Mixed-metal cluster chemistry. 28. Core enlargement of tungsten-iridium clusters with alkynyl, ethyndiyl, and butadiyndiyl reagents

Reaction of [WIr3(mu-CO)3(CO)8(eta-C5Me5)] (1c) with [W(C[triple bond]CPh)(CO)3(eta-C5H5)] afforded the edge-bridged tetrahedral cluster [W2Ir3(mu4-eta2-C2Ph)(mu-CO)(CO)9(eta-C5H5)(eta-C5Me5)] (3) and the edge-bridged trigonal-bipyramidal cluster [W3Ir3(mu4-eta2-C2Ph)(mu-eta2-C=CHPh)(Cl)(CO)8(eta-C5Me5)(eta-C5H5)2] (4) in poor to fair yield. Cluster 3 forms by insertion of [W(C[triple bond]CPh)(CO)3(eta-C5H5)] into Ir-Ir and W-Ir bonds, accompanied by a change in coordination mode from a terminally bonded alkynyl to a mu4-eta2 alkynyl ligand. Cluster 4 contains an alkynyl ligand interacting with two iridium atoms and two tungsten atoms in a mu4-eta2 fashion, as well as a vinylidene ligand bridging a W-W bond. Reaction of [WIr3(CO)11(eta-C5H5)] (1a) or 1c with [(eta-C5H5)(CO)2 Ru(C[triple bond]C)Ru(CO)2(eta-C5H5)] afforded [Ru2WIr3(mu5-eta2-C2)(mu-CO)3(CO)7(eta-C5H5)2(eta-C5R5)] [R = H (5a), Me (5c)] in low yield, a structural study of 5a revealing a WIr3 butterfly core capped and spiked by Ru atoms; the diruthenium ethyndiyl precursor has undergone Ru-C scission, with insertion of the C2 unit into a W-Ir bond of the cluster precursor. Reaction of [W2Ir2(CO)10(eta-C5H5)2] with the diruthenium ethyndiyl reagent gave [RuW2Ir2{mu4-eta2-(C2C[triple bond]C)Ru(CO)2(eta-C5H5)}(mu-CO)2(CO)6(eta-C5H5)3] (6) in low yield, a structural study of 6 revealing a butterfly W2Ir2 unit capped by a Ru(eta-C5H5) group resulting from Ru-C scission; the terminal C2 of a new ruthenium-bound butadiyndiyl ligand has been inserted into the W-Ir bond. Reaction between 1a, [WIr3(CO)11(eta-C5H4Me)] (1b), or 1c and [(eta-C5H5)(CO)3W(C[triple bond]CC[triple bond]C)W(CO)3(eta-C5H5)] afforded [W2Ir3{mu4-eta2-(C2C[triple bond]C)W(CO)3(eta-C5H5)}(mu-CO)2(CO)2(eta-C5H5)(eta-C5R5)] [R = H (7a), Me (7c); R5 = H4Me (7b)] in good yield, a structural study of 7c revealing it to be a metallaethynyl analogue of 3.     

Role of the A-ring of bryostatin analogues in PKC binding: synthesis and initial biological evaluation of new A-ring-modified bryologs

The syntheses of three newly designed bryostatin analogues are reported. These simplified analogues, which lack the A-ring present in the natural product but possess differing groups at C9, were obtained using a divergent approach from a common intermediate. All three analogues exhibit potent, single-digit nanomolar affinity to protein kinase C.     

Simple methods for the direct assembly, functionalization, and patterning of acid-terminated monolayers on Si111

This article describes mild methods to directly assemble, functionalize, and pattern monolayers of undecylenic acid on hydrogen-terminated Si(111). These monolayers were assembled under very mild conditions from a neat solution of undecylenic acid containing 0.1 mol % 4-(decanoate)-2,2,6,6-tetramethylpiperidinooxy at room temperature without the need for UV light. Because of these mild conditions, monolayers exposing carboxylic acids could be assembled in one step without the need to protect the acid prior to its assembly. The monolayers were extensively characterized by horizontal attenuated total reflection infrared spectroscopy, X-ray photoelectron spectroscopy (XPS), and contact angle goniometry. The monolayers bonded to the silicon surface preferentially through the olefin with no detectable bonds between the carboxylic acids and silicon. The crystallinity of the monolayer was studied by infrared spectroscopy through the antisymmetric--v(a)(CH(2))--and symmetric--v(s)(CH(2))--stretches for methylene. Because it is important for future applications to assemble functional surfaces, methods to react the acid-terminated monolayers with trifluoroacetic anhydride and triethylamine to yield a symmetric anhydride on the monolayer were studied. These anhydrides were reacted with a variety of milligram-quantity amines to yield amide-terminated surfaces. This method was general, and a variety of amines could be bonded to the monolayer. The stabilities of these monolayers upon exposure to ambient conditions and under a variety of solvents were described. Because patterned monolayers have found wide applications, we have developed methods to pattern 1-octadecylamine and poly(ethylenimine) on the micrometer scale using soft lithography. In addition, polymer brushes of polynorbornene with thicknesses from 32 to 150 nm were grown from monolayers patterned with the Grubbs' catalyst. The patterned surfaces were imaged by scanning electron microscopy, scanning probe microscopy, and ellipsometry to determine the thicknesses of the patterns and the fidelity of the method.     

Diatropicity of 3,4,7,8,9,10,13,14-octadehydro[14]annulenes: a combined experimental and theoretical investigation

The synthesis and study of a series of octadehydro[14]annulenes is described. The aromaticity of these annulenes was investigated through examination of experimental data from arene-fused systems as well as calculated nucleus-independent chemical shifts (NICS) and bond lengths. Benzene ring fusion to the parent system results in a stepwise loss in aromaticity as the number of fused rings is increased from one to two to three. This decrease in annulenic ring current is manifested in the alkene proton chemical shifts (0-2 benzenes) as well as the NICS (0-3 benzenes). Comparison of isomeric thiophene-fused annulenes shows further evidence of ring current competition as these allow for observation of intermittent degrees of delocalization throughout the annulenic core. A consistent relationship between the magnitude of the NICS values and the degree of benzannelation is also observed.     

New diamide-diamine ligands and their zirconium and hafnium dichloride and bis(dimethylamide) complexes

The multigram syntheses of the protio ligands (2-NC(5)H(4))CH(2)N(CH(2)CH(2)NHSiMe(2)R)(2) (R = Me, H(2)N(2)NN' 3; R = (t)Bu, H(2)N(2)NN() 4) are described via reactions of the previously reported (2-NC(5)H(4))CH(2)N(CH(2)CH(2)NH(2))(2) (1). A new synthesis of 1 is reported starting from 2-aminomethylpyridine and N-tosylaziridine, proceeding via (2-NC(5)H(4))CH(2)N(CH(2)CH(2)NHTs)(2) (2). Reaction of H(2)N(2)NN' or H(2)N(2)NN* with (n)BuLi gives good yields of the dilithiated derivatives Li(2)N(2)NN' and Li(2)N(2)NN*. Reaction of H(2)N(2)NN' or H(2)N(2)NN* with [MCl(2)(CH(2)SiMe(3))(2)(Et(2)O)(2)] gives the cis-dichloride complexes [MCl(2)(L)] (L = N(2)NN', M = Zr 7 or Hf 8; L = N(2)NN(), M = Zr 9). The corresponding reactions of H(2)N(2)NN' or H(2)N(2)NN* with [Zr(NMe(2))(4)] afford the bis(dimethylamide) derivatives [Zr(NMe(2))(2)(L)] (L = N(2)NN' 10 or N(2)NN* 11). All of these protonolysis reactions proceed smoothly and in good yields. Attempts to prepare the titanium complexes [Ti(X)(2)(N(2)NN')] (X = Cl or NMe(2)) were unsuccessful. The X-ray crystal structures of (2-NC(5)H(4))CH(2)N(CH(2)CH(2)NHTs)(2).EtOH, [ZrCl(2)(N(2)NN')].0.5C(6)H(6), [Zr(NMe(2))(2)(N(2)NN')], and [Zr(NMe(2))(2)(N(2)NN*)] are reported.     

In situ tissue pathology from spatially encoded mass spectrometry classifiers visualized in real time through augmented reality

Integration between a hand-held mass spectrometry desorption probe based on picosecond infrared laser technology (PIRL-MS) and an optical surgical tracking system demonstrates in situ tissue pathology from point-sampled mass spectrometry data. Spatially encoded pathology classifications are displayed at the site of laser sampling as color-coded pixels in an augmented reality video feed of the surgical field of view. This is enabled by two-way communication between surgical navigation and mass spectrometry data analysis platforms through a custom-built interface. Performance of the system was evaluated using murine models of human cancers sampled in situ in the presence of body fluids with a technical pixel error of 1.0 ± 0.2 mm, suggesting a 84% or 92% (excluding one outlier) cancer type classification rate across different molecular models that distinguish cell-lines of each class of breast, brain, head and neck murine models. Further, through end-point immunohistochemical staining for DNA damage, cell death and neuronal viability, spatially encoded PIRL-MS sampling is shown to produce classifiable mass spectral data from living murine brain tissue, with levels of neuronal damage that are comparable to those induced by a surgical scalpel. This highlights the potential of spatially encoded PIRL-MS analysis for in vivo use during neurosurgical applications of cancer type determination or point-sampling in vivo tissue during tumor bed examination to assess cancer removal. The interface developed herein for the analysis and the display of spatially encoded PIRL-MS data can be adapted to other hand-held mass spectrometry analysis probes currently available.

Integration between a hand-held mass spectrometry desorption probe based on picosecond infrared laser technology (PIRL-MS) and an optical surgical tracking system demonstrates in situ tissue pathology from point-sampled mass spectrometry data.     

Benzannelated analogs of phenanthro[1,2-b]- and [2,1-b]thiophene: Synthesis and structural characterization by two-dimensional NMR and X-ray techniques

Syntheses of benzo[3,4]phenanthro[1,2-b]thiophene, benzo[3,4]phenanthro[2,1-b]thiophene and their 1-methyl analogs are reported as potential constituents of solvent refined coal liquids and for mutagenicity testing. The attempted synthesis of the 13-methyl analogs which gave the 11-methyl isomers is also described. Total assignments of the ¹H- and ¹³C-nmr spectra based on long range optimized heteronuclear protoncarbon two-dimensional chemical shift correlation are reported. Carbon assignments obtained for benzo[3,4]-phenanthro[1,2-b]thiophene using this approach were confirmed with a 125 MHz ¹³C–¹³C INADEQUATE spectrum. X-Ray crystal structures were determined for benzo[3,4]phenanthro[1,2-b]thiophene and 1-methyl-benzo[3,4]phenanthro[2,1-b]thiophene. Both molecules were helically distorted from planarity. Close intramolecular contacts between the bay region H1–H13 and ClMe-H13 of 2.03 and 2.28 Å, respectively, were responsible for the distortions. There were no close intermolecular contacts of <3.5Å. both molecules refined to an R value of <0.05.     

Controlling cell attachment selectively onto biological polymer-colloid templates using polymer-on-polymer stamping

A new patterning approach using polymer-on-polymer stamping (POPS) has been developed to fabricate polymer-colloid templates for controlling selective cell attachment. In this paper, a polyamine surface patterned onto a poly(acrylic acid)/poly(allylamine hydrochloride) (PAA/PAH) cell resistant multilayer platform serves as a template for the deposition of close- or loose-packed colloidal particles. Peptides containing the RGD adhesion sequence were used to modify the PAH/colloid surface for specific cell attachment. Cell behavior was studied by varying colloidal packing array density, pattern geometry, and surface chemistry. It was found that loose-packed RGD-modified colloidal arrays enhance cell adhesion, as observed through the development of focal adhesion contacts and orientation of actin stress fibers, but close-packed colloidal arrays induce a rounded and nonadhesive cell morphology and yield a smaller number of attached cells. On loose-packed arrays, cells adjust their shapes to the pattern geometry when the stripe width is smaller than 50 microm and increase their extent of attachment when the concentration of surface RGD peptides is increased. This new biomaterials system allows the examination of cell behavior as a function of RGD surface distribution on the molecular to micrometer scale and reveals cellular response to different surface roughnesses.     

The effect of vicinyl olefinic halogens on cross-coupling reactions using Pd(0) catalysis

(trans) 1-Chloro-2-iodoethylene (3), (trans) 1-bromo-2-iodoethylene (4), (trans) 1,2-diiodoethylene (5) and (cis and trans) 1,2-dibromoethylene (11) were reacted under Suzuki, Sonogashira and Negishi cross-coupling conditions using Pd catalysis to obtain mono coupled products. Only olefin template 3 provided the desired coupling products reliably under all reaction conditions. Compound 5 did not provide cross coupled products under any of the reaction conditions used. The Negishi reaction was the only one that worked for templates 4 and 11. Studies indicate that oxidative addition of the most reactive carbon-halogen bond to Pd(0) is followed by elimination of the second halide, when the second halide is a bromide or an iodide. This happens to a much lesser degree when the second halogen is a chloride.     

Novel carbohydrate-appended metal complexes for potential use in molecular imaging

Seven discrete sugar-pendant diamines were complexed to the {M(CO)(3)}(+) ((99m)Tc/Re) core: 1,3-diamino-2-propyl beta-D-glucopyranoside (L(1)), 1,3-diamino-2-propyl beta-D-xylopyranoside (L(2)), 1,3-diamino-2-propyl alpha-D-mannopyranoside (L(3)), 1,3-diamino-2-propyl alpha-D-galactopyranoside (L(4)), 1,3-diamino-2-propyl beta-D-galactopyranoside (L(5)), 1,3-diamino-2-propyl beta-(alpha-D-glucopyranosyl-(1,4)-D-glucopyranoside) (L(6)), and bis(aminomethyl)bis[(beta-D-glucopyranosyloxy)methyl]methane (L(7)). The Re complexes [Re(L(1)-L(7))(Br)(CO)(3)] were characterized by (1)H and (13)C 1D/2D NMR spectroscopy which confirmed the pendant nature of the carbohydrate moieties in solution. Additional characterization was provided by IR spectroscopy, elemental analysis, and mass spectrometry. Two analogues, [Re(L(2))(CO)(3)Br] and [Re(L(3))(CO)(3)Br], were characterized in the solid state by X-ray crystallography and represent the first reported structures of Re organometallic carbohydrate compounds. Conductivity measurements in H(2)O established that the complexes exist as [Re(L(1)-L(7))(H(2)O)(CO)(3)]Br in aqueous conditions. Radiolabelling of L(1)-L(7) with [(99m)Tc(H(2)O)(3)(CO)(3)](+) afforded in high yield compounds of identical character to the Re analogues. The radiolabelled compounds were determined to exhibit high in vitro stability towards ligand exchange in the presence of an excess of either cysteine or histidine over a 24 h period.