Functional Analysis of the Extended N-Terminal Region in PLC-δ1 (MlPLC-δ1) from the Mud Loach,Misgurnus mizolepis

Mud loach phospholipase C-δ1 (MlPLC-δ1) contains all the characteristic domains found in mammalian PLC-δ isozymes (pleckstrin homology domain, EF-hands, X–Y catalytic region, and C2 domain) as well as an extended 26-amino acid (aa)-long N-terminal region that is an alternative splice form of PLC-δ1 and is novel to vertebrate PLC-δ. In the present structure–function analysis, deletion of the extended N-terminal region caused complete loss of phosphatidylinositol (PI)- and phosphatidylinositol 4,5-bisphosphate (PIP₂)-hydrolyzing activity in MlPLC-δ1. Additionally, recombinant full-length MlPLC-δ1 PLC activity was reduced in a dose-dependent manner by coincubation with the 26-aa protein fragment. Using a protein–lipid overlay assay, both full-length MlPLC-δ1 and the 26-aa protein fragment had substantial affinity for PIP₂, whereas deletion of the 26-aa region from MlPLC-δ1 (MlPLC-δ1-deletion) resulted in lower affinity for PIP₂. These results suggest that the novel N-terminal exon of MlPLC-δ1 could play an important role in the regulation of PLC-δ1.     

PHYTOCHROME-MEDIATED RAPID CHANGES IN THE LEVEL OF PHOSPHOINOSITIDES IN ETIOLATED LEAVES OF Zea mays

The role of the active form of phytochrome in Zea mays on the polyphosphoinositide cycle was studied. As little as 15 s of red irradiation of etiolated leaves immediately increased the level of phosphatidylinositol bisphosphate (PIP₂) 3–6-fold compared to unirradiated leaves. The elevated level of PIP₂ decreased with longer red irradiations up to 5 min, but remained higher than in unirradiated leaves. The level of PIP₂ decreased if red irradiation was followed by far-red irradiation. Far-red alone had no effect. Levels of phosphatidylinositol phosphate (PIP) and phosphatidylinositol did not change significantly. Since red irradiation significantly changed PIP, but not PIP, photocontrol appears to be at the PIP kinase and phospholipase level. In related studies of the effect of light on phospholipids, 5 min of red irradiation induced significant decreases in phosphatidylcholine and phosphatidylethanola-mine.     

General Synthesis of Phosphatidylinositol Phosphates

Abstract

A general method for synthesis of 3-phosphorylated phosphatidylinositols is described.

Phosphatidylinositol (PI) and phosphatidylinositol phosphates (PIP_n), such as PI-4-P, PI-4,5-P₂ undergo receptor-mediated cleavage by phosphatidylinositol-specific phospholipase C, and are precursors of second messengers important in diverse cellular signaling pathways. In contrast, the 3-phosphorylated phosphatidylinositols, such as PI-3-P (1), PI-3,4-P₂ (2) and PI-3,4,5-P₃ (3), which are formed in response to signals of growth factors, are resistant to hydrolysis by this enzyme, and their cellular function is only beginning to emerge [1,2]. These compounds are formed in minute quantities, and therefore have to be synthesized for many practical applications.     

A Rapidly Reversible Chemical Dimerizer System to Study Lipid Signaling in Living Cells

Chemical dimerizers are powerful tools for non‐invasive manipulation of enzyme activities in intact cells. Here we introduce the first rapidly reversible small‐molecule‐based dimerization system and demonstrate a sufficiently fast switch‐off to determine kinetics of lipid metabolizing enzymes in living cells. We applied this new method to induce and stop phosphatidylinositol 3‐kinase (PI3K) activity, allowing us to quantitatively measure the turnover of phosphatidylinositol 3,4,5‐trisphosphate (PIP₃) and its downstream effectors by confocal fluorescence microscopy as well as standard biochemical methods.     

Microscopic Characterization of GRP1 PH Domain Interaction with Anionic Membranes

The pleckstrin homology (PH) domain of general receptor for phosphoionositides 1 (GRP1-PHD) binds specifically to phosphatidylinositol (3,4,5)-triphosphate (PIP₃), and acts as a second messenger. Using an extensive array of molecular dynamics (MD) simulations employing highly mobile membrane mimetic (HMMM) model as well as complementary full membrane simulations, we capture differentiable binding and dynamics of GRP1-PHD in the presence of membranes containing PC, PS, and PIP₃ lipids in varying compositions. While GRP1-PHD forms only transient interactions with pure PC membranes, incorporation of anionic lipids resulted in stable membrane-bound configurations. We report the first observation of two distinct PIP₃ binding modes on GRP1-PHD, involving PIP₃ interactions at a “canonical” and at an “alternate” site, suggesting the possibility of simultaneous binding of multiple anionic lipids. The full membrane simulations confirmed the stability of the membrane bound pose of GRP1-PHD as captured from our HMMM membrane binding simulations. By performing additional steered membrane unbinding simulations and calculating nonequilibrium work associated with the process, as well as metadynamics simulations, on the protein bound to full membranes, allowing for more quantitative examination of the binding strength of the GRP1-PHD to the membrane, we demonstrate that along with the bound PIP₃, surrounding anionic PS lipids increase the energetic cost of unbinding of GRP1-PHD from the canonical mode, causing them to dissociate more slowly than the alternate mode. Our results demonstrate that concurrent binding of multiple anionic lipids by GRP1-PHD contributes to its membrane affinity, which in turn control its signaling activity. © 2019 Wiley Periodicals, Inc.     

Synthesis of well‐defined miktoarm star polymers of poly(dimethylsiloxane) by the combination of chlorosilane and benzyl chloride linking chemistry

A series of novel four‐arm A₂B₂ and A₂BC and five‐arm A₂B₂C miktoarm star polymers, where A is poly(dimethylsiloxane) (PDMS), B is polystyrene (PS), and C is polyisoprene (PI), were successfully synthesized by the combination of chlorosilane and benzyl chloride linking chemistry. This new and general methodology is based on the linking reaction of in‐chain benzyl chloride functionalized poly(dimethylsiloxane) (icBnCl–PDMS) with the in‐chain diphenylalkyl (icD) living centers of PS‐DLi‐PS, PS‐DLi‐PI, or (PS)₂‐DLi‐PI. icBnCl–PDMS was synthesized by the selective reaction of lithium PDMS enolate (PDMSOLi) with the chlorosilane groups of dichloro[2‐(chloromethylphenyl)ethyl]methylsilane, leaving the benzyl chloride group intact. The icD living polymers, characterized by the low basicity of DLi to avoid side reactions with PDMS, were prepared by the reaction of the corresponding living chains with the appropriate chloro/bromo derivatives of diphenylethylene, followed by a reaction with BuLi or the living polymer. The combined molecular characterization results of size exclusion chromatography, ¹H NMR, and right‐angle laser light scattering revealed a high degree of structural and compositional homogeneity in all miktoarm stars prepared. The power of this general approach was demonstrated by the synthesis of a morphologically interesting complex miktoarm star polymer composed of two triblock terpolymer (PS‐b‐PI‐b‐PDMS) and two diblock copolymer (PS‐b‐PI) arms. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 6587–6599, 2006     

Effect of PIP2 on Bilayer Structure and Phase Behavior of DOPC: An X‐ray Scattering Study

Phosphatidylinositol 4,5‐bis‐phosphate (PIP₂) is an important lipid in regulation of several cellular processes, particularly membrane fusion. We use X‐ray diffraction from solid‐supported multilamellar 1,2‐dioleoyl‐sn‐glycero‐3‐phosphocholine (DOPC)/PIP₂ samples to study changes in bilayer structure and the lyotropic phase behavior induced by physiologically relevant concentrations of PIP₂. Electron‐density profiles reconstructed from X‐ray reflectivity measurements indicate that PIP₂ strongly affects structural parameters such as lipid head‐group width, bilayer thickness, and lamellar repeat spacing of DOPC bilayer stacks. In addition, at lower degrees of hydration, a few molar per cent of PIP₂ facilitates stalk‐phase formation and also leads to formation of a hexagonal phase, which is not observed in pure DOPC. These results indicate that the role of PIP₂ in membrane fusion could be, in part, due to its effect on the properties of the lipid bilayer matrix. Furthermore, coexistence of two lamellar phases with different lattice constants is observed in single‐component PIP₂ samples.     

C(1)-Phenethyl Derivatives of [closo-1-CB11H12]− and [closo-1-CB9H10]− Anions: Difunctional Building Blocks for Molecular Materials

C(1)-vinylation of [closo-1-CB₉H₁₀]⁻ ( A ) and [closo-1-CB₁₁H₁₂]⁻ ( B ) with 4-benzyloxystyryl iodide followed by hydrogenation of the double bond and reductive deprotection of the phenol functionality led to C(1)-(4-hydroxyphenethyl) derivatives. The phenol functionality was protected as the acetate. The esters were then treated with PhI(OAc)₂ and the resulting isomers were separated kinetically (for derivatives of anion A ) or by chromatography (for derivatives of anion B ) giving the difunctionalized building blocks in overall yields of 9 % and 50 %, respectively. A similar series of reactions was performed starting with anions A and B and 4-methoxystyryl bromide and iodide. Significant differences in the reactivity of derivatives of the two carborane anions were rationalized with DFT computational results. Application of the difunctionalized carboranes as building blocks was demonstrated through preparation of two ionic liquid crystals. The extensive synthetic work is accompanied by single crystal XRD analysis of six derivatives.     

Design,synthesis, and gas permeation properties of polyimides containing pendent imidazolium groups

Film‐forming polymers containing ionic groups have attracted considerable attention as emerging materials for gas separation applications. The aim of this article was to synthesize new film‐forming polyimides containing imidazolium groups (PI‐IMs) and establish their structure–performance relationship. In this context, a new aromatic diamine, namely, N¹‐(4‐aminophenyl)‐N¹‐(4‐(2‐phenyl‐1H‐imidazol‐1‐yl)phenyl)benzene‐1,4‐diamine (ImTPADA), was synthesized and polycondensed with three aromatic dianhydrides, namely, 4,4′‐(hexafluoroisopropylidene)diphthalic anhydride, 4,4‐(4,4‐isopropylidenediphenoxy) bis(phthalic anhydride), and 4,4′‐oxydiphthalic anhydride to form the corresponding polyimides containing pendent 2‐phenylimidazole groups (PI‐IEs). Next, PI‐IMs were prepared by N‐quaternization of pendent 2‐phenylimidazole groups present in PI‐6FDA using methyl iodide followed by anion exchange with bis(trifluoromethane)sulfonimide lithium salt (LiTf₂N). PI‐IEs and PI‐IMs exhibited reasonably high molecular weights, amorphous nature, good solubility, and could be cast into self‐standing films from their DMAc solutions. Thermogravimetric analysis showed that 10% weight loss temperature of PI‐IEs and PI‐IMs were in the range 545–475 °C and 303–306 °C, respectively. Gas permeability analysis of films of PI‐IEs and PI‐IMs was investigated by variable‐volume method and it was observed that incorporation of ionic groups into PI‐6FDA resulted in increased permeability while maintaining selectivity. In particular, polymer bearing Tf₂N⁻ anion exhibited high CO₂ permeability (33.3 Barr) and high selectivity for CO₂/CH₄ (41.1) and CO₂/N₂ (35.4). © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018 , 56, 1721–1729     

N-phenyl-6-chloro-4-hydroxy-2-quinolone-3-carboxamides: Molecular Docking,Synthesis, and Biological Investigation as Anticancer Agents

Cancer is a multifactorial disease and the second leading cause of death worldwide. Diverse factors induce carcinogenesis, such as diet, smoking, radiation, and genetic defects. The phosphatidylinositol 3-kinase (PI3Kα) has emerged as an attractive target for anticancer drug design. Eighteen derivatives of N-phenyl-6-chloro-4-hydroxy-2-quinolone-3-carboxamide were synthesized and characterized using FT-IR, NMR (¹H and ¹³C), and high-resolution mass spectra (HRMS). The series exhibited distinct antiproliferative activity (IC₅₀ µM) against human epithelial colorectal adenocarcinoma (Caco-2) and colon carcinoma (HCT-116) cell lines, respectively: compounds 16 (37.4, 8.9 µM), 18 (50.9, 3.3 µM), 19 (17.0, 5.3 µM), and 21 (18.9, 4.9 µM). The induced-fit docking (IFD) studies against PI3Kαs showed that the derivatives occupy the PI3Kα binding site and engage with key binding residues.     

Investigation of thiol‐ene addition reaction on poly(isoprene) under UV irradiation: Synthesis of graft copolymers with “V”‐shaped side chains

Poly(isoprene) (PI) with pendant functional groups was successfully synthesized by thiol‐ene addition reaction under 365 nm UV irradiation, and the functionalized PI was further modified and used to prepare graft copolymers with “V”‐shaped side chains. First, the pendant ? SCH₂CH(OH)CH₂OH groups were introduced to PI by thiol‐ene addition reaction between 1‐thioglycerol and double bonds, and the results showed that the addition reaction carried out only on double bonds of 1,2‐addition isoprene units. After the esterification of hydroxyl groups by 2‐bromoisobutyryl bromide, the forming macroinitiator was used to initiate the atom transfer radical polymerization (ATRP) of styrene (St) and tert‐butyl acrylate (tBA), and the graft copolymers PI‐g‐PS ₂ and PI‐g‐PtBA ₂ or PI‐g‐PAA ₂ (by hydrolysis of PI‐g‐PtBA ₂) were obtained, respectively. It was confirmed that the graft density of side chains on PI main chains could be easily controlled by variation of the contents of modified 1,2‐addition isoprene units on PI. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 3797–3806, 2010     

Synthesis of 4μ‐PS2PEO2, 4μ‐PS2PCL2, 4μ‐PI2PEO2, and 4μ‐PI2PCL2 star‐shaped copolymers by the combination of glaser coupling with living anionic polymerization and ring‐opening polymerization

4μ‐A₂B₂ star‐shaped copolymers contained polystyrene (PS), poly(isoprene) (PI), poly(ethylene oxide) (PEO) or poly(ε‐caprolactone) (PCL) arms were synthesized by a combination of Glaser coupling with living anionic polymerization (LAP) and ring‐opening polymerization (ROP). Firstly, the functionalized PS or PI with an alkyne group and a protected hydroxyl group at the same end were synthesized by LAP and then modified by propargyl bromide. Subsequently, the macro‐initiator PS or PI with two active hydroxyl groups at the junction point were synthesized by Glaser coupling in the presence of pyridine/CuBr/N,N,N ′,N ″,N ″‐penta‐methyl diethylenetri‐amine (PMDETA) system and followed by hydrolysis of protected hydroxyl groups. Finally, the ROP of EO and ε‐CL monomers was carried out using diphenylmethyl potassium (DPMK) and tin(II)‐bis(2‐ethylhexanoate) (Sn(Oct)₂) as catalyst for target star‐shaped copolymers, respectively. These copolymers and their intermediates were well characterized by SEC, ¹H NMR, MALDI‐TOF mass spectra and FT‐IR in details. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010     

Kinetic analysis of PI3K reactions with fluorescent PIP<Subscript>2</Subscript> derivatives

Phosphatidylinositol 3-kinase (PI3K) signaling plays important roles in cell differentiation, proliferation, and migration. Increased mutations and expression levels of PI3K are hallmarks for the development of certain cancers. Pharmacological targeting of PI3K activity has also been actively pursued as a novel cancer therapeutic. Consequently, measurement of PI3K activity in different cell types or patient samples holds the promise as being a novel diagnostic tool. However, the direct measurement of cellular PI3K activity has been a challenging task. We report here the characterization of two fluorescent PIP₂ derivatives as reporters for PI3K enzymatic activity. The reporters are efficiently separated from their corresponding PI3K enzymatic products through either thin layer chromatography (TLC) or capillary electrophoresis (CE), and can be detected with high sensitivity by fluorescence. The biophysical and kinetic properties of the two probes are measured, and their suitability to characterize PI3K inhibitors is explored. Both probes show similar capacity as PI3K substrates for inhibitor characterization, yet also possess distinct properties that may suggest their different applications. These characterizations have laid the groundwork to systematically measure cellular PI3K activity, and have the potential to generate molecular fingerprints for diagnostic and therapeutic applications.     

Facile Synthesis of 7‐epi‐Taxane and Its Derivatives and Preliminary Evaluation of Anticancer Activity

7‐epi‐Taxane has been achieved efficiently in gram scale from natural taxane via inversion of the 7‐hydroxyl group simply using Ag₂O as catalyst and DMF as solvent. The catalyst could be quantitatively recovered by filtration without loss of catalytic activity. This condition is also applicable to the direct epimerization of taxane derivatives (e.g., docetaxel and paclitaxel) to 7‐epi‐taxane derivatives (e.g., 7‐epi‐docetaxel and 7‐epi‐paclitaxel). Furthermore, 33 ester derivatives of 7‐epi‐taxane with different amino acid moieties at the position of C‐13 were successfully synthesized via esterification without protecting C‐7‐OH. Bioassay results revealed that compounds 13 and 18 have good selectivity against prostatic cancer cell line DU145, with IC₅₀ value as low as 15.9 nmol/L for 18 .     

The synthesis of diene – alkyl methacrylate diblock and heteroarm star copolymers

The synthesis of A₂B₂ heteroarm stars, where A is either polyisoprene (PI) or polybutadiene (PB) and B is either poly(methyl methacrylate) (PMMA) or poly(butyl methacrylate) (PBMA) has been achieved using living anionic polymerization. Following polymerization of the diene in hexane by sec‐BuLi, the solvent was changed to THF and the living chains were linked in pairs – without loss of anionic reactivity – using 1,2‐bis[4‐(1‐phenylethenyl)]ethane (EPEB). Star synthesis was completed by the addition of MMA or BMA monomer at −78°C. The diblocks were prepared by sequential polymerization. The resulting stereochemistries were those of greatest interest from a practical standpoint, i.e., PI or PB with a high 1,4‐content (which is highly elastic) and syndiotactic PMMA (which has a high T_g).     

Cyclometalation of Arylazo Compounds. Part 1 synthesis and cyclopalladation of some substituted 1-arylazonaphthalenes. 1st Communication on compounds with a metal-arene σ-bond

The syntheses of 1-phenylazonaphthalene ( 1a ) and its [3′-methyl- ( 1b ), 4′-methoxy- ( 1c ), 3′-methoxy- ( 1d )] derivatives are described. Cyclopalladation of these azo ligands with Pd(II) acetate or Na₂PdCl₄ leads to complexes with Pd(II) coordinated on the azo N_β-atom and a Pd? C σ-bond at C(2) in the naphthalene moiety. The preference of Pd(II) for this type of metalation at C(2) over the palladation at the ortho positions of the phenyl ring or at the peri position of the naphthyl ring is believed to be largely due to steric effects and the different reactivities of the two arene moieties. Substitution of the acetato-bridge with bromide or iodide allows the syntheses of the corresponding bromo- and iodo-bridged complexes, and a chloro-bridged dimer complex can be converted to a monomeric ethylenediamino-Pd(II)-azo species with ethylenediamine. Cyclopalladation of sulfonated azo ligands leads to water-soluble Pd(II) complexes with a Pd-C σ-bond at C(2).     

Importance of weak interactions and conformational equilibrium in N-butyl-N-methylpiperidinium bis(trifluromethanesulfonyl) imide room temperature ionic liquids: Vibrational and theoretical studies

Piperidinium cation-based room temperature ionic liquids (RTILs) constitute an important class of ILs because of their unique electrochemical properties as well as non-aromatic nature of the cation. However, detailed structural studies are yet to be done. In this paper, we discuss the molecular structure and vibrational spectra of N-butyl-N-methylpiperidinium bis(trifluromethanesulfonyl) imide, (PIP₁₄NTf₂; where, PIP₁₄ is N-butyl-N-methylpiperidinium and NTf₂ is bis(trifluromethanesulfonyl) imide), obtained with a combined approach of infrared (IR) and Raman spectroscopies in the liquid state and density functional theory (DFT) and Hartree–Fock (H–F) based theoretical calculations. DFT calculations, which are found to produce the most stable geometry compared to other two methods (MP2 and H–F), reproduce the experimental IR and Raman spectra reasonably well. Our findings reveal structural properties that profoundly influence intermolecular interactions and melting point. There exists a large variation in the melting point of the ILs studied. While the bromide salt of the piperidinium derivative (PIP₁₄Br) is solid with very high melting point (241 °C), the corresponding NTf₂ salt is low viscous liquid at room temperature (mp: −25 °C). bmimBr (bmim = 1-butyl-1-methylimidazolium) exhibits a substantially lower melting point of 79 °C than PIP₁₄Br, suggesting that more number of strong classical hydrogen bonding interactions in the latter is primarily responsible for the much higher melting point. In addition, involvement of the alkyl group in PIP₁₄ in H-bonding interaction provides additional rigidity in n-butyl chain which is otherwise absent in bmimBr. Interaction energy for PIP₁₄Br is found to be higher than PIP₁₄NTf₂, showing a positive correlation between interaction energy and melting point. A blue shift in CH stretching wavenumber as evident from IR and Raman spectra of PIP₁₄Br IL is a clear indication of the stronger hydrogen bonding as compared to PIP₁₄NTf₂ IL. Furthermore, we experimentally observe the existence of cisoid–transoid conformational equilibrium of NTf₂⁻ anion in the Raman spectrum of PIP₁₄NTf₂ for the first time and determined that transoid NTf₂⁻ anion to be more stable than the corresponding cisoid conformer by 1.04 kcal/mol using DFT. Examination of various conformational possibilities of the cation shows that the butyl group preferentially exists in gauche conformation.     

1,3-Oxathiole and Thiirane Derivatives from the Reactions of Azibenzil and α-diazo amides with thiocarbonyl compounds

The reactions of α-diazo ketones 1a,b with 9H-fluorene-9-thione ( 2f ) in THF at room temperature yielded the symmetrical 1,3-dithiolanes 7a,b , whereas 1b and 2,2,4,4-tetramethylcyclobutane-1,3-dithione ( 2d ) in THF at 60° led to a mixture of two stereoisomeric 1,3-oxathiole derivatives cis- and trans- 9a (Scheme 2). With 2-diazo-1,2-diphenylethanone ( 1c ), thio ketones 2a–d as well as 1,3-thiazole-5(4H)-thione 2g reacted to give 1,3-oxathiole derivatives exclusively (Schemes 3 and 4). As the reactions with 1c were more sluggish than those with 1a,b , they were catalyzed either by the addition of LiClO₄ or by Rh₂(OAc)₄. In the case of 2d in THF/LiClO₄ at room temperature, a mixture of the monoadduct 4d and the stereoisomeric bis-adducts cis- and trans- 9b was formed. Monoadduct 4d could be transformed to cis- and trans- 9b by treatment with 1c in the presence of Rh₂(OAc)₄ (Scheme 4). Xanthione ( 2e ) and 1c in THF at room temperature reacted only when catalyzed with Rh₂(OAc)₄, and, in contrast to the previous reactions, the benzoyl-substituted thiirane derivative 5a was the sole product (Scheme 4). Both types of reaction were observed with α-diazo amides 1d,e (Schemes 5–7). It is worth mentioning that formation of 1,3-oxathiole or thiirane is not only dependent on the type of the carbonyl compound 2 but also on the α-diazo amide. In the case of 1d and thioxocyclobutanone 2c in THF at room temperature, the primary cycloadduct 12 was the main product. Heating the mixture to 60°, 1,3-oxathiole 10d as well as the spirocyclic thiirane-carboxamide 11b were formed. Thiirane-carboxamides 11d–g were desulfurized with (Me₂N)₃P in THF at 60°, yielding the corresponding acrylamide derivatives (Scheme 7). All reactions are rationalized by a mechanism via initial formation of acyl-substituted thiocarbonyl ylides which undergo either a 1,5-dipolar electrocyclization to give 1,3-oxathiole derivatives or a 1,3-dipolar electrocyclization to yield thiiranes. Only in the case of the most reactive 9H-fluorene-9-thione ( 2f ) is the thiocarbonyl ylide trapped by a second molecule of 2f to give 1,3-dithiolane derivatives by a 1,3-dipolar cycloaddition.     

Self-crosslinkable polymers. IV. Copolymerization of 1-ethenyl-4-(2,3-epoxy-1-propoxy)benzene with vinylpyridines

Soluble and self-crosslinkable linear copolymers with pendant epoxy and pyridyl groups were obtained from 1-ethenyl-4-(2,3-epoxy-1-propoxy)benzene (M₁) and vinylpyridines (M₂) by the action of α,α′-azobisisobutyronitrile. The monomer reactivity ratios were determined in tetrahydrofuran at 60°C (r₁, r₂, and vinylpyridine given): 0.467, 0.638, 4-vinylpyridine; 0.556, 1.25, 2-vinylpyridine; 0.639, 1.38, 5-ethyl-2-vinylpyridine. The Q and e values for 1-ethenyl-4-(2,3-epoxy-1-propoxy)-benzene were calculated as 1.3–1.6 and ?1.1–?1.3, respectively, with the reported Q–e values for these vinylpyridines. The intrinsic viscosities of the copolymers were found to be 0.15–0.30 in tetrahydrofuran at 30°C and to be dependent on the copolymer composition. The copolymers with these vinylpyridines were amorphous, had no clear melting points, and became insoluble crosslinked polymers under heating without further addition of any curing agents.     

Ringerweiterung unter Lactonisierung von methylierten 1-(3′-Hydroxypropyl)-2-oxocyclododecan-1-carbonitrilen

Ring Enlargement by Lactonization of Methylated 1-(3′-Hydroxypropy1)-2-oxocyclododecane-1-carbonitriles The title compounds were prepared by Michael reaction of 2-oxocyclododecane-1-carbonitrile ( 1 ) and acrylaldehyde and its derivatives followed by NaBH₄ reduction or methylation of the aldehyde group with [(CH₃)₂Ti(i-PrO)₂] (Scheme 1). In all cases, the ring enlargement was performed with Bu₄NF/THF to give different methylated derivatives of 12-cyano-15-pentadecanolide ( 13 ) in 95–99% yield. The Yields of the rearrangement products are not dependent on the positions and numbers of the CH₃ groups in the side chain of 3 . The lactonization reaction is of unremarkable stereoselectivity.