On the use of 17O NMR for understanding molecular and silica-grafted tungsten oxo siloxide complexes.

17O-labelled tungsten siloxide complexes [WOCl2(OSitBu3)2] (1-Cl) and [WOMe2(OSitBu3)2] (1-Me) were prepared and characterized by 17O MAS NMR, with input from theoretical calculations of NMR parameters. Guidelines linking 17O NMR parameters and the coordination sphere of molecular and silica-grafted tungsten oxo species are proposed. The grafting of 1-Me on SiO2-700 afforded material 2, with surface species [(SiO)WOMe2(OSitBu3)] as shown by elemental analysis, IR and 1H and 13C MAS NMR. The DFT calculations of the grafting mechanism are in line with the observed reactivity. They indicate the occurrence of several isomeric species of close energy for the grafted W centers, precluding efficient 17O MAS NMR studies. The lack of catalytic activity in olefin metathesis and ring-opening olefin metathesis polymerization indicates that initiation by α-H elimination is not operative in 2, contrary to related tungsten surface species, which illustrates the crucial influence of the nature of the metal coordination sphere.

Interactions in saccharide/cation/water systems: Insights from density functional theory.

Interactions between saccharides and ions in aqueous solutions are of great importance in many fields (chemistry, physico-chemistry, biology, food industries). Thus, this work proposes to develop a methodology dealing with the characterization and the understanding of interactions between saccharides and cations in presence of water molecules, by a quantum mechanics approach. In the first part, the saccharide hydration properties (xylose, glucose, sucrose) in pure water are determined. Results show that the saccharide coordination numbers, as well as the saccharides hydration enthalpy, increase with the saccharide hydrophilic group number. In the second part, the influence of cations on saccharides hydration properties, and inversely, is evaluated. In saccharide/cation/water systems, the decrease in hydration enthalpy of cations and saccharides shows that both species are dehydrated and that saccharide dehydration depends on the nature of the cation. The dehydration sequence of saccharides was explained from the study of saccharide/cation interactions.

Androgen receptor agonists increase lean mass, improve cardiopulmonary functions and extend survival in preclinical models of Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a neuromuscular disease that predominantly affects boys as a result of mutation(s) in the dystrophin gene. DMD is characterized by musculoskeletal and cardiopulmonary complications, resulting in shorter life-span. Boys afflicted by DMD typically exhibit symptoms within 3-5 years of age and declining physical functions before attaining puberty. We hypothesized that rapidly deteriorating health of pre-pubertal boys with DMD could be due to diminished anabolic actions of androgens in muscle, and that intervention with an androgen receptor (AR) agonist will reverse musculoskeletal complications and extend survival. While castration of dystrophin and utrophin double mutant (mdx-dm) mice to mimic pre-pubertal nadir androgen condition resulted in premature death, maintenance of androgen levels extended the survival. Non-steroidal selective-AR modulator, GTx-026, which selectively builds muscle and bone was tested in X-linked muscular dystrophy mice (mdx). GTx-026 significantly increased body weight, lean mass and grip strength by 60-80% over vehicle-treated mdx mice. While vehicle-treated castrated mdx mice exhibited cardiopulmonary impairment and fibrosis of heart and lungs, GTx-026 returned cardiopulmonary function and intensity of fibrosis to healthy control levels. GTx-026 elicits its musculoskeletal effects through pathways that are distinct from dystrophin-regulated pathways, making AR agonists ideal candidates for combination approaches. While castration of mdx-dm mice resulted in weaker muscle and shorter survival, GTx-026 treatment increased the muscle mass, function and survival, indicating that androgens are important for extended survival. These preclinical results support the importance of androgens and the need for intervention with AR agonists to treat DMD-affected boys.

Aqueous Solvation of SmI2: A Born-Oppenheimer Molecular Dynamics Density Functional Theory Cluster Approach.

We report the results of Born-Oppenheimer molecular dynamics (BOMD) simulations on the aqueous solvation of the SmI2 molecule at room temperature using the cluster microsolvation approach including 32 water molecules. The electronic structure calculations were done using the M062X hybrid exchange-correlation functional in conjunction with the 6-31G** basis sets for oxygen and hydrogen. For the iodine and samarium atoms the Stuttgart-Köln relativistic effective-core potentials were utilized with their associated valence basis sets. Starting from the optimized geometry of SmI2 embeded in the microsolvation environment, we find a swift substitution of the iodine ions by eight tightly bound water molecules around Sm(II). Through the Sm-O radial distribution function and the evolution of the Sm-O distances, the present study predicts a first rigid Sm(II) solvation shell from 2.6 to 3.4 Å, whose integration leads to a coordination number of 8.4 water molecules, and a second softer solvation sphere from 3.5 to ca. 6 Å. The Sm(II)-O radial distribution function is in excellent agreement with that reported for Sr2+ from EXAFS studies, a fact that can be explained because Sr2+ and Sm2+ have almost identical ionic radii (ca. 1.26 Å) and coordination numbers: 8 for Sr2+ and 8.4 for Sm2+. The theoretical EXAFS spectrum was obtained from the BOMD trajectory and is discussed in the light of the experimental spectra for Sm(III). Once microsolvation is achieved, no water exchange events were found to occur around Sm2+, in agreement with the experimental data for Eu2+ (which has a nearly identical charge-to-ionic radius relation as Sm2+), where the mean residence time of a water molecule in [Eu(H2O)8]2+ is known to be ca. 230 ps.

17O MAS NMR studies of oxo-based olefin metathesis catalysts: a critical assessment of signal enhancement methods.

The DFS enhancement method as applied to 17O MAS NMR was critically assessed, first on NaPO3, a simple binary glass system, and in a second step, on a series of catalysis-related organometallic molecules and materials. The robustness of DFS was investigated for the wide range of anisotropic parameters (quadrupolar coupling and chemical shift anisotropy) encountered in these samples. Emphasis has been put on the variation of signal enhancements with respect to the DFS final sweep frequency, pulse amplitude and pulse duration, while line shape distortion issues were also addressed. Finally, the robustness of DFS enhancement of the 17O MAS NMR signal is shown through its successful application to silica-supported olefin metathesis catalysts.

Versatile coordination of a reactive P,N-ligand toward boron, aluminum and gallium and interconversion reactivity.

The synthesis and reactivity of the first Group 13 complexes bearing a dearomatized phosphino-amido ligand are reported, i.e. alane AlEt2(L) , gallane GaCl2(L) and borane B(Cl)(Ph)(L) . The three complexes react very differently with Group 13 trihalogenides, providing access to zwitterionic anti-·GaCl3 and the unique bis(metalloid) ·BCl2, with the boron center part of a highly unusual anionic four-membered ring (charge on C) and Ga bound to P. The coordination chemistry and the various transformations are supported by DFT calculations, X-ray crystallography and multinuclear NMR spectroscopic data.

Aqueous microsolvation of CdCl2: density functional theory and Born-Oppenheimer molecular dynamics studies.

We report a systematic study of aqueous microsolvation of CdCl2. The optimized structures and binding energies of the CdCl2-(H2O)n clusters with n = 1-24 have been computed at the B3PW91/6-31G** level. The solvation patterns obtained at the DFT level are verified at the MP2/AVTZ level for n < 6. Unlike HgCl2-(H2O)n case, where there are at most three Hg-O(w) orbital interactions, Cd also establishes four equatorial orbital interactions with water for n > 6 leading to a planar square bipyramid hexacoordination around Cd. The first solvation shell is fully attained with 12 water molecules. At the same level of theory the water binding energies are much larger than those previously found for HgCl2 due to the stronger Cd-O(w) interactions arising from the smaller core of Cd. For the largest system studied, CdCl2-(H2O)24, both penta- and hexa-coordination stable patterns around Cd are found. However, Born-Opphenheimer molecular dynamics simulations starting from these optimized geometries at 700 K reveal the greater stability of the Cd-pentacoordinated species, where a CdCl2-(H2O)3 trigonal bipyramid effective solute appears. The Cd-O(water) radial distribution function shows a bimodal distribution with two maxima at 2.4 Å and 4.2 Å, revealing the different coordination spheres, even with such a small number of solvating water molecules.

Aqueous solvation of HgClOH. Stepwise DFT solvation and Born-Oppenheimer molecular dynamics studies of the HgClOH-(H2O)24 complex.

We address the aqueous solvation of HgClOH through a systematic study of stepwise hydration considering the HgClOH-(H2O)n structures with n = 1-24. After calibration of the DFT method, the electronic calculations have been carried out using the B3PW91 exchange-correlation functional. For n < 5 the main geometrical parameters and incremental binding energies are in agreement with counterpoise-corrected MP2/AVTZ static values and BO-MP2 dynamic averages. For n > 15 three direct water-Hg interactions appear during the hydration process and a pentacoordinated trigonal bipyramid apical pattern around Hg is found. 22 water molecules are needed to build the first solvation shell. Unlike microsolvated HgCl2, no stable equatorial trigonal bipyramid was found. Optimizations with the Polarizable Continuum Model lead to structures with extremely large Hg-O(water) distances because of a dominant solvation effect on the explicit water molecules; however, this overestimation diminishes for large values of n. A DFT Born-Oppenheimer molecular dynamics simulation at T = 700 K revealed the stability of the HgClOH-(H2O)24 complex with an average trigonal bipyramid Hg-coordination pattern, in accordance with the static cluster description. After thermalization is achieved, the exchange rate of the Hg-coordinated water molecules is estimated to be ca. 10(11) s(-1).

Aqueous solvation of Hg(OH)2: energetic and dynamical density functional theory studies of the Hg(OH)2-(H2O)n (n = 1-24) structures.

A systematic study of the hydration of Hg(OH)2 by the stepwise solvation approach is reported. The optimized structures, solvation energies, and incremental free energies of 1-24 water molecules interacting with the solute have been computed at the B3PW91 level using 6-31G(d,p) basis sets for the O and H atoms. The mercury atom was treated with the Stuttgart-Köln relativistic core potential in combination with an extended optimized valence basis set. One to three direct Hg-water interactions appear along the solvation process. The first solvation shell is fully formed with 24 water molecules. A stable pentacoordinated Hg trigonal bipyramid structure appears for n > 15. Density functional theory (DFT) Born-Oppenheimer molecular dynamics simulations showed the thermal stability of the Hg(OH)2-(H2O)24 structure at room temperature and the persistence of the trigonal bipyramid coordination around Hg. The Gibbs free energy for the first solvation shell is significantly larger for the fully solvated Hg(OH)2 than the one previously obtained for the HgCl2 case, due to σ-acceptor and π-donor properties involving the hydroxyl groups of the solute. This suggests that the transmembrane passage of Hg(OH)2 into the cell via simple diffusion is less favorable compared to the case when the metal is coordinated with two Cl groups.

Theoretical study of the aqueous solvation of HgCl2: Monte Carlo simulations using second-order Moller-Plesset-derived flexible polarizable interaction potentials.

A study of the solvation of HgCl(2) including ab initio aggregates of up to 24 water molecules and the results of extensive Monte Carlo simulations for the liquid phase using MP2-derived interaction potentials is presented. The interaction potentials are flexible, polarizable, and include non-additive effects. We conclude that a cluster description of the solvation mechanism is limited when compared to the condensed phase. The molecular image derived from the MC simulations is peculiar. It resembles that of a hydrophobic solute, which explains the rather easy passage of this neutral molecule through the cell membrane; however, it also shows an intermittent binding of one, two, or three water molecules to HgCl(2) in the fashion of a hydrophilic solute.

Catalytic hydrosilylation of olefins with organolanthanides: A DFT study. Part I: Hydrosilylation of propene by SiH4.

Investigation of the catalytic hydrosilylation of propene by primary silane in the presence of Cp(2)SmH has been carried out using DFT calculations. Using SiH(4) as a model, it is shown that a catalytic cycle based on the hydride complex is unlikely. The activation of silane after insertion of propene is not competitive compared to the allylic activation of propene or the silyl formation. An alternative catalytic cycle, based on a silyl complex, is proposed. This alternative pathway accounts for the experimental observation. The allylic activation of propene is shown to be one of the main routes for the catalyst deactivation.

Catalytic hydrosilylation of olefins with organolanthanide complexes: a DFT study. Part II: Influence of the substitution on olefin and silane.

The reaction mechanism of the catalytic hydrosilylation of olefins in the presence of the samarium hydride (η(5)-C(5)H(5))(2)SmH has been investigated for several silanes and olefins with DFT calculations. For any substrate, the active species is the silyl complex, formed in situ from the reaction of the metal hydride with the silane. In agreement with the experimental data, the substitution of hydrogen by methyl groups in the silane decreases the catalytic turn-over. This result is shown to have electronic origins: the methyl group decreases the electron density on the silicon atom, which weakens the Sm-Si bond and decreases the ability for the silyl group to stabilise the positively charged group in a σ-bond metathesis transition state. Substituting hydrogen by alkyl groups on the olefin modifies mostly steric effects, and, depending on the position of the substituting group, it can result in an increase or a decrease of the catalytic yield.

Copper(I) complexes derived from mono- and diphosphino-boranes: Cu-->B interactions supported by arene coordination.

The monophosphino-boranes o-iPr(2)P(C(6)H(4))BR(2) (1: R = Ph and 3: R = Cy) and diphosphino-boranes [o-R(2)P(C(6)H(4))](2)BPh (5: R = Ph and 6: R = iPr) readily react with CuCl to afford the corresponding complexes {[o-iPr(2)P(C(6)H(4))BPh(2)]Cu(mu-Cl)}(2) 2, {[o-iPr(2)P(C(6)H(4))BCy(2)]Cu(mu-Cl)}(2) 4, {[o-Ph(2)P(C(6)H(4))](2)BPh}CuCl 7, and {[o-iPr(2)P(C(6)H(4))](2)BPh}CuCl 8. The presence of Cu-->B interactions supported by arene coordination within complexes 2, 7, and 8 has been unambiguously evidenced by NMR spectroscopy and X-ray diffraction studies. The unique eta(2)-BC coordination mode adopted by complexes 7 and 8 has been thoroughly analyzed by density-functional theory (DFT) calculations.

Ligand effect on the NMR, vibrational and structural properties of tetra- and hexanuclear ruthenium hydrido clusters: a theoretical investigation.

Structural and spectroscopic properties of tetranuclear ruthenium hydrido clusters, and to a less extent, of hexanuclear ruthenium hydrido clusters, are investigated theoretically. Some of these (H)(n)Ru(k)(L)(m) (k = 4, 6) clusters were experimentally synthesized and characterized. Non-existing structures are also considered in order to examine the role of ligands on their structure, vibrational spectra and (1)H NMR chemical shifts. The calculated properties are found in very good agreement with experimental data, when available. Beyond the intrinsic interest elicited by transition metal clusters, these compounds are also considered in this paper as relevant to diamagnetic ruthenium nanoparticles as well as building blocks of hcp surfaces, which is the ruthenium nanoparticle lattice. On the basis of the very good agreement between experiments and theory, the structural and spectroscopic properties of several model clusters are also predicted in order to bring additional data which may help to analyze the spectral signature of ruthenium nanoparticles. A particular emphasis is put on (1)H NMR, which is of high practical importance for characterizing the presence of hydrides in ruthenium clusters and nanoparticles. Several topics are discussed: the structural preference of surface hydrides for terminal-, edge-bridging or face-capping coordination modes, hydrides adsorption energies, the possible presence of interstitial hydrogen atoms, the dependence of (1)H chemical shifts on ligands and on electron counting.

DFT calculations of 1H and 13C NMR chemical shifts in transition metal hydrides.

Transition metal hydrides are of great interest in chemistry because of their reactivity and their potential use as catalysts for hydrogenation. Among other available techniques, structural properties in transition metal (TM) complexes are often probed by NMR spectroscopy. In this paper we will show that it is possible to establish a viable methodological strategy in the context of density functional theory, that allows the determination of 1H NMR chemical shifts of hydride ligands attached to transition metal atoms in mononuclear systems and clusters with good accuracy with respect to experiment. 13C chemical shifts have also been considered in some cases. We have studied mononuclear ruthenium complexes such as Ru(L)(H)(dppm)2 with L = H or Cl, cationic complex [Ru(H)(H2O)(dppm)2]+ and Ru(H)2(dppm)(PPh3)2, in which hydride ligands are characterized by a negative 1H NMR chemical shift. For these complexes all calculations are in relatively good agreement compared to experimental data with errors not exceeding 20% except for the hydrogen atom in Ru(H)2(dppm)(PPh3)2. For this last complex, the relative error increases to 30%, probably owing to the necessity to take into account dynamical effects of phenyl groups. Carbonyl ligands are often encountered in coordination chemistry. Specific issues arise when calculating 1H or 13C NMR chemical shifts in TM carbonyl complexes. Indeed, while errors of 10 to 20% with respect to experiment are often considered good in the framework of density functional theory, this difference in the case of mononuclear carbonyl complexes culminates to 80%: results obtained with all-electron calculations are overall in very satisfactory agreement with experiment, the error in this case does not exceed 11% contrary to effective core potentials (ECPs) calculations which yield errors always larger than 20%. We conclude that for carbonyl groups the use of ECPs is not recommended, although their use could save time for very large systems, for instance in cluster chemistry. The reliance of NMR chemical shielding on dynamical effects, such as intramolecular rearrangements or trigonal twists, is also examined for H2Fe(CO)4, K+[HFe(CO)](-), HMn(CO)5 and HRe(CO)5. The accuracy of the theory is also examined for complexes with two dihydrogen ligands (Tp*RuH(H2)2 and [FeH(H2)(DMPE)2]+) and a ruthenium cluster, [H3Ru4(C6H6)4(CO)]+. It is shown that for all complexes studied in this work, the effect of the ligands on the chemical shielding of hydrogen coordinated to metal is suitably calculated, thus yielding a very good correlation between experimental chemical shifts and theoretical chemical shielding.

New nonsymmetric P(OH)3 species. Comparison with the C3 isomer and themochemistry at the DFT, MP2, and CCSD(T) levels of theory.

Two new less-symmetric P(OH)3 isomers that are more stable than the C3 structure are found at the density functional theory (B3PW91, B3LYP), MP2, and CCSD(T) levels with the large aug-cc-pvdz/pvtz basis sets. The C1 and C3 structures are qualitatively different from those found for the As(OH)3 molecule. An additional lower lying P(OH)3 structure with Cs symmetry has been obtained. With the largest basis set the Cs isomer is predicted to be the most stable. However, the inclusion of zero-point-energy corrections induces an inversion between the Cs and C1 isomers, with the latter becoming the lowest energy structure at the highest correlated level. Increasing inclusion of electronic correlation effects reduces the energy difference between the C1 and Cs structures while the C1-C3 energy difference and C1-Cs interconversion barrier become larger. In all cases, energy differences and barrier heights are around 1 kcal/mol.

Cognitive functions in primary central nervous system lymphoma: literature review and assessment guidelines.

BACKGROUND: Treatment-related neurotoxicity has been recognized as a significant problem in patients with primary central nervous system lymphoma (PCNSL) as effective treatment has increased survival rates. There is, however, a paucity of research on cognitive functions in this population. DESIGN: In a review of the literature, a total of 17 articles that described cognitive outcome in adult PCNSL patients were identified. RESULTS: The studies that assessed cognitive functions after whole-brain radiotherapy combined with chemotherapy reported cognitive impairment in most patients. Patients treated with chemotherapy alone had either stable or improved cognitive performance in most studies. Methodological problems, however, limited the ability to ascertain the specific contribution of disease and various treatment interventions to cognitive outcome. On the basis of the literature review, a battery of cognitive and quality-of-life (QoL) measures to be used in prospective clinical trials was proposed. The battery is composed of five standardized neuropsychological tests, covering four domains sensitive to disease and treatment effects (attention, executive functions, memory, psychomotor speed), and QoL questionnaires, and meets criteria for use in collaborative trials. CONCLUSION: The incorporation of formal and systematic cognitive evaluations in PCNSL studies will improve our understanding of treatment-related neurotoxicity in this population.

Study of the interpolyelectrolyte reaction between chitosan and alginate: influence of alginate composition and chitosan molecular weight.

The interpolyelectrolyte reaction between chitosan (CHI) and alginate (ALG) was followed by conductimetry and potentiometry. Five chitosan samples, all with almost the same degree of N-acetylation (DA approximately 0.20) and molecular weights ranging from 5 x 10(3) to 2.5 x 10(5) Da were used. The polyelectrolyte complex was formed using alginate samples with three different M/G values (0.44, 1.31 and 1.96). The composition of the complex, Z (Z = [CHI]/[ALG]) resulted 0.70 +/- 0.02, independently of the molecular weight of chitosan and the composition of the alginate used. The degree of complexation was 0.51 with no dependence on the alginate composition.

Are the carbon monoxide complexes of Cp(2)M (M = Ca, Eu, or Yb) carbon or oxygen bonded? An answer from DFT calculations.

DFT calculations have been performed on the CO adducts of the bivalent lanthanides, Cp(2)M(CO)(x), where M is Eu or Yb and x is 1 or 2, the alkaline earth metallocene Cp(2)Ca(CO), and the methylisocyanide adducts of Yb. The calculated nu(CO) values are in agreement with experiment for Cp(2)M(CO) when M is Ca or Eu, but in striking disagreement when the CO is bound to the metal by way of the carbon atom in CO in the case of Yb. The calculated nu(CO) values for M = Yb are brought into agreement with experiment when the CO is allowed to bond to Cp(2)Yb by way of the oxygen atom.

DFT study of H--H activation by Cp(2) LnH d(0) complexes.

The energy required to activate the H--H bond in the entire series of Cp(2)LnH complexes has been calculated by DFT (B3PW91) methods. The activation energies have been calculated to vary from 0.5 to 8.0 kcal x mol(-1), indicating an overall facile reaction. The electronegativity of the lanthanide in its most stable oxidation state is suggested to be a leading factor for interpreting the trends in activation energy. The geometry of the transition state is best viewed as an almost linear H(3)(-) ligand with short H--H distances and strong M--H interaction, through the wingtip H centers, with Ln. The exchange reaction is thus established to be a sigma bond metathesis reaction.