Cobalt(III)-pyen systems as potential carriers of β-ketoester-based ligands.

Two cobalt(III) complexes containing different β-ketoesters, namely [Co(L1)(pyen)](ClO)·HO (1) and [Co(L2)(pyen)](ClO) (2) (pyen = N,N'-bis(pyridin-2-ylmethyl)ethylenediamine; L1 = methylacetoacetate; L2 = ethyl 4-chloroacetoacetate) have been prepared and investigated as prototypes of bioreductive prodrugs. The presence of β-ketoester and pyen ligands in 1 and 2, as well as the perchlorate counterions, was supported by IR spectroscopy and CHN elemental analysis. The composition molecular structure of both complexes was confirmed by NMR spectroscopy and ESI mass spectrometry.

DNA-interacting properties of two analogous square-planar cis-chlorido complexes: copper versus palladium.

Two square-planar coordination compounds, namely [Cu(CPYA)Cl] (1) and [Pd(CPYA)Cl] (2), were prepared from the ligand 4-chloro-N-(pyridin-2-ylmethyl)aniline (CPYA) and two chloride salts, and were fully characterized, including by X-ray diffraction. Spectroscopic, electrophoretic and AFM studies revealed that the two isostructural compounds were interacting differently with DNA. In both cases, the initial interaction involves electrostatic contacts of the CPYA ligand in the minor groove (as suggested by molecular docking), but subsequent strong binding occurs with the palladium(II) complex 2, whereas the binding with the copper complex 1 is weaker and concentration dependent.

Reactivity and Mechanisms of Photoactivated Heterometallic [Ru Ni ] and [Ru Ni Ru ] Catalysts for Dihydrogen Generation from Water.

Two heterometallic photocatalysts were designed and probed for water reduction. Both [(bpy) Ru Ni (L )](ClO ) (1) and [(bpy) Ru Ni (L ) Ru (bpy) ](ClO ) (2) can generate the low-valent precursor involved in hydride formation prior to dihydrogen generation. However, while the bimetallic [Ru Ni ] (1) requires the presence of an external photosensitizer to trigger catalytic activity, the trimetallic [Ru Ni Ru ] (2) displays significant coupling between the catalytic and light-harvesting units to promote intramolecular multielectron transfer and perform photocatalysis at the Ni center.

Evaluation of cobalt(III) complexes as potential hypoxia-responsive carriers of esculetin.

Differentiation between hypoxic and normoxic tissues have been exploited for the development of selective chemotherapeutic agents. In this context, cobalt(III)-based coordination compounds have been designed and investigated as prospective hypoxia-responsive drug delivery systems. Three cobalt(III) complexes, namely [Co(esc)(pyen)]ClO·(CHOH) (1) [Co(esc)(TPA)]ClO·3HO (2) and [Co(bipy)(esc)]ClO·2.

Investigation of cobalt(III)-phenylalanine complexes for hypoxia-activated drug delivery.

Four cobalt(iii)-phenylalanine complexes, [Co(Phe)(py2en)](ClO4)2·H2O (1), [Co(Phe)(TPA)](ClO4)2·H2O (2), [Co(Phe)(py2enMe2)](ClO4)2·H2O (3) and [Co(bipy)2(Phe)](ClO4)2·H2O (4), were investigated as prototype models for hypoxia-activated delivery of melphalan - a phenylalanine derivative anticancer drug of the class of nitrogen mustards. Single crystal X-ray diffraction analysis provided the molecular structures of 1-4, as a single isomer/conformer. According with NMR and theoretical calculations, the solid-state structures of 2 and 4 are maintained in solutions.

Evaluation of 5-hydroxy-1,4-naphthoquinone-cobalt(III) complexes for hypoxia-activated drug delivery.

Three novel PyNcobalt(III) complexes with the 5-hydroxy-1,4-naphthoquinone nuclei (NQ) were evaluated as potential hypoxia-activated anticancer prodrugs. The complexes were synthesized and fully characterized by IR and UV-Visible spectroscopies, ESI mass spectrometry and CHN elemental analysis. Structural information was obtained from density functional theory (DFT) calculations.

Binucleating Hydrazonic Ligands and Their μ-Hydroxodicopper(II) Complexes as Promising Structural Motifs for Enhanced Antitumor Activity.

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.

Aroylhydrazones constitute a promising class of 'metal-protein attenuating compounds' for the treatment of Alzheimer's disease: a proof-of-concept based on the study of the interactions between zinc(II) and pyridine-2-carboxaldehyde isonicotinoyl hydrazone.

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.

Investigation of cobalt(iii)-triazole systems as prototypes for hypoxia-activated drug delivery.

Three novel cobalt(iii)-triazole complexes with structural and redox properties suitable for hypoxia-activated drug delivery were obtained. A major influence of the ancillary ligands (TPA, py2en, py2enMe2) on the electronic properties and reactivity of their complexes was observed. An [O2]-dependent reduction to cobalt(ii) by ascorbic acid provided evidence of hypoxic selectivity.

A study on the properties and reactivity of naphthoquinone-cobalt(III) prototypes for bioreductive prodrugs.

Our group has recently initiated a study on the development of new prototypes for bioreductive prodrugs, based on Co(III) complexes with the ligand 2,2'-bis(3-hydroxy-1,4-naphthoquinone), H2bhnq. The focus of this work is to investigate the dissociation of bhnq(-2) from the complex upon reduction, and the effects of pH, redox potential, oxygen concentration and nature of the auxiliary ligands on this reaction. The bhnq(2-) ligand is a "non-cytotoxic" agent that was chosen as a probe for the reactivity studies due to its suitable chromophoric properties, at the same time that it resembles more cytotoxic naphthoquinones relevant for cancer therapy.

Cobalt lawsone complexes: searching for new valence tautomers.

Bi-stable molecular systems presenting valence tautomerism are associated with the development of new functional materials, which can be used for applications in organic electric conductors, optoelectronic and molecular magnetic devices. The properties of these materials can be adjusted with slight chemical changes and can be induced by external stimuli. Typical examples of valence tautomer compounds are coordination complexes of Co and o-dioxolene ligands, notably quinone like ones.

Lawsone dimerization in cobalt(III) complexes toward the design of new prototypes of bioreductive prodrugs.

Dimerization of lawsone occurs upon reaction with Co(BF(4))(2)·6H(2)O and N,N'-bis(pyridin-2-ylmethyl)ethylenediamine (py(2)en) to produce the mononuclear complex [Co(III)(bhnq)(py(2)en)]BF(4)·H(2)O (1). This complex has been investigated as a prototype of a bioreductive prodrug, where the bhnq(2-) ligand acts as a model for cytotoxic naphthoquinones. Cyclic voltammetry data in aqueous solution have shown a quasi-reversible Co(III)/Co(II) process at E(1/2) = -0.

Evaluation of the antioxidant capacity of synthesized coumarins.

Coumarins are secondary metabolites that are widely distributed within the plant kingdom, some of which have been extensively studied for their antioxidant properties. The antioxidant activity of coumarins assayed in the present study was measured by different methods, namely the 1,1-diphenyl-2-picryl-hydrazyl (DPPH(•)) method, cyclic voltammetry and the antioxidant capacity against peroxyl radicals (ACAP) method. The 7,8-dihydroxy-4-methylcoumarin (LaSOM 78), 5-carboxy-7,8-dihydroxy-4-methylcoumarin (LaSOM 79), and 6,7-dihydroxycoumarin (Esculetin) compounds proved to be the most active, showing the highest capacity to deplete the DPPH radicals, the highest antioxidant capacity against peroxyl radicals, and the lowest values of potential oxidation.

Aqua-(4,4'-bipyridine-κN)bis-(1,4-dioxo-1,4-dihydronaphthalen-2-olato-κO,O)zinc 4,4'-bipyridine mono-solvate dihydrate.

The reaction of 2-hy-droxy-1,4-naphtho-quinone and 4,4'-bipyridine with zinc acetate produced the title compound, [Zn(C(10)H(5)O(3))(2)(C(10)H(8)N(2))(H(2)O)]·C(10)H(8)N(2)·2H(2)O. The bond lengths and angles around the metal atom indicate a deviation from octa-hedral geometry. The two naphtho-quinone ligands coordinate in a cis fashion, with the 4,4'-bipyridine ligand and the water mol-ecules completing the coordination sphere of the metal atom.

A new nitrosyl ruthenium complex: synthesis, chemical characterization, in vitro and in vivo antitumor activities and probable mechanism of action.

This study describes the synthesis of a new ruthenium nitrosyl complex with the formula [RuCl(2)NO(BPA)] [BPA = (2-hydroxybenzyl)(2-methylpyridyl)amine ion], which was synthesized and characterized by spectroscopy, cyclic voltammetry, X-ray crystallography, and theoretical calculation data. The biological studies of this complex included in vitro cytotoxic assays, which revealed its activity against two different tumor cell lines (HeLa and Tm5), with efficacy comparable to that of cisplatin, a metal-based drug that is administered in clinical treatment. The in vivo studies showed that [RuCl(2)NO(BPA)]is effective in reducing tumor mass.

A modular approach to redox-active multimetallic hydrophobes of discoid topology.

A new modular [Fe(II)(Fe(III)L(2))(3)](PF(6))(2) species with discoid (disk-like) topology exhibits redox and surfactant properties and points to a new approach for multimetallic Langmuir film precursors.

Synthesis, electrochemical studies and anticancer activity of ferrocenyl oxindoles.

A series of (E) and (Z)-ferrocenyl oxindoles were prepared by coupling substituted oxindoles to ferrocenylcarboxyaldehyde in the presence of morpholine as a catalyst. The redox behavior of these isomers was determined by cyclic voltammetry. The effects of the oxindole derivatives on the migration of human breast cancer cells were evaluated using the wound-healing assay and the Boyden chamber cell-migration assay.

Design of molecular scaffolds based on unusual geometries for magnetic modulation of spin-diverse complexes with selective redox response.

A weakly coupled heterometallic [CuFe] complex has been prepared in which the metal centers are coordinated to a new electroactive ligand. The spin-diverse system delivers distinct ground states upon application of selective redox potentials. Ligand oxidation fosters radical generation, and the initial ground state associated with a weakly coupled [CuFe] core switches to a ground state associated with the [Fe-radical] coupling; the Cu(II) ion remains uncoupled.

Structural, spectroscopic, and electrochemical behavior of trans-phenolato cobalt(III) complexes of asymmetric NN'O ligands as archetypes for metallomesogens.

In order to understand and predict structural, redox, magnetic, and optical properties of more complex and potentially mesogenic electroactive compounds such as [Co(III)(L(t-BuLC))2]ClO4 (1), five archetypical complexes of general formula [Co(III)(L(RA))2]ClO4, where R = H (2), tert-butyl (3), methoxy (4), nitro (5), and chloro (6), were obtained and studied by means of several spectrometric, spectroscopic, and electrochemical methods. The complexes 2, 4, and 6 were characterized by single-crystal X-ray diffraction, and show the metal center in an approximate D2h symmetry. Experimental results support the fact that the electron donating or withdrawing nature of the phenolate-appended substituents changes dramatically the redox and spectroscopic properties of these compounds.

Electronic effects of electron-donating and -withdrawing groups in model complexes for iron-tyrosine-containing metalloenzymes.

Three new iron(III) complexes with the ligand N,N'-bis(2-hydroxybenzyl)-N,N'-bis(pyridin-2-ylmethyl)ethylenediamine, H2bbpen, containing electron-donating and -withdrawing groups (Me, Br, NO2) in the 5-position of the phenol rings were synthesized and fully characterized by IR spectroscopy, ESI mass spectrometry, and CHN elemental analyses. X-ray structures of the iron(III) complexes containing NO2 and Me groups were determined. The effects of the substituents on the electronic properties of the complexes were detected by UV-visible spectroscopy, cyclic voltammetry, and X-ray crystallography.

Structural and electronic behavior of unprecedented five-coordinate iron(III) and gallium(III) complexes with a new phenol-rich electroactive ligand.

A new asymmetric pentadentate ligand was designed to impose low symmetry to trivalent ions. Five-coordinate Fe3+ and Ga3+ complexes were investigated by crystallographic, electrochemical, and electron paramagnetic resonance methods showing enhanced redox reversibility. Calculations were performed to account for the observed trends.

Influence of ligand rigidity and ring substitution on the structural and electronic behavior of trivalent iron and gallium complexes with asymmetric tridentate ligands.

Species 1-6 are [M(III)(L)2]ClO4 complexes formed with the PhO--CH=N-CH2-Py imines, (L(I))- and (L(tBuI))-, and PhO--CH2-NH-CH2-Py amines, (L(A))- and (L(tBuA))-, in which PhO- is a phenolate ring and Py is a pyridine ring and the prefix tBu indicates the presence of tertiary butyl groups occupying the positions 4 and 6 of the phenol ring. Monometallic species with d5 high-spin iron (1, 2, 3, 4) and d10 gallium (5, 6) were synthesized and characterized to assess the influence of the ligand rigidity and the presence of tertiary butyl-substituted phenol rings on their steric, electronic, and redox behavior. Characterization by elemental analysis, mass spectrometry, IR, UV-visible, and EPR spectroscopies, and electrochemistry has been performed, and complexes [FeIII(L(tBuI))2]ClO4 (2), [FeIII(L(tBuA))2]ClO4 (4), and [Ga(III)(L(tBuI))2]ClO4 (5) have been characterized by X-ray crystallography.

A new heterobinuclear FeIIICuII complex with a single terminal FeIII-O(phenolate) bond. Relevance to purple acid phosphatases and nucleases.

A novel heterobinuclear mixed valence complex [Fe(III)Cu(II)(BPBPMP)(OAc)(2)]ClO(4), 1, with the unsymmetrical N(5)O(2) donor ligand 2-bis[{(2-pyridylmethyl)aminomethyl}-6-{(2-hydroxybenzyl)(2-pyridylmethyl)}aminomethyl]-4-methylphenol (H(2)BPBPMP) has been synthesized and characterized. A combination of data from mass spectrometry, potentiometric titrations, X-ray absorption and electron paramagnetic resonance spectroscopy, as well as kinetics measurements indicates that in ethanol/water solutions an [Fe(III)-(mu)OH-Cu(II)OH(2)](+) species is generated which is the likely catalyst for 2,4-bis(dinitrophenyl)phosphate and DNA hydrolysis. Insofar as the data are consistent with the presence of an Fe(III)-bound hydroxide acting as a nucleophile during catalysis, 1 presents a suitable mimic for the hydrolytic enzyme purple acid phosphatase.

New Fe(III)Zn(II) complex containing a single terminal Fe-O(phenolate) bond as a structural and functional model for the active site of red kidney bean purple acid phosphatase.

The new heterodinuclear complex [Fe(III)Zn(II)(BPBPMP)(OAc)(2)]ClO(4) (1) with the unsymmetrical N(5)O(2) donor ligand 2-bis[((2-pyridylmethyl)-aminomethyl)-6-[(2-hydroxybenzyl)(2-pyridylmethyl)]-aminomethyl]-4-methylphenol (H(2)BPBPMP) has been synthesized and characterized by X-ray crystallography, which reveals that the complex cation has an Fe(III)Zn(II)(mu-phenoxo)-bis(mu-carboxylato) core. Solution studies of 1 indicate that a pH-induced change of the bridging acetate occurs, and the formation of an active [(OH)Fe(III)Zn(II)(OH(2))] species as a highly efficient catalyst under weakly acidic conditions for phosphate diesters hydrolysis is proposed.