The preparation and catalytic hydroformylation activity of some halocarbonylrhodium(I) complexes containing phosphinoalkylorganosilicon ligands

The synthesis and properties of a series of trans-halocarbonylrhodium(I) complexes containing the phosphinoalkylorganosilicon ligands Me₃SiCH₂PPh₂, Me₃Si(CH₂)₃PPh₂, and PPh₂CH₂(Me)$\text{Si(OSiMe}{}_2\text{)}{}_3\text{O}$ have been investigated. The complexes could be prepared by an exchange reaction involving RhCl(CO)(PPh₃)₂ and the organosilicon ligands or in better yields by the reaction of Rh₂Cl₂(CO)₄ with the ligands. Iodorhodium derivatives were obtained as the exclusive products in the latter reaction if a small amount of LiI was present. The catalytic activity of RhCl(CO)(PPh₂CH₂SiMe₃)₂ was similar to that of RhCl(CO)(PPh₃)₂ in the hydroformylation of hex-1-ene at 100°C and 1000 psi pressure of H₂/CO. The catalytic properties of the iodo derivatives RhI(CO)L₂ [L = Me₃SiCH₂PPh₂, Me₃Si(CH₂)₃PPh₂, and PPh₂CH₂(Me)$\text{Si(OSiMe}{}_2\text{)}{}_3\text{O}$] varied considerably, with RhI(CO)(PPh₂CH₂SiMe₃)₂ producing an unexpectedly low linear/branched aldehyde product ratio.     

Synthesis of (1R,2S)-1-amino-2-vinylcyclopropanecarboxylic acid vinyl-ACCA) derivatives: key intermediates for the preparation of inhibitors of the hepatitis C virus NS3 protease

(1R,2S)-1-Amino-2-vinylcyclopropanecarboxylic acid (vinyl-ACCA) is a key building block in the synthesis of potent inhibitors of the hepatitis C virus NS3 protease such as BILN 2061, which was recently shown to dramatically reduce viral load after administration to patients infected with HCV genotype 1. We have developed a scalable process that delivers derivatives of this unusual amino acid in >99% ee. The strategy was based on the dialkylation of a glycine Schiff base using trans-1,4-dibromo-2-butene as an electrophile to produce racemic vinyl-ACCA, which was subsequently resolved using a readily available, inexpensive esterase enzyme (Alcalase 2.4L). Factors that affect diastereoselection in the initial dialkylation steps were examined and the conditions optimized to deliver the desired diastereomer selectively. Product inhibition, which was encountered during the enzymatic resolution step, initially resulted in prolonged cycle times. Enrichment of racemic vinyl-ACCA through a chemical resolution via diastereomeric salt formation or the use of forcing conditions in the enzymatic reaction both led to improvements in throughput and the development of a viable process. The chemistry described herein was scaled up to produce multikilogram quantities of this building block.     

Radical copolymerization of vinylidene fluoride with perfluoroalkylvinyl ethers

The radical copolymerization of perfluoromethylvinyl ether (PMVE) and perfluoropropylvinyl ether (PPVE) with vinylidene fluoride (VDF), initiated by tertiobutyl peroxypivalate (TBPPI) and ditertiobutyl peroxide (DTBP), respectively, are presented. The kinetics of copolymerization were investigated for each monomer from series of at least eight reactions for which the initial [VDF]₀/[fluorinated vinyl ether]₀ molar ratios ranged between 20/80 and 80/20. The copolymer compositions of these random-type copolymers were calculated by means of ¹⁹F NMR spectroscopy and allowed one to quantify the respective amounts of each monomeric unit in the copolymer. According to the Tidwell and Mortimer method, the reactivity ratios (r_i) of both comonomers for each type of copolymerization were obtained : r_VDF = 3.40 ± 0.40 and r_PMVE = 0 at 74 °C; and r_VDF = 1.15 ± 0.36 and r_PPVE = 0 at 120 °C. Moreover, the glass transition temperatures (T_g’s) of poly(VDF-co-PMVE) and poly(VDF-co-PPVE) copolymers containing different amounts of VDF and PMVE or PPVE, were determined and the theoretical glass transition temperatures of poly(PMVE) and poly(PPVE) homopolymer were deduced.     

Delaying Anticancer Drug Delivery by Self-Assembly and Branching Effects of Minimalist Dendron–Drug Conjugates

Self-assembly of a covalently-bound lipophilic drug to a dendronic scaffold for making organic nanoparticles is reported as a proof of concept in nanovectorization. A minimalist structural approach with a small PEG-dendron conjugated to paclitaxel (PTX), incorporating safe succinic and gallic acids, is efficient to provide the expected anticancer bioactivity, but also significantly retards and targets intracellular delivery of PTX in 2D and 3D lung cancer cell cultures. A branching effect of dendrons is crucial, when compared to linear PTX conjugates. Transmission electron microscopy (TEM) and dynamic light-scattering (DLS) studies indicate the formation of stable, low-disperse nanoparticles at 10⁻⁵ m in H₂0, which could also be responsible for the biological effects. An ultrasensitive LC-MS/MS method was used for the determination of intracellular PTX concentration over time, along with the survival rates of cancer cells. Similarly, cell survival assays were successfully correlated to a 3D cell culture with spheroids for mimicking tumors, when treated with PTX conjugates. Our work opens the way to a full evaluation program required for new chemical entities.     

High-precision index measurement in anisotropic crystals using white-light spectral interferometry

White-light spectral interferometry appears an excellent tool for precise determination of indices, and has already been successfully applied to different isotropic or weakly dispersive materials such as glass or rhodamine films. In this paper, we extend the spectral method to the measurement of anisotropic media with strong dispersion. The method is discussed below and allows an accuracy of the order of 10^-5 on the principal indices of a birefringent silver thiogallate (AgGaS₂) crystal.     

Microwave spectrum of ethyl iodide: Nuclear quadrupole interaction and centrifugal distortion analysis

The microwave spectrum of ethyl iodide has been reinvestigated between 4 and 80 GHz. A total of 181 ground-state transitions with J ≤ 26 and $\text{F ≤}\text{57}\text{2}$ have been analyzed using numerical diagonalization of the quadrupole Hamiltonian. The following rotational and quadrupole coupling constants have been determined (in MHz): A′ = 29 116.321; B′ = 2979.5639; C′ = 2796.4520; χ_aa = ?1478.111; χ_bb = 564.464; χ_cc = 913.648, and χ_ab = 896.38. The quadrupole coupling constants have been transformed to their principal axis system. All the quartic centrifugal distortion constants have been significantly determined, the standard deviation of the fit being only σ = 31 kHz.