Alkene Transfer Hydrogenation with Alkaline-Earth Metal Catalysts.

The alkene transfer hydrogenation (TH) of a variety of alkenes has been achieved with simple AeN''2 catalysts [Ae=Ca, Sr, Ba; N''=N(SiMe3 )2 ] using 1,4-cyclohexadiene (1,4-CHD) as a H source. Reaction of 1,4-CHD with AeN''2 gave benzene, N''H, and the metal hydride species N''AeH (or aggregates thereof), which is a catalyst for alkene hydrogenation. BaN''2 is by far the most active catalyst. Hydrogenation of activated C=C bonds (e.g. styrene) proceeded at room temperature without polymer formation. Unactivated (isolated) C=C bonds (e.g. 1-hexene) needed a higher temperature (120 °C) but proceeded without double-bond isomerization. The ligands fully control the course of the catalytic reaction, which can be: 1) alkene TH, 2) 1,4-CHD dehydrogenation, or 3) alkene polymerization. DFT calculations support formation of a metal hydride species by deprotonation of 1,4-CHD followed by H transfer. Convenient access to larger quantities of BaN''2 , its high activity and selectivity, and the many advantages of TH make this a simple but attractive procedure for alkene hydrogenation.

Simple Alkaline-Earth Metal Catalysts for Effective Alkene Hydrogenation.

Alkaline earth metal amides (AeN''2 : Ae=Ca, Sr, Ba, N''=N(SiMe3 )2 ) catalyze alkene hydrogenation (80-120 °C, 1-6 bar H2 , 1-10 mol % cat.), with the activity increasing with metal size. Various activated C=C bonds (styrene, p-MeO-styrene, α-Me-styrene, Ph2 C=CH2 , trans-stilbene, cyclohexadiene, 1-Ph-cyclohexene), semi-activated C=C bonds (Me3 SiCH=CH2 , norbornadiene), or non-activated (isolated) C=C bonds (norbornene, 4-vinylcyclohexene, 1-hexene) could be reduced. The results show that neutral Ca or Ba catalysts are active in the challenging hydrogenation of isolated double bonds. For activated alkenes (e.g. styrene), polymerization is fully suppressed due to fast protonation of the highly reactive benzyl intermediate by N''H (formed in the catalyst initiation). Using cyclohexadiene as the H source, the first Ae metal catalyzed H-transfer hydrogenation is reported. DFT calculations on styrene hydrogenation using CaN''2 show that styrene oligomerization competes with styrene hydrogenation. Calculations also show that protonation of the benzylcalcium intermediate with N''H is a low-energy escape route, thus avoiding oligomerization.

Calcium Hydride Catalyzed Highly 1,2-Selective Pyridine Hydrosilylation.

Reaction of the calcium hydride complex (DIPPnacnac-CaH⋅THF)2 with pyridine is much faster and selective than that of the corresponding magnesium hydride complex (DIPPnacnac = [(2,6-iPr2 C6 H3 )NC(Me)]2 CH). With a range of pyridine, picoline and quinoline substrates, exclusive transfer of the hydride ligand to the 2-position is observed and also at higher temperatures no 1,2→1,4 isomerization is found. The heteroleptic product DIPPnacnac-Ca(1,2-dihydropyridide)⋅(pyridine) shows fast ligand exchange into homoleptic calcium complexes and therefore could not be isolated. Calcium hydride reduction of isoquinoline gave well-defined homoleptic products which could be characterized by X-ray diffraction: Ca(1,2-dihydroisoquinolide)2 ⋅(isoquinoline)4 and Ca3 (1,2-dihydroisoquinolide)6 ⋅(isoquinoline)6 . The striking selectivity difference in the dearomatization of pyridines by Mg or Ca complexes could be explained by DFT theory and was utilized in catalysis. Whereas hydroboration of pyridine with pinacol borane with a calcium hydride catalyst gave only minor conversion, the hydrosilylation of pyridine and quinolines with PhSiH3 yields exclusively 1,2-dihydropyridine and 1,2-dihydroquinoline silanes with 80-90 % conversion. Similar results can be achieved with the catalyst Ca[N(SiMe3 )2 ]2 ⋅(THF)2 . These calcium complexes represent the first catalysts for the 1,2-selective hydrosilylation of pyridines.

New Techniques to Assess In Vitro Release of siRNA from Nanoscale Polyplexes.

PURPOSE: Release of siRNA from nanoscale polyplexes is a crucial yet little investigated process, important during all stages of therapeutic research. Here we develop new methods to characterize polyplex stability early on in the development of new materials. METHODS: We used double fluorescent labeled siRNA to compare binding and stability of a panel of chemically highly diverse nanoscale polyplexes, including peptides, lipids, nanohydrogels, poly-L-lysine brushes, HPMA block copolymers and manganese oxide particles. Conventional EMSA and heparin competition methods were contrasted with a newly developed microscale thermophoresis (MST) assay, a near-equilibrium method that allows free choice of buffer conditions. Integrity of FRET-labeled siRNA was monitored in the presence of nucleases, in cell culture medium and inside living cells. This approach characterizes all relevant steps from polyplex stability, over uptake to in vitro knockdown capability. RESULTS: Diverging polyplex binding properties revealed drawbacks of conventional EMSA and heparin competition assays, where MST and FRET-based siRNA integrity measurements offered a better discrimination of differential binding strength. Since cell culture medium left siRNA in all polyplexes essentially intact, the relevant degradation events could be pinpointed to occur inside cells. Differential binding strength of the variegated polyplexes correlated only partially with intracellular degradation. The most successful compounds in RNAi showed intermediate binding strength in our assays. CONCLUSIONS: We introduce new methods for the efficient and informative characterization of siRNA polyplexes with special attention to stability. Comparing FRET-labeled siRNA in different polyplexes associates successful knockdown with intermediate siRNA stability in various steps from formulation to intracellular persistence.

How big is a Cp? Novel cycloheptatrienyl zirconium complexes with tri-, tetra- and pentasubstituted cyclopentadienyl ligands.

The new bulky cyclopentadienyl anions 1,2,4-tri(cyclopentyl)cyclopentadienide and 2,3-diisopropyl-1,4-dimethyl-5-trimethylsilyl-cyclopentadienide were prepared. These and the already known 1,2,4-tri(cyclohexyl)-, 1,2,4-tri(isopropyl)-, 2,3-diisopropyl-1,4-dimethyl-, 1,3,4-triisopropyl-2,5-dimethyl-, pentaphenyl-, and p-butylphenyl-tetraphenyl-cyclopentadienide as well as tert-butylindenide were coordinated to the cycloheptatrienylzirconium fragment [(CHT)ZrCl(tmeda)]. The nine zirconium complexes of the [(CHT)Zr(Cp)] type were characterized by elemental analysis and NMR spectroscopy. For five of the sandwich complexes X-ray crystal structure determination could be carried out; structures of the four others were obtained by DFT calculations. The data serve as a basis for cone angle measurements of cyclopentadienyl ligands to evaluate the steric demand of these ligands.

Multifunctional two-photon active silica-coated Au@MnO Janus particles for selective dual functionalization and imaging.

Monodisperse multifunctional and nontoxic Au@MnO Janus particles with different sizes and morphologies were prepared by a seed-mediated nucleation and growth technique with precise control over domain sizes, surface functionalization, and dye labeling. The metal oxide domain could be coated selectively with a thin silica layer, leaving the metal domain untouched. In particular, size and morphology of the individual (metal and metal oxide) domains could be controlled by adjustment of the synthetic parameters. The SiO2 coating of the oxide domain allows biomolecule conjugation (e.g., antibodies, proteins) in a single step for converting the photoluminescent and superparamagnetic Janus nanoparticles into multifunctional efficient vehicles for theranostics. The Au@MnO@SiO2 Janus particles were characterized using high-resolution transmission electron microscopy (HR-)TEM, powder X-ray diffraction (PXRD), optical (UV-vis) spectroscopy, confocal laser fluorescence scanning microscopy (CLSM), and dynamic light scattering (DLS). The functionalized nanoparticles were stable in buffer solution or serum, showing no indication of aggregation. Biocompatibility and potential biomedical applications of the Au@MnO@SiO2 Janus particles were assayed by a cell viability analysis by coincubating the Au@MnO@SiO2 Janus particles with Caki 1 and HeLa cells. Time-resolved fluorescence spectroscopy in combination with CLSM revealed the silica-coated Au@MnO@SiO2 Janus particles to be highly two-photon active; no indication for an electronic interaction between the dye molecules incorporated in the silica shell surrounding the MnO domains and the attached Au domains was found; fluorescence quenching was observed when dye molecules were bound directly to the Au domains.

Catechol-initiated polyethers: multifunctional hydrophilic ligands for PEGylation and functionalization of metal oxide nanoparticles.

Bifunctional CA-PEG (catechol-poly(ethylene glycol)) and multifunctional CA-PEG-PGA/PEVGE (poly(glycidyl amine)/poly(ethylene glycol vinyl glycidyl ether)) ligands for the functionalization and solubilization of nanoparticles are introduced. Tunable polymers with polydispersities <1.25 and molecular weights in the range 500-7700 g mol(-1) containing a catechol moiety for conjugation to metal oxide nanoparticles were prepared. The functional PEG ligands were synthesized starting from the acetonide-protected catechol initiator 2,2-dimethyl-1,3-benzodioxole-5-propanol (CA-OH) for oxyanionic polymerization. CA-OH was used both for homopolymerization of ethylene oxide (EO) as well as copolymerization with functional epoxides N,N-diallyl glycidyl amine (DAGA), releasing primary amino groups and ethylene glycol vinyl glycidyl ether (EVGE), exhibiting a double bond for click-type reactions, to generate CA-PEG and CA-PEG-PGA/PEVGE. We demonstrate the potential of the functional ligands by binding to MnO nanoparticles, rendering the PEGylated nanoparticles highly stable in aqueous environment. Furthermore, addressability of the functional groups has been proven, for example, by coupling with fluoresceine isothiocyanate (FITC), to allow for optical monitoring of the nanoparticle fate in biological systems.

How big is a Cp? Cycloheptatrienyl zirconium complexes with bulky cyclopentadienyl and indenyl ligands.

A combination of phase-transfer and traditional alkylation strategies has been employed to synthesise sterically encumbered 1,3-di(cyclohexyl) and 1,3-di(tert-butyl) substituted indenes in multi-gram quantities. These indenyl ligands and sterically demanding alkyl cyclopentadienyl ligands have been used to prepare a series of [(η(7)-C(7)H(7))Zr(η(5)-L)] (L = Cp and Ind) complexes by straightforward salt metathesis between [(η(7)-C(7)H(7))ZrCl(tmeda)] and the corresponding sodium indenide or cyclopentadienide. All of these Zr complexes have been characterized by elemental analysis, NMR spectroscopy and single crystal X-ray diffraction. The structural information derived from these studies was employed to evaluate the steric demand of these ligands in a realistic manner.

1,1'-Bis[bis-(4-tert-butyl-phen-yl)meth-yl]ferrocene.

The molecule of the title compound, [Fe(C26H31)2], is located on an inversion center. The two cyclopentadienyl rings exhibit a staggered conformation, which results from the bulky bis(4-tert-butylphenyl)methyl substituents situated on opposite sides of the molecule.

Bis(η-1-tert-butyl-inden-yl)nickel(II).

The title compound, [Ni(C(13)H(15))(2)], shows a slightly distorted sandwich structure with two independent mol-ecules in the asymmetric unit. Both Ni atoms are located on crystallographic centres of inversion.