Miscibility of an acylated hepatitis A synthetic antigen derivative [palmitoyl VP3(110-121)] with lipids: a monolayer study

Mixed monolayers of an acylated derivative of hepatitis A synthetic peptide VP3(110-121) with neutral, cationic or anionic lipids were spread at the air/water interface. Deviations from ideality as well as thermodynamic values were calculated at different surface pressures using the free-excess energy, the interaction parameter and the enthalpy. The miscibility at the collapse point was also checked. Maximum deviations from ideality were found for mixtures containing the anionic lipid phosphatidylglycerol (PG), and it seems that the monolayer composition is not stable through compression, as the peptide is ejected from the film. Films containing neutral [dipalmitoylphosphatidylcholine (DPPC)] or cationic [stearylamine (SA)] lipids showed more regular behaviour. As the peptide has a net negative charge it is probable that electrostatic interactions are in part responsible of the good miscibility of palmitoyl VP3(110-121) with SA. In order to prepare liposomes containing palmitoyl VP3(110–121), lipids such as SA or DPPC/SA will be a more suitable choice than anionic lipids such as PG. Received: 26 May 2000 Accepted: 22 September 2000     

Interaction of the Hepatitis A peptide VP3(110–121) with lipid mono and bilayer models of cellular membranes

 The surface activity of HAV-VP3(110–121) peptide was studied at different concentrations in an aqueous solution. Saturation was reached at 0.62 μM concentration. The ability of the peptide to insert into monolayers of CL, SA, DPPC, DPPC/5% CL and DPPC/5% SA was also performed. Mixed mono-layers composed of this peptide and the lipid mixtures were also studied as far as the miscibility of the two components is concerned. The mixed monolayers showing small negative deviations from ideality. The values of excess free energy of mixing (ΔG ^E _M) suggest that the energy associated to the miscibility process is almost non-significant except for a 0.2 molar fraction of DPPC/SA and 0.6 molar fraction of DPPC/CL. The peptide has an expanding effect upon the monolayers but due to its amphoteric character this interaction is not dependent on the electrical charge of the lipids. In fluorescence studies, the peptide showed some degree of interaction with the lipid polar heads, but no interactions were detected with its alkylchains. This results show that after incubation with DPPC/5% CL and DPPC/5% SA liposomes the peptide remains in the outer part of the bilayers. Received: 20 January 1997 Accepted: 28 May 1997     

Physico-chemical characterization of liposomes with covalently attached hepatitis A VP3(101-121) synthetic peptide.

The covalent conjugation of a 20-mer peptide belonging to the VP3 capsid protein of hepatitis A virus to the surface of preformed liposomes was investigated. Three different bonds (disulfide, thioether and amide) were established between the peptide sequence and liposomes bearing at their surface appropriate reactive groups. The effect of the relative concentration of the N-[4-(p-maleimidophenyl)butyryl]dipalmitoylphosphatidylethanolamine anchor in liposomes on stability during coupling of the peptide sequence was studied. The interaction of the three liposomal preparations with phospholipids in a biomembrane model system, monolayers at the air-water interface, is also reported. The results showed that although the peptides associate with liposomes in similar yields for the three strategies studied, differences can be observed when their interaction with phospholipid monolayers composed of dipalmitoylphosphatidylcholine is analysed.     

Spirodialkylation of 3-(Phenylthio)-3-Sulfolene and Subsequent Synthetic Transformations

3-(Phenylthio)-3-sulfolene (1) underwent spirodialkylation to give products 2 which were desulfonylated to afford the dienes 3. The Diels-Alder reaction of 3 was achieved for some reactive dienophiles to yield spiro compounds. Compounds 2 were also converted to sulfonyldienes 9 which reacted as Michael acceptors.     

Comparative investigation of the copper(II) complexes of (R)-, (S)- and (R,S)-1-phenyl-N,N-bis(pyridine-3-ylmethyl)ethanamine along with the related complex of (R,S)-1-cyclohexyl-N,N-bis(pyridine-3-ylmethyl)ethanamine. Synthetic, magnetic, and structural studies

The interaction of the enantiopure (R)- and (S)-1-phenyl-N,N-bis(pyridine-3- ylmethyl)ethanamine ligands, R-L ¹ and S-L ¹ , with copper(II) chloride followed by addition of hexafluorophosphate resulted in the isolation of the corresponding enantiomeric complexes [Cu(R-L ¹ )Cl](PF₆) (1), [Cu(S-L ¹ )Cl](PF₆) (2) and [Cu(S-L ¹ )Cl](PF₆)??0.5Et₂O (3), in which dimerization occurs through two long Cu??????Cl interactions, the ??-chloro bridges being thus strongly asymmetric. The organic ligand is bound to the metal centre via its N₃-donor dipyridylmethylamine fragment in a planar fashion, such that each copper centre is in a square planar environment (or distorted square pyramidal with a long axial bond length if the additional interaction is considered). When R,S-L ¹ was employed in a parallel synthesis, the similar racemic complex [Cu(R,S-L ¹ )Cl](PF₆)??0.5MeOH (4) was obtained, in which the L ¹ ligands in each dimeric unit have opposite hands. In contrast to the complexes of L ¹ , the reaction of Cu(II) chloride with the related ligand, (R)-1-cyclohexyl-N,N-bis(pyridine-3-ylmethyl)ethanamine (R-L ² ), yielded the mononuclear complex [Cu(R,S-L ² )Cl₂] (5), displaying a distorted square pyramidal coordination geometry. The structure of this product along with its corresponding circular dichroism spectrum revealed that racemisation of the starting R-L ² ligand has occurred under the relatively mild (basic) conditions employed for the synthesis. A temperature-dependent magnetic studies of the complexes 1, 2 and 5 indicate that a week ferromagnetic interaction is operative in each dicopper core in 1 and 2 with 2J?=?1.2?cm^?1. On the other hand, a week antiferromagnetic intermolecular interaction is operative for 5.     

Miscibility in blends of poly(3-hydroxybutyrate) and poly(vinylidene chloride-co-acrylonitrile)

Miscibility behavior of poly(3-hydroxybutyrate) [PHB]/poly(vinylidene chloride-co-acrylonitrile) [P(VDC-AN)] blends have been investigated by differential scanning calorimetry and optical microscopy. Each blend showed a single T_g, and a large melting point depression of PHB. All the blends containing more than 40% PHB showed linear spherulitic growth behavior and the growth rate decreased with P(VDC-AN) content. The interaction parameter χ₁₂, obtained from melting point depression analysis, gave the value of −0.267 for the PHB/P(VDC-AN) blends. All results presented in this article lead to the conclusion that PHB/P(VDC-AN) blends are completely miscible in all proportions from a thermodynamic viewpoint. The miscibility in these blends is ascribed to the specific molecular interaction involving the carbonyl groups of PHB. © 1997 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 35: 2645–2652, 1997     

Synthesis via pummerer intermediates. III. Rearrangements of 3-(methylsulfinyl)quinolinones, 3-(methylsulfinyl)cinnolinones, 3-(methylsulfinyl)chromanones and 3-(methylsulfinyl)chromones with acetic anhydride and with thionyl chloride

The reaction of 1-methyl-3-(methylsulfinyl)-4(1H)quinolinone ( 1 ) with acetic anhydride and thionyl chloride gave 3-[[(acetyloxy)methyl]thio]]-1-methyl-4(1H)quinolinone ( 2 ) and 3-[(chloromethyl)thio]-1-methyl-4(1H)quinolinone ( 3 ) respectively. 3-(Methylsulfinyl)-4(1H)cinnolinone ( 4 ) gave the corresponding products when treated under similar conditions. Treatment of 8-methoxy-3-(methylsulfinyl)-4H-1-benzopyran-4-one ( 11 ) with acetic anhydride and thionyl chloride gave bis addition vinyl Pummerer products 2,3-bis(acetyloxy)-2,3-dihydro-8-methoxy-3-(methylthio)-4H-1-benzopyran-4-one ( 12 ) and 2,3-dichloro-2,3-dihydro-8-methoxy-3-(methylthio)-4H-1-benzopyran-4-one ( 13 ), respectively.     

Preparation,molecular structures,and characteristic properties of (E)-1-(2-furyl)- and (E)-1-(2-thienyl)-2-(3-guaiazulenyl)ethylenes and (E)-1-(3-furyl)- and (E)-1-(3-thienyl)-2-(3-guaiazulenyl)ethylenes

Wittig reactions of 2-furaldehyde (20) [and thiophene-2-carbaldehyde (21)] with (3-guaiazulenylmethyl)triphenylphosphonium bromide (19) in ethanol containing NaOEt at 25 °C for 24 h under argon give (E)-1-(2-furyl)-2-(3-guaiazulenyl)ethylene (22E) and (E)-1-(2-thienyl)-2-(3-guaiazulenyl)ethylene (23E) in 53 and 36% yields. Similarly, Wittig reactions of 3-furaldehyde (29) [and thiophene-3-carbaldehyde (30)] with 19 under the same reaction conditions as for 20 and 21 afford (E)-1-(3-furyl)-2-(3-guaiazulenyl)ethylene (31E) and (E)-1-(3-thienyl)-2-(3-guaiazulenyl)ethylene (32E) in 32 and 46% yields. Molecular structures and characteristic properties as well as preparation of the title E (i.e., one of the geometrical isomers) forms, with a view to comparative study, are reported. Moreover, reactions of those conjugated π-electron systems with TCNE (=tetracyanoethylene) in benzene [and in DMF (=N,N-dimethylformamide)] at 25 °C for 24 h under argon yield unique products, possessing interesting molecular structures, respectively, whose characteristic properties and crystal structures are documented, also.     

(RS)-, (R)- and (S)-3-benzyl-3-ethyl 2-oxetanone polymerization with chiral and achiral initiators

The polymerization of 3-benzyl-3-ethyl 2-oxetanones leads to three types of polymers: polyRS (enantiomer excess,ee=0), polyR or polyS (Ree >See) and polyracemate. All these polymers are crystalline and the thermal properties (T _g, meltingT _M and H _M) depend mainly on theee of the polymer. The propagation of the polymerization is not stereospecific. The use of heating-cooling cycles leads to a pure crystalline form melting at the highest temperature. The polyracemate has the behaviour of a pure polymer which melts at a lower temperature, a prolonged heating in the melt induces a strong racemization.

---

Zusammenfassung Die Polymerisation von 3-benzyl-3-ethyl 2-oxetanon führt zu drei Polymer Typen: PolyRS (überschuss des Enantiomers,EE=0), PolyR oder PolyS (REE > SEE) und Polyracemate. Alle Polymere sind kristallin und die thermischen Eigenschaften (T _g, SchmelzeT _M und H _M) hängen wesentlich vonEE des Polymers ab. Die Fortpflanzung der Polymerisation ist nicht stereospeeifisch. Die Verwendung von Aufheitzen Abkühl Zyklen führt zu einer reinen kristallinen Form, die bei der höchsten Temperatur schmilzt. Das Polyracemat verhält sich wie ein reines Polymer, das bei niedrigeren Temperatur schmilzt; es racemisiert im Laufe einer verlängerten Erhitzung im Schemlzfluss.

     

Miscibility of solution-chlorinated polyethylene with poly(α-methylstyrene-co-acrylonitrile)

Statistical copolymers of α-methylstyrene and acrylonitrile (MSAN) form single-phase blends with solution-chlorinated polyethylene within a restricted composition range, even though no combination of the corresponding homopolymers is miscible. The phase behavior can be successfully described using the general mean-field expression which predicts miscibility on the basis of the intramolecular interactions of the comonomers. By deriving the absolute value of one of the six system interactions from a subsidiary determination of the miscibility limits of poly (methylmethacrylate) in MSAN, values of all the remaining interaction parameters have been determined using a novel phase boundary-fitting technique.     

A Facile Synthetic Method for （3Z, 6Z, 9S, 10R）-9, 10-Epoxy-3, 6- heneicosadiene, Sex Pheromone Component of Hyphantria Cunea （Drug）

Total synthesis of (3Z, 6Z, 9S, 10R)-9, 10-epoxy-3, 6-heneicosadiene, sex pheromone component of Hyphantria cunea (Drug), was achieved using Sharpless AE kinetic resolution and alkylative epoxide rearrangement as key steps.     

分子动力学模拟3(5)-(9-蒽基)吡唑分子在自组装膜上的选择性沉积

采用平衡分子动力学和拉伸分子动力学模拟方法研究了模板诱导有机发光小分子3(5)-(9-蒽基)吡唑(ANP)在自组装膜上的选择性沉积,并利用伞形取样方法和加权柱状图分析法计算了沉积过程的均力势.模拟中以二氧化硅为底板分别构筑2种不同密度的烷烃链自组装膜模板,即低密度的液体扩展相和高密度的液体压缩相.平衡分子动力学结果显示,ANP分子容易沉积至低密度的液体扩展相中,难以沉积至高密度的液体压缩相中.拉伸分子动力学结果表明,当ANP分子沉积至液体压缩相表面时,在进入烷烃膜时遇到较大阻力,因而不易进入到烷烃链单层膜中;而ANP分子在进入液体扩展相的过程中受到的阻力较小.通过比较这2种不同密度自组装膜与ANP分子之间的结合自由能,发现ANP分子进入液体压缩相的能垒较高,而ANP分子与液体扩展相结合更加稳定,导致有机发光小分子在不同密度的模板上具有选择吸附性.所得模拟结果与实验现象一致,在分子水平上为实验提供了更加丰富的微观信息.     

Multiple Peptide Synthesis Methods and Their Applications. New Synthetic Methods (87)

Rapid developments in the biotechnology of new proteins, as well as advances in immunology and the development of pharmaceuticals based on inhibitors and antagonists, have led to immense demands for synthetic peptides. Simultaneous preparation of 100–150 completely different peptides, having chain lengths of up to 20 amino acids can nowadays be achieved using multiple synthesis methods. The yields and qualities of the peptides so obtained are high enough to permit reliable in vivo and in vitro screening for biological activities. Moreover, it is possible to optimize synthetic conditions and to carry out comparative studies on the secondary structures and conformational mapping of proteins. Special multiple synthesis methods facilitate the epitope mapping of larger peptides for diagnostic purposes and for the development of vaccines based on a few hundreds of free or rod-bound peptides that are useful for immunoassays. Multiple methods of peptide synthesis also enable the preparation of so-called peptide libraries which could comprise hundreds of thousands of peptides, and by which new perspectives for the screening of lead structures will be opened up. Peptide synthesis using a combination of photolabile protecting groups and photolithographic procedures enables the assembling of peptide libraries on small plates for use in miniature immunoassays. Furthermore, lipopeptide-antigen conjugates allow both the preparation of peptide-specific and monoclonal antibodies as well as a complete screening of epitopes of B-, T-helper and T-killer cells. Applications in the areas of AIDS diagnosis, the development of vaccines, and screening for the hormone analogues, demonstrate just some of the possibilities that have been opened up by multiple peptide synthesis methods.     

Miscibility of poly(ϵ-caprolactone) and of poly(styrene-co-acrylonitrile) with poly(styrene-co-acrylic acid)

The miscibility of poly (?-caprolactone) (PCL) with poly (styrene-co-acrylic acid) (SAA) and of poly (styrene-co-acrylonitrile) (SAN) with SAA was examined as a function of the comonomer composition in the copolymers. For PCL/SAA blends it was found that PCL is miscible with SAA within a specific range of copolymer compositions. Segmental interaction energy densities were evaluated by analysis of the equilibrium melting point depression and application of a binary interaction model. The results suggest that the intramolecular repulsion in SAA copolymer plays an important role in inducing the miscibility. Additionally, the critical AA content in SAA for the blend to be homogeneous was predicted by correlating the segmental interaction energy densities with the binary interaction model. For SAN/SAA blends, it was also found that SAA is miscible with SAN within a specific range of copolymer compositions. From the binary interaction model, segmental interaction energy denisties between different monomer units were estimated from the miscibility map and were found to be positive for all pairs, indicating that the miscibility of the blends is due to the strong repulsion in the SAA copolymers.     

3-(Furyl)-3-(diethoxyphosphoryl)acrylates: Synthesis and reaction with nitromethane

A series of 3-(furyl)-3-(diethoxyphosphoryl)acrylates was synthesized by the reaction of 2- and 3-furoyl phosphonates with ethoxycarbonylmethylenetriphenylphosphorane. It was shown that in all cases diethoxyphosphoryl and ester groups were in trans-position with respect to the double bond disregarding the structure of the furan fragment. Potassium fluoride catalyzed addition of nitromethane to the compounds synthesized was studied. It was found that this reaction proceeded regioselectively to form 2-[(furyl)(diethoxyphosphoryl) methyl]-3-nitropropanoic acids.     

Synthesis of lithium,sodium, cesium,and calcium salts of (E)-4- or (E,S)-3-methyl-2-(5-arylisoxazol-3-yl)-methyleneaminobutanoic, (E,S)-4-methyl-2- or (E,2S,3S)-3-methyl-2-(5-arylisoxazol-3-yl)methyleneaminopentanoic,and (E)-6-(5-arylisoxazol-3-yl)methyleneaminohexanoic acids

Preparative method for the synthesis of lithium, sodium, cesium, and calcium salts of (E)-4-(5-arylisoxazol-3-yl)methyleneaminobutanoic, (E)-6-(5-arylisoxazol-3-yl)methyleneaminohexanoic, (E,S)-3-methyl-2-(5-arylisoxazol-3-yl)methyleneaminobutanoic, (E,S)-4-methyl-2-(5-arylisoxazol-3-yl)methyleneaminopentanoic and (E,2S,3S)-3-methyl-2-(5-arylisoxazol-3-yl)methyleneaminopentanoic acids was developed by reacting 5-phenyl(4-tolyl)isoxazole-3-carbaldehydes with amino acids like 4-aminobutyric and 6-aminocaproic acids, L-valine, L-leucine or L-isoleucine in the presence of lithium hydride, sodium methoxide, cesium carbonate or calcium hydride in boiling methanol.