Lipid bilayer disruption by polycationic polymers: the roles of size and chemical functional group

Polycationic polymers are used extensively in biology to disrupt cell membranes and thus enhance the transport of materials into the cell. The highly polydisperse nature of many of these materials makes obtaining a mechanistic understanding of the disruption processes difficult. To design an effective mechanistic study, a monodisperse class of polycationic polymers, poly(amidoamine) (PAMAM) dendrimers, has been studied in the context of supported dimyristoylphosphatidylcholine (DMPC) lipid bilayers using atomic force microscopy (AFM). Aqueous solutions of amine-terminated generation 7 (G7) PAMAM dendrimers caused the formation of 15-40-nm-diameter holes in lipid bilayers. This effect was significantly reduced for smaller G5 dendrimers. For G3, no hole formation was observed. In addition to dendrimer size, surface chemistry had a strong influence on dendrimer-lipid bilayer interactions. In particular, acetamide-terminated G5 did not cause hole formation in bilayers. In all instances, the edges of bilayer defects proved to be points of highest dendrimer activity. A proposed mechanism for the removal of lipids by dendrimers involves the formation of dendrimer-filled lipid vesicles. By considering the thermodynamics, interaction free energy, and geometry of these self-assembled vesicles, a model that explains the influence of polymer particle size and surface chemistry on the interactions with lipid membranes was developed. These results are of general significance for understanding the physical and chemical properties of polycationic polymer interactions with membranes that lead to the transport of materials across cell membranes.     

Multi-arm star polyisobutylenes: 3. New insight into the chemistry of star formation: Star-star coupling and core contraction

Details of the chemistry of linking living polyisobutylene (PIB⊕) pre-arms with divinylbenzene (DVB) to multi-arm PIB stars have been studied by triple-detector size-exclusion chromatography (SEC). Computer-aided deconvolution of multimodal differential refractive index (RI), laser light scattering (LLS), and ultraviolet (UV) traces obtained by SEC indicates the formation of complex product mixtures. The observations were interpreted in terms of inter-and intramolecular reactions of initially-formed active stars. Thus intermolecular or star-star couplings are proposed to lead to higher order (secondary, tertiary, etc.) stars, whereas intramolecular reactions result in core-contraction. The mechanism of these reactions has been outlined. The effect of PIB⊕ pre-arm length on star-star coupling was analyzed.     

Some aspects of the living isobutylene polymerization

The possibilities of increasing the livingness in cationic isobutylene polymerizations has been investigated. It has been assumed that the living chain-end is polarized but non-dissociated and relatively stable, therefore, i) shifting of the dissociation equilibrium by adding salts with common or non-common anion in excess, and ii) increasing of the stability of the chain-end by complexing it with electrondonors, may increase the livingness of the system. Indeed, the addition of n-Bu₄NCl or n-Bu₄NI to systems with BCl₃ or TiCl₄ coinitiators, as well as the addition of dimethyl sulphoxide as electrondonor in a broad concentration range, improved the living character. The possibility of complexation of the chain-end by the monomer has also been supported     

Complex dynamic behavior of fluctuating smectic- A films as studied by scattering with coherent X-rays

Coherent dynamic x-ray scattering has been used to study the thermally excited layer fluctuations in freely suspended smectic films of the compound 4O.8. Using 8-keV x rays and films with a thickness around 0.3 &mgr;m we resolve relaxation times down to a few &mgr;s. A combination of damped and oscillatory behavior is observed for the layer undulations, which can be attributed to inertial effects. These are due to the surface contribution to the free energy which cannot be disregarded for thin films.     

Molecular heterogeneity analysis of poly(amidoamine) dendrimer-based mono- and multifunctional nanodevices by capillary electrophoresis

Poly(amidoamine) (PAMAM) dendrimer-based nanodevices are of recent interest in targeted cancer therapy. Characterization of mono- and multifunctional PAMAM-based nanodevices remains a great challenge because of their molecular complexity. In this work, various mono- and multifunctional nanodevices based on PAMAM G5 (generation 5) dendrimer were characterized by UV-Vis spectrometry, (1)H NMR, size exclusion chromatography (SEC), and capillary electrophoresis (CE). CE was extensively utilized to measure the molecular heterogeneity of these PAMAM-based nanodevices. G5-FA (FA denotes folic acid) conjugates (synthesized from amine-terminated G5.NH(2) dendrimer, approach 1) with acetamide and amine termini exhibit bimodal or multi-modal distributions. In contrast, G5-FA and bifunctional G5-FA-MTX (MTX denotes methotrexate) conjugates with hydroxyl termini display a single modal distribution. Multifunctional G5.Ac(n)-FI-FA, G5.Ac(n)-FA-OH-MTX, and G5.Ac(n)-FI-FA-OH-MTX (Ac denotes acetamide; FI denotes fluorescein) nanodevices (synthesized from partially acetylated G5 dendrimer, approach 2) exhibit a monodisperse distribution. It indicates that the molecular distribution of PAMAM conjugates largely depends on the homogeneity of starting materials, the synthetic approaches, and the final functionalization steps. Hydroxylation functionalization of dendrimers masks the dispersity of the final PAMAM nanodevices in both synthetic approaches. The applied CE analysis of mono- and multifunctional PAMAM-based nanodevices provides a powerful tool to evaluate the molecular heterogeneity of complex dendrimer conjugate nanodevices for targeted cancer therapeutics.     

A synthetic and in silico study on the highly regioselective Diels-Alder reaction of the polyenic antifungal antibiotics natamycin and flavofungin

The tetraenic macrolide antibiotic natamycin and the pentaenic macrolide flavofungin gave monoadducts on Diels-Alder reaction with 4-phenyl-1,2,4-triazoline-3,5-dione. The regioselectivity of the reaction as well as the conformation of the products was studied using theoretical calculations.     

Competition between dissolution and redox reactions in the electrochemistry ofn-GaP

The lowering of the photocorrosion ofn-GaP in 1M KOH in the presence of several redox systems was investigated using neutron activation analysis. After thermal neutron irradiation of GaP and annihilation of irradiation induced defects by annealing processes the photodissolution was investigated by measuring the activity of the corresponding electrolyte solutions. The dependence of the stabilization of the photoelectrode on concentration and redox potential of the reduced form of the redox couples I^–, Fe (CN) ₆ ^4– and SO ₃ ^2– was measured. It was found that the stabilization is growing with growing concentration and lowering of the redox potential of the corresponding redox couple.     

Dichlorocarbene Addition to

In contrast to the terminal phosphinidene complex PhPW(CO)(5) (2), which adds to [5]metacyclophane (1) in a 1,4-fashion, dichlorocarbene preferentially adds in a 1,2-fashion to the formal "anti-Bredt" type double bond of the aromatic ring of 1 to afford the norcaradiene 11b, which immediately rearranges to the bridged cycloheptatriene 12b and further by a [1,5] sigmatropic chlorine migration to the isomeric 13b as the first observable product. More slowly, the latter isomerizes via a dissociative mechanism to give 15b. A computational study supports the notion that the [1,5] chlorine migration in the rearrangement 12b --> 13b, for which an activation barrier of 70.2 kJ mol(-)(1) was calculated, is essentially concerted with minor charge separation. In contrast, the analogous [1,5] chlorine migration in the flat model compound 7,7-dichlorocycloheptatriene (12a) displays features of a dissociative pathway.