Overestimation in angular path integration precedes Alzheimer's dementia.

Path integration (PI) is impaired early in Alzheimer's disease (AD) but reflects multiple sub-processes that may be differentially sensitive to AD. To characterize these sub-processes, we developed a novel generative linear-angular model of PI (GLAMPI) to fit the inbound paths of healthy elderly participants performing triangle completion, a popular PI task, in immersive virtual reality with real movement. The model fits seven parameters reflecting the encoding, calculation, and production errors associated with inaccuracies in PI. We compared these parameters across younger and older participants and patients with mild cognitive impairment (MCI), including those with (MCI+) and without (MCI-) cerebrospinal fluid biomarkers of AD neuropathology. MCI patients showed overestimation of the angular turn in the outbound path and more variable inbound distances and directions compared with healthy elderly. MCI+ were best distinguished from MCI- patients by overestimation of outbound turns and more variable inbound directions. Our results suggest that overestimation of turning underlies the PI errors seen in patients with early AD, indicating specific neural pathways and diagnostic behaviors for further research.

How do (perceptual) distracters distract?

When a target stimulus occurs in the presence of distracters, decisions are less accurate. But how exactly do distracters affect choices? Here, we explored this question using measurement of human behaviour, psychophysical reverse correlation and computational modelling. We contrasted two models: one in which targets and distracters had independent influence on choices (independent model) and one in which distracters modulated choices in a way that depended on their similarity to the target (interaction model). Across three experiments, participants were asked to make fine orientation judgments about the tilt of a target grating presented adjacent to an irrelevant distracter. We found strong evidence for the interaction model, in that decisions were more sensitive when target and distracter were consistent relative to when they were inconsistent. This consistency bias occurred in the frame of reference of the decision, that is, it operated on decision values rather than on sensory signals, and surprisingly, it was independent of spatial attention. A normalization framework, where target features are normalized by the expectation and variability of the local context, successfully captures the observed pattern of results.

Effects of copper occupancy on the conformational landscape of peptidylglycine α-hydroxylating monooxygenase.

The structures of metalloproteins that use redox-active metals for catalysis are usually exquisitely folded in a way that they are prearranged to accept their metal cofactors. Peptidylglycine α-hydroxylating monooxygenase (PHM) is a dicopper enzyme that catalyzes hydroxylation of the α-carbon of glycine-extended peptides for the formation of des-glycine amidated peptides. Here, we present the structures of apo-PHM and of mutants of one of the copper sites (H107A, H108A, and H172A) determined in the presence and absence of citrate. Together, these structures show that the absence of one copper changes the conformational landscape of PHM. In one of these structures, a large interdomain rearrangement brings residues from both copper sites to coordinate a single copper (closed conformation) indicating that full copper occupancy is necessary for locking the catalytically competent conformation (open). These data suggest that in addition to their required participation in catalysis, the redox-active metals play an important structural role.

Iron/Magnetite Nanoparticles as Magnetic Delivery Systems for Antitumor Drugs.

In this study we investigate on the possible use of a new kind of magnetic nanostructures as drug delivery systems for anticancer drugs. The starting particles are formed by an inner core of iron, coated by magnetite as a stabilizing, magnetic layer. These units are further coated by a poly(ethylenglycol) (PEG) layer to make them less prone to the attack by macrophages and to favour longer stays in the blood stream. The resulting particles consist of several magnetic cores encapsulated by a polymer layer around 5 nm thick. The crystal structure of the designed nanostructures, as determined by X-ray powder diffraction, is compatible with a crystalline magnetite component, whereas the magnetization hysteresis data indicate a superparamagnetic behavior. Both the initial susceptibility and the saturation magnetization are lower than for the bare magnetic cores, but still significant. Drug adsorption and release tests were performed on two anticancer drugs, namely 5-fluorouracil and doxorubicin. Both are found to adsorb on the particles, but only the latter appears to be released at a reasonable rate, which is found to be very slow for 5-fluorouracil.

Preparation of multi-functionalized Fe3O4/Au nanoparticles for medical purposes.

In this work, we investigate a route towards the synthesis of multi-functionalized nanoparticles for medical purposes. The aim is to produce magnetite/gold (Fe3O4/Au) nanoparticles combining several complementary properties, specifically, being able to carry simultaneously an antitumor drug and a selected antibody chosen so as to improve specificity of the drug vehicle. The procedure included, firstly, the preparation of Fe3O4 cores coated with Au nanoparticles: this was achieved by using initially the layer-by-layer technique in order to coat the magnetite particles with a three polyelectrolyte (cationic-anionic-cationic) layer. With this, the particles became a good substrate for the growth of the gold layer in a well-defined core-shell structure. The resulting nanoparticles benefit from the magnetic properties of the magnetite and the robust chemistry and the biostability of gold surfaces. Subsequently, the Fe3O4/Au nanoparticles were functionalized with a humanized monoclonal antibody, bevacizumab, and a chemotherapy drug, doxorubicin. Taken together, bevacizumab enhances the therapeutic effect of chemotherapy agents on some kinds of tumors. In this work we first discuss the morphology of the particles and the electrical characteristics of their surface in the successive synthesis stages. Special attention is paid to the chemical stability of the final coating, and the physical stability of the suspensions of the nanoparticles in aqueous solutions and phosphate buffer. We describe how optical absorbance and electrokinetic data provide a follow up of the progress of the nanostructure formation. Additionally, the same techniques are employed to demonstrate that the composite nanoparticles are capable of loading/releasing doxorubicin and/or bevacizumab.

Nanoengineering of doxorubicin delivery systems with functionalized maghemite nanoparticles.

Superparamagnetic iron oxide nanoparticles are developing as promising candidates for biomedical applications such as targeted drug delivery. In particular, they represent an alternative to existing antitumor drug carriers, because of their ultra-fine size, low toxicity and magnetic characteristics. Nevertheless, there is a need to functionalize them in order to achieve good biocompatibility, efficient modification for further attachment of biomolecules, and improved stability. In this work we describe the functionalization of superparamagnetic maghemite nanoparticles encapsulated in a silica shell. After their chemical modification with positive (3-aminopropyl)trimethoxysilane, a gold layer was deposited in order to facilitate incorporation of the antitumor drug, doxorubicin (DOX), up to a maximum loading of 80 µmol/g. In vitro cell uptake of nanocomposites was performed with DLD-1 colon cancer cells and PLC-PRF-5 liver cancer cells. Confocal microscopy photos illustrate that doxorubicin-loaded nanoparticles accumulate in both the cytoplasm and the cell nuclei. Cell survival efficiency with maghemite nanocomposites was determined via the MTT assay, and the cytotoxicity study proved that they exhibited significant toxicity against both types of cancer cells, although the improvement over free DOX treatment is more evident in the case of DLD-1 cancer cells when the most dilute drug and particle solutions are compared.

Coordination of peroxide to the Cu(M) center of peptidylglycine α-hydroxylating monooxygenase (PHM): structural and computational study.

Many bioactive peptides, such as hormones and neuropeptides, require amidation at the C terminus for their full biological activity. Peptidylglycine α-hydroxylating monooxygenase (PHM) performs the first step of the amidation reaction-the hydroxylation of peptidylglycine substrates at the Cα position of the terminal glycine. The hydroxylation reaction is copper- and O(2)-dependent and requires 2 equiv of exogenous reductant. The proposed mechanism suggests that O(2) is reduced by two electrons, each provided by one of two nonequivalent copper sites in PHM (Cu(H) and Cu(M)). The characteristics of the reduced oxygen species in the PHM reaction and the identity of the reactive intermediate remain uncertain. To further investigate the nature of the key intermediates in the PHM cycle, we determined the structure of the oxidized form of PHM complexed with hydrogen peroxide. In this 1.98-Å-resolution structure (hydro)peroxide binds solely to Cu(M) in a slightly asymmetric side-on mode. The O-O interatomic distance of the copper-bound ligand is 1.5 Å, characteristic of peroxide/hydroperoxide species, and the Cu-O distances are 2.0 and 2.1 Å. Density functional theory calculations using the first coordination sphere of the Cu(M) active site as a model system show that the computed energies of the side-on L(3)Cu(M)(II)-O(2) (2-) species and its isomeric, end-on structure L(3)Cu(M)(I)-O(2) (·-) are similar, suggesting that both these intermediates are significantly populated within the protein environment. This observation has important mechanistic implications. The geometry of the observed side-on coordinated peroxide ligand in L(3)Cu(M)(II)O(2) (2-) is in good agreement with the results of a hybrid quantum mechanical-molecular mechanical optimization of this species.

Maghemite functionalization for antitumor drug vehiculization.

In this paper we describe the preparation and characterization of magnetic nanocomposites designed for applications in targeted drug delivery. Combining superparamagnetic behavior with proper surface functionalization in a single entity makes it possible to have altogether controlled location and drug loading, and release capabilities. The colloidal vehicles consist of maghemite (γ-Fe2O3) cores surrounded by a gold shell through an intermediate silica coating. The external Au layer confers the particles a high degree of biocompatibility and reactive sites for the transported drug binding. In addition, it permits to take advantage of the strong optical resonance, making it easy to visualize the particles or even control their payload release through temperature changes. The results of the analysis of relaxivity demonstrate that these nanostructures can be used as T2 contrast agents in magnetic resonance imaging (MRI), but the magnetic cores will be mainly useful in manipulating the particles using external magnetic fields. We describe how optical absorbance and electrokinetic data provide a followup of the progress of the nanostructure formation. Additionally, these techniques, together with confocal microscopy, are employed to demonstrate that the component nanoparticles are capable of loading significant amounts of the antitumor drug doxorubicin, very efficient in the chemotherapy of a wide range of tumors. Colon adenocarcinoma cells were used to test the in vitro release capabilities of the drug-loaded nanocomposites.

Electrophoretic characterization of insulin growth factor (IGF-1) functionalized magnetic nanoparticles.

The synthesis of composite nanoparticles consisting of a magnetite core coated with a layer of the hormone insulin growth factor 1 (IGF-1) is described. The adsorption of the hormone in the different formulations is first studied by electrophoretic mobility measurements as a function of pH, ionic strength, and time. Because of the permeable character expected for both citrate and IGF-1 coatings surrounding the magnetite cores, an appropriate analysis of their electrophoretic mobility must be addressed. Recent developments of electrokinetic theories for particles covered by soft surface layers have rendered possible the evaluation of the softness degree from raw electrophoretic mobility data. In the present contribution, the data are quantitatively analyzed based on the theoretical model of the electrokinetics of soft particles. As a result, information is obtained on both the thickness and the charge density of the surrounding layer. It is shown that IGF-1 adsorbs onto the surface of citrate-coated magnetite nanoparticles, and adsorption is confirmed by dot-blot analysis. In addition, it is also demonstrated that the external layer of IGF-1 exerts a shielding effect on the surface charge of citrate-magnetite particles, as suggested by the mobility reduction upon contacting the particles with the hormone. Aging effects are demonstrated, providing an electrokinetic fingerprint of changes in adsorbed protein configuration with time.

Surface modification of glass plates and silica particles by phospholipid adsorption.

The effect of phospholipid adsorption on the hydrophobicity of glass plates and on the surface charge of silica particles using contact angle and electrophoretic mobility measurements, respectively, was investigated. Deposition of successive statistical monolayers of dipalmitoylphosphatidylcholine (DPPC) on the glass surface showed zig-zag changes of water contact angle, especially on the first few monolayers. This behavior is qualitatively coherent with the oscillations observed in zeta potential values for increasing DPPC concentration. The results indicate that the phospholipid is adsorbed vertically on the plates, exposing alternately its polar head and non-polar hydrocarbon chains in successive layers. On the other hand, experiments conducted on glass plates prior hydrophobized by contact with n-tetradecane suggest that DPPC molecules may to some extent dissolve in the relatively thick n-alkane film and then expose their polar heads over the film surface thus producing polar electron-donor interactions. The effect of both DPPC and dioleoylphosphatidylcholine (DOPC) on the electrokinetic potential of silica spheres confirms adsorption of the phospholipids, leading to a decrease in the (originally negative) zeta potential of silica and even reversal of its sign to positive at acidic pH. Hydrophobic interactions between phospholipid molecules in the medium and those already adsorbed may explain the overcharging. The adsorption of neutral phospholipids may reduce the zeta potential as a consequence of the shift of the electrokinetic or slip plane. The effect is more evident in the case of DOPC, suggesting a less efficient packing of this phospholipid because of the presence of double bonds in its molecule, which in fact is well known.

Hexanickel enediolate cluster generated in an acireductone dioxygenase model reaction.

A nickel(II) enediolate cluster (2) forms upon treatment of [(6-Ph(2)TPA)Ni(PhC(O)C(OH)C(O)Ph)]ClO(4) (1) with Me(4)NOH x 5 H(2)O in CH(3)CN. Crystallographic studies of 2 revealed a hexanuclear structure of S(6) symmetry with a formula of {[Ni(PhC(O)C(O)C(O)Ph)(CH(3)OH)] x 1.33 CH(3)OH}(6). Because isolation of bulk amounts of 2 from the reaction involving 1 proved impossible, a solvation analogue of 2 (labeled 5) was generated from admixture of Ni(ClO(4))(2) x 6 H(2)O, 2-hydroxy-1,3-diphenylpropane-1,3-dione, and Me(4)NOH x 5 H(2)O in CH(3)OH/CH(3)CN. Complex 5 is formulated as {[Ni(PhC(O)C(O)C(O)Ph)(H(2)O)] x H(2)O x 0.25 CH(3)CN}(6) based on elemental analysis, a molecular weight determination, UV-vis, and a magnetic moment measurement. Treatment of 5 with O(2) and 6-Ph(2)TPA (6 equiv) results in the formation of CO and [(6-Ph(2)TPA)Ni(O(2)CPh)(2)(H(2)O)] (3), the latter of which was isolated in 69% yield. The level of (18)O incorporation in this reaction matches that for a reaction wherein 2 is generated from 1. These results provide evidence that a nickel(II) enediolate cluster is the O(2) reactive species in a previously reported model reaction for nickel(II)-containing acireductone dioxygenase.

Synthesis, characterization, and ligand exchange reactivity of a series of first row divalent metal 3-hydroxyflavonolate complexes.

A series of divalent metal flavonolate complexes of the general formula [(6-Ph(2)TPA)M(3-Hfl)]X (1-5-X; X = OTf(-) or ClO(4)(-); 6-Ph(2)TPA = N,N-bis((6-phenyl-2-pyridyl)methyl)-N-((2-pyridyl)methyl)amine; M = Mn(II), Co(II), Ni(II), Cu(II), Zn(II); 3-Hfl = 3-hydroxyflavonolate) were prepared and characterized by X-ray crystallography, elemental analysis, FTIR, UV-vis, (1)H NMR or EPR, and cyclic voltammetry. All of the complexes have a bidentate coordinated flavonolate ligand. The difference in M-O distances (Delta(M-O)) involving this ligand varies through the series, with the asymmetry of flavonolate coordination increasing in the order Mn(II) approximately Ni(II) < Cu(II) < Zn(II) < Co(II). The hypsochromic shift of the absorption band I (pi-->pi*) of the coordinated flavonolate ligand in 1-5-OTf (relative to that in free anion) increases in the order Ni(II) < Mn(II) < Cu(II) < Zn(II), Co(II). Previously reported 3-Hfl complexes of divalent metals fit well with this ordering. (1)H NMR studies indicate that the 3-Hfl complexes of Co(II), Ni(II), and Zn(II) exhibit a pseudo-octahedral geometry in solution. EPR studies suggest that the Mn(II) complex 1-OTf may form binuclear structures in solution. The mononuclear Cu(II) complex 4-OTf has a distorted square pyramidal geometry. The oxidation potential of the flavonolate ligand depends on the metal ion present and/or the solution structure of the complex, with the Mn(II) complex 1-OTf exhibiting the lowest potential, followed by the pseudo-octahedral Ni(II) and Zn(II) 3-Hfl complexes, and the distorted square pyramidal Cu(II) complex 4-OTf. The Mn(II) complex [(6-Ph(2)TPA)Mn(3-Hfl)]OTf (1-OTf) is unique in the series in undergoing ligand exchange reactions in the presence of M(ClO(4))(2).6H(2)O (M = Co, Ni, Zn) in CD(3)CN to produce [(6-Ph(2)TPA)M(CD(3)CN)(n)](X)(2), [Mn(3-Hfl)(2).0.5H(2)O], and MnX(2) (X = OTf(-) or ClO(4)(-)). Under similar conditions, the 3-Hfl complexes of Co(II), Ni(II), and Cu(II) undergo flavonolate ligand exchange to produce [(6-Ph(2)TPA)M(CD(3)CN)(n)](X)(2) (M = Co, Ni, Cu; n = 1 or 2) and [Zn(3-Hfl)(2).2H(2)O]. An Fe(II) complex of 3-Hfl, [(6-Ph(2)TPA)Fe(3-Hfl)]ClO(4) (8), was isolated and characterized by elemental analysis, FTIR, UV-vis, (1)H NMR, cyclic voltammetry, and a magnetic moment measurement. This complex reacts with O(2) to produce the diiron(III) mu-oxo compound [(6-Ph(2)TPAFe(3Hfl))(2)(mu-O)](ClO(4))(2) (6).

A trinuclear nickel(II) enediolate complex: synthesis, characterization, and O2 reactivity.

Using a new N(4)-donor chelate ligand having a mixture of hydrophobic phenyl and hydrogen-bond-donor appendages, a trinuclear nickel(II) complex of the doubly deprotonated form of 2-hydroxy-1,3-diphenylpropane-1,3-dione was isolated, characterized (X-ray crystallography, elemental analysis, UV-vis, (1)H NMR, FTIR, and magnetic moment measurement), and evaluated for O(2) reactivity. This complex, [(6-NA-6-Ph(2)TPANi)(2)(mu-PhC(O)C(O)C(O)Ph)(2)Ni](ClO(4))(2) (4), has two terminal pseudooctahedral Ni(II) centers supported by the tetradentate chelate ligand and a central square-planar Ni(II) ion ligated by oxygen atoms of two bridging enediolate ligands. In CH(3)CN, 4 exhibits a deep orange/brown color and lambda(max) = 463 nm (epsilon = 16 000 M(-1)cm(-1)). The room temperature magnetic moment of 4, determined by Evans method, is mu(eff) = 5.3(2) mu(B). This is consistent with the presence of two noninteracting high-spin Ni(II) centers, a diamagnetic central Ni(II) ion, and an overall quintet ground state. Exposure of a CH(3)CN solution of 4 to O(2) results in the rapid loss of the orange/brown color to give a green solution. The products identified from this reaction are [(kappa(3)-6-NA-6-Ph(2)TPA)Ni(O(2)Ph)(H(2)O)]ClO(4) (5), benzil [PhC(O)C(O)Ph], and CO. Identification of 5 was achieved via its independent synthesis and a comparison of its (1)H NMR and mass spectral features with those of the 6-NA-6-Ph(2)TPA-containing product generated upon reaction of 4 with O(2). The independently prepared sample of 5 was characterized by X-ray crystallography, elemental analysis, UV-vis, mass spectrometry, and FTIR. The O(2) reactivity of 4 has relevance to the active-site chemistry of Ni(II)-containing acireductone dioxygenase (Ni(II)ARD).

Acireductone dioxygenase- (ARD-) type reactivity of a nickel(II) complex having monoanionic coordination of a model substrate: product identification and comparisons to unreactive analogues.

A mononuclear Ni(II) complex ([(6-Ph2TPA)Ni(PhC(O)C(OH)C(O)Ph)]ClO4 (1)), supported by the 6-Ph2TPA chelate ligand (6-Ph2TPA = N,N-bis((6-phenyl-2-pyridyl)methyl)-N-((2-pyridyl)methyl)amine) and containing a cis-beta-keto-enolate ligand having a C2 hydroxyl substituent, undergoes reaction with O2 to produce a Ni(II) monobenzoate complex ([(6-Ph2TPA)Ni(O2CPh)]ClO4 (3)), CO, benzil (PhC(O)C(O)Ph), benzoic acid, and other minor unidentified phenyl-containing products. Complex 3 has been identified through independent synthesis and was characterized by X-ray crystallography, 1H NMR, FAB-MS, FTIR, and elemental analysis. A series of cis-beta-keto-enolate Ni(II) complexes supported by the 6-Ph2TPA ligand ([(6-Ph2TPA)Ni(PhC(O)CHC(O)Ph)]ClO4 (4), [(6-Ph2TPA)Ni(CH3C(O)CHC(O)CH3)]ClO4 (5), and [(6-Ph2TPA)Ni(PhC(O)CHC(O)C(O)Ph) (6)) have been prepared and characterized. While these complexes exhibit structural and/or spectroscopic similarity to 1, all are unreactive with O2. The results of this study are discussed in terms of relevance to Ni(II)-containing acireductone dioxygenase enzymes, as well as in the context of recently reported cofactor-free, quercetin, and beta-diketone dioxygenases.

A cadmium hydroxide complex of a N3S-donor ligand containing two hydrogen bond donors: synthesis, characterization, and CO2 reactivity.

Treatment of the ebnpa (N-2-(ethylthio)ethyl-N,N-bis((6-neopentylamino-2-pyridyl)methyl)amine) ligand with a molar equivalent amount of Cd(ClO(4))(2).5H(2)O in CH(3)CN followed by the addition of [Me(4)N]OH.5H(2)O yielded the cadmium hydroxide complex [(ebnpaCd)(2)(mu-OH)(2)](ClO(4))(2) (1). Complex 1 has a binuclear cation in the solid-state with secondary hydrogen-bonding and CH/pi interactions involving the ebnpa ligand. In acetonitrile, 1 forms a binuclear/mononuclear equilibrium mixture. The formation of a mononuclear species has been confirmed by conductance measurements of 1 at low concentrations. Variable temperature studies of the binuclear/mononuclear equilibrium provided the standard enthalpy and entropy associated with the formation of the monomer as DeltaH degrees = +31(2) kJ mol(-1) and DeltaS degrees = +108(8) J mol(-1) K(-1), respectively. Enhanced secondary hydrogen-bonding interactions involving the terminal Cd-OH moiety may help to stabilize the mononuclear complex. Treatment of 1 with CO(2) in acetonitrile results in the formation of a binuclear cadmium carbonate complex, [(ebnpaCd)(2)(mu-CO(3))](ClO(4))(2) (2).

Glyoxalase I-type hemithioacetal isomerization reactivity of a mononuclear Ni(II) deprotonated amide complex.

The synthesis, characterization, and hemithioacetal isomerization reactivity of a mononuclear Ni(II) deprotonated amide complex, [(bppppa-)Ni]ClO4.CH3OH (1, bppppa- = monoanion of N,N-bis-[(6-phenyl-2-pyridyl)methyl]-N-[(6-pivaloylamido-2-pyridyl)methyl]amine), are reported. Complex 1 was characterized by X-ray crystallography, 1H NMR, UV-vis, FTIR, and elemental analysis. Treatment of 1 with an equimolar amount of the hemithioacetal PhC(O)CH(OH)SCD3 in dry acetonitrile results in the production of the thioester PhCH(OH)C(O)SCD3 in approximately 60% yield. This reaction is conveniently monitored via 2H NMR spectroscopy. A protonated analogue of 1, [(bppppa)Ni](ClO4)2 (2), is unreactive with the hemithioacetal, thus indicating the requirement of the anionic chelate ligand in 1 for hemithioacetal isomerization reactivity. Complex 1 is unreactive with the thioester product, PhCH(OH)C(O)SCD3, which indicates that the pKa value for the PhCH(OH)C(O)SCD3 proton of the thioester must be significantly higher than the pKa value of the C-H proton of the hemithioacetal (PhC(O)CH(OH)SCD3). Complex 1 is the first well-characterized Ni(II) coordination complex to exhibit reactivity relevant to Ni(II)-containing E. coli glyoxalase I. Treatment of NiBr2.2H2O with PhC(O)CH(OH)SCD3 in the presence of 1-methylpyrrolidine also yields thioester product, albeit the reaction is slower and involves the formation of multiple -SCD3 labeled species, as detected by 2H NMR spectroscopy. The results of this study provide the first insight into hemithioacetal isomerization promoted by a synthetic Ni(II) coordination complex versus a simple Ni(II) ion.

Chemistry of a Ni(II) acetohydroxamic acid complex: formation, reactivity with water, and attempted preparation of zinc and cobalt analogues.

Mononuclear Ni(II), Co(II), and Zn(II) complexes of the bppppa (N,N-bis[(6-phenyl-2-pyridyl)methyl]-N-[(6-pivaloylamido-2-pyridyl)methyl]amine) ligand have been synthesized and characterized by X-ray crystallography, 1H NMR, UV-vis (Ni(II) and Co(II)) and infrared spectroscopy, and elemental analysis. Each complex has the empirical formula [(bppppa)M](ClO4)2 (M = Ni(II), 2; Zn(II), 3; Co(II), 4) and in the solid state exhibits a metal center having a coordination number of five; albeit, the cation of 2 also has a sixth weak interaction involving a perchlorate anion. Treatment of [(bppppa)Ni](ClO4)2 (2) with 1 equiv of acetohydroxamic acid results in the formation of [(bppppa)Ni(HONHC(O)CH3)](ClO4)2 (1), a novel Ni(II) complex having a coordinated neutral acetohydroxamic acid ligand. In 1, one phenyl-appended pyridyl donor of the bppppa chelate ligand is dissociated from the metal center and acts as a hydrogen bond acceptor for the hydroxyl group of the bound acetohydroxamic acid ligand. Treatment of 1 with excess water results in the formation of 2 and free acetohydroxamic acid. We hypothesize that this reaction occurs due to disruption of the intramolecular hydrogen bonding interaction involving the bound acid. In this series of reactions, the bppppa ligand exhibits behavior reminiscent of a type III hemilabile ligand in terms of one phenylpyridyl donor. Treatment of 3 or 4 with acetohydroxamic acid results in no reaction, indicating that the bppppa-ligated Ni(II) derivative 2 exhibits unique coordination chemistry with respect to reaction with acetohydroxamic acid within this series of complexes. We attribute this reactivity to the ability of the bppppa-ligated Ni(II) center to adopt a pseudo-octahedral geometry, whereas the Zn(II) and Co(II) complexes retain five coordinate metal centers.

Neutral acetohydroxamic acid coordination to a mononuclear Ni(II) center stabilized by an intramolecular hydrogen-bonding interaction.

Treatment of a new chelate ligand having both amide- and phenyl-appended pyridyl moieties with Ni(ClO4).6H2O and acetohydroxamic acid in methanol solution results in the production of a novel pseudo-octahedral Ni(II) complex having a neutral acetohydroxamic acid ligand stabilized by a hydrogen-bonding interaction.