Experimental and Computational Study of a Confirmed Borylene-to-Diborene Dimerization.

While the dimerization of heavier group 13 carbene analogues to the corresponding alkene analogues is known and relatively well understood, the dimerization of dicoordinate borylenes (LRB:, L = neutral donor; R = anionic substituent) to the corresponding diborenes (LRB═BRL) has never been directly observed. In this study we present the first example of a formal borylene-to-diborene dimerization through abstraction of a labile phosphine ligand from the tricoordinate hydroborylene precursor (CAAC)(Me3P)BH (CAAC = cyclic alkyl(amino)carbene) by bulky Lewis-acidic dihaloboranes (BX2Y, X = Cl, Br, Y = aryl, boryl), generating the corresponding dihydrodiborene (CAAC)HB═BH(CAAC) and (Me3P)BX2Y as the byproduct. An in-depth experimental and computational mechanistic analysis shows that this seemingly simple process (2 LL'BH + 2 BX2Y → LHB═BHL + 2 L'BX2Y) is in fact based on a complex sequence of finely tuned processes, involving the one-electron oxidation of and PMe3 abstraction from the borylene precursor by BX2Y, multiple halide transfers between (di)boron intermediates and BX2Y/[BX3Y]-, and multiple one-electron redox processes between diboron intermediates and the borylene precursor, which make the reaction ultimately autocatalytic in [(CAAC)(Me3P)BH]•+. The findings suggest that [LBXR]• boryl radicals are more likely coupling partners than dicoordinate LRB: borylenes in the reductive coupling of base-stabilized LBX2R boranes to LRB═BRL diborenes.

Performing a Three-Dimensional Finite Element Analysis to Simulate and Quantify the Contact Pressure in the Canine Elbow Joint: A Pilot Study.

OBJECTIVE: The aim of this study was to measure surface pressures and force distribution on radius and ulna in healthy and dysplastic elbow joints in different positions using the finite element analysis (FEA). STUDY DESIGN: FEA was performed on computed tomographic data of healthy and fragmented coronoid process diseased elbow joints of Labrador Retrievers. It considered the articular cartilage, collateral ligaments, triceps and biceps muscle. The analysis of each joint was performed in four positions (standing position: 145 degrees and three positions of the stance phase of gait: beginning: 115 degrees, middle: 110 degrees, end: 145 degrees joint angle) in consideration of different ground reaction forces (standing: 88.3 N; stance phase of gait: 182.5 N). RESULTS: Mean values of total force of 317.5 N (standing), 590.7 N (beginning), 330.9 N (middle) and 730.9 N (end) were measured. The percentual force distribution resulted in a total of 49.56 ± 26.58% on the ulna with a very inhomogeneous distribution. A significant difference was detected between the positions 'standing' and 'end' (p = 0.0497) regardless of the joint condition. In some FEA results, visual assessment of the surface pressures indicated an increase in pressure in the region of the medial compartment without a uniform pattern. An increase in pressure resulted in an area increase in the pressure marks on the joint surface and measurable pressure was increased at a larger joint angle. CLINICAL SIGNIFICANCE: FEA can provide information about the transmission of force in the joint. Prior to the use of FEA in scientific clinical research for the simulation of force, further model improvements are necessary.

A Stable N-Heterocyclic Silylene with a 1,1'-Ferrocenediyl Backbone.

The N-heterocyclic silylene [{Fe(η5 -C5 H4 -NDipp)2 }Si] (1DippSi, Dipp=2,6-diisopropylphenyl) shows an excellent combination of pronounced thermal stability and high reactivity towards small molecules. It reacts readily with CO2 and N2 O, respectively affording (1DippSiO2 )2 C and (1DippSiO)2 as follow-up products of the silanone 1DippSiO. Its reactions with H2 O, NH3 , and FcPH2 (Fc=ferrocenyl) furnish the respective oxidative addition products 1DippSi(H)X (X=OH, NH2 , PHFc). Its reaction with H3 BNH3 unexpectedly results in B-H, instead of N-H, bond activation, affording 1DippSi(H)(BH2 NH3 ). DFT results suggest that dramatically different mechanisms are operative for these H-X insertions.

Synthesis and reduction chemistry of mixed-Lewis-base-stabilised chloroborylenes.

The one-electron reduction of (CAACMe)BCl3 (CAACMe = 1-(2,6-diisopropylphenyl)-3,3,5,5-tetramethylpyrrolidin-2-ylidene) yields the dichloroboryl radical [(CAACMe)BCl2]˙. Furthermore, the twofold reduction of (CAACMe)BCl3 in the presence of a range of Lewis bases (L = CAACMe, N-heterocyclic carbene, phosphine) yields a series of doubly base-supported (CAACMe)LBCl chloroborylenes, all of which were structurally characterised. NMR and UV-vis spectroscopic and electrochemical data for (CAACMe)LBCl show that the boron centre becomes more electron-rich and the HOMO-LUMO gap widens as L becomes less π-accepting. A [(CAACMe)BCl2]- boryl anion coordination polymer was isolated as a potential intermediate in these reductions. In most cases the reduction of the chloroborylenes resulted in the formation of the corresponding hydroborylenes or derivatives thereof, as well as ligand C-H activation products.

Making Use of the Direct Process Residue: Synthesis of Bifunctional Monosilanes.

The industrial production of monosilanes Men SiCl4-n (n=1-3) through the Müller-Rochow Direct Process generates disilanes Men Si2 Cl6-n (n=2-6) as unwanted byproducts ("Direct Process Residue", DPR) by the thousands of tons annually, large quantities of which are usually disposed of by incineration. Herein we report a surprisingly facile and highly effective protocol for conversion of the DPR: hydrogenation with complex metal hydrides followed by Si-Si bond cleavage with HCl/ether solutions gives (mostly bifunctional) monosilanes in excellent yields. Competing side reactions are efficiently suppressed by the appropriate choice of reaction conditions.

The reductive coupling of dinitrogen.

The coupling of two or more molecules of dinitrogen (N2) occurs naturally under the radiative conditions present in the ionosphere and may be achieved synthetically under ultrahigh pressure or plasma conditions. However, the comparatively low N-N single-bond enthalpy generally renders the catenation of the strongly triple-bonded N2 diatomic unfavorable and the decomposition of nitrogen chains a common reaction motif. Here, we report the surprising organoboron-mediated catenation of two N2 molecules under near-ambient conditions to form a complex in which a [N4]2- chain bridges two boron centers. The reaction entails reductive coupling of two hypovalent-boron-bound N2 units in a single step. Both this complex and a derivative protonated at both ends of the chain were characterized crystallographically.

Reactive Dimerization of an N-Heterocyclic Plumbylene: C-H Activation with PbII.

The N-heterocyclic plumbylene [Fe{(η5 -C5 H4 )NSiMe3 }2 Pb:] is in equilibrium with an unprecedented dimer in solution, whose formation involves the cleavage of a strong C-H bond and concomitant formation of a Pb-C and an N-H bond. According to a mechanistic DFT assessment, dimer formation does not involve direct PbII insertion into a cyclopentadienyl C-H bond, but is best described as an electrophilic substitution. The bulkier plumbylene [Fe{(η5 -C5 H4 )NSitBuMe2 }2 Pb:] shows no dimerization, but compensates its electrophilicity by the formation of an intramolecular Fe-Pb bond.

Intercepting the Disilene-Silylsilylene Equilibrium.

The equilibrium between disilenes (R2 Si=SiR2 ) and their silylsilylene (R3 Si-SiR) isomers has previously been inferred but not directly observed, except in the case of the parent system H2 Si=SiH2 . Here, we report a new method to prepare base-coordinated disilenes with hydride substituents. By varying the bulk of the coordinating base and other silicon substituents, we have been able to control the rearrangement of disilene adducts to their silylsilylene tautomers. Remarkably, 1,2 migration of a trimethylsilyl group is preferred over hydrogen migration. A DFT study of the reaction mechanism provides a rationale for the observed reactivity and detailed information on the bonding situation in base-stabilized disilenes.

Hydrosilane Synthesis by Catalytic Hydrogenolysis of Chlorosilanes and Silyl Triflates.

Hydrogenolysis of the chlorosilanes and silyl triflates (triflate = trifluoromethanesulfonate, OTf-) Me3- nSiX1+ n (X = Cl, OTf; n = 0, 1) to hydrosilanes at mild conditions (4 bar of H2, room temperature) is reported using low loadings (1 mol %) of the bifunctional catalyst [Ru(H)2CO( HPNP iPr)] ( HPNP iPr = HN(CH2CH2P( iPr)2)2). Endergonic chlorosilane hydrogenolysis can be driven by chloride removal, e.g., with NaBArF4 [BArF4- = B(C6H3-3,5-(CF3)2)4-]. Alternatively, conversion to silyl triflates enables facile hydrogenolysis with NEt3 as the base, giving Me3SiH, Me2SiH2, and Me2SiHOTf, respectively, in high yields. An outer-sphere mechanism for silyl triflate hydrogenolysis is supported by density functional theory computations. These protocols provide key steps for synthesis of the valuable hydrochlorosilane Me2SiClH, which can also be directly obtained in yields of over 50% by hydrogenolysis of chlorosilane/silyl triflate mixtures.

Lewis Base Catalyzed Selective Chlorination of Monosilanes.

A preparatively facile, highly selective synthesis of bifunctional monosilanes R2 SiHCl, RSiHCl2 and RSiH2 Cl is reported. By chlorination of R2 SiH2 and RSiH3 with concentrated HCl/ether solutions, the stepwise introduction of Si-Cl bonds is readily controlled by temperature and reaction time for a broad range of substrates. In a combined experimental and computational study, we establish a new mode of Si-H bond activation assisted by Lewis bases such as ethers, amines, phosphines, and chloride ions. Elucidation of the underlying reaction mechanisms shows that alcohol assistance through hydrogen-bond networks is equally efficient and selective. Remarkably, formation of alkoxysilanes or siloxanes is not observed under moderate reaction conditions.

Thermal Synthesis of Perchlorinated Oligosilanes: A Fresh Look at an Old Reaction.

A combined experimental and theoretical study of the high-temperature reaction of SiCl4 and elemental silicon is presented. The nature and reactivity of the product formed upon rapid cooling of the gaseous reaction mixture is investigated by comparison with the defined model compounds cyclo-Si5 Cl10 , n-Si5 Cl12 and n-Si4 Cl10 . A DFT assessment provides mechanistic insight into the oligosilane formation. Experimental 29 Si NMR investigations, supported by quantum-chemical 29 Si NMR calculations, consistently show that the reaction product is composed of discrete molecular perchlorinated oligosilanes. Low-temperature chlorination is an unexpectedly selective means for the transformation of cyclosilanes to acyclic species by endocyclic Si-Si bond cleavage, and we provide a mechanistic rationalization for this observation. In contrast to the raw material, the product obtained after low-temperature chlorination represents an efficient source of neo-Si5 Cl12 or the amine-stabilized disilene EtMe2 N⋅SiCl2 Si(SiCl3 )2 through reaction with aliphatic amines.

C2-domain mediated nano-cluster formation increases calcium signaling efficiency.

Conventional protein kinase Cs (cPKCs) are key signaling proteins for transducing intracellular Ca2+ signals into downstream phosphorylation events. However, the lifetime of individual membrane-bound activated cPKCs is an order of magnitude shorter than the average time needed for target-protein phosphorylation. Here, we employed intermolecular Förster resonance energy transfer (FRET) in living cells combined with computational analysis to study the spatial organization of cPKCs bound to the plasma membrane. We discovered Ca2+-dependent cPKC nano-clusters that significantly extend cPKC's plasma-membrane residence time. These protein patterns resulted from self-assembly mediated by Ca2+-binding C2-domains, which are widely used for membrane-targeting of Ca2+-sensing proteins. We also established clustering of other unrelated C2-domain containing proteins, suggesting that nano-cluster formation is a key step for efficient cellular Ca2+-signaling.

Unraveling the Amine-Induced Disproportionation Reaction of Perchlorinated Silanes-A DFT Study.

A detailed quantum-chemical study on the amine-induced disproportionation reaction of perchlorinated silanes to neo-Si5 Cl12 is reported. The key intermediate in the resulting mechanistic scenario is a dichlorosilylene amine adduct, which is in tune with recent experimental findings. Yet, at variance with the generally accepted notion of silicon-chain growth by concerted silylene insertion into Si-Cl bonds of lower silanes, the formation of neo-Si5 Cl12 follows more complex pathways. The reactivity is dominated by the Lewis-base character of the dichlorosilylene amine adduct and characterized by three elementary steps that bear close resemblance to the key elementary steps identified earlier for the chloride-induced disproportionation of Si2 Cl6 . NBO and QTAIM analyses of the key reactive species SiCl2 ⋅NMe3 and SiCl3 (-) provide a rationale for these striking similarities.

A Disilene Base Adduct with a Dative Si-Si Single Bond.

An experimental and theoretical study of the base-stabilized disilene 1 is reported, which forms at low temperatures in the disproportionation reaction of Si2 Cl6 or neo-Si5 Cl12 with equimolar amounts of NMe2 Et. Single-crystal X-ray diffraction and quantum-chemical bonding analysis disclose an unprecedented structure in silicon chemistry featuring a dative Si→Si single bond between two silylene moieties, Me2 EtN→SiCl2 →Si(SiCl3 )2 . The central ambiphilic SiCl2 group is linked by dative bonds to the amine donor and the bis(trichlorosilyl)silylene acceptor, which leads to push-pull stabilization. Based on experimental and theoretical examinations a formation mechanism is presented that involves an autocatalytic reaction of the intermediately formed anion Si(SiCl3 )3 (-) with neo-Si5 Cl12 to yield 1.

Chloride-induced aufbau of perchlorinated cyclohexasilanes from Si2Cl6: a mechanistic scenario.

A surprisingly simple preparative procedure, addition of Si2Cl6 to a solution of [nBu4N]Cl in CH2Cl2, leads to the formation of the chloride-complexed cyclic dianions [Si6Cl12⋅2Cl](2-), [(SiCl3)Si6Cl11⋅2Cl](2-), or [1,y-(SiCl3)2Si6Cl10⋅2Cl](2-) (y = 1, 3, 4), depending on the stoichiometric ratio of the reactants and the reaction temperature (25-85 °C). Below -40 °C the open-chain oligosilane chloride adducts [Si3Cl9](-), [Si3Cl10](2-), [Si4Cl11](-), and [Si6Cl15](-) are formed, again depending on the reaction conditions chosen. All species were characterized by X-ray crystallography. The underlying reaction mechanism is elucidated by DFT calculations. It incorporates all experimental findings and involves a few key elementary steps: 1) chloride-induced liberation of SiCl3(-) or higher silanides, 2) their addition to neutral silanes yielding larger oligosilane chloride adducts, 3) dimerization of larger silanides to (substituted) cyclohexasilane dichloride adducts with inverse sandwich structure.

Infrared spectroscopic studies of cells and tissues: triple helix proteins as a potential biomarker for tumors.

In this work, the infrared (IR) spectra of living neural cells in suspension, native brain tissue, and native brain tumor tissue were investigated. Methods were developed to overcome the strong IR signal of liquid water so that the signal from the cellular biochemicals could be seen. Measurements could be performed during surgeries, within minutes after resection. Comparison between normal tissue, different cell lineages in suspension, and tumors allowed preliminary assignments of IR bands to be made. The most dramatic difference between tissues and cells was found to be in weaker IR absorbances usually assigned to the triple helix of collagens. Triple helix domains are common in larger structural proteins, and are typically found in the extracellular matrix (ECM) of tissues. An algorithm to correct offsets and calculate the band heights and positions of these bands was developed, so the variance between identical measurements could be assessed. The initial results indicate the triple helix signal is surprisingly consistent between different individuals, and is altered in tumor tissues. Taken together, these preliminary investigations indicate this triple helix signal may be a reliable biomarker for a tumor-like microenvironment. Thus, this signal has potential to aid in the intra-operational delineation of brain tumor borders.

Isoprenoid biosynthesis via the MEP pathway: in vivo Mössbauer spectroscopy identifies a [4Fe-4S]2+ center with unusual coordination sphere in the LytB protein.

The MEP pathway for the biosynthesis of isoprene units is present in most pathogenic bacteria, in the parasite responsible for malaria, and in plant plastids. This pathway is absent in animals and is accordingly a target for the development of antimicrobial drugs. LytB, also called IspH, the last enzyme of this pathway catalyzes the conversion of (E)-4-hydroxy-3-methylbut-2-enyl diphosphate (HMBPP) into a mixture of isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) using an oxygen sensitive iron sulfur cluster. The exact nature of this iron sulfur cluster is still a matter of debate. We have used (57)Fe Mössbauer spectroscopy to investigate the LytB cluster in whole E. coli cells and in the anaerobically purified enzyme: In LytB an unusual [4Fe-4S](2+) cluster is attached to the protein by three conserved cysteines and contains a hexacoordinated iron linked to three sulfurs of the cluster and three additional oxygen or nitrogen ligands.

Effect of nitric oxide on cytotoxicity of Taxol: enhanced Taxol transcellular permeability.

The present studies were aimed at testing the hypothesis that nitric oxide (NO) may enhance Taxol-induced cytotoxicity in carcinoma cells by increasing influx of Taxol into intracellular compartments. Prostate carcinoma cells (PC-3, LNCaP) and neuroblastoma cells (SKNDZ, CHP212) were used to investigate both transmembrane permeability and cytotoxicity of Taxol in the presence and absence of S-nitrosocaptopril (CapNO), a nitric oxide donating compound. The order of permeability rate of Taxol across the four cell lines was SKNDZ>LNCaP>PC-3>CHP212. Pretreatment of the cell lines with CapNO (100 microM) enhanced permeability of Taxol across prostate PC-3 and LNCaP cells, but not neuroblastoma SKNDZ and CHP212 cells. Taxol inhibited cell growth at nanomolar levels with IC(50)s of 0.21, 17.4, 96.4 and 842.9 nM corresponding to SKNDZ, PC-3, LNCaP and CHP212 cells, respectively. However, CapNO inhibited proliferation of the four cell lines at millimolar levels with IC(50)s ranging from 0.3 to 1.1 mM. Enhancing effect of CapNO (100 microM) on Taxol cytotoxicity were found in PC-3 and LNCaP cells, but not in SKNDZ and CHP212. The findings suggest that the cytotoxic potency of Taxol is mainly dependent upon the cell membrane permeabilization to Taxol, and the enhancing effect of CapNO on Taxol-induced cytotoxicity is primarily mediated via the increased influx of Taxol by NO into intracellular compartments, while NO-induced cytotoxicity cannot be excluded.