Ab Initio Electronic, Magnetic, and Optical Properties of Fe Phthalocyanine on Cr2O3(0001).

The organic molecules adsorbed on antiferromagnetic surfaces can produce interesting interface states, characterized by charge transfer mechanisms, hybridization of molecular-substrate orbitals, as well as magnetic couplings. Here, we apply an ab initio approach to study the adsorption of Fe phthalocyanine on stoichiometric Cr2O3(0001). The molecule binds via a bidentate configuration forming bonds between two opposite imide N atoms and two protruding Cr ones, making this preferred over the various possible adsorption structures. In addition to the local modifications at these sites, the electronic structure of the molecule is weakly influenced. The magnetic structure of the surface Cr atoms shows a moderate influence of molecule adsorption, not limited to the atoms in the close proximity of the molecule. Upon optical excitation at the onset, electron density moves toward the molecule, enhancing the ground state charge transfer. We investigate this movement of charge as a mechanism at the base of light-induced modifications of the magnetic structure at the interface.

Self-Assembled Monolayers of N-Heterocyclic Olefins on Au(111).

Self-assembled monolayers (SAMs) of N-heterocyclic olefins (NHOs) have been prepared on Au(111) and their thermal stability, adsorption geometry, and molecular order were characterized by X-ray photoelectron spectroscopy, polarized X-ray absorption spectroscopy, scanning tunneling microscopy (STM), and density functional theory (DFT) calculations. The strong σ-bond character of NHO anchoring to Au induced high geometrical flexibility that enabled a flat-lying adsorption geometry via coordination to a gold adatom. The flat-lying adsorption geometry was utilized to further increase the surface interaction of the NHO monolayer by backbone functionalization with methyl groups that induced high thermal stability and a large impact on work-function values, which outperformed that of N-heterocyclic carbenes. STM measurements, supported by DFT modeling, identified that the NHOs were self-assembled in dimers, trimers, and tetramers constructed of two, three, and four complexes of NHO-Au-adatom. This self-assembly pattern was correlated to strong NHO-Au interactions and steric hindrance between adsorbates, demonstrating the crucial influence of the carbon-metal σ-bond on monolayer properties.

A systematic study of the valence electronic structure of cyclo(Gly-Phe), cyclo(Trp-Tyr) and cyclo(Trp-Trp) dipeptides in the gas phase.

The electronic energy levels of cyclo(glycine-phenylalanine), cyclo(tryptophan-tyrosine) and cyclo(tryptophan-tryptophan) dipeptides are investigated with a joint experimental and theoretical approach. Experimentally, valence photoelectron spectra in the gas phase are measured using VUV radiation. Theoretically, we first obtain low-energy conformers through an automated conformer-rotamer ensemble sampling scheme based on tight-binding simulations. Then, different first principles computational schemes are considered to simulate the spectra: Hartree-Fock (HF), density functional theory (DFT) within the B3LYP approximation, the quasi-particle GW correction, and the quantum-chemistry CCSD method. Theory allows assignment of the main features of the spectra. A discussion on the role of electronic correlation is provided, by comparing computationally cheaper DFT scheme (and GW) results with the accurate CCSD method.

Enhancement of Magnetic Stability in Antiferromagnetic CoO Films by Adsorption of Organic Molecules.

Antiferromagnets are a class of magnetic materials of great interest in spintronic devices because of their stability and ultrafast dynamics. When interfaced with an organic molecular layer, antiferromagnetic (AF) films are expected to form a spinterface that can allow fine control of specific AF properties. In this paper, we investigate spinterface effects on CoO, an AF oxide. To access the magnetic state of the antiferromagnet, we couple it to a ferromagnetic Co film via an exchange bias (EB) effect. In this way, the formation of a spinterface is detected through changes induced on the CoO/Co EB system. We demonstrate that C60 and Gaq3 adsorption on CoO shifts its blocking temperature; in turn, an increase in both the EB fields and the coercivities is observed on the EB-coupled Co layer. Ab initio calculations for the CoO/C60 interface indicate that the molecular adsorption is responsible for a charge redistribution on the CoO layer that alters the occupation of the d orbitals of Co atoms and, to a smaller extent, the p orbitals of oxygen. As a result, the AF coupling between Co atoms in the CoO is enhanced. Considering the granular nature of CoO, a larger AF stability upon molecular adsorption is then associated with a larger number of AF grains that are stable upon reversal of the Co layer.

Molecular dynamics study of the Cu2+ binding-induced "structuring" of the N-terminal domain of human prion protein.

In this work, we report molecular dynamics simulations on a fragment of the human prion protein spanning residues 31-120, with copper(II) bound to the repeat region in several ways corresponding to the known intra- and inter-repeat coordination modes, or to the metal site located at His111. The results of this study point to a different structuring tendency of the protein fragment depending on copper binding mode, with the highest degree of structuring in the case of intrarepeat Cu(II) coordination corresponding to high copper concentration.

Heteronuclear and homonuclear Cu2+ and Zn2+ complexes with multihistidine peptides based on zebrafish prion-like protein.

The homeostasis of metal ions, especially copper and zinc, is a major factor that may influence the prion diseases and the biological function of prion protein (PrP). The His-rich regions are basic sites for metal binding and antioxidant activity of the PrP structures. Animal prion-like proteins contain also His-rich domains, and their coordination chemistry may provide better insight into the chemistry and biology of PrP structures and related diseases. Herein, we report an equilibrium study on heteronuclear Zn(2+)-Cu(2+) complexes with zrel-PrP fragments from zebrafish. Potentiometric, spectroscopic, and mass spectrometric methods showed that the binding of copper is much more effective than the binding of zinc. At physiological pH, both metals bind to the histidine imidazole N donors of the studied peptides.

Effect of Cu(II) on the complex between kanamycin A and the bacterial ribosomal A site.

The solution structure of kanamycin A interacting with a ribosomal A-site fragment was solved by transferred-NOE techniques and found to agree with the structure of the complex observed in the crystal. Despite the fast exchange conditions found for the interaction, the bound form was identified by NOESY spectroscopy. At 600 MHz, NOE effects are only observed for the RNA-associated antibiotic. Dissociation constants were measured by NMR spectroscopy for two sites of interaction (K(d1)=150+/-40 microM; K(d2)=360+/-50 microM). Furthermore, the effects of the Cu(II) ion on the antibiotic, on the RNA fragment that mimics the bacterial ribosomal A site, and on the complex formed between these two entities were analyzed. The study led to the proposal of a model that localizes the copper ion within the kanamycin-RNA complex.

Solution structures of cyclosporin a and its complex with dysprosium(III) in SDS micelles: NMR and molecular dynamics studies.

Cyclosporin A (CsA) is a cyclic naturally occurring peptide used to prevent graft rejection in organ transplantations. Its immunosuppressive activity is due to the formation of a complex with cyclophilin A (Cyp), in which the cis 9MeLeu-10MeLeu amide bond of CsA assumes a trans conformation. The mechanism of the conformational inversion has not been delineated, but it has been postulated that metal ions binding induces a conformational change that enables CsA to bind Cyp. In this work, we solved the structures of CsA in sodium dodecyl sulfate (SDS) micelles (which enhance its solubility and mimic the hydrophobic environment clinically used for drug delivery) and its complex with Dy(III) ion, whose coordination chemistry is frequently used to reproduce the effect of Ca(II). The paramagnetic properties of Dy(III) allowed us to build up a structure using proton relaxation enhancements, which remains stable in a MD simulation in the micelle environment.

NMR studies of the Zn2+ interactions with rat and human beta-amyloid (1-28) peptides in water-micelle environment.

Alzheimer's disease is a fatal neurodegenerative disorder involving the abnormal accumulation and deposition of peptides (amyloid-beta, Abeta) derived from the amyloid precursor protein. Here, we present the structure and the Zn2+ binding sites of human and rat Abeta(1-28) fragments in water/sodium dodecyl sulfate (SDS) micelles by using 1H NMR spectroscopy. The chemical shift variations measured after Zn2+ addition at T>310 K allowed us to assign the binding donor atoms in both rat and human zinc complexes. The Asp-1 amine, His-6 Ndelta, Glu-11 COO-, and His-13 Nepsilon of rat Abeta28 all enter the metal coordination sphere, while His-6 Ndelta, His-13, His-14 Nepsilon, Asp-1 amine, and/or Glu-11 COO- are all bound to Zn2+ in the case of human Abeta28. Finally, a comparison between the rat and human binding abilities was discussed.

Structural features of the Cu(II) complex with the rat Abeta(1-28) fragment.

The interaction between Cu(II) and the rat amyloid beta (1-28) fragment in micellar solutions at pH 7.5 was investigated by CD and NMR spectroscopy; the proton-copper distances were used in restrained molecular dynamics simulations to obtain a structural model of the Cu(II) complex.

1H and 13C NMR study of the complex formed by copper(II) with the nucleoside antibiotic sinefungin.

Sinefungin (SFG) is an antifungal and antiparasitic nucleoside antibiotic composed by ornithine and adenosine moieties both having the potential to bind copper(II). NMR studies performed at physiological pH have shown that the alpha-amino and the carboxylate groups in the ornithine unit are the preferred donor sites for Cu(II) binding. On the contrary, at acidic pH, Cu(II) complexation starts from adenosine nitrogen being the alpha-amino group still protonated and not available for metal binding. The proton paramagnetic relaxation enhancements measured at neutral pH allowed to obtain the 3D structure of the 1:2 Cu(II)-SFG complex. Molecular dynamics calculations were revealing for the existence of secondary Cu(II) interaction with the purine nitrogens of the adenosine moiety.

SIMQUADNMR: a program for simulation and interpretation of multiple quantum-filtered NMR spectra of quadrupolar nuclei.

In this paper, we present a computer program which simulates NMR multiple quantum-filtered spectra of quadrupolar nuclei as a function of physical parameters, of the type of experiment and experimental conditions. The program works by solving relaxation theory equations for the given system, and it can be useful in order to plan the ideal conditions to set up specific experiments or to give a physical interpretation of experimental results. The program allows to independently follow the dependence of individual coherences and relaxation rates as a function of up to 50 parameters regarding the physical properties of the system under investigation, sample conditions and instrumental setup making it an helpful tool also for teaching purposes.

Fine tuning the structure of the Cu2+ complex with the prion protein chicken repeat by proline isomerization.

The interaction between the single hexarepeat unit of chicken prion protein [ChPrP(54-59)] and Cu(II) was investigated by NMR, finding different coordination modes for the trans/trans and cis/trans isomers.

The structure of the Ce(III)-angiotensin II complex as obtained from NMR data and molecular dynamics calculations.

Angiotensin II is shown by nuclear magnetic resonance (NMR) to form a complex in water at pH 4.0 with cerium(III), the ideal paramagnetic probe for Ca(2+). Paramagnetic shifts induced by the metal were used for the determination of dissociation constant and complex stoichiometry. ROESY cross-peaks and 3 J(HN-H)(alpha) coupling constants were converted into distance and angular constraints to determine the structure of the complex by molecular dynamics using the simulated annealing protocol. The complex is kinetically labile and involves the Asp-1 side chain and the Phe-8 terminal carboxylates as binding groups resembling a hairpin which has been suggested as a possible biologically active structure.

Coordination pattern, solution structure and DNA damage studies of the copper(II) complex with the unusual aminoglycoside antibiotic hygromycin B.

The aminoglycosidic antibiotic hygromycin B presents a peculiar chemical structure, characterized by two sugar rings joined via a spiro connection. The Cu(ii) complex of hygromycin B in water solution was characterized by (1)H-NMR, UV-Vis, EPR and CD spectroscopy, combined with potentiometric measurements. The spin-lattice relaxation enhancements were interpreted by the Solomon-Bloembergen-Morgan theory, allowing us to calculate copper-proton distances that were used to build a model of the complex by molecular mechanics and dynamics calculations. The fidelity of the proposed molecular model was checked by ROESY maps. Moreover DNA damage by the Cu(ii)-hygromycin B system was also investigated, showing single and double strand scissions exerted by the complex at concentrations in the range 1-5 mM. Addition of either hydrogen peroxide or ascorbic acid to each sample resulted in the shift of the cleavage potency towards lower concentrations of the complex.

1H and 13C-NMR and molecular dynamics studies of cyclosporin a interacting with magnesium(II) or cerium(III) in acetonitrile. Conformational changes and cis-trans conversion of peptide bonds.

Cyclosporin A (CsA) is an important drug used to prevent graft rejection in organ transplantations. Its immunosuppressive activity is related to the inhibition of T-cell activation through binding with the proteins Cyclophilin (Cyp) and, subsequently, Calcineurin (CN). In the complex with its target (Cyp), CsA adopts a conformation with all trans peptide bonds and this feature is very important for its pharmacological action. Unfortunately, CsA can cause several side effects, and it can favor the excretion of calcium and magnesium. To evaluate the possible role of conformational effects induced by these two metal ions in the action mechanism of CsA, its complexes with Mg(II) and Ce(III) (the latter as a paramagnetic probe for calcium) have been examined by two-dimensional NMR and relaxation rate analysis. The conformations of the two complexes and of the free form have been determined by restrained molecular dynamics calculations based on the experimentally obtained metal-proton and interproton distances. The findings here ratify the formation of 1:1 complexes of CsA with both Mg(II) and Ce(III), with metal coordination taking place on carbonyl oxygens and substantially altering the peptide structure with respect to the free form, although the residues involved and the resulting conformational changes, including cis-trans conversion of peptide bonds, are different for the two metals.

Tandem repeat-like domain of "similar to prion protein" (StPrP) of Japanese pufferfish binds Cu(II) as effectively as the mammalian protein.

The main structural domains of prion proteins, in particular the N-terminal region containing characteristic amino acid repeats, are well conserved among different species, despite divergence in primary sequence. The repeat region seems to play an important role, as verified by pathogenicity only observed in organisms having repeats composed of eight residues. In this work three different peptides belonging to the tandem repeat region of StPrP-2 from the Japanese pufferfish Takifugu rubripes have been considered; the coordination modes and conformations of their complexes with Cu(II) have been investigated by using potentiometric titrations, spectroscopic data, and restrained molecular dynamics simulations. In all cases the histidine imidazole(s) provide the anchoring site for copper, with the further involvement of amide nitrogens depending on the peptide sequence and on pH. An increase in copper binding affinity has been observed going from the shortest peptide, corresponding to a single repeat and containing two histidines, to the longest one, encompassing three repeats with six histidines.

Structure and stability of the CuII complexes with tandem repeats of the chicken prion.

Prion protein (PrP) misfolding is one of the pivotal issues in understanding the rudiments of neurodegenerative disorders. The conformational change of mammalian cellular PrP to scrapie PrP is caused by an unknown agent, but there is reasonable evidence supporting the key role of copper ions in this process. The structure of the avian PrP was found to be very similar to the mammalian protein, although there is only 30% homology in the secondary structure. This work shows that copper ions are very effectively bound by hexarepeat fragments of chicken prion protein, although not as effectively as it was found in the case of mammalian protein. By means of potentiometric and spectroscopic techniques (nuclear magnetic resonance, circular dichroism, UV-vis, and electronic paramagnetic resonance), it was shown that Cu(II) ions coordinate to the chicken PrP hexapeptide domain in physiological pH via imidazole nitrogen donors of His residue(s). The binding pattern changes the structure of peptide involved, indicating a possible impact of Cu(II) ions in the biology and pathology of nonmammalian PrP, which could be similar to that found for mammalian PrP. The present study shows that, similar to the human prion octapeptide repeats, chicken prion hexapeptide repeats might bind copper ions in two different ways, depending on the number of repeats and metal/ligand molar ratio: (i) an intra-repeat coordination mode in which copper ion is chelated by His imidazole and deprotonated amide nitrogen in monomeric peptide and (ii) an inter-repeat coordination mode in which a polymeric peptide ligand (dimer and trimer) forms polyimidazole complexes that are very stable at physiological pH. Two proline residues inserted into the hexapeptide unit have a critical impact on the metal-binding ability.

Interaction of the human prion PrP(106-126) sequence with copper(II), manganese(II), and zinc(II): NMR and EPR studies.

The synthetic peptide encompassing residues 106-126 (PrP106-126, KTNMKHMAGAAAAGAVVGGLG) of the human prion protein was considered for its binding properties toward copper(II), manganese(II) and zinc(II) at pH 5.7. 1H and 13C 1D spectra, 1H spin-lattice relaxation rates, and 1H-15N and 1H-13C HSQC 2D experiments were obtained in the absence and in the presence of metal ions. While Zn(II) was found to yield negligible effects upon any NMR parameter, metal-peptide association was demonstrated by the paramagnetic effects of Cu(II) and Mn(II) upon 1D and 2D spectra. Delineation of structures of metal complexes was sought by interpreting the paramagnetic effect on 1H spin-lattice relaxation rates. Exchange of peptide molecules from the metal coordination sphere was shown to provide sizable contribution to the observed relaxation rates. Such contribution was calculated in the case of Cu(II); whereas the faster paramagnetic rates of peptide molecules bound to Mn(II) were determining spin-lattice relaxation rates almost exclusively dominated by exchange. Proton-metal distances were therefore evaluated in the case of the Cu(II) complex only and used as restraints in molecular dynamics calculations where from the structure of the complex was obtained. The peptide was shown to bind copper through the imidazole nitrogen and the ionized amide nitrogen of His-111 and the amino-terminal group with the terminal carboxyl stabilizing the coordination sphere through ionic interactions. The data were interpreted as to demonstrate that the hydrophobic C-terminal region was not affecting the copper-binding properties of the peptide and that this hydrophobic tail is left free to interact with other target molecules. As for the complex with Mn(II), qualitative information was obtained on carbonyl oxygens of Gly-124 and Leu-125, beyond the terminal Gly-126 carboxyl, being at close distance from the metal ion, that also interacts, most likely, through a hydrogen bond of metal-bound water, with the imidazole ring of His-111.