Anion Transport Using Core Functionalized Hyperbranched Polymers and Evidence of a Dense Packed Limit Based on Molecular Weight.

Being able to bind, select, and transport species is central to a number of fields, including medicine, materials, and environmental science. In particular, recognizing a specific species from one phase and transporting it across, or into another phase, has obvious applications in environ-mental science, for example, removal of unwanted or toxic materials from an aqueous or organic phase. In this paper, we describe an approach that uses a functionalized dendritic polymer to bind and transport a small anionic molecule across an organic phase (and between two aqueous phases). The design was based on encapsulation principles borrowed from nature, where anions are bound and transported by proteins that have specific sites within their globular ordered structures. For the work reported here, a globular dendritic polymer functionalized with an isophthalamide-based receptor was used to replace the protein structure and anion-binding site. Along with control experiments, the binding and transport properties of two functionalized HBPs were assessed using a Pressman U tube experiment. Both HBPs demonstrated an enhanced ability to bind and transport anions (when compared to the anion-binding site used in isolation). Furthermore, optimum binding and transport occurred when the smaller of the two HBPs were used. This supports our previous observations regarding the existence of a dense packed limit for HBPs.

Effect of Terminal-Group Functionality on the Ability of Dendrimers to Bind Proteins.

It is known that dendrimers can bind proteins with good selectively. This selectivity comes about from an optimization based on matching the size of the dendrimer with the size of the protein's interfacial binding area. In this paper, we report how this selectivity can be moderated by the functionality on the surface of the dendrimer. Specifically, we describe the synthesis of amino acid functionalized dendrimers and the effect of functionality on the dendrimer's ability to bind and inhibit the enzymatic protein, chymotrypsin. The results show how dendrimer binding can be increased or decreased depending on the terminal functionality. These results will allow new ligands to be designed and synthesized, possessing increased and selective protein-binding abilities.

Bimolecular catalysis and turnover from a macromolecular host system.

The synthesis of a globular macromolecule and its application as a bimolecular catalyst are reported. The macromolecular structure supports (at least) two zinc-metalated porphyrin units, each capable of binding a single reactant. The proximity of the two bound reactants results in an increased local concentration, leading to a maximum 300-fold increase in the reaction rate. In contrast to other synthetic catalysts, where bidentate products inhibit further reactions, this macromolecular system allows the product to be displaced by the reactants leading to turnover and catalysis. We believe that this is due to the dynamics of the macromolecular host system, which maintains enough flexibility to adopt a favorable/reactive geometry, which allows the reactants to get close and react while possessing sufficient rigidity/poor geometry to reduce and disrupt any cooperative/inhibitive bidentate binding.

Catalytic hyperbranched polymers as enzyme mimics; exploiting the principles of encapsulation and supramolecular chemistry.

Nature uses the principles of encapsulation and supramolecular chemistry to bind and orientate substrates within active catalytic sites. Over the years, synthetic chemistry has generated a number of small molecule active site mimics capable of catalysing reactions involving bound substrates. Another approach uses larger molecules that better represent an enzymes globular structure. These molecules mimic an enzymes structure by incorporating binding/catalytic sites within the globular structure of the polymer. As such, the electronic and steric properties around the binding/catalytic site(s) can be controlled and fine-tuned. One class of polymer that is particularly adept at mimicking the globular structure of enzymes are dendritic polymers. This review will concentrate on the use of hyperbranched polymers as synthetic enzyme mimics.

Synthesis of Oligomeric and Monomeric Functionalized Graphene Oxides and a Comparison of Their Abilities to Perform as Protein Ligands and Enzyme Inhibitors.

Graphene oxide (GO) is a versatile, monomolecular layered nanomaterial that possesses various oxygen-containing functionality on its large surface. These characteristics allow GO to interact with a variety of materials and to be applied towards a number of areas. The strength and selectivity of these interactions can be improved significantly through further functionalization. In this paper, we describe the functionalization of GO and its application as a protein ligand and an enzyme inhibitor. The work reported in this paper details how chymotrypsin inhibition can be improved using GO functionalized with a monomeric and oligomer layer of tyrosine. The results indicated that the mono- and oligo-functionalized systems performed extremely well, with Ki values nearly four times better than GO alone. Our original premise was that the oligomeric system would bind better because of the length of the oligomeric arms and potential for a high degree of flexibility. However, the results clearly showed that the shorter monomeric system was the better ligand/inhibitor. This was due to weaker intramolecular interactions between the aromatic side chains of tyrosine and the aromatic surface of GO. Although these are possible for both systems, they are cooperative and therefore stronger for the oligomeric functionalized GO. As such, the protein must compete and overcome these cooperative intramolecular interactions before it can bind to the functionalized GO, whereas the tyrosines on the surface of the monomeric system interact with the surface of GO through a significantly weaker monovalent interaction, but interact cooperatively with the protein surface.

Dendrimers as size selective inhibitors to protein-protein binding.

This communication describes how the "quantized" size effect of dendrimers can be exploited towards a size selective binding mechanism for the inhibition of protein-protein binding.

Increased Oxygen Solubility in Aqueous Media Using PEG-Poly-2,2,2-trifluoroethyl Methacrylate Copolymer Micelles and Their Potential Application As Volume Expanders and As an Artificial Blood Product.

One of the most important functions of blood is to solubilize and distribute oxygen within the body. As such, it is vital that this property is replicated (safely) by any artificial blood product. In this paper, we describe the facile synthesis of a series of simple diblock polymers capable of self-assembling into micellar structures at concentrations around 3 × 10-3 mg/mL. Using a dissolved oxygen meter, we were able to demonstrate that aqueous solutions of these aggregated structures could retain higher amounts oxygen and release it (into the aqueous bulk phase). The increased oxygen retention was quantified by measuring the rate of oxygen release and its half-life. These experiments indicated that oxygen retention/binding was dependent on the fluorine concentration. 19F NMR experiments on a micellar solution saturated with oxygen showed small upfield shifts in the fluorine peaks, which provided qualitative evidence that indicated oxygen binding occurred within the fluorine region of the polymer aggregates. Using a modified enzyme/glucose oxidation assay, we were able to establish that the aqueous oxygen concentrations were 33% higher in a solution of polymer.

Synthesis and characterization of immobilized PAMAM dendrons.

This communication describes the synthesis and characterization of immobilized PAMAM dendrons onto a surface modified silicon wafer substrate (functionalized using plasma polymerized PAA) using a "growing from" strategy.

Porphyrin cored hyperbranched polymers as heme protein models.

The single step synthesis of an Fe(II) porphyrin cored hyperbranched polymer, possessing similar size and topology to the natural heme containing proteins, is reported: UV spectroscopy successfully demonstrated the ability of this polymer to reversibly bind oxygen.

Controlling microenvironments and modifying anion binding selectivities using core functionalised hyperbranched polymers.

An isophthalamide anion binding site has been incorporated into hyperbranched polymers resulting in a change in the selectivity of the receptor from chloride to bromide.

Graphene Oxide-Gallic Acid Nanodelivery System for Cancer Therapy.

Despite the technological advancement in the biomedical science, cancer remains a life-threatening disease. In this study, we designed an anticancer nanodelivery system using graphene oxide (GO) as nanocarrier for an active anticancer agent gallic acid (GA). The successful formation nanocomposite (GOGA) was characterized using XRD, FTIR, HRTEM, Raman, and UV/Vis spectroscopy. The release study shows that the release of GA from the designed anticancer nanocomposite (GOGA) occurs in a sustained manner in phosphate-buffered saline (PBS) solution at pH 7.4. In in vitro biological studies, normal fibroblast (3T3) and liver cancer cells (HepG2) were treated with different concentrations of GO, GOGA, and GA for 72 h. The GOGA nanocomposite showed the inhibitory effect to cancer cell growth without affecting normal cell growth. The results of this research are highly encouraging to go further for in vivo studies.

Formation of A2B2 supramolecular porphyrin co-polymers.

New supramolecular A2B2 co-polymers formed in solution from a rigid diporphyrin monomer (the A2 unit) and a short flexible dipyridine monomer (the B2 unit) are reported; NMR experiments show that complete binding occurs at mM concentrations; UV titrations reveal that the dipyridine unit and a monomeric control ligand have identical binding constants, confirming that linear polymers were generated (in preference to small cyclic oligomers); at 2 x 10(-2) M polymers with an average molecular weight of 17,100 g mol-1 and containing approximately 14 porphyrin units have formed.

Dendrimers as scaffolds for the synthesis of spherical porphyrin arrays.

This communication describes a self assembled porphyrin sphere. The globular macromolecular assembly contains 12 terminal porphyrins and has a molecular mass in excess of 15,000 g mol-1.

Exploiting dense shell/packing principles to invoke stereoselectivity in a reaction accelerated by a chiral dendrimer.

As dendrimers approach their dense shell or dense packed limit, a certain amount of conformational organization exists. Any substrate binding within the dendrimer's external layer will experience the same organizational effects. This paper describes how these effects can be exploited towards stereocontrol with respect to binding and reactivity.

Pyridine encapsulated hyperbranched polymers as mimetic models of haeme containing proteins, that also provide interesting and unusual porphyrin-ligand geometries.

This communication describes the use of non-covalent chemistry to construct recyclable porphyrin cored HBPs. The non-covalent design allows the polymeric backbone to be rescued and reused after porphyrin degradation. The steric environment within the polymeric encapsulated ligand notably affected the porphyrin coordination geometry.

Postsynthetic modification at the focal point of a hyperbranched polymer.

Functionalization at the focal point of hyperbranched polyester was achieved using a series of amines and a postsynthetic reaction utilizing an activated p-nitrophenyl ester unit. An element of dense packing was also detected, as evident from differences in levels of incorporation between linear and bulky reagents.

Catalysis inside dendrimers.

Catalytic sites can be placed at the core, at interior positions or at the periphery of a dendrimer. There are many examples of the use of peripherally functionalized dendrimers in catalysis and this subject has been thoroughly reviewed in the recent literature. This review is concerned only with dendrimer based catalysis involving catalytic sites at the core of a dendrimer and within the interior voids. In covering the significant achievements in this area, we have concentrated on examples that highlight key features with respect to positive and/or negative catalytic activity.