Neil B. McKeown

The influence of surface modification on the cytotoxicity of PAMAM dendrimers

The influence of surface modification on the cytotoxicity of PAMAM dendrimers was examined using Caco-2 cells. Dendrimers were modified by conjugating either lauroyl chains or polyethylene glycol (PEG) 2000 onto the surface of cationic PAMAM dendrimers (G2, G3, G4). The cytotoxicity of unmodified dendrimers towards Caco-2 cells was appreciably higher for cationic (whole generation) compared with anionic (half generation) dendrimers and for both types increased with increasing size (generation) and concentration. A marked decrease in the cytotoxicity of cationic PAMAM dendrimers was noted when the surface was modified, with the addition of six lauroyl or four PEG chains being particularly effective in decreasing cytotoxicity. This decrease in cytotoxicity is thought to be due to a reduction/shielding of the positive charge on the dendrimer surface by the attached chains. The cytotoxicity of dendrimer-based delivery systems is likely to be very different from the parent dendrimer.

An Efficient Polymer Molecular Sieve for Membrane Gas Separations

Bicyclic Bridge to Improvement Polymers of intrinsic microporosity are a recently developed class of contorted rigid glassy ladderlike polymers having very high free volume (open internal spaces). The intrinsic porosity of these materials has made them of interest for ultrahigh permeability gas separation membranes. However, while the polymers show good gas permeability, they have only moderate gas selectivity. Carta et al. (p. 303; see the Perspective by Guiver and Lee) hypothesized that if they could replace the dioxin-like rings in their polymers with stiffer bridged bicyclic rings, they could improve the membrane properties of the polymer. By exploiting reactions connected to the formation of Trögers base to form the multiple covalent bonds needed to make the bicyclic rings, the resulting polymers showed significantly improved selectivity and permeability. Intrinsically porous polymers made using reactions associated with Tröger’s base manifested enhanced membrane properties. [Also see Perspective by Guiver and Lee] Microporous polymers of extreme rigidity are required for gas-separation membranes that combine high permeability with selectivity. We report a shape-persistent ladder polymer consisting of benzene rings fused together by inflexible bridged bicyclic units. The polymer’s contorted shape ensures both microporosity—with an internal surface area greater than 1000 square meters per gram—and solubility so that it is readily cast from solution into robust films. These films demonstrate exceptional performance as molecular sieves with high gas permeabilities and good selectivities for smaller gas molecules, such as hydrogen and oxygen, over larger molecules, such as nitrogen and methane. Hence, this polymer has excellent potential for making membranes suitable for large-scale gas separations of commercial and environmental relevance.

Engineering of Dendrimer Surfaces to Enhance Transepithelial Transport and Reduce Cytotoxicity

AbstractPurpose. To evaluate the cytotoxicity, permeation, and transport mechanisms of PAMAM dendrimers and surface-modified cationic PAMAM dendrimers using monolayers of the human colon adenocarcinoma cell line, Caco-2. Methods. Cytotoxicity was determined using the MTT assay. The effect of dendrimers on monolayer integrity was determined from measurements of transepithelial electrical resistance (TEER) and [14C]mannitol apparent permeability coefficient (Papp). The Papp of dendrimers through monolayers was measured in both the apical (A)-to-basolateral (B) and B→A directions at 4°C and 37°C and also in the presence and absence of ethylenediamine tetraacetic acid (EDTA) and colchicine. Results. The cytotoxicity and permeation of dendrimers increased with both concentration and generation. The cytotoxicity of cationic dendrimers (G2, G3, G4) was greater than that of anionic dendrimers (G2.5, G3.5) but was reduced by conjugation with lauroyl chloride; the least cytotoxic conjugates were those with six attached lauroyl chains. At 37°C the Papp of cationic dendrimers was higher than that of anionic dendrimers and, in general, increased with the number of attached lipid chains. Cationic dendrimers decreased TEER and significantly increased the Papp of mannitol. Modified dendrimers also reduced TEER and caused a more marked increase in the Papp of mannitol. The Papp values of dendrimers and modified dendrimers were higher in the presence of EDTA, lower in the presence of colchicine, and lower at 4°C than at 37°C. Conclusions. The properties of dendrimers may be significantly modified by surface engineering. Conjugation of cationic PAMAM dendrimers with lauroyl chloride decreased their cytotoxicity and increased their permeation through Caco-2 cell monolayers. Both PAMAM dendrimers and lauroyl-PAMAM dendrimer conjugates can cross epithelial monolayers by paracellular and transcellular pathways.

High-Performance Membranes from Polyimides with Intrinsic Microporosity†

Membranes with high permeability to gases are formed from polyimides with rigid backbones that incorporate a spiro-centre. A route to this new range of high-free-volume polyimides is demonstrated, and exceptional performance is obtained for a polymer containing a dimethyl binaphthyl unit.

A Spirobifluorene‐Based Polymer of Intrinsic Microporosity with Improved Performance for Gas Separation

A highly gas-permeable polymer with enhanced selectivities is prepared using spirobifluorene as the main structural unit. The greater rigidity of this polymer of intrinsic microporosity (PIM-SBF) facilitates gas permeability data that lie above the 2008 Robeson upper bound, which is the universal performance indicator for polymer gas separation membranes.

Polyamidoamine Starburst dendrimers as solubility enhancers.

The solubility of the hydrophobic drug ibuprofen has been compared in an aqueous solution of polyamidoamine (PAMAM) G4 dendrimer and sodium dodecyl sulphate (SDS). The PAMAM G4 dendrimer solution significantly enhanced the solubility of ibuprofen compared to 2% SDS solution. It was found that the solubility of ibuprofen in dendrimer solution was directly proportional to dendrimer concentration and inversely proportional to temperature. The influence of dendrimer solution pH on the solubility enhancement of ibuprofen suggests that it involves an electrostatic interaction between the carboxyl group of the ibuprofen molecule and the amine groups of the dendrimer molecule.

Heme-like coordination chemistry within nanoporous molecular crystals

Iron Exposure The macrocyclic heme motif coordinates iron ions in proteins and plays a widespread role in biochemical oxidative catalysis. Bezzu et al. (p. 1627) prepared crystals in which analogous iron-centered macrocycles were aligned in pairs. The outer faces of the pairs exposed the iron ions to vacant cavities, where ligand exchange could take place; the inner faces were bound together by rigid bridging ligands lending the crystals structural integrity. The stability and high porosity of these crystals lend themselves to potential catalytic applications. Metal-organic framework compounds expose iron atoms for reactions in a manner analogous to heme sites in proteins. Crystal engineering of nanoporous structures has not yet exploited the heme motif so widely found in proteins. Here, we report that a derivative of iron phthalocyanine, a close analog of heme, forms millimeter-scale molecular crystals that contain large interconnected voids (8 cubic nanometers), defined by a cubic assembly of six phthalocyanines. Rapid ligand exchange is achieved within these phthalocyanine nanoporous crystals by single-crystal–to–single-crystal (SCSC) transformations. Differentiation of the binding sites, similar to that which occurs in hemoproteins, is achieved so that monodentate ligands add preferentially to the axial binding site within the cubic assembly, whereas bidentate ligands selectively bind to the opposite axial site to link the cubic assemblies. These bidentate ligands act as molecular wall ties to prevent the collapse of the molecular crystal during the removal of solvent. The resulting crystals possess high surface areas (850 to 1000 square meters per gram) and bind N2 at the equivalent of the heme distal site through a SCSC process characterized by x-ray crystallography.

Triptycene Induced Enhancement of Membrane Gas Selectivity for Microporous Tröger's Base Polymers

A highly gas permeable polymer with exceptional size selectivity is prepared by fusing triptycene units together via a poly-merization reaction involving Trögers base formation. The extreme rigidity of this polymer of intrinsic microporosity (PIM-Trip-TB) facilitates gas permeability data that lie well above the benchmark 2008 Robeson upper bounds for the important O2 /N2 and H2 /N2 gas pairs.

Phthalocyanine-containing polymers

The optical and electronic properties of the phthalocyanine (Pc) macrocycle make it suitable for a wide range of applications. The enormous diversity of Pc-containing polymers, developed over thirty years of research, offers the prospect of readily processed materials in which covalent linkages can be used to control the ordering and arrangement of the Pc units. This article reviews both the synthesis and study of Pc-containing polymers. The types of polymer are classified by the way in which the macrocycle is incorporated within the macromolecular structure as either network, main-chain or side-chain polymers. In addition, recent work on the incorporation of the Pc macrocycle as polymer end-groups or as the core unit in a number of dendrimers is also described.

A nanoporous network polymer derived from hexaazatrinaphthylene with potential as an adsorbent and catalyst support

The synthesis and properties of a nanoporous network polymer incorporating 5,6,11,12,17,18-hexaazatrinapthylene (Hatn) as the rigid functional unit is described. This material is readily prepared from the efficient dibenzodioxane forming reaction between 2,3,8,9,14,15-hexachloro-5,6,11,12,17,18-hexaazatrinaphthylene and 5,5′,6,6′-tetrahydroxy-3,3,3′,3′-tetramethyl-1,1′-spirobisindane and exhibits a high BET surface area (775 m2 g−1) similar to that obtained from related nanoporous networks based on phthalocyanine and porphyrin macrocycles. The ability of the Hatn unit to bind to metal ions was shown by the sequential binding of three palladium(II) dichloride moieties to a soluble model Hatn compound using a 1H NMR titration experiment. When exposed to an excess of palladium(II) dichloride in chloroform solution, the Hatn nanoporous network is shown to adsorb 3.9 mmol g−1 of the metal complex. The resulting material retains porosity (BET surface area = 347 m2 g−1) and should be useful as a heterogeneous catalyst. The Hatn network polymer is also shown to be effective for the adsorption of phenol from aqueous solution with a maximum adsorption of 5 mmol g−1, which is a significant improvement over the performance of activated carbon reported in similar studies.