Redox cycling of iridium(III) complexes gives versatile materials for photonics applications

The cyclometallated iridium(III) complex [Me4N][Ir(ppy)2(cat)] (Hppy = 2-phenylpyridine; H2cat = benzene-1,2-diol) has been prepared under inert atmosphere and has been structurally characterized by single crystal X-ray diffraction. Under ambient conditions, the fully reduced complex (as formulated) undergoes rapid one-electron oxidation both in solution and in the solid state to a species containing a semiquinone ligand. The resultant neutral complex [Ir(ppy)2(sq)] (sq = o-semiquinone) was also prepared by exposing the reaction mixture to O2 during the course of the reaction. Electron paramagnetic resonance (EPR) spectroscopy confirms the diamagnetic nature of the complex [Me4N][Ir(ppy)2(cat)] and indicates that the unpaired electron in [Ir(ppy)2(sq)] resides primarily on the sq ligand. The photophysical, electrochemical, and spectroelectrochemical properties of [Ir(ppy)2(sq)] were investigated and reveal the changes in absorption as the complex is converted into the catecholate and quinone forms

Giant Polymer Compartments for Confined Reactions

In nature, various specific reactions only occur in spatially controlled environments. Cell compartment and subcompartments act as the support required to preserve the bio-specificity and functionality of the biological content, by affording absolute segregation. Inspired by this natural perfect behavior, bottom-up approaches are on focus to develop artificial cell-like structures, crucial for understanding relevant bioprocesses and interactions or to produce tailored solutions in the field of therapeutics and diagnostics. In this review, we discuss the benefits of constructing polymer-based single and multicompartments (capsules and giant unilamellar vesicles (GUVs)), equipped with biomolecules as to mimic cells. In this respect, we outline key examples of how such structures have been designed from scratch, namely, starting from the application-oriented selection and synthesis of the amphiphilic block copolymer. We then present the state-of-the-art techniques for assembling the supramolecular structure while permitting the encapsulation of active compounds and the incorporation of peptides/membrane proteins, essential to support in situ reactions, e.g., to replicate intracellular signaling cascades. Finally, we briefly discuss important features that these compartments offer and how they could be applied to engineer the next generation of microreactors, therapeutic solutions, and cell models

Porphyrin-polymer nanocompartments: singlet oxygen generation and antimicrobial activity

A new water-soluble photocatalyst for singlet oxygen generation is presented. Its absorption extends to the red part of the spectrum, showing activity up to irradiation at 660 nm. Its efficiency has been compared to that of a commercial analogue (Rose Bengal) for the oxidation of L-methionine. The quantitative and selective oxidation was promising enough to encapsulate the photocatalyst in polymersomes. The singlet oxygen generated in this way can diffuse and remain active for the oxidation of L-methionine outside the polymeric compartment. These results made us consider the use of these polymersomes for antimicrobial applications. E. Coli colonies were subjected to oxidative stress using the photocatalyst-polymersome conjugates and nearly all the colonies were damaged upon extensive irradiation while under the same red LED light irradiation, liquid cultures in the absence of porphyrin or porphyrin-loaded polymersomes were unharme

Bio-catalytic nanocompartments for in situ production of glucose-6-phosphate

Cells are sophisticated biocatalytic systems driving a complex network of biochemical reactions. A bioinspired strategy to create advanced functional systems is to design confined spaces for complex enzymatic reactions by using a combination of synthetic polymer assemblies and natural cell components. Here, we developed bio-catalytic nanocompartments that contain phosphoglucomutase protected by a biomimetic polymer membrane, which was permeabilized for reactants through insertion of an engineered α-hemolysin pore protein. These bio-catalytic nanocompartments serve for production of glucose-6-phosphate, and thus possess great potential for applications in an incomplete glycolysis, pentose phosphate pathway, or in plant biological reactions

Brushing the surface: cascade reactions between immobilized nanoreactors

Functionalization of hard or soft surfaces with, for example, ligands, enzymes or proteins, is an effective and practical methodology for the development of new applications. We report the assembly of two types of nanoreactors based upon poly(dimethylsiloxane)-block-poly(2-methyl-2-oxazoline) (PDMS-b-PMOXA) diblock copolymers as scaffold, uricase and lactoperoxidase as bio-catalysts located within the nanoreactors, and melittin as the biopores inserted into the hydrophobic shell. The nanoreactors were immobilized on poly(2-hydroxyethyl methacrylate)-co-poly(2-aminoethyl methacrylate hydrochloride) (PHEMA-co-P(2-AEMA·HCl) brushes-grafted wafer surfaces by utilizing the strong supramolecular interactions between biotin and streptavidin. The (PHEMA-co-P(2-AEMA·HCl) brushes on silicon surfaces were prepared by a surface initiating atom transfer radical polymerization (ATRP) "graft-from" technique. Cascade reactions between different surface-anchored nanoreactors were demonstrated by converting Amplex Red to the fluorescent probe resorufin by using the H2O2 produced from uric acid and H2O. The detailed properties of the nanoreactors on the functionalized surface including the binding behaviours and cascade reactions were investigated using emission spectroscopy, transmission electron microscopy (TEM), light scattering (LS), atomic force microscopy (AFM) and a quartz crystal microbalance (QCM-D). The results are proof-of-principle for the preparation of catalytically functional engineered surface materials and lay the foundation for applying this advanced functional surface material in biosensing, implanting and antimicrobial materials preparation

Porphyrin Containing Polymersomes with Enhanced ROS Generation Efficiency: in vitro evaluation

Abstract Porphyrins are molecules possessing unique photophysical properties making them suitable for application in photodynamic therapy. The incorporation of porphyrins into natural or synthetic nano-assemblies such as polymersomes is a strategy to improve and prolong their therapeutic capacities and to overcome their limitations as therapeutic and diagnostic agents. Here, 5,10,15,20-tetrakis(1-(6-ethoxy-6-oxohexyl)-4-pyridin-1-io)-21H,23H-porphyrin tetrabromide porphyrin is inserted into polymersomes in order to demonstrate that the encapsulation enhances its ability to generate highly reactive singlet oxygen (1O2) upon irradiation in vitro. The photoactivation of the free and polymersome-encapsulated porphyrin is evaluated by electron spin resonance and cell viability assays on three different mammalian cell lines. The results indicate that by encapsulating the porphyrin, a controlled ROS delivery within the cells is achieved, at the same time avoiding side effects such as dark toxicity, non-specific porphyrin release and over time decreased activity in vitro. This work focuses on showing a not-toxic model system for modern therapeutic nanomedicine, which works under mild irradiation and dosage conditions

Combinatorial Strategy for Studying Biochemical Pathways in Double Emulsion Templated Cell-Sized Compartments

Abstract Cells rely upon producing enzymes at precise rates and stoichiometry for maximizing functionalities. The reasons for this optimal control are unknown, primarily because of the interconnectivity of the enzymatic cascade effects within multi-step pathways. Here, an elegant strategy for studying such behavior, by controlling segregation/combination of enzymes/metabolites in synthetic cell-sized compartments, while preserving vital cellular elements is presented. Therefore, compartments shaped into polymer GUVs are developed, producing via high-precision double-emulsion microfluidics that enable: i) tight control over the absolute and relative enzymatic contents inside the GUVs, reaching nearly 100% encapsulation and co-encapsulation efficiencies, and ii) functional reconstitution of biopores and membrane proteins in the GUVs polymeric membrane, thus supporting in situ reactions. GUVs equipped with biopores/membrane proteins and loaded with one or more enzymes are arranged in a variety of combinations that allow the study of a three-step cascade in multiple topologies. Due to the spatiotemporal control provided, optimum conditions for decreasing the accumulation of inhibitors are unveiled, and benefited from reactive intermediates to maximize the overall cascade efficiency in compartments. The non-system-specific feature of the novel strategy makes this system an ideal candidate for the development of new synthetic routes as well as for screening natural and more complex pathways

"Active surfaces" as Possible Functional Systems in Detection and Chemical (Bio) Reactivity

This article presents design strategies to demonstrate approaches to generate functionalized surfaces which have the potential for application in molecular systems; sensing and chemical reactivity applications are exemplified. Some applications are proven, while others are still under active investigation. Adaptation and extension of our strategies will lead to interfacing of different type of surfaces, specific interactions at a molecular level, and possible exchange of signals/cargoes between them. Optimization of the present approaches from each of five research groups within the NCCR will be directed towards expanding the types of functional surfaces and the properties that they exhibit

An amphiphilic graft copolymer-based nanoparticle platform for reduction-responsive anticancer and antimalarial drug delivery

Medical applications of anticancer and antimalarial drugs often suffer from low aqueous solubility, high systemic toxicity, and metabolic instability. Smart nanocarrier-based drug delivery systems provide means of solving these problems at once. Herein, we present such a smart nanoparticle platform based on self-assembled, reduction-responsive amphiphilic graft copolymers, which were successfully synthesized through thiol–disulfide exchange reaction between thiolated hydrophilic block and pyridyl disulfide functionalized hydrophobic block. These amphiphilic graft copolymers self-assembled into nanoparticles with mean diameters of about 30–50 nm and readily incorporated hydrophobic guest molecules. Fluorescence correlation spectroscopy (FCS) was used to study nanoparticle stability and triggered release of a model compound in detail. Long-term colloidal stability and model compound retention within the nanoparticles was found when analyzed in cell media at body temperature. In contrast, rapid, complete reduction-triggered disassembly and model compound release was achieved within a physiological reducing environment. The synthesized copolymers revealed no intrinsic cellular toxicity up to 1 mg mL−1. Drug-loaded reduction-sensitive nanoparticles delivered a hydrophobic model anticancer drug (doxorubicin, DOX) to cancer cells (HeLa cells) and an experimental, metabolically unstable antimalarial drug (the serine hydroxymethyltransferase (SHMT) inhibitor (±)-1) to Plasmodium falciparum-infected red blood cells (iRBCs), with higher efficacy compared to similar, non-sensitive drug-loaded nanoparticles. These responsive copolymer-based nanoparticles represent a promising candidate as smart nanocarrier platform for various drugs to be applied to different diseases, due to the biocompatibility and biodegradability of the hydrophobic block, and the protein-repellent hydrophilic block

Protein-Polymer Supramolecular Assemblies : a Key Combination for Multifunctionality

2D/3D structures resulting from self-assembly of amphiphilic block copolymers can be combined with bioactive compounds, such as proteins and enzymes, to create supramolecular assemblies with specific desired properties and functionality. Chemical tuning of the architecture and properties of supramolecular assemblies to accommodate sensitive biomolecules allows the development of new soft hybrid materials that benefit from the robustness of polymers and from the functionality of biomolecules. The encapsulation/insertion of biomolecules (enzymes, mimics, proteins) in self-assembling block copolymer vesicles enables design of 'nanoreactors' both in solutions and at surfaces for highly diverse applications, ranging from production of antibiotics to creation of artificial organelles. When membrane proteins are inserted into polymer membranes, it is possible to generate functional membranes or active surfaces with a rapid and specific response. In addition, the selective binding of ligand-terminated polymers holds potential for targeted delivery of drugs, or for immobilization on solid support, to provide functional 3D assemblies on an extended surface