Self-Replicating Systems

This review aims to provide a clear and succinct overview into the science and study of self-replicating systems. Over the past 25 years, there has been a surge of development in research towards self-replication and self-replicating systems. The interest in these systems relates to one of the most fundamental questions posed in all fields of science - How did life on Earth begin? Investigating how the self-replication process evolved may hold the key to understanding the emergence and evolution of living systems and, ultimately, gain a clear insight to the origin of life on Earth. This tutorial review aims to highlight the fundamental prerequisites of self-replication along with the important research that has been conducted over the past few decades

Synthesis and aggregation of a porphyrin cored hyperbranched polyglycidol and its application as a macromolecular photosensitizer for photodynamic therapy.

Macromolecules are potentially useful delivery systems for cancer drugs as their size allows them to utilize the enhanced permeability and retention effect (EPR), which facilitates selective delivery to (and retention within) tumors. In addition, macromolecular delivery systems can prolong circulation times as well as protecting and solubilizing toxic and hydrophobic drug moieties. Overall these properties and abilities can result in an enhanced therapeutic effect. Photodynamic therapy (PDT) combines the use of oxygen and a photosensitizer (PS), that become toxic upon light-irradiation. We proposed that a PS encapsulated within a water-soluble macromolecule could exploit the EPR effect and safely and selectively deliver the PS to a tumor. In this paper, we describe the synthesis of a porphyrin cored hyperbranched polymer that aggregated into larger micellar structures. DLS and TEM indicated that these aggregated structures had diameters of 45 nm and 20 nm for the solvated and non-solvated species respectively. The porphyrin cored HBP (PC-HBP), along with the non-encapsulated porphyrin (THPP), were screened against EJ bladder carcinoma cells in the dark and light. Both THPP and PC-HBP displayed good toxicity in the light, with LD50 concentrations of 0.5 μM and 1.7 μM respectively. However, in the dark, the non-incorporated porphyrin (THPP) displayed significant toxicity, generating an LD50 of 4 μM. On the other hand, no dark toxicity was observed for the polymer system (PC-HBP) at concentrations of 100 μM or less. As such, incorporation within the large polymer aggregate serves to eliminate dark toxicity, whilst maintaining excellent toxicity when irradiated

The 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

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 possess various oxygen containing functionality on its large surface. These characteristics allow GO to interact with a variety of materials, for application to 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, due to 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 mono-valent interaction, but interact cooperatively with the protein surface

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

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 of fluorinated amphiphilic polymers and the morphological dependence on their oxygen binding capacity

Water-soluble materials that can bind, sense, and deliver oxygen are important for several applications. These include catalysis, environmental sensors, smart packaging, agriculture, and medicine. Herein we report the synthesis of two related fluorinated amphiphilic polymers that can self-assemble into small micelles (20-30 nm) or larger vesicles (>300 nm). We found that the oxygen binding capacity of these polymers was dependent on the morphology of their self-assembled structures. At a constant fluorine concentration of 1.5 mg/mL, the oxygen solubility within the vesicle solution was 55% higher than that measured in pure water and 25% higher than the corresponding micelle solution. The increased concentration of oxygen in the vesicle solution indicated a significantly higher level of oxygen binding, which was attributed to additional oxygen trapped within the vesicle’s aqueous interior

Dendrimers as potential drug carriers; encapsulation of acidic hydrophobes within water soluble PAMAM derivatives

This paper describes the synthesis of three neutral water soluble poly(amidoamine) (PAMAM) dendrimer derivatives. The ability of the two larger dendrimers to bind small acidic hydrophobic molecules is reported. Spectroscopic data and pH behaviour suggested that the acidic hydrophobes were forming stable ion pairs with the dendrimer's internal, basic tertiary nitrogens. With respect to forming 1:1 and 2:1 substrate/dendrimer complexes, both of the larger dendrimers were equally efficient at binding. All dendrimer/substrate complexes were completely miscible with water in all proportions (i.e. infinitely water soluble). When the bound substrates are drug moieties, then the resulting complexes could be considered as potential drug delivery systems. Flow calorimetry demonstrated that the dendrimers were able to release their hydrophobic guests when in contact with a biological cell