AGMA1, a prevailingly cationic amphoteric polyamidoamine obtained by polyaddition of (4-aminobutyl)guanidine (agmatine) to 2,2-bis(acrylamido)acetic acid, was studied as a potential DNA carrier and transfection promoter. Fluorescein-labeled AGMA1 was prepared by conjugation with fluorescein isothiocyanate and its cell uptake, blood permanence, and body distribution studied. In spite of its cationic character, AGMA1 is neither toxic nor hemolytic in the pH range 4.0-7.4, circulates for a long time in the blood without preferentially localizing in the liver, easily enters HT-29 cells, gives stable complexes with DNA, and is endowed with good transfection efficiency, suggesting the ability to transport in the cytoplasm a DNA payload without any measurable membranolytic activity. If compared with other transfection promoters, including polyamidoamines of different structures, AGMA1 is apparently endowed with a unique combination of desirable requirements for a nonviral DNA polymer carrier and warrants potential as a transfection agent in vivo.

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Novel 1-vinylpyrrolidin-2-one (VP) derivatives, namely 3,3-di(ethoxycarbonyl)-1-vinylpyrrolidin-2-one (DEVP) and 3-(ethoxycarbonyl)-1-vinylpyrrolidin-2-one (EVP), were obtained through a two-step synthetic pathway involving the abstraction of a hydrogen atom α to the lactam CO, followed by condensation with ethyl chloroformate. By properly selecting the reaction conditions, DEVP could be obtained in high yields, through a straightforward purification procedure. Both DEVP and EVP were converted to sodium 1-vinylpyrrolidin-2-one-3-carboxylate (VP-COONa) by saponification of the ester group, followed by decarboxylation reaction in the case of DEVP. All monomers were homo- and copolymerized with VP by radical polymerization, the structure of the polymer obtained was determined by means of 1H and 13C NMR spectroscopy, and molecular weights were analyzed by means of size exclusion chromatography. The resultant DEVP- and EVP-based polymers also underwent hydrolysis with alkali solutions, followed by decarboxylation reaction in the case of DEVP units, which led in all cases to one carboxylate function linked to the lactam ring. The reactivity ratios for the copolymerization of DEVP with VP were determined in methanol solution according to the Kelen−Tüdös procedure, through polymerization experiments performed at different feed, in which compositional drifts were followed by monitoring monomer conversions by means of 1H NMR spectroscopy. The values of the reactivity ratios obtained were r DEVP = 0.63 and r VP = 0.33. The validity of these parameters was checked by means of the classical Skeist equation.

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A straightforward synthesis of amphiphilic β‐cyclodextrin‐poly(4‐acryloylmorpholine) (β‐CD‐PACM) polymers of controlled molecular weight, consisting of the radical polymerization of 4‐acryloylmorpholine in the presence of 6‐deoxy‐6‐mercapto‐β‐cyclodextrin (β‐CD‐SH) as chain‐transfer agent, has been established. These derivatives carry a single β‐cyclodextrin (β‐CD) moiety at one terminus and their average molecular weight is in the order of 104. Thus, their β‐CD content is ∼ 10% by weight. No evidence of un‐functionalized PACM was found in the final products. The chain‐transfer constant (CT) of β‐CD‐SH was found to be 1.30 by independently determining the reaction constants of both chain‐transfer and propagation reactions. This ensures that the molecular weight, hence the β‐CD content of the polymers, does not significantly vary with conversion. These β‐CD‐PACM polymers are highly soluble in water as well as in several organic solvents such as chloroform and lower alcohols. They proved capable of solubilizing in water poorly soluble drugs such as 9‐[(2‐hydroxyethoxy)methyl]guanine (Acyclovir) and of gradually releasing them in aqueous systems. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 1607–1617, 2008

Summary: A novel functionalised poly(1‐vinylpyrrolidin‐2‐one) (PVP) derivative, carrying a pre‐determined amount of 2‐(2‐pyridinyldithio)ethylamine moieties as side substituents, P(VP‐co‐VP‐SS‐Py), has been prepared from carboxylated VP copolymers, in turn obtained by copolymerising 1‐vinylpyrrolidin‐2‐one with 3,3‐di‐(ethoxycarbonyl)‐1‐vinylpyrrolidin‐2‐one in the presence of radical initiators. Using reaction solvents acting in the mean time as chain transfer agents could control its molecular weight. P(VP‐co‐VP‐SS‐Py) proved to be extremely reactive towards exchange reactions with molecules containing mercapto functions, including bioactive peptides. The exchange derivative with reduced glutathione, chosen as a model compound, was easily prepared.

The reactivity of carboxy‐terminated poly(1‐vinylpyrrolidin‐2‐one) (PVP‐COOH) 40‐mers 1 with various small bi‐functionalized molecules has been investigated. A number of new differently functionalized PVP 3–11 have been successfully obtained demonstrating that the presence of the bulky PVP chain did not hamper the reactivity of the carboxy group. This would imply that in solution the carboxyl group is not buried inside the coil, but well exposed to the solvent, as further confirmed by a molecular dynamics conformational study. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 1683–1698, 2008

Dibenzothiophene derivativesDibenzothiophene derivatives R 0110 A Convenient Procedure for the Synthesis of Tetrathia-[7]-helicene and the Selective α-Functionalization of Terminal Thiophene Ring. -(MAIORANA*, S.; PAPAGNI, A.; LICANDRO, E.; ANNUNZIATA, R.; PARAVIDINO, P.; PERDICCHIA, D.; GIANNINI, C.; BENCINI, M.; CLAYS, K.; PERSOONS, A.; Tetrahedron 59 (2003) 34, 6481-6488; Dip. Chim. Org. Ind., Univ. Stud. Milano, CNR, I-20133 Milano, Italy; Eng.) -M. Schroeter 48-108