DFT Study on the Recovery of Hoveyda–Grubbs‐Type Catalyst Precursors in Enyne and Diene Ring‐Closing Metathesis

DFT (B3LYP‐D) calculations have been used to better understand the origin of the recovered Hoveyda–Grubbs derivative catalysts after ring‐closing diene or enyne metathesis reactions. For that, we have considered the activation process of five different Hoveyda–Grubbs precursors in the reaction with models of usual diene and enyne reactants as well as the potential precursor regeneration through the release/return mechanism. The results show that, regardless of the nature of the initial precursor, the activation process needs to overcome relatively high energy barriers, which is in agreement with a relatively slow process. The precursor regeneration process is in all cases exergonic and it presents low energy barriers, particularly when compared to those of the activation process. This indicates that the precursor regeneration should always be feasible, unlike the moderate recoveries sometimes observed experimentally, which suggests that other competitive processes that hinder recovery should take place. Indeed, calculations presented in this work show that the reactions between the more abundant olefinic products and the active carbenes usually require lower energy barriers than those that regenerate the initial precatalyst, which could prevent precursor regeneration. On the other hand, varying the precursor concentration with time obtained from the computed energy barriers shows that, under the reaction conditions, the precursor activation is incomplete, thereby suggesting that the origin of the recovered catalyst probably arises from incomplete precursor activation.     

Cation-pi Interactions and oxidative effects on Cu+ and Cu2+ binding to Phe, Tyr, Trp, and His amino acids in the gas phase. Insights from first-principles calculations

The coordination properties of the four natural aromatic amino acids (AA(arom) = Phe, Tyr, Trp, and His) to Cu+ and Cu2+ have been exhaustively studied by means of ab initio calculations. For Cu+-Phe, Cu+-Tyr and Cu+-Trp, the two charge solvated tridentate N/O/ring and bidentate N/ring structures, with the metal cation interacting with the pi system of the ring, were found to be the lowest ones, relative DeltaG(298K) energies being less than 0.5 kcal/mol. The Cu+-His ground-state structure has the metal cation interacting with the NH2 group and the imidazole N. For these low-lying structures vibrational features are also discussed. Unlike Cu+ complexes, the ground-state structure of Cu2+-Phe, Cu2+-Tyr, and Cu2+-Trp does not present cation-pi interactions due to the oxidation of the aromatic ring induced by the metal cation. The ground-state structure of Cu2+-His does not present oxidation of the amino acid, the coordination to Cu2+ being tridentate with the oxygen of the carbonyl group, the nitrogen of the amine, and the N of the imidazole. Other less stable isomers, however, show oxidation of His, particularly of the imidazole ring, which can induce spontaneous proton-transfer reactions from the NH of the imidazole to the NH2 of the backbone. Finally, the computed binding energies for Cu+-AA(arom) and Cu2+-AA(arom) systems have been computed, the order found for the single charged systems being Cu+-His > Cu+-Trp > Cu+-Tyr > Cu+-Phe, in very good agreement with the experimental data.     

Diamine‐Catalyzed Addition of ZnEt2 to PhC(O)CF3: Two Mechanisms and Autocatalytic Asymmetric Enhancement

NMR spectroscopic studies of the catalytic addition reaction of ZnEt₂ to PhC(O)CF₃ in the presence of three very efficient catalysts [TMEDA, tBuBOX, and L ; where L is a chiral diamine synthesized from optically pure (R,R)‐1,2‐diphenylethylenediamine and (S)‐2,2′‐bis‐(bromomethyl)‐1,1′‐binaphthalene] reveal large differences in their behavior. For the ligands TMEDA and tBuBOX, the catalysis shows no unusual features and proceeds via [(N?N)Zn(Et){OC(CF₃)(Et)Ph}]. For N?N? L , the observation of autocatalytic asymmetric enhancement during the catalysis, and unusual inverse concentration dependence on the reaction rate, indicate the participation of an additional novel catalytic cycle that goes through a dinuclear intermediate containing one ZnEt₂ and one ZnEt fragment connected by N?N and OR bridges. Interestingly, the ¹⁹F NMR signals of the main product of the reaction ([Zn(Et){OC*(CF₃)(Et)Ph}]₂) allowed us to assess the enantioselectivity of the processes in situ without the assistance of chiral chromatography.     

Three dimensional models of Cu(2+)-Aβ(1-16) complexes from computational approaches

Elucidation of the coordination of metal ions to Aβ is essential to understand their role in its aggregation and to rationally design new chelators with potential therapeutic applications in Alzheimer disease. Because of that, in the last 10 years several studies have focused their attention in determining the coordination properties of Cu(2+) interacting with Aβ. However, more important than characterizing the first coordination sphere of the metal is the determination of the whole Cu(2+)-Aβ structure. In this study, we combine homology modeling (HM) techniques with quantum mechanics based approaches (QM) to determine plausible three-dimensional models for Cu(2+)-Aβ(1-16) with three histidines in their coordination sphere. We considered both ε and δ coordination of histidines 6, 13, and 14 as well as the coordination of different possible candidates containing oxygen as fourth ligand (Asp1, Glu3, Asp7, Glu11, and CO(Ala2)). Among the 32 models that enclose COO(-), the lowest energy structures correspond to [O(E3),N(δ)(H6),N(ε)(H13),N(ε)(H14)] (1), [O(E3),N(δ)(H6),N(δ)(H13),N(δ)(H14)] (2), and [O(D7),N(ε)(H6),N(δ)(H13),N(δ)(H14)] (3). The most stable model containing CO(Ala2) as fourth ligand in the Cu(2+) coordination sphere is [O(c)(A2),N(ε)(H6),N(δ)(H13),N(ε)(H14)] (4). An estimation of the relative stability between Glu3 (1) and CO(Ala2) (4) coordinated complexes seems to indicate that the preference for the latter coordination may be due to solvent effects. The present results also show the relationship between the peptidic and metallic moieties in defining the overall geometry of the complex and illustrate that the final stability of the complexes results from a balance between the metal coordination site and amyloid folding upon complexation.     

Interaction of glycine with isolated hydroxyl groups at the silica surface: first principles B3LYP periodic simulation

The adsorption of a glycine molecule on a model silica surface terminated by an isolated hydroxyl group has been studied ab initio using a double-zeta polarized Gaussian basis set, the hybrid B3LYP functional, and a full periodic treatment of the silica surface/glycine system. The hydroxylated silica surface has been simulated using either a 2D slab or a single polymer strand cut out from the (001) surface of an all-silica edingtonite. A number of B3LYP-optimized structures have been found by docking glycine on the silica surface exploiting all possible hydrogen bond patterns. Whereas glycine is generally adsorbed in its neutral form, two structures show glycine adsorbed as a zwitterion, the surface playing the role of a "solid solvent" whereas intrastrand hydrogen bond cooperativity stabilizes the zwitterions. The adsorbed zwitterionic structures are no longer formed at a lower glycine coverage as simulated by enlarging the unit cell so as to break intrastrand hydrogen bonds, showing the importance of H-bond cooperativity in stabilizing the zwitterionic forms. Each structure has been characterized by computing its harmonic vibrational spectrum at the Gamma point, which also allowed us to calculate the free energy of adsorption. The experimental infrared features of chemical-vapor-deposited glycine on a silica surface are in agreement with those computed for glycine adsorbed in its neutral form and engaging three hydrogen bonds with the surface silanols, two of them involving the C=O bond and one originating from the glycine OH group. The NH(2) group plays only a minor role as a weak hydrogen bond donor.     

In vitro evaluation of osteoblast‐like cells on hydroxyapatite‐coated porous stainless steel implants by synchrotron radiation x‐ray fluorescence

The successful application of artificial implants requires osseointegration in the implanted structures. To stimulate bone growth, synthetic hydroxyapatite obtained by the coprecipitation process was coated onto porous stainless steel substrates in order to enhance the biocompatibility and, consequently, mineralization. The substrate of choice was porous 316L stainless steel for its high resistance, mechanical strength and low density due to its foam structure. The aim of the present study was to investigate the biological response of the fabricated implants cultured with MC3T3‐E1 mouse osteoblast‐like cells by analyzing the variation in the elemental concentration, mainly calcium, along with the cellular differentiation and mineralization. By employing synchrotron radiation x‐ray fluorescence spectroscopy (SRXRF), intracellular elemental distribution and concentration could be determined, revealing a clear increase in the total calcium content. This preliminary data suggests that synthetic hydroxyapatite on porous stainless steel substrates might be successfully used for biocompatible medical implants. Copyright © 2009 John Wiley & Sons, Ltd.