Cláudio N. Verani

Efficient Water Oxidation Using CoMnP Nanoparticles.

The development of efficient water oxidation catalysts based on inexpensive and Earth-abundant materials is a prerequisite to enabling water splitting as a feasible source of alternative energy. In this work, we report the synthesis of ternary cobalt manganese phosphide nanoparticles from the solution-phase reaction of manganese and cobalt carbonyl complexes with trioctylphosphine. The CoMnP nanoparticles (ca. 5 nm in diameter) are nearly monodisperse and homogeneous in nature. These CoMnP nanoparticles are capable of catalyzing water oxidation at an overpotential of 0.33 V with a 96% Faradaic efficiency when deposited as an ink with carbon black and Nafion. A slight decrease in activity is observed after 500 cycles, which is ascribed to the etching of P into solution, as well as the oxidation of the surface of the nanoparticles. Manganese-based ternary phosphides represent a promising new system to explore for water oxidation catalysis.

Metals in Anticancer Therapy: Copper(II) Complexes as Inhibitors of the 20S Proteasome

Selective 20S proteasomal inhibition and apoptosis induction were observed when several lines of cancer cells were treated with a series of copper complexes described as [Cu(L(I))Cl] (1), [Cu(L(I))OAc] (2), and [Cu(HL(I))(L(I))]OAc (3), where HL(I) is the ligand 2,4-diiodo-6-((pyridine-2-ylmethylamino)methyl)phenol. These complexes were synthesized, characterized by means of ESI spectrometry, infrared, UV-visible and EPR spectroscopies, and X-ray diffraction when possible. After full characterization species 1-3 were evaluated for their ability to function as proteasome inhibitors and apoptosis inducers in C4-2B and PC-3 human prostate cancer cells and MCF-10A normal cells. With distinct stoichiometries and protonation states, this series suggests the assignment of species [CuL(I)](+) as the minimal pharmacophore needed for proteasomal chymotryspin-like activity inhibition and permits some initial inference of mechanistic information.

Comparative Activities of Nickel(II) and Zinc(II) Complexes of Asymmetric [NN'O] Ligands as 26S Proteasome Inhibitors

In this study, we compare the proteasome inhibition capabilities of two anticancer candidates, [Ni(L(IA))(2)] (1) and [Zn(L(IA))(2)] (2), where L(IA-) is the deprotonated form of the ligand 2,4-diiodo-6-(((2-pyridinylmethyl)amino)methyl)phenol. Species 1 contains nickel(II), a considerably inert ion that favors covalency, whereas 2 contains zinc(II), a labile transition metal ion that favors predominantly ionic bonds. We report on the synthesis and characterization of 1 and 2 using various spectroscopic, spectrometric, and structural methods. Furthermore, the pharmacological effects of 1 and 2, along with those of the salts NiCl(2) and ZnCl(2), were evaluated in vitro and in cultured human cancer cells in terms of their proteasome-inhibitory and apoptotic cell-death-inducing capabilities. It is shown that neither NiCl(2) nor 1 have the ability to inhibit the proteasome activity at any sustained levels. However, ZnCl(2) and 2 showed superior inhibitory activity versus the chymotrypsin-like activity of both the 26S proteasome (IC(50) = 5.7 and 4.4 micromol/L, respectively) and the purified 20S proteasome (IC(50) = 16.6 and 11.7 micromol/L, respectively) under cell-free conditions. Additionally, inhibition of proteasomal activity in cultured prostate cancer cells by 2 was associated with higher levels of ubiquitinated proteins and apoptosis. Treatment with either the metal complex or the salt was relatively nontoxic toward human normal cells. These results strengthen the current working hypothesis that fast ligand dissociation is required to generate an [ML(IA)](+) pharmacophore, capable of interaction with the proteasome. This interaction, possibly via N-terminal threonine amino acids present in the active sites, renders the proteasome inactive. Our results present a compelling rationale for 2 along with its gallium(III) and copper(II) congeners to be further investigated as potential anticancer drugs that act as proteasome inhibitiors.

Bioinspired Five-Coordinate Iron(III) Complexes for Stabilization of Phenoxyl Radicals†

Considerable effort has been directed towards the integration of biomimetic principles into molecular materials that have customized and controllable properties. The notion of stimulus-triggered molecular switching between two or more ground states of comparable energy is particularly relevant because such switching leads to detectable electronic and structural changes. Coordination complexes that merge transition-metal ions with ligands that stabilize organic radicals are among the most promising candidates for redox-responsive switching processes. Among the electroactive ligands that have been well characterized, those that contain phenolate moieties are significant because of their synthetic versatility and redox accessibility. This importance has been highlighted by studies on metal–phenoxyl complexes that have several geometries. Iron(III) complexes that contain phenolates tend to favor an octahedral geometry and are electrochemically reversible, but usually do not withstand multiple redox cycles. Thus, an understanding of the alternative geometries of such complexes becomes a necessary strategy for the future development of redox switches. We are investigating bioinspired designs that incorporate the basic geometries that are present in redox-versatile enzymes, such as tyrosine hydroxylase and intradiol dioxygenase, in which five-coordinate iron(III) centers support radical-based mechanisms for generating l-3,4-dihydroxyphenylalanine (l-DOPA) and cleaving catechol-type rings, respectively. We have reported the behavior of high-spin iron(III) complexes that are confined to low-symmetry, pentadentate N2O3 environments. [6] In these complexes, the assignment of oxidation states becomes challenging because of the contributions of ligandand metal-centered orbitals to the same redox process, and the presence of five unpaired electrons. Nonetheless, we have shown that high oxidation states are unavailable to the metal ion, and that the ligand supports up to three consecutive oxidations, which leads to antiferromagnetic interactions. Relative to octahedral fields, these fivecoordinate environments are expected to yield low-degeneracy molecular orbitals (MOs) that are sensitive to subtle but noticeable structural changes in the ligands. These changes should lead to orbital rearrangements that modify the sequence by which phenolate oxidations occur. Herein, we investigate the behavior of the five-coordinate species [FeL] (1) and [FeL] (2, Scheme 1), in which a low-symmetry ligand field is purposefully enforced around the 3d metal ion by the N2O3 ligands. Ligands [L ] and [L] both contain N2O3 environments with three phenolate moieties, denoted A, A’, and B; phenolates A and A’ share the same amine group and are chemically equivalent, whereas phenolate B is attached to either an azomethine group in L or to a methylamine group in L. Both species have four accessible ground states: [FeL]/[FeL] , [FeLC], [FeLCC], and [FeLCCC]. The aim of this study is to determine the sequence in which each of the phenolate rings is oxidized in the presence of the azomethine and the methylamine groups, and to test the feasibility of consecutive, multielectronic oxidations by ion-pairing effects with the supporting electrolyte. This study is intended to contribute to the fundamental understanding of the redox and electronic behavior of high-spin 3d 5 ions in five-coordinate ligand fields, and provide significant insight into bioinspired redox cycling. Complexes 1 and 2 were synthesized as previously described and crystals that were suitable for analysis by [*] M. M. Allard, J. A. Sonk, Dr. M. J. Heeg, Prof. H. B. Schlegel, Prof. C. N. Verani Department of Chemistry, Wayne State University 5101 Cass Ave. Detroit, MI 48202 (USA) E-mail: cnverani@chem.wayne.edu Homepage: http://chem.wayne.edu/veranigroup/

Metal complexes as inhibitors of the 26S proteasome in tumor cells

The ubiquitin/proteasome pathway is the main mechanism available for eukaryotic cells to eliminate defective proteins and enzymes. Tumor cells -particularly those in solid tumors such as prostate cancer- seem to display increased proteasomal activity associated to cell growth. When such activity is inhibited apoptotic cell death takes place. Thus, the understanding of the chemical mechanisms by which this inhibition occurs is relevant to the development of new therapeutic antineoplastic agents. Here a short review is presented on the synthesis, characterization, and activity of metal-containing species with asymmetric ligands containing the methylpyridin-amino-methylphenol moiety. These complexes were scrupulously investigated structurally and spectroscopically, and have been shown to inhibit the chymotrypsin-like activity of the 20S and 26S proteasome in vitro and in vivo. Recent developments in the understanding of such inhibition are discussed and point out to the influence exerted by ligand substituents, the electronic configurations and charges of the metal ion, and the role of counterions.

Ligand Transformations and Efficient Proton/Water Reduction with Cobalt Catalysts Based on Pentadentate Pyridine‐Rich Environments

A series of cobalt complexes with pentadentate pyridine-rich ligands is studied. An initial Co(II) amine complex 1 is prone to aerial oxidation yielding a Co(III) imine complex 2 that is further converted into an amide complex 4 in presence of adventitious water. Introduction of an N-methyl protecting group to the ligand inhibits this oxidation and gives rise to the Co(II) species 5. Both the Co(III) 4 and Co(II) 5 show electrocatalytic H2 generation in weakly acidic media as well as in water. Mechanisms of catalysis seem to involve the protonation of a Co(II)-H species generated in situ.

Molecular order in Langmuir-Blodgett monolayers of metal-ligand surfactants probed by sum frequency generation.

Molecular organization of Langmuir-Blodgett (LB) monolayers of novel copper-containing metal-ligand surfactants was characterized by the surface-selective vibrational sum frequency generation (SFG) spectroscopy. The orientational and conformational order inferred from the SFG peak amplitudes and line shapes were correlated with the two-dimensional phases of the monolayers observed in the compression isotherms. The octadecyl-pyridin-2-ylmethyl-amine (L(PyC18)) ligand by itself shows good amphiphilic properties, as indicated by the high monolayer collapse pressure at the air/water interface, but its LB films transferred onto fused silica exhibit a high degree of trans-gauche conformational disorder in the alkyl tails. Coordination of copper(II) ions to the chelating head group enhances the molecular alignment and reduces the fraction of gauche defects of the alkyl chains. Monolayers of single-tail (L(PyC18)Cu(II)Cl(2)) and double-tail [(L(PyC18))(2)Cu(II)]Cl(2) metallosurfactants show distinctly different behavior of their molecular organization as a function of the area per molecule. Our observations suggest metal-ligand interactions as a pathway to induce molecular order in LB monolayer films.

Interfacial Behavior and Film Patterning of Redox‐Active Cationic Copper(II)‐Containing Surfactants

Herein, we describe the synthesis and characterization of a novel series of single-tail amphiphiles LPyCn (Py=pyridine, Cn=C18, C16, C14, C10) and their copper(II)-containing complexes, which are of relevance for patterned films. The N-(pyridine-2-ylmethyl)alkyl-1-amine ligands and their complexes [CuIICl2(LPyC18)] (1), [CuIICl2(LPyC16)] (2), [CuIICl2(LPyC14)] (3), [CuIIBr2(LPyC18)] (4), [CuIIBr2(LPyC16)] (5), and [CuIIBr2(LPyC10)] (6) were synthesized, isolated, and characterized by means of mass spectrometry, IR and NMR spectroscopies, and elemental analysis. Complexes 1, 2, 3, and 6 had their molecular structure solved by X-ray diffraction methods, which showed that the local geometry around the metal center is distorted square planar. With the aim of using these species as precursors for redox-responsive films, an assessment of their electrochemical properties involved cyclic voltammetry in different solvents, with different supporting electrolytes and scan rates. Density functional theory calculations of relevant species in bulk and at interfaces were used to evaluate their electronic structure and dipole moments. The morphology and order of the resulting films at the air/water interface were studied by isothermal compression and Brewster angle microscopy. Biphasic patterned Langmuir films were observed for all complexes except 3 and 6, and dependence on the chain length and the nature of the halogen coligand determine the characteristics of the isotherms and their intricate topology. Complexes 3 and 6, which have shorter chain lengths, failed to exhibit organization. These results exemplify the first comprehensive study of the behavior of single-tail metallosurfactants, which are likely to lead to high-end technological applications based on their patterned films.

Rectification in Nanoscale Devices Based on an Asymmetric Five‐Coordinate Iron(III) Phenolate Complex

Rectification consists of an asymmetric flow of electric current. In a macroscopic electrical circuitry, rectifiers, such as vacuum tubes or solid-state diodes, control the mobility of current, enabling it to flow in one direction and preventing reversibility. This directionality is fundamental to the conversion of alternating into direct current. Molecular rectification, which was proposed in the celebrated Aviram–Ratner ansatz, anticipates the feasibility of a current flow in one direction that takes place in an electrode jmolecule j electrode junction. Central to this paradigm is the existence of asymmetric molecules that incorporate electron-donor and electron-acceptor moieties, [DA], with an excited state [DA ] of higher, but accessible, energy. Usually, donor and acceptor are separated by a sor p-bridge to decrease electronic coupling, and if the requirements are fulfilled, rectification occurs with contributions from Schottky, asymmetric, and/or unimolecular mechanisms. Schottky rectification is based on interfacial dipoles from electrode contact or on covalent bonding between the molecule and the electrode. Asymmetric and unimolecular mechanisms rely on the use of frontier molecular orbitals of the molecule; whereas the former relies on an asymmetric placement of the HOMO or the LUMO in the electrode jmolecule j electrode assembly, the latter is based on small HOMO–LUMO gaps that allow for through-molecule current flow. Although experimental distinction between asymmetric and unimolecular contributions can be ambiguous, there is consensus that electroactive molecules with local low symmetry constitute good candidates for this enterprise, and welldocumented cases of molecular rectification heavily rely on the formation of high-quality Langmuir–Blodgett (LB) films. Although it has been shown that self-assembled monolayers of polypyridine–cobalt(II) complexes in octahedral environments can act as single-electron transistors and induce increased resistance (Coulomb blockade) at cryogenic temperatures, the incorporation of transition-metal complexes into electrode jmolecule junctions has generally employed symmetric molecules and has been rather slow in development. Examples involve assemblies based on metalloporphyrins, terpyridine–ruthenium(II) complexes, as well as trivalent cobalt and rhodium azo-containing species in octahedral environments that are capable of the symmetric conductance that is relevant for memory-switching devices. An example of rectification based on an octahedral bipyridine/acac–ruthenium(II) system has been reported (acac = acetylacetonate), but the effect of lowering global symmetries around the metal center is yet to be tested. Our group is engaged in an effort to integrate bioinspired asymmetry principles into new molecular materials, with the aim of developing redox-responsive metallosurfactants with topologies that display unique structural, spectroscopic, and surface patterning behavior. We recently reported on the redox and electronic behavior of five-coordinate complexes where the iron(III) ion is bound to low-symmetry, phenolaterich, [N2O3] environments, and it was shown that geometric and electronic constraints determine the sequence by which the metal and each of the phenolate substituents gets oxidized. Herein, a new iron(III) species [FeL] (1; Scheme 1) is reported. This species shows marked local asymmetries and is based on a newly synthesized amphiphilic and redox-active [N2O3] ligand. The complex takes advantage of the presence of the phenylenediamino–metal and phenyl/ phenolate moieties that can act as electron-acceptors and electron-donors, respectively. The viability of 1 as a precursor

The Mechanisms of Rectification in Au|Molecule|Au Devices Based on Langmuir–Blodgett Monolayers of Iron(III) and Copper(II) Surfactants†

Langmuir-Blodgett films of metallosurfactants were used in Au|molecule|Au devices to investigate the mechanisms of current rectification.