Ligand-assisted reduction of osmium tetroxide with molecular hydrogen via a [3+2] mechanism

Osmium tetroxide is reduced by molecular hydrogen in the presence of ligands in both polar and nonpolar solvents. In CHCl3 containing pyridine (py) or 1,10-phenanthroline (phen), OsO4 is reduced by H2 to the known Os(VI) dimers L2Os(O)2(mu-O)2Os(O)2L2 (L2 = py2, phen). However, in the absence of ligands in CHCl3 and other nonpolar solvents, OsO4 is unreactive toward H2 over a week at ambient temperatures. In basic aqueous media, H2 reduces OsO4(OH)n(n-) (n = 0, 1, 2) to the isolable Os(VI) complex, OsO2(OH)4(2-), at rates close to that found in py/CHCl3. Depending on the pH, the aqueous reactions are exergonic by deltaG = -20 to -27 kcal mol(-1), based on electrochemical data. The second-order rate constants for the aqueous reactions are larger as the number of coordinated hydroxide ligands increases, k(OsO4) = 1.6(2) x 10(-2) M(-1) s(-1) < k(OsO4(OH)-) = 3.8(4) x 10(-2) M(-1) s(-1) < k(OsO4(OH)2(2-)) = 3.8(4) x 10(-1) M(-1) s(-1). The observation of primary deuterium kinetic isotope effects, k(H2)/k(D2) = 3.1(3) for OsO4 and 3.6(4) for OsO4(OH)-, indicates that the rate-determining step in each case involves H-H bond cleavage. Density functional calculations and thermochemical arguments favor a concerted [3+2] addition of H2 across two oxo groups of OsO4(L)n and argue against H* or H- abstraction from H2 or [2+2] addition of H2 across one Os=O bond. The [3+2] mechanism is analogous to that of alkene addition to OsO4(L)n to form diolates, for which acceleration by added ligands has been extensively documented. The observation that ligands also accelerate H2 addition to OsO4(L)n highlights the analogy between these two reactions.     

Conformational dependence of the intrinsic acidity of the aspartic acid residue sidechain in N-acetyl- -aspartic acid-N′-methylamide

The sidechain conformational potential energy hypersurfaces (PEHS) for the γ_L, β_L, α_L, and α_D backbone conformations of N-acetyl- -aspartate-N′-methylamide were generated. Of the 81 possible conformers initially expected for the aspartate residue, only seven were found after geometric optimizations at the B3LYP/6-31G(d) level of theory. No stable conformers could be located in the δ_L, _L, γ_D, δ_D, and _D backbone conformations. The ‘adiabatic’ deprotonation energies for the endo and exo forms of N-acetyl- -aspartic acid-N′-methylamide were calculated by comparing their optimized relative energies against those found for the seven stable conformers of N-acetyl- -aspartate-N′-methylamide. Sidechain conformational PEHSs were also generated for the estimation of ‘vertical’ deprotonation energies for both endo and exo forms of N-acetyl- -aspartic acid-N′-methylamide. All backbone–sidechain (N–H⁻O–C) and backbone–backbone (N–HO=C) hydrogen bond interactions were analyzed. A total of two backbone–backbone and four backbone–sidechain interactions were found for N-acetyl- -aspartate-N′-methylamide. The deprotonated sidechain of N-acetyl- -aspartate-N′-methylamide may allow the aspartyl residue to form strong hydrogen bond interactions (since it is negatively charged) which may be significant in such processes as protein–ligand recognition and ligand binding. As a primary example, the molecular geometry of the aspartyl residue may be important in peptide folding, such as that in the RGD tripeptide.     

Strong intramolecular secondary si.N bonds in trifluorosilylhydrazines

The simple silylhydrazines F(3)SiN(Me)NMe(2) (1), F(2)Si(N(Me)NMe(2))(2) (2), and F(3)SiN(SiMe(3))NMe(2) (3) have been prepared by reaction of SiF(4) with LiN(Me)NMe(2) and LiN(SiMe(3))NMe(2), while F(3)SiN(SnMe(3))NMe(2) (4) was prepared from SiF(4) and (Me(3)Sn)(2)NNMe(2) (5). The compounds were characterized by gas-phase IR and multinuclear NMR spectroscopy ((1)H, (13)C, (14/15)N, (19)F, (29)Si, (119)Sn), as well as by mass spectrometry. The crystal structures of compounds 1-5 were determined by X-ray crystallography. The structures of free molecules 1 and 3 were determined by gas-phase electron diffraction. The structures of 1, 2, and 4 were also determined by ab initio calculations at the MP2/6-311+G** level of theory. These structural studies constitute the first experimental proof for the presence of strong Si.N beta-donor-acceptor bonds between the SiF(3) and geminal NMe(2) groups in silylhydrazines. The strength of these non-classical Si.N interactions is strongly dependent on the nature of the substituent at the alpha-nitrogen atom of the SiNN unit, and has the order 3>4>1. The valence angles at these extremely deformed alpha-nitrogen atoms, and the Si.N distances are (crystal/gas): 1 104.2(1)/106.5(4) degrees, 2.438(1)/2.510(6) A; 3 83.6(1)/84.9(4) degrees, 2.102(1)/2.135(9) A; 4 89.6(1) degrees, 2.204(2) A.     

Direct aziridination of alkenes by a cationic (salen)ruthenium(VI) nitrido complex

[RuVI(N)(salchda)(CH3OH)]PF6 (1) (salchda = N,N'-bis(salicylidene)o-cyclohexyldiamine dianion) reacts readily with 2,3-dimethyl-2-butene at room temperature in the presence of pyridine or 1-methylimidazole to give initially [RuIV(Az1(-H))(salchda)(py)]PF6 (2, Az1 = 2,2,3,3-tetramethylaziridine), which is then slowly reduced to [RuIII(Az1)(salchda)(py)]PF6 (3). 1 also reacts with a variety of aryl-substituted alkenes such as styrene and trans-beta-methylstyrene in the presence of py or 1-MeIm to give the corresponding ruthenium(III) aziridine complexes. The structures of 3 and [RuIII(Az2)(salchda)(1-MeIm)]PF6 (4, Az2 = trans-2-methyl-3-phenylaziridine) have been determined by X-ray crystallography. The Ru-N(aziridine) distances (2.1049, 2.097 A) are consistent with a neutral aziridine ligand. The C-C and C-N distances in the aziridine ligands are all indicative of single bonds.     

Collective and single-molecule interactions of alpha5beta1 integrins

A novel biomimetic system was used to study collective and single-molecule interactions of the alpha5beta1 receptor-GRGDSP ligand system with an atomic force microscope (AFM). Bioartificial membranes, which display peptides that mimic the cell adhesion domain of the extracellular matrix protein fibronectin, are constructed from peptide-amphiphiles. The interaction measured with the immobilized alpha5beta1 integrins and GRGDSP peptide-amphiphiles is specifically related to the integrin-peptide binding. It is affected by divalent cations in a way that accurately mimics the adhesion function of the alpha5beta1 receptor. The recognition of the immobilized receptor was significantly increased for a surface that presented both the primary recognition site (GRGDSP) and the synergy site (PHSRN) compared to the adhesion measured with surfaces that displayed only the GRGDSP peptide. At the collective level, the separation process of the receptor-ligand pairs is a combination of multiple unbinding and stretching events that can accurately be described by the wormlike chain (WLC) model of polymer elasticity. In contrast, stretching was not observed at the single-molecule level. The dissociation of single alpha5beta1-GRGDSP pairs under loading rates of 1-305 nN/s revealed the presence of two activation energy barriers in the unbinding process. The high-strength regime above 59 nN/s maps the inner barrier at a distance of 0.09 nm along the direction of the force. Below 59 nN/s a low-strength regime appears with an outer barrier at 2.77 nm and a much slower transition rate that defines the dissociation rate (off-rate) in the absence of force (k(off) degrees = 0.015 s(-1)).     

Efficient synthesis of cellulose furoates in 1-<Emphasis Type="Italic">N</Emphasis>-butyl-3-methylimidazolium chloride

The ionic liquid 1-N-butyl-3-methylimidazolium chloride ([C₄mim]⁺Cl⁻) was investigated as reaction media for the homogeneous acylation of cellulose with 2-furoyl chloride in the presence of pyridine. The preparation of cellulose furoate depending on the reaction conditions, the cellulose type and the pyridine content was studied. Cellulose furoates with a degree of substitution in the range from 0.46 to 3.0 were accessible, i.e., under mild conditions, with a low excess of reagent and in a short reaction time. The products were characterized by elemental analysis, perpropionylation, ¹H- and ¹³C NMR spectroscopy and FTIR spectroscopy. Thomas Heinze is the member of the European Polysaccharide Network of Excellence (EPNOE), www.epnoe.eu     

First organocatalyzed asymmetric Michael addition of aldehydes to vinyl sulfones

[reaction: see text] The first asymmetric direct Michael addition of aldehydes to vinyl sulfones catalyzed by N-iPr-2,2'-bipyrrolidine is described. 1,4-Adducts are obtained in good yields and enantioselectivities. The determination of absolute configuration allowed us to postulate a Si,Si transition state model, as shown previously for nitroolefins.     

Dissipation functions and conservation laws of molecular liquids and solids

Thermodynamics of molecular liquids (anisotropic liquids, liquid crystals, etc.) and molecular solids (e.g. dielectrics, pyroelectrics, molecular crystals) are treated in a unified way, using an internal energy potentialU and a dissipation functionD. Assuming that the motion of the mass points making up the molecule is essential in determiningU we write down the appropriate field equations of motion and the entropy equation. With the assumed invariance ofU under a group of space-time transformations and the invariance ofD under rigid body uniform motions, we derive the conservation laws of mass, momentum, energy and angular momentum. In particular, we show that the total stress tensor is asymmetric.Furthermore, a symmetric stress tensor does not guarantee angular momentum conservation. The complete specification ofD leads to symmetry relations between the dissipative coefficients in an unambiguous way, without invoking the concept of so called forces and fluxes, in contrast to the conventional Onsager approach. Our formalism allows for a class of different dissipation functions, and is applicable to linear or nonlinear molecular media of arbitrary symmetry. It covers simple materials as special cases.     

Solid-phase synthesis of imidazo[1,2-a]pyridine using sodium benzenesulfinate as a traceless linker

[formula: see text] The preparation of the first library of imidazo[1,2-a]pyridine derivatives on a solid support is described. A sulfone linker strategy was applied in the synthesis. Key steps involved in the solid-phase synthetic procedure include (i) alpha-haloketone resin formation by sulfinate-->sulfone alkylation, (ii) imidazo[1,2-a]pyridine ring formation by treatment with 2-aminopyridine, (iii) sulfone anion alkylation, and (iv) traceless product release by oxidation-elimination. A library of 12 imidazo[1,2-a]pyridines was synthesized.     

On the representation of electrostatic fields around ab initio charge distributions

Summary We compare two methods (Mulliken charges and a distributed multipole analysis, DMA) of representing an ab initio charge distribution for calculating the electrostatic field and potential outside the molecule, using pyrimidine and the RNA base uracil as examples. This is done using a 3-D graphical display of the electrostatic fields, which, when used with real-time rotation, zooming and clipping, has many advantages for qualitatively assessing the electrostatic interactions of a molecule. The errors involved in using Mulliken point charges may be of similar magnitude to the total electrostatic field in regions which are important in recognition processes. The DMA representation automatically includes the anisotropic electrostatic effects of non-spherical features in the charge distribution of each atom, and yet the displayed electrostatic fields around the atoms which have lone-pair density do not show marked anisotropy.