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The bis{(μ2-chloro)[2-(imidazol-4-yl)ethyl][(1-methylimidazol-2-yl)methyl]amine}dicopper(II) bis[tetrachloro-cuprate (II)] complex [Cu2(HISMIMA)2Cl2]2(CuCl4)2 (HISMIMA:[(2-(imidazol-4-yl)ethyl)(1-methylimidazol-2-yl)methyl)amine]) was obtained by serendipity during the reaction of the mononuclear [Cu(HISMIMA)Cl2] complex and gaseous nitric oxide in methanolic solution. The title complex unit cell has the composition: an anion complex {[Cu2(HISMIMA)2Cl2][CuCl4]2}2- (1) and a cation complex [Cu2(HISMIMA)2Cl2]2+ (2). Cation 2 displays a crystallographic centrosymmetric Cu2Cl2 core with each CuII atom coordinated to the tripodal ligand in a square pyramidal geometry (Addison parameter τ=0.07). In 1, a distorted octahedral geometry is observed, in which the CuII ions are coordinated in a way similar to that in 2 but with an additional interaction with the [CuCl4]2- ions. Cyclic voltammetric experiments reveal that the title complex does not dissociate in acetonitrile solution and has E1/2=-0.24 V vs NHE (ΔEp=0.19 V, ipa/ipc=0.75) for the CuIICuII to CuICuI process at the Cu(μ-Cl)2Cu core. [Copyright &y& Elsevier]

The new copper(II)–nitrite complex [CuII(L)(ONO)]ClO4 (2), L=[(bis(1-methylimidazol-2-yl)methyl)(2-(pyridyl-2-yl)ethyl)amine] was synthesized and characterized by cyclic voltammetry, UV–Vis spectroscopy, X-band EPR and X-ray crystallography. Complex 2 crystallizes in the monoclinic system, space group P21/n and has the metal center in a somewhat distorted square pyramidal geometry, with three nitrogen atoms from the chelate ligand and one nitrite ion outlining the basal plane. One imidazole nitrogen from the tripodal molecule is at the apical position at 2.158(2) A˚ from the metal. Spectrophotometric and electrochemical experiments in water solution reveal that complex 2 readily releases the nitrite ligand in this medium (t1/2<10 s at 25 °C) yielding the precursor complex 1, [CuII(L)(S)]2+. The affinity of complex 1 for nitrite was evaluated by spectrophotometric titration, following the appearance of the Cu(II)–nitrite band at 376 nm, and by the cyclic voltammetric peak potential data. Both experiments were carried out in methanolic solution (μ=0.1 mol L−1, TBAPF6, T=25±1 °C). The formation constant value obtained from the voltammetric experiments (1.2 ± 0.1 × 103 M−1) agrees quite well with that from the spectrophotometric titration (1.4 ± 0.2 × 103 M−1) and is within the range of values observed for other Cu(II)–nitrite complexes. The geometrical arrangements of the tripodal ligand and the nitrite ion coordination allows considering complex 2 a potential biomimetic structural model for type II copper in nitrite reductases. [Copyright &y& Elsevier]

Three mononuclear copper(II) complexes ( C1 – C3 ) containing the ligand 2-(2-aminomethyl)pyridine ( aep ) and some modifications of it were designed to get insights on the influence of pendant second sphere groups (thiophene and benzene) on their physicochemical and catalytic properties. Complexes C1 – C3 were synthesized reacting copper(II) chloride with the precursor ligand LP1 , N -(2-(pyridin-2-yl)ethylidene)-1-(thiophen-2-yl)methanamine, and the ligands L2 , 2-(pyridin-2-yl)- N -(thiophen-2-y-lmethyl)ethanamine, and L3 , N -benzyl-2-(pyridin-2-yl)ethanamine, respectively. The complexes were isolated and characterized by several methods. Single crystal X-ray crystallographic studies revealed that C1 results from the cleavage of the Schiff base PL1 , yielding the distorted square planar copper(II) complex coordinated to one molecule of aep and two chloride ions, which have been already published. All complexes present the same coordination sphere; C2 and C3 have also pendant arms. These groups induce singular crystal packing by different intermolecular interactions, which correlates with the decomposition temperatures of the complexes. In addition, electronic, redox and catalytic properties are also influenced. Complex C3 is the most efficient in the oxidation of 3,5-di- tert -butylcatechol (3,5-DTBC) and presents catalytic efficiency of 72.9 L mol −1  s −1 . It is 4.5 and 11-fold greater than those determined for C1 and C2 , respectively. Complexes reaction orders of 0.70 ± 0.04 for C1 , 1.6 ± 0.1 for C2 and 0.913 ± 0.002 for C3 indicate different catalytic species in each case, with mechanisms involving more than one active species for C1 and C2 . Different mechanisms can explain the catalytic behavior of these complexes. [ABSTRACT FROM AUTHOR]

Cisplatin and its analogues are some of the most widely used anticancer drugs. However, toxicity and resistance have limited their use, and gallium compounds have emerged as an alternative, due to their remarkable antitumor activity and low toxicity. In this paper, we report on four new mononuclear gallium(III) complexes with the general formula [ Ga(bhi-R) 2 ] + , where bhi-R ( R = – NO 2 , – Br , – Cl and – OCH 3 ) is the deprotonated form of imidazole/phenol-containing tridentate Schiff bases. The molecular structures of C1 – C4 were solved by single crystal X-ray diffraction revealing mononuclear and isostructural complexes, with the metal center in distorted octahedral geometries. In all cases, the gallium(III) is coordinated to two ligand molecules arranged in meridional fashion, through the imidazole and imino nitrogen atoms, and to the phenolate oxygen. Complexes C1 – C4 were also characterized in solution by spectroscopic and spectrometric techniques. DFT calculations were performed to assist the interpretation of experimental results, and also allowed to establish the reasons why only meridional isomers were obtained. The stability of all complexes was evaluated in PBS buffer (1% DMSO) over 24 h, and results indicate partial hydrolysis in this period. Finally, the biological activity of C1 – C4 was evaluated on human tumor cell lines MCF-7 (breast adenocarcinoma), A-549 (lung adenocarcinoma epithelial) and PC-3 (prostate adenocarcinoma). Complex C1 was the most active, being effective and selective for A-549. The IC 50 (94.12 ± 4.62) of C1 is lower than the value (135.10 ± 6.50) obtained for cisplatin, which was tested as a metallodrug reference under the same experimental conditions. [ABSTRACT FROM AUTHOR]

Two copper(II) mononuclear complexes were synthesized and investigated as promiscuous oxidative catalysts: [Cu(pymimi)Cl 2 ]: [(2-(pyridyl-2-yl)ethyl)((1-methylimidazol-2-yl)methyl)imine](bischlorido)copper(II), C1 , and [Cu(pymima)Cl 2 ]: [(2-(pyridyl-2-yl)ethyl)((1-methylimidazol-2-yl)methyl)amine] (bischlorido)copper(II), C2 . Both complexes were characterized by the following techniques: X-ray crystallography, decomposition point, elemental analysis, IR, UV–Vis and EPR spectroscopies, conductimetric analysis and electrochemistry. DFT calculations at the B3LYP level were carried out to corroborate structural, vibrational and spin Hamiltonian parameters ( g x , g y and g z ). TDDFT electronic spectra were calculated at CAMB3LYP level. Cyclohexane peroxidation promoted by C1 and C2 yielded the following overall conversions/turnover numbers: 48%/531 s −1 and 46%/508 s −1 , respectively. Both complexes also catalyze the conversion of 3,5-di- tert -butylcatechol (3,5-DTBC) to 3,5-di- tert -butylquinone (3,5-DTBQ) with turnover numbers of 6.0 × 10 −2 s −1 for C1 and 11.0 × 10 −2 s −1 for C2 . Complexes C1 and C2 can be classified as substrate promiscuous catalysts due to their ability to promote the oxidation of two different substrates, in the presence of distinct oxidants (O 2 , for catechol and H 2 O 2 for cyclohexane). [ABSTRACT FROM AUTHOR]

The prototypical drug carrier [CoII(L 1 )Cl]PF 6 (1), where L1 is a tripodal amine bound to pyridine and methyl-imidazoles, had its electrocatalytic water splitting activity studied under different pH conditions. This species contains a high-spin 3 d 7 CoII metal center, and is capable of generating both H 2 from water reduction and O 2 from water oxidation. Turnover numbers reach 390 after 3 h for water reduction. Initial water oxidation activity is molecular, with TONs of 71 at pH 7 and 103 at pH 11.5. The results reveal that species 1 can undergo several redox transformations, including reduction to the 3 d 8 CoI species that precedes a LS3 d 6 hydride for water reduction, as well as nominal CoIV O and CoIII-OOH species required for water oxidation. Post-catalytic analyses confirm the molecular nature of reduction and support initial molecular activity for oxidation. A prototypical drug carrier [CoII(L1)Cl]PF 6 (L1, tripodal amine bound to pyridine/methylimidazoles) had its electrocatalytic water splitting activity studied vs. pH, and is capable of water reduction (TON 3h = 390) and water oxidation (TON 3h ≈ 103). Post-catalytic analysis supports the molecular nature of reduction and suggests initial molecular oxidative activity. [Display omitted] • A Co-containing drug carrier based on a tripodal amine had its electrocatalytic water splitting activity studied. • Electrocatalytic water splitting activity was studied at different pHs. • The Co-containing drug carrier generates H 2 from water reduction with TON 3h 390. • The Co-containing drug carrier generates O 2 from water oxidation with TON 3h 103. • Post-catalytic analysis supports the molecular nature of reduction and oxidation. [ABSTRACT FROM AUTHOR]

Cobalt(III) complexes are well-suited systems for cytotoxic drug release under hypoxic conditions. Here, we investigate the effect of cytotoxic azide release by cobalt-containing carrier-prototypes for antitumoral prodrugs. In addition, we study the species formed after reduction of Co 3 + → Co 2 + in the proposed models for these prodrugs. Three new complexes, [Co III (L)(N 3 ) 2 ]BF 4 (1) , [{Co II (L)(N 3 )} 2 ](ClO 4 ) 2 (2) , and [Co II (L)Cl]PF 6 (3) , L = [( bis (1-methylimidazol-2-yl)methyl)(2-(pyridyl-2-yl)ethyl)amine], were synthesized and studied by several spectroscopic, spectrometric, electrochemical, and crystallographic methods. Reactivity and spectroscopic data reveal that complex 1 is able to release N 3 − either after reduction with ascorbic acid, or by ambient light irradiation, in aqueous phosphate buffer (pH 6.2, 7.0 and 7.4) and acetonitrile solutions. The antitumoral activities of compounds 1–3 were tested in normoxia on MCF-7 (human breast adenocarcinoma), PC-3 (human prostate) and A-549 (human lung adenocarcinoma epithelial) cell lines, after 24 h of exposure. Either complexes or NaN 3 presented IC 50 values higher than 200 μM, showing lower cytotoxicity than the clinical standard antitumoral complex cisplatin, under the same conditions. Complexes 1 – 3 were also evaluated in hypoxia on A-549 and results indicate high IC 50 data (> 200 μM) after 24 h of exposure. However, an increase of cancer cell susceptibility to 1 and 2 was observed at 300 μM. Regarding complex 3 , no cytotoxic activity was observed in the same conditions. The data presented here indicate that the tridentate ligand L is able to stabilize both oxidation states of cobalt (+ 3 and + 2). In addition, the cobalt(III) complex generates the low cytotoxic cobalt(II) species after reduction, which supports their use as as carrier prototypes for antitumoral prodrugs. [ABSTRACT FROM AUTHOR]

Abstract: Continuing our interest in tridentate ligands to develop new prototypes of cobalt-based metallodrugs for combating cancer, modifications in the backbone of HL1, [(2-hydroxybenzyl)(2-(pyridil-2-yl)ethyl]amine) were proposed in order to modulate the redox potential of new Co(III) complexes. Three ligands with electron withdrawing groups were synthesized: HL2: [(2-hydroxy-5-nitrobenzyl)(2-(pyridil-2-yl)ethyl]amine); HL3: [(2-hydroxybenzyl)(2-(pyridil-2-yl)ethyl]imine) and HL4: [(2-hydroxy-5-nitrobenzyl)(2-(pyridil-2-yl)ethyl]imine). They were used to obtain the respective mononuclear complexes 2, 3 and 4, which are discussed compared to the previous reported complex 1 (obtained from HL1). The new complexes were characterized and studied by several techniques including X-ray crystallography, elemental and conductimetric analysis, IR, UV–vis and 1H NMR spectroscopies, and electrochemistry. The substitutions of the group in the para position of the phenol (HL1 and HL2) and the imine instead of the amine (HL3 and HL4), promote anodic shifts in the complexes reduction potentials. The influence of these substitutions in the biological activities of the Co(III) complexes against the murine melanoma cell line (B16F10) was also evaluated. Little effect was observed on cellular viability decrease for all free ligands, however the coordination to Co(III) enhances their activities in the following range: 1 > 4 ≈ 2 > 3. The data suggest that no straight correlation can be addressed between the reduction potential of the Co(III) center and the cell viability. [Copyright &y& Elsevier]

Abstract: Aiming to investigate the use of tridentate ligands to develop new bireductively activated prodrugs, two N2O-donor ligands (HL1: [(2-hydroxybenzyl)(2-(imidazol-2-yl)ethyl)]amine; and HL2: [(2-hydroxybenzyl)(2-(pyridil-2-yl)ethyl]amine) were used to synthesize new Co(III) complexes, 1 and 2. Both complexes were characterized by X-ray crystallography, mass spectrometry, electrochemistry, IR, UV–visible and 1H NMR spectroscopies. Electrochemical data in methanol revealed that the Co(III)→Co(II) reduction of 1 (−0.84V vs. normal hydrogen electrode – NHE) is more positive than 2 (−1.13V vs. NHE), while it was expected to be more negative due to better σ-donor ability of imidazole ring in HL1, compared to pyridine in HL2. Considering that reduction processes on Co(III) center may involve the lowest unoccupied molecular orbital (LUMO), it might play an important role on the electronic properties of the complexes, and could explain the observed redox potentials. Then, geometry optimizations of 1 and 2 were performed using the density functional theory (DFT), and different group participation in their LUMO is demonstrated. Using Saccharomyces cerevisiae cells as eukaryotic model, it is shown that in situ generated reduced species, 1red and 2red , have high capacity to inhibit cellular growth, with IC50 (0.50mM for both complexes) lower than cisplatin IC50 (0.6mM) at the same time of exposure. Regarding to their ability to promote S. cerevisiae cells death, after 24h, cells became susceptible only when exposed to 1red and 2red : (i) at concentrations higher than 0.5mM in a non-dose dependence, and (ii) in anaerobic metabolism. These data reveal the potential of 1 and 2 as bioreductively activated prodrugs, since their oxidized forms do not present expressive activities when compared to their reduced forms. [Copyright &y& Elsevier]

Abstract: A vanadyl complex with the ligand (bis(1-methylimidazol-2-yl)methyl)(2-(pyridyl-2-yl)ethyl)amine was synthesized and fully characterized by X-ray crystallography, elemental analyses, cyclic voltammetry and infrared, electronic and electron paramagnetic resonance spectroscopies. This compound was designed under the so called hybrid concept. It shows to be able to promiscuously use hydrogen peroxide to oxidize bromide and to catalyze the oxidation of benzene and cyclohexane with very good selectivities. [Copyright &y& Elsevier]

Abstract: Myo-inositol-1,2,3,4,5,6-hexakisphosphate, also known as phytate, is a natural metal chelate present in cereals, an important feedstock worldwide. This article reports the characterization of three metal storage model complexes: the homometallic Mn(II) myo-inositol-1,2,3,4,5,6-hexakisphosphate (IP6), the heterometallic Zn(II), Mn(II) analogue Na4MnZn4(C6H6O24P6)·(NO3)2 ·8H2O (MnZn4IP6) and the homometallic Zn(II) metal complex Na3Zn5(C6H6O24P6)OH·9H2O (Zn5IP6). The techniques of high-resolution 23Na, 13C and 31P NMR, electron paramagnetic resonance (EPR) and X-ray photoelectron spectroscopy (XPS) were applied in this study. The complexation of Zn(II) and Mn(II) by phosphate groups of IP6 is demonstrated by NMR and XPS results. 13C NMR results show a conformation for IP6 consisting of five equatorial phosphate groups to one axial group showing only one chemical environment for Zn and two for Mn, when characterized by XPS and EPR, in both Mn complexes. These results support, for the first time, a probable supramacromolecular structure for phytate complexes of transition metals. Based on the similarity between the EPR spectra of wheat seeds and that of the MnZn4IP6 compound, the manganese storage centers in wheat grains can be assigned to similar heterometallic phytate complexes. [Copyright &y& Elsevier]