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An analytical method for the determination of 8-hydroxyquinoline-2-carboxaldehyde isonicotinoyl hydrazone (INHHQ) is reported for the first time. The electrochemical method involving INHHQ was perf...

Misfolded prion protein (PrPSc) is known for its role in fatal neurodegenerative conditions, such as Creutzfeldt-Jakob disease. PrP fragments and their mutants represent important tools in the investigation of the neurotoxic mechanisms and in the evaluation of new compounds that can interfere with the processes involved in neuronal death. Metal-catalyzed oxidation of PrP has been implicated as a trigger for the conformational changes in protein structure, which, in turn, lead to misfolding. Targeting redox-active biometals copper and iron is relevant in the context of protection against the oxidation of biomolecules and the generation of oxidative stress, observed in several conditions and considered an event that might promote sporadic prion diseases as well as other neurodegenerative disorders. In this context, ortho-pyridine aroylhydrazones are of interest, as they can act as moderate tridentate ligands towards divalent metal ions such as copper(II). In the present work, we explore the potentiality of this chemical class as peptide protecting agents against the deleterious metal-catalyzed oxidation in the M112A mutant fragment of human PrP, which mimics relevant structural features that may play an important role in the neurotoxicity observed in prion pathologies. The compounds inhere studied, especially HPCFur, showed an improved stability in aqueous solution compared to our patented lead hydrazone INHHQ, displaying a very interesting protective effect toward the oxidation of methionine and histidine, processes that are related to both physiological and pathological aging.

International audience; Two novel unsymmetrical binucleating aroylhydrazonic ligands and four dicopper(II) complexes carrying fluorescent benzopyranothiophene (BPT) or boron dipyrromethene (BODIPY) entities were synthesized and fully characterized. Complex 1, derived from the BPT-containing ligand H3L1, had its crystal structure elucidated through X-ray diffraction measurements. The absorption and fluorescence profiles of all the compounds obtained were discussed. Additionally, the stability of the ligands and complexes was monitored by UV–vis spectroscopy in DMSO and biologically relevant media. All the compounds showed moderate to high cytotoxicity towards the triple negative human breast cancer cell line MDA-MB-231. BPT derivatives were the most cytotoxic, specially H3L1, reaching an IC50 value up to the nanomolar range. Finally, fluorescence microscopy imaging studies employing mitochondria- and nucleus-staining dyes showed that the BODIPY-carrying ligand H3L2 was highly cell permeant and suggested that the compound preferentially accumulates in the mitochondria.

The interaction of oxidovanadium(V) with INHOVA (the condensation product of isoniazid and o-vanillin) lead to the formation of the ester-like complex [VO(INHOVA)EtO(OH2)]Cl·H2O (1). Crystals suitable for X-ray diffraction methods were obtained. The complex crystallizes as a dimer in the space group P21/c of the monoclinic system. A detailed analysis, including solid-state vibrational spectroscopy and electronic spectroscopy in DMSO solution, was performed for both INHOVA and complex (1). A complete theoretical study based on DFT was also carried out. The calculations were of valuable assistance in the spectra assignments and interpretation. The electrochemical characterization allows determining the redox behavior of INHOVA and complex (1). Cytotoxicity was assayed against the chronic myelogenous leukemia K562 cell line. The IC50 values obtained denote that both the ligand and complex (1) are good candidates for further studies., Centro de Química Inorgánica

Quality of vegetable oils is affected by the presence of metals, even at low concentrations. A study was conducted to advance evaluate the degradation of canola induced by the presence of copper CuO (expected to be less reactive than Cu 2+ ). Samples were heated at 90 °C for fourteen days and the results suggested that contamination does influence not only the oxidation rate but also the extension of the degradation processes. FT-IR and Raman spectra showed the decreasing of the carbonyl absorption belonging to triglycerides during the oxidation process, which was most pronounced in the CuO contaminated oil, indicating the increasing of the hydrolysis process. Furthermore, the oxidation of the olefinic bonds also appears to be copper-mediated, since the cis C H vibration band decreases to a larger extent in the metal-containing samples. CuO exerted a greater degradation as it caused a more pronounced decrease of both the number of unsaturations and carbonyl groups of esters, besides the more effective decrease in the induction time and the higher production of secondary oxidation products.

Alzheimer's and Parkinson's diseases share similar amyloidogenic mechanisms, in which metal ions might play an important role. In this last neuropathy, misfolding and aggregation of α-synuclein (α-Syn) are crucial pathological events. A moderate metal-binding compound, namely, 8-hydroxyquinoline-2-carboxaldehyde isonicotinoyl hydrazone (INHHQ), which was previously reported as a potential ‘Metal-Protein Attenuating Compound’ for Alzheimer's treatment, is well-tolerated by healthy Wistar rats and does not alter their major organ weights, as well as the tissues' reduced glutathione and biometal levels, at a concentration of 200 mg kg− 1. INHHQ definitively crosses the blood-brain barrier and can be detected in the brain of rats so late as 24 h after intraperitoneal administration. After 48 h, brain clearance is complete. INHHQ is able to disrupt, in vitro, anomalous copper-α-Syn interactions, through a mechanism probably involving metal ions sequestering. This compound is non-toxic to H4 (human neuroglioma) cells and partially inhibits intracellular α-Syn oligomerization. INHHQ, thus, shows definite potential as a therapeutic agent against Parkinson's as well. Fil: Cukierman, Daphne Schneider. Pontifícia Universidade Católica do Rio de Janeiro; Brasil Fil: Pinheiro, Ana Beatriz. Pontifícia Universidade Católica do Rio de Janeiro; Brasil Fil: Castiñeiras-Filho, Sergio L.P.. Pontifícia Universidade Católica do Rio de Janeiro; Brasil Fil: da Silva, Anastácia Sá P.. Pontifícia Universidade Católica do Rio de Janeiro; Brasil Fil: Miotto, Marco César. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario. Universidad Nacional de Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario; Argentina Fil: De Falco, Anna. Pontifícia Universidade Católica do Rio de Janeiro; Brasil Fil: de P. Ribeiro, Thales. Universidade Federal do Rio de Janeiro; Brasil Fil: Maisonette, Silvia. Pontifícia Universidade Católica do Rio de Janeiro; Brasil Fil: da Cunha, Alessandra L.M.C.. Pontifícia Universidade Católica do Rio de Janeiro; Brasil Fil: Hauser-Davis, Rachel A.. Pontifícia Universidade Católica do Rio de Janeiro; Brasil Fil: Fernandez, Claudio Oscar. Pontifícia Universidade Católica do Rio de Janeiro; Brasil Fil: Aucélio, Ricardo Q.. Pontifícia Universidade Católica do Rio de Janeiro; Brasil Fil: Outeiro, Tiago F.. Universität Göttingen; Alemania Fil: Pereira, Marcos D.. Universidade Federal do Rio de Janeiro; Brasil Fil: Fernandez, Claudio Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario. Universidad Nacional de Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario; Argentina Fil: Rey, Nicolás A.. Pontifícia Universidade Católica do Rio de Janeiro; Brasil

Very few inorganic antineoplastic drugs have entered the clinic in the last decades, mainly because of toxicity issues. Because copper is an essential trace element of ubiquitous occurrence, decreased side effects could be expected in comparison with the widely used platinum anticancer compounds. In the present work, two novel hydrazonic binucleating ligands and their μ-hydroxo dicopper(II) complexes were prepared and fully characterized. They differ by the nature of the aromatic group present in their aroylhydrazone moieties: while H3L1 and its complex, 1, possess a thiophene ring, H3L2 and 2 contain the more polar furan heterocycle. X-ray diffraction indicates that both coordination compounds are very similar in structural terms and generate dimeric arrangements in the solid state. Positive-ion electrospray ionization mass spectrometry analyses confirmed that the main species present in a 10% dimethyl sulfoxide (DMSO)/water solution should be [Cu2(HL)(OH)]+ and the DMSO-substituted derivative [Cu2(L)(DMSO)]+. Scattering techniques [dynamic light scattering (DLS) and small-angle X-ray scattering] suggest that the complexes and their free ligands interact with bovine serum albumin (BSA) in a reversible manner. The binding constants to BSA were determined for the complexes through fluorescence spectroscopy. Moreover, to gain insight into the mechanism of action of the compounds, calf thymus DNA binding studies by UV-visible and DLS measurements using plasmid pBR322 DNA were also performed. For the complexes, DLS data seem to point to the occurrence of DNA cleavage to Form III (linear). Both ligands and their dicopper(II) complexes display potent antiproliferative activity in a panel of four cancer cell lines, occasionally even in the submicromolar range, with the complexes being more potent than the free ligands. Our data on cellular models correlate quite well with the DNA interaction experiments. The results presented herein show that aroylhydrazone-derived binucleating ligands, as well as their dinuclear μ-hydroxodicopper(II) complexes, may represent a promising structural starting point for the development of a new generation of highly active potential antitumor agents.

Aroylhydrazones are versatile compounds with a series of applications, from biological to technological spheres. The simplicity of their preparation allows for a great chemical variability and synthetic manageability. However, the process can be not as straightforward as one would imagine. Some parameters such as specific reactants, the amount of acid employed as catalyst and reaction temperature can have a direct impact on the obtained product. In the present work, we describe two series of novel isoniazid-derived compounds prepared from a pair of different aldehyde precursors, as well as the solvolysis, under harsh synthetic conditions, of the initially formed aroylhydrazones, leading to unexpected dihydrazones. All compounds were unequivocally characterized in solution using 1D and 2D NMR experiments in DMSO‑d6 and, in the solid-state, by other classic techniques. System I is composed by 2-(1H-pyrazol-1-yl)benzaldehyde and its hydrazone derivatives, while system II comprises 2-(4-metoxyphenoxy)benzaldehyde and its related Schiff-base products. The first aldehyde was obtained for the first time via the copper-catalyzed Ullmann C–N coupling between 2-bromobenzaldehyde and pyrazole. Single crystals of its aroylhydrazone and dihydrazone derivatives were isolated and thoroughly characterized, including Hirshfeld surfaces and energy frameworks studies. Finally, we describe an NMR and theoretically-based proposed reaction pathway for the unexpected formation of the dihydrazones involving the solvolysis of the initially formed isonicotinoyl hydrazone followed by attack to a second free aldehyde molecule.

Hydrazones and several substituted hydrazones are associated with a broad spectrum of biological activities, as well as compounds containing the thiophene ring. In this context, a novel di-hydrazone derived from 2-thiophenecarboxylic acid hydrazide was synthesized and completely characterized by elemental analysis, XRD, FT-IR, Raman and UV–Vis spectroscopies, thermogravimetry, 1H NMR, 1H–1H COSY and 1H–1H ROESY. A preliminary in silico pharmacological evaluation was also performed in order to assess the performance of the new compound regarding some molecular properties relevant for a drug's pharmacokinetics in the human body.

Hydrazones constitute a class of compounds presenting azomethine R′R″N N CH R hydrogens, which show diverse properties and a wide range of applications. A hydrazone derived from the antituberculosis drug isoniazid, namely, N,N′-diisonicotinoyl-2-hydroxy-5-methylisophthalaldehyde hydrazone (DMD) was synthesized and chemically characterized. Its luminescent properties were also investigated, as well as the possibility of using this compound as a constituent of the emitting layer for the fabrication of OLEDs. Co-deposited devices were fabricated using the organic molecule BSBF as matrix and DMD as dopant. All the devices presented a broad electroluminescence band, in which it was possible to recognize the DMD emission along with emissions of some of the other organic layers. The best results were obtained with 35% DMD doping, achieving a luminance of about 35 cd/m2.

In this work, Density Functional Theory was used in the theoretical study of the coordination of three ligands derived from 8-hydroxyquinoline (8-HQ) with N-acylhydrazone: 8-hydroxyquinoline-2-carboxaldehyde isonicotinoyl hydrazone (INHHQ), 2-[(8-hydroxyquinolinyl)methylene] acetohydrazide (8-H2QH) and 2-[(8-hydroxyquinolinyl)methylene] hydrazinecarboxamide (8-H2QS); with the Zn2+ion. These complexes prevent interactions of the metal ions present in the brain, with the β-amyloid peptide (Aβ), avoiding the formation of aggregates that are responsible for the development of the Alzheimer's disease. The results show that the three ligands coordinate the Zn2+ion in a tridentate form through the O and N atoms of the 8-hydroxyquinoline center and the N of the hydrazonic group, completing the coordination sphere with two chloride ions, creating a bipyramidal structure trigonal, different from the structures of the complexes reported in the literature.

With the increasing life expectancy of the world’s population, neurodegenerative diseases, such as Alzheimer’s disease (AD), will become a much more relevant public health issue. This fact, coupled with the lack of efficacy of the available treatments, has been driving research directed to the development of new drugs for this pathology. Metal-protein attenuating compounds (MPACs) constitute a promising class of agents with potential application on the treatment of neurodegenerative diseases, such as AD. Currently, most MPACs are based on 8-hydroxyquinoline. Recently, our research group has described the hybrid aroylhydrazone containing the 8-hydroxyquinoline group INHHQ as a promising MPAC. By studying the known structure-related ligand HPCIH, which does not contain the phenol moiety, as a simplified chemical model for INHHQ, we aimed to clarify the real impact of the aroylhydrazone group for the MPAC activity of a compound with potential anti-Alzheimer’s activity. The present work describes a detailed solution and solid-state study of the coordination of HPCIH with Zn2+ ions, as well as its in vitro binding-ability towards this metal in the presence of the Aβ(1–40) peptide. Similar to INHHQ, HPCIH is able to efficiently compete with Aβ(1–40) for Zn2+ ions, performing as expected for an MPAC. The similarity between the behaviors of both ligands is remarkable. Taken together, the data presented herein point to aroylhydrazones, such as the compounds HPCIH and the previously published INHHQ, as encouraging MPACs for the treatment of AD. Fil: Cukierman, Daphne S.. Pontifícia Universidade Católica do Rio de Janeiro; Brasil Fil: Accardo, Elio. Pontifícia Universidade Católica do Rio de Janeiro; Brasil Fil: Gomes, Rosana Garrido. Pontifícia Universidade Católica do Rio de Janeiro; Brasil Fil: De Falco, Anna. Pontifícia Universidade Católica do Rio de Janeiro; Brasil Fil: Miotto, Marco César. Universidad Nacional de Rosario; Argentina Fil: Freitas, Maria Clara Ramalho. Universidade Federal do Rio de Janeiro; Brasil Fil: Lanznaster, Mauricio. Universidade Federal Fluminense; Brasil Fil: Fernández, Claudio O.. Universidad Nacional de Rosario; Argentina Fil: Rey, Nicolás A.. Pontifícia Universidade Católica do Rio de Janeiro; Brasil

The catalytic mechanism that involves the cleavage of the phosphate diester model BDNPP (bis(2,4-dinitrophenyl) phosphate) catalyzed through a dinuclear copper complex is investigated in the current study. The metal complex was originally designed to catalyze catechol oxidation, and it showed an interesting catalytic promiscuity case in biomimetic systems. The current study investigates two different reaction mechanisms through quantum mechanics calculations in the gas phase, and it also includes the solvent effect through PCM (polarizable continuum model) single-point calculations using water as solvent. Two mechanisms are presented in order to fully describe the phosphate diester hydrolysis. Mechanism 1 is of the S(N)2 type, which involves the direct attack of the μ-OH bridge between the two copper(II) ions toward the phosphorus center, whereas mechanism 2 is the process in which hydrolysis takes place through proton transfer between the oxygen atom in the bridging hydroxo ligand and the other oxygen atom in the phosphate model. Actually, the present theoretical study shows two possible reaction paths in mechanism 1. Its first reaction path (p1) involves a proton transfer that occurs immediately after the hydrolytic cleavage, so that the proton transfer is the rate-determining step, which is followed by the entry of two water molecules. Its second reaction path (p2) consists of the entry of two water molecules right after the hydrolytic cleavage, but with no proton transfer; thus, hydrolytic cleavage is the rate-limiting step. The most likely catalytic path occurs in mechanism 1, following the second reaction path (p2), since it involves the lowest free energy activation barrier (ΔG(⧧) = 23.7 kcal mol(-1), in aqueous solution). A kinetic analysis showed that the experimental k(obs) value of 1.7 × 10(-5) s(-1) agrees with the calculated value k1 = 2.6 × 10(-5) s(-1); the concerted mechanism is kinetically favorable. The KIE (kinetic isotope effect) analysis applied to the second reaction path (p2) in mechanism 1 was also taken into account to assess the changes that take place in TS1-i (transition state of mechanism 1) and to perfectly characterize the mechanism described herein.

Colloidal suspensions of oxocarbon-encapsulated gold nanoparticles have been synthesized in a one-step procedure by pulsed-laser ablation (PLA) at 532 nm of a solid gold target placed in aqueous solution containing CO2 absorbers, but without any stabilizing agent. Multi-wavelength surface enhanced Raman spectroscopy allows the identification of adsorbed amorphous carbon and graphite, Au-carbonyl, Au coordinated CO2-derived bicarbonates/carbonates and hydroxyl groups around the AuNPs core. Scanning electron microscopy, energy dispersive x-ray analysis and high resolution transmission electron microscopy highlight the organic shell structure around the crystalline metal core. The stability of the colloidal solution of nanocomposites (NCs) seems to be driven by solvation forces and is achieved only in neutral or basic pH using monovalent hydroxide counter-ions (NaOH, KOH). The NCs are characterized by a blue shift of the localized surface plasmon resonance (LSPR) band typical of metal-ligand stabilization by terminal ?-back bonding, attributed to a core charging effect caused by Au-carbonyls. Total organic carbon measurements detect the final content of organic carbon in the colloidal solution of NCs that is about six times higher than the value of the water solution used to perform PLA. The colloidal dispersions of NCs are stable for months and are applied as analytical probes in amino glycoside antibiotic LSPR based sensing.