The reactions of some 1,1,1-tribromo-alkyl systems with thiolate anions

Compounds containing a 1,1,1-tribromoethyl group are normally dehydrobrominated by reaction with sodium thiolates. If a 1,1,1-tribromobut-3-ene fragment is present cyclisation to a 2,2-dibromocyclopropylmethyl thioether or rearrangement are also observed.     

Stereochemistry of acid cleavage of the compounds (cis -and trans-4-methylcyclohexyl)Fe(CO)2(η5-C5H5)

Cleavage of the title compounds with DCl and CF₃CO₂D in CH₂Cl₂ proceeds with retention of configuration at the α-carbon atom. The mechanism probably involved protonation of the iron, followed by reductive elimination of alkane.     

Easily prepared chiral scorpionates: tris(2-oxazolinyl)boratoiridium(i) compounds and their interactions with MeOTf

Optically active C 3-symmetric monoanionic ligands are uncommon in organometallic chemistry. Here we describe the synthesis of readily prepared tris(4 S-isopropyl-2-oxazolinyl)phenylborate [To (P)] and fluxional, zwitterionic four- and five-coordinate iridium(I) compounds [Ir(To (P))(eta (4)-C 8H 12)] ( 4) and [Ir(To (P))(CO) 2] ( 5). The highly fluxional nature of 4 and 5 makes structural assignment difficult, and the interaction between the iridium(I) center and the [To (P)] ligand is established by solid-state and solution (15)N NMR methods that permit the direct comparison between solution and solid-state structures. Although iridium cyclooctadiene 4 is a mixture of four- and five-coordinate species, the dicarbonyl 5 is only the five-coordinate isomer. The addition of electrophiles MeOTf and MeI provides the oxazoline N-methylated product rather than the iridium methyl oxidative addition product. N-Methylation was unequivocally proven by through-bond coupling observed in (1)H- (15)N HMBC experiments.     

Synthesis, characterization and Stat3 inhibitory properties of the prototypical platinum(IV) anticancer drug, [PtCl3(NO2)(NH3)2] (CPA-7)

This paper describes a reinvestigation of the literature concerning the synthesis and structural characterization of the platinum(IV)-based anticancer drug known as CPA-7 and believed to be the compound fac-[PtCl3(NO2)(NH 3)2]. CPA-7 has previously been extensively investigated for its ability to control tumor cell growth by inhibition of Stat3 signaling, but very little information is available concerning its synthesis or spectroscopic properties. A reproducible synthetic route is shown to produce an active material which is characterized by IR and (1)H, (14)N, (15)N, and (195)Pt NMR spectroscopy, and single crystal X-ray crystallography. The freshly prepared drug is obtained as a single isomer which may in fact be fac- or mer-[PtCl3(NO2)(NH3)2], but recrystallization resulted in a disordered crystal containing approximately equal amounts of the two geometric isomers.     

Synthetic, crystallographic, computational, and biological studies of 1,4-difluorobenzo[c]phenanthrene and its metabolites

1,4-Difluorobenzo[c]phenanthrene (1,4-DFBcPh) and its putative metabolites, the dihydrodiol and diol epoxides, have been synthesized and structurally characterized, and the extent of DNA binding by the metabolites has been assessed. 1,4-DFBcPh and 1,4-difluoro-10-methoxybenzo[c]phenanthrene were prepared by photochemical cyclization of appropriate naphthylphenylethylenes. The dihydrodiol was synthesized from 1,4-difluoro-10-methoxybenzo[c]phenanthrene, and the diol epoxides were diastereoselectively synthesized from the dihydrodiol. Interesting differences were noted in 1H NMR spectra of the series 1 (syn) diol epoxides of benzo[c]phenanthrene (BcPh) and 1,4-DFBcPh; the BcPh diol epoxide displays a quasi-diequatorial orientation of the hydroxyl groups, but in the 1,4-DFBcPh case these are diaxially disposed. This difference probably stems from the presence of the fjord-region fluorine atom in 1,4-DFBcPh. A through-space, fjord-region H-F coupling has also been observed for 1,4-DFBcPh and its derivatives. Comparative X-ray crystallographic analyses of BcPh and 1,4-DFBcPh and their dihydrodiols show that introduction of fluorine increases the molecular distortion by about 6-7 degrees . As a guide to estimating the molecular distortion and its effects, and for comparison with the X-ray structures in known cases, optimized structures of BcPh, 1,4-DFBcPh, and 1,4-DMBcPh (the dimethyl analogue) as well as their dihydrodiols and diol epoxides were computed. Relative aromaticities of these compounds were assessed by nucleus-independent chemical shift calculations, and 13C NMR chemical shifts were computed by gauge-inducing atomic orbital calculations. 1,4-DFBcPh and its dihydrodiol were subjected to metabolism, and the amount of DNA binding in human breast cancer MCF-7 cells was assessed. The extent of DNA binding was then compared with that for BcPh and its dihydrodiol and the potent carcinogen benzo[a]pyrene. The 1,4-DFBcPh series 2 (anti) diol epoxide-derived DNA adducts were also compared with those arising from intracellular oxidation of the dihydrodiol with subsequent DNA binding. These experiments showed that increased molecular distortion decreased metabolic activation to the terminal metabolites but that diol epoxide metabolites that are formed are the DNA-damaging species.     

Transient shear flow behavior of concentrated long glass fiber suspensions in a sliding plate rheometer

In order to eventually predict the behavior of long fiber suspensions in complex flows commonly found in processing operations, it is necessary to understand their rheology and its connection to the evolution of fiber orientation and configuration in well defined flows. In this paper we report the transient behavior at the startup of shear flow of a polymer melt containing long glass fibers with a length (L) >1 mm, using a sliding plate rheometer (SPR). The operation of the SPR was confirmed by comparing the transient shear viscosity (η⁺) for a polymer melt and a melt containing short glass fibers (L < 1 mm) with measurements obtained from a cone-and-plate device, using a modified sample geometry that was designed to avoid wall effects. For the long fiber systems, measurements could only be obtained in the SPR because these systems would not stay within the gap of the rotational rheometer. Transient stress growth behavior of the long fiber systems was obtained as a function of shear rate and fiber concentration for samples prepared with three different initial orientations. Results showed that, unlike short fiber systems (with a random planar initial orientation) that usually exhibit a single overshoot peak followed by a steady state, η⁺ of the long fiber suspensions often passed through multiple transient regions, depending on the fiber concentration and applied shear rate. Additionally, η⁺ of the long fiber suspensions was found to be highly dependent on the initial orientation of the sheared samples. Finally, the initial and final fiber orientations of the long glass fiber samples were measured and used to initiate an explanation of the viscosity behavior. The results obtained in this research will be useful for future assessment of a quantitative correlation between transient rheology and the evolution of fiber orientation.     

Cellular responses to patterned poly(acrylic acid) brushes

We use patterned poly(acrylic acid) (PAA) polymer brushes to explore the effects of surface chemistry and topography on cell-surface interactions. Most past studies of surface topography effects on cell adhesion have focused on patterned feature sizes that are larger than the dimensions of a cell, and PAA brushes have been characterized as cell repellent. Here we report cell adhesion studies for RBL mast cells incubated on PAA brush surfaces patterned with a variety of different feature sizes. We find that when patterned at subcellular dimensions on silicon surfaces, PAA brushes that are 30 or 15 nm thick facilitate cell adhesion. This appears to be mediated by fibronectin, which is secreted by the cells, adsorbing to the brushes and then engaging cell-surface integrins. The result is detectable accumulation of plasma membrane within the brushes, and this involves cytoskeletal remodeling at the cell-surface interface. By decreasing brush thickness, we find that PAA can be 'tuned' to promote cell adhesion with down-modulated membrane accumulation. We exemplify the utility of patterned PAA brush arrays for spatially controlling the activation of cells by modifying brushes with ligands that specifically engage IgE bound to high-affinity receptors on mast cells.