Sustainable Ketalization of Glycerol with Ethyl Levulinate Catalyzed by the Iron(III)-Based Metal-Organic Framework MIL-88A

The catalytic properties of a simple iron-containing MOF based on fumaric acid, MIL-88A, were investigated in the ketalization of ethyl levulinate with glycerol. The corresponding product is a component of current interest as a renewable building block for many uses. Under the following conditions (solventless, 120 °C, stoichiometric ratio, 1% cat.), the reaction proceeds with good yields (85%), and the catalyst can be recovered and recycled without loss of activity, despite some changes in the crystalline lattice and morphology. Moreover, the residual iron content in the product is in the order of units of ppm (≤2), which demonstrates the robustness of the MOF under the reaction conditions.     

The strange case of the “oscillating” catalysts

The field of stereoselective propene polymerization has been dramatically innovated by the discovery of homogeneous metallocene-based catalysts with well-defined and tunable molecular structure. Of all, “oscillating” metallocenes are probably the most ingenious and challenging example of catalyst design. Their catalytic species were built to “flip-flop” between a chiral and an achiral conformation, at a rate intermediate between those of monomer insertion and chain transfer. The result of this molecular switching would be a polypropylene with an isotactic/atactic stereoblock structure, performing as a thermoplastic elastomer. This essay discusses how the real polymerization mechanism differs from what the catalyst inventors had in mind, but also how - through fortunate circumstances -their optimism has been rewarded.     

Improving performance of polarizable continuum model for study of large molecules in solution

We present a new implementation of the polarizable continuum model (PCM) that significantly improves its performance, especially for large solutes. This approach avoids the separation between electronic and nuclear sources in the calculation of the solvation charges, allowing the extension of iterative procedures to all the PCM versions [dielectric (D), conductor (C), and integral equation formalism (IEF)], so that the best method and/or algorithm can be selected, depending on the system at hand. In particular, the new balanced two-term iterative procedure with total charges avoids any nonlinear computational step and memory occupation. Furthermore, it also shows a good convergence for the C-PCM and IEF-PCM versions, which were quite problematic for the conventional separate charges approach. Also, first and second analytical derivatives are available in this context for Hartree–Fock and Kohn–Sham models. A number of examples are analyzed; they show that the new algorithms couple fully satisfactory numerical accuracy with remarkable computational efficiency. ©1999 John Wiley & Sons, Inc. J Comput Chem 20: 1186–1198, 1999     

Effective generation of molecular cavities in polarizable continuum model by DefPol procedure

A new computational strategy for the building of molecular cavities (named DefPol) has been linked to the most recent implementation of the polarizable continuum model (PCM) for the representation of solvent effects on physicochemical properties of large molecules. Free energies, analytical gradients, and Hessians can be computed in this framework in the rigid cavity approximation. Coupling DefPol cavities with a number of other recent improvements of the standard algorithm (e.g., effective use of symmetry, iterative procedures with linear scaling) significantly enlarges the dimensions of systems amenable to refined computations and strongly reduces the gap between computations for isolated molecules and in solution. © 1999 John Wiley & Sons, Inc. J Comput Chem 20: 1693–1701, 1999     

A Rapid and Simple UHPLC-MS/MS Method for Quantification of Plasma Globotriaosylsphingosine (lyso-Gb3)

Fabry disease (FD) is a rare X-linked lysosomal storage disorder caused by α-galactosidase A gene (GLA) mutations, resulting in loss of activity of the lysosomal hydrolase, α-galactosidase A (α-Gal A). As a result, the main glycosphingolipid substrates, globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3), accumulate in plasma, urine, and tissues. Here, we propose a simple, fast, and sensitive method for plasma quantification of lyso-Gb3, the most promising secondary screening target for FD. Assisted protein precipitation with methanol using Phree cartridges was performed as sample pre-treatment and plasma concentrations were measured using UHPLC-MS/MS operating in MRM positive electrospray ionization. Method validation provided excellent results for the whole calibration range (0.25–100 ng/mL). Intra-assay and inter-assay accuracy and precision (CV%) were calculated as <10%. The method was successfully applied to 55 plasma samples obtained from 34 patients with FD, 5 individuals carrying non-relevant polymorphisms of the GLA gene, and 16 healthy controls. Plasma lyso-Gb3 concentrations were larger in both male and female FD groups compared to healthy subjects (p < 0.001). Normal levels of plasma lyso-Gb3 were observed for patients carrying non-relevant mutations of the GLA gene compared to the control group (p = 0.141). Dropping the lower limit of quantification (LLOQ) to 0.25 ng/mL allowed us to set the optimal plasma lyso-Gb3 cut-off value between FD patients and healthy controls at 0.6 ng/mL, with a sensitivity of 97.1%, specificity of 100%, and accuracy of 0.998 expressed by the area under the ROC curve (C.I. 0.992 to 1.000, p-value < 0.001). Based on the results obtained, this method can be a reliable tool for early phenotypic assignment, assessing diagnoses in patients with borderline GalA activity, and confirming non-relevant mutations of the GLA gene.     

Catalytic and bulk solvent effects on proton transfer: Formamide as a case study

Structural, thermodynamic, and kinetic aspects of the tautomerization of formamide through direct and solvent-assisted proton transfer have been investigated. Both specific and bulk effects of the solvent play a role in determining the overall result so that only a mixed discrete-continuum model is sufficiently reliable. Structural modifications induced by the solvent are significant, but have only a slight effect on thermodynamic and kinetic quantities. The same remarks apply to the vibrational shifts induced by the solvent. © 1997 John Wiley & Sons, Inc. J Comput Chem 18 : 1993–2000, 1997     

Development and validation of force-field parameters for molecular simulations of peptides and proteins containing open-shell residues

Parameters suitable for extending the AMBER force field for nucleic acids and proteins to open-shell derivatives of amino acid residues are proposed and tested. Two new atom types (radical carbon [CE] and hydrogen directly bonded to it [HE]) are introduced, whose parameters have been determined by a best fitting of quantum-mechanical computations of the simplest analogue of glycine radical (GlyR) in a peptide. The new force field is able to fit the reference results concerning both the structural parameters and the relative stabilities of the different conformers. It has been next applied to a conformational study of the distortions induced by extraction of the glycine H^α atom in an initially helical structure of a dodecamer of alanine including a central glycine residue. Our results show that the helical structure corresponds to a local energy minimum, but deeper minima are found which correspond to a fully planar GlyR residue included in a distorted helical sequence. © 1997 John Wiley & Sons, Inc. J Comput Chem 18 : 1720–1728, 1997     

Quantum mechanical study of regioselectivity of radical additions to substituted olefins

Regiochemical trends in the addition of free radicals to substituted olefins are investigated by different quantum chemical approaches with special reference to oxygen centered radicals. From a methodological point of view, density functional methods provide correct general trends but they do not reach quantitative accuracy, especially for intermediate complexes. More reliable results are obtained by single point post‐Hartree–Fock computations at density functional geometries. A number of test computations show that reoptimization of the geometry and computation of vibrational frequencies by correlated methods can be safely avoided. As a consequence, the overall computational approach has very reasonable computer costs. From a more chemical point of view, a careful analysis of computational results points out the significant role of anomeric and polar effects in tuning the common filicity of carbon centered radicals. © 2000 John Wiley & Sons, Inc. J Comput Chem 21: 675–691, 2000     

Effect of Clay/Diamond and Clay/Carbon Nanosystems on Structure-Properties Relationships of iPP

The effect of the addition of two combined fillers, smectite clay and diamond and smectite clay and carbon nanoparticles, on structure, morphology, isothermal and non isothermal crystallization behaviour, tensile and thermal properties of isotactic polypropylene (iPP) has been investigated by using several techniques: wide angle X-ray diffraction, optical and scanning electron microscopy, thermogravimetry, differential scanning calorimetry and tensile techniques. It was found that nanoparticles of diamond and carbon favour the nucleation of the β-form of iPP crystal, whereas the clay nanolayers do not have any influence on the crystal structure of iPP. The thermal stability of iPP/(clay+diamond) and iPP/(clay+carbon) is improved with respect to neat iPP, whereas no influence is detected when only clay is added to iPP. At the given crystallization conditions, the overall crystallization peak of iPP/(clay+diamond) almost exactly overlaps the crystallization peak of neat iPP, whereas in the case of iPP/clay and iPP/(clay+carbon) the maximum of the crystallization peaks is shifted to higher temperature. The spherulite growth rate, G values do not differ from one another. The iPP/(clay+carbon) system shows ductile behavior. The other systems show brittle behavior with failure before necking. These results were related with the very high percentage of beta phase present in the samples of iPP/(clay+carbon).     

The mechanism of spin polarization in aromatic free radicals

 The spin-polarization mechanism in aromatic systems is analyzed with reference to the prototypical phenoxyl, cyclohexadienyl and benzyl radicals. In particular, a decomposition into “first-order” and “second-order” contributions is proposed, which helps to rationalize the different nature of the spin density for atoms in α or in β positions with respect to the radical center. The different weights of the two contributions are discussed on the basis of Hartree–Fock and density functional computations. Received: 17 September 1999 / Accepted: 3 February 2000 / Published online: 29 June 2000