-dash]CPh)NR)] (R = Cy (7) or Mes (8)) which are analogues of 4. No reaction was observed between 6 and DippNCNDipp

Pincer Complexes Derived from Tridentate Schiff Bases for Their Use as Antimicrobial Metallopharmaceuticals

Within the current challenges in medicinal chemistry, the development of new and better therapeutic agents effective against infectious diseases produced by bacteria, fungi, viruses, and parasites stands out. With chemotherapy as one of the main strategies against these diseases focusing on the administration of organic and inorganic drugs, the latter is generally based on the synergistic effect produced by the formation of metal complexes with biologically active organic compounds. In this sense, Schiff bases (SBs) represent and ideal ligand scaffold since they have demonstrated a broad spectrum of antitumor, antiviral, antimicrobial, and anti-inflammatory activities, among others. In addition, SBs are synthesized in an easy manner from one-step condensation reactions, being thus suitable for facile structural modifications, having the imine group as a coordination point found in most of their metal complexes, and promoting chelation when other donor atoms are three, four, or five bonds apart. However, despite the wide variety of metal complexes found in the literature using this type of ligands, only a handful of them include on their structures tridentate SBs ligands and their biological evaluation has been explored. Hence, this review summarizes the most important antimicrobial activity results reported this far for pincer-type complexes (main group and d-block) derived from SBs tridentate ligands

Antibacterial Activity of a Cationic Antimicrobial Peptide against Multidrug-Resistant Gram-Negative Clinical Isolates and Their Potential Molecular Targets

Antimicrobial resistance reduces the efficacy of antibiotics. Infections caused by multidrug-resistant (MDR), Gram-negative bacterial strains, such as Klebsiella pneumoniae (MDRKp) and Pseudomonas aeruginosa (MDRPa), are a serious threat to global health. However, cationic antimicrobial peptides (CAMPs) are promising as an alternative therapeutic strategy against MDR strains. In this study, the inhibitory activity of a cationic peptide, derived from cecropin D-like (ΔM2), against MDRKp and MDRPa clinical isolates, and its interaction with membrane models and bacterial genomic DNA were evaluated. In vitro antibacterial activity was determined using the broth microdilution test, whereas interactions with lipids and DNA were studied by differential scanning calorimetry and electronic absorption, respectively. A strong bactericidal effect of ΔM2 against MDR strains, with minimal inhibitory concentration (MIC) and minimal bactericidal concentrations (MBC) between 4 and 16 μg/mL, was observed. The peptide had a pronounced effect on the thermotropic behavior of the 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC)/1,2-dimyristoyl-sn-glycero-3-phosphorylglycerol (DMPG) membrane models that mimic bacterial membranes. Finally, the interaction between the peptide and genomic DNA (gDNA) showed a hyperchromic effect, which indicates that ΔM2 can denature bacterial DNA strands via the grooves