Roeland J. M. Nolte

Biohybrid Polymer Capsules

An overview of the wide range of polymer-based capsules that have been constructed from synthetic and biological building blocks or from biological building blocks that are taken out of their natural environment, using both hyperbranched and self-assembly approaches, was reviewed. The capsules that are discussed can be considered as the simplest mimics of an organelle or cell and contain a cavity in which chemical reactions can take place or cargo can be stored. The chemical tool box available for constructing polymer micelles and polymersomes is much larger, and natural motifs have been actively incorporated into their designs. Regarding LbL, polymersome, or polymeric micelle nanoreactors, it can be predicted that natures biocatalysts will be increasingly used for encapsulation in these synthetic systems, holding promise for future nanoscale diagnostic devices. One of the main challenges in this field will be the effective stimulation of responsive polymersomes since most stimuli reported thus far cannot be applied in living organisms.

Mastering molecular matter. Supramolecular architectures by hierarchical self-assembly

Since the serendipitous event that led to the first synthesis of a molecule by the hands of Man in 1826, the creation of molecular matter depended for 150 years on linking together molecules from other molecular building blocks with the help of strong covalent bonds. The advent of supramolecular chemistry in the last decades of the 20th century has provided chemists with a wealth of new possibilities to synthesize molecular structures and materials that are held together by relatively weak, non-covalent interactions, such as hydrogen bonding, π–π stacking, electrostatic and van der Waals interactions. Using nature as a source of inspiration, the creation of even more complex supramolecular architectures has recently become possible by applying the concept of hierarchical self-assembly, i.e. the non-covalent organization of molecules and macromolecules which takes places over distinct multiple levels, in which the assembly processes gradually decrease in strength. This review will focus on some recent discoveries in the field of spontaneous hierarchical organization of synthetic amphiphiles, disk-like molecules and concave building blocks into well-defined nano-sized assemblies.

Helical Molecular Programming

From hexahelices to nanometer-sized fibers: Helical molecular, macromolecular, and supramolecular structures have moved into the forefront of chemical research in the last years. The information that determines the formation and sense of the helical architecture can be incorporated in the constituent molecular building blocks. The combined use of several complimentary helical assembling techniques in a hierarchical process, a method used by nature, will ultimately allow the design and construction of helical architectures such as 1 with a predefined organization and function.

A virus-based single-enzyme nanoreactor

Most enzyme studies are carried out in bulk aqueous solution, at the so-called ensemble level, but more recently studies have appeared in which enzyme activity is measured at the level of a single molecule, revealing previously unseen properties. To this end, enzymes have been chemically or physically anchored to a surface, which is often disadvantageous because it may lead to denaturation. In a natural environment, enzymes are present in a confined reaction space, which inspired us to develop a generic method to carry out single-enzyme experiments in the restricted spatial environment of a virus capsid. We report here the incorporation of individual horseradish peroxidase enzymes in the inner cavity of a virus, and describe single-molecule studies on their enzymatic behaviour. These show that the virus capsid is permeable for substrate and product and that this permeability can be altered by changing pH.

Autonomous movement of platinum-loaded stomatocytes

Polymer stomatocytes are bowl-shaped structures of nanosize dimensions formed by the controlled deformation of polymer vesicles. The stable nanocavity and strict control of the opening are ideal for the physical entrapment of nanoparticles which, when catalytically active, can turn the stomatocyte morphology into a nanoreactor. Herein we report an approach to generate autonomous movement of the polymer stomatocytes by selectively entrapping catalytically active platinum nanoparticles within their nanocavities and subsequently using catalysis as a driving force for movement. Hydrogen peroxide is free to access the inner stomatocyte cavity, where it is decomposed by the active catalyst (the entrapped platinum nanoparticles) into oxygen and water. This generates a rapid discharge, which induces thrust and directional movement. The design of the platinum-loaded stomatocytes resembles a miniature monopropellant rocket engine, in which the controlled opening of the stomatocytes directs the expulsion of the decomposition products away from the reaction chamber (inner stomatocyte cavity).

Epoxidation of polybutadiene by a topologically linked catalyst

Nature has evolved complex enzyme architectures that facilitate the synthesis and manipulation of the biopolymers DNA and RNA, including enzymes capable of attaching to the biopolymer substrate and performing several rounds of catalysis before dissociating. Many of these ‘processive’ enzymes have a toroidal shape and completely enclose the biopolymer while moving along its chain, as exemplified by the DNA enzymes T4 DNA polymerase holoenzyme and λ-exonucleoase. The overall architecture of these systems resembles that of rotaxanes, in which a long molecule or polymer is threaded through a macrocycle. Here we describe a rotaxane that mimics the ability of processive enzymes to catalyse multiple rounds of reaction while the polymer substrate stays bound. The catalyst consists of a substrate binding cavity incorporating a manganese(III) porphyrin complex that oxidizes alkenes within the toroid cavity, provided a ligand has been attached to the outer face of the toroid to both activate the porphyrin complex and shield it from being able to oxidize alkenes outside the cavity. We find that when threaded onto a polybutadiene polymer strand, this catalyst epoxidizes the double bonds of the polymer, thereby acting as a simple analogue of the enzyme systems.

Macroscopic Hierarchical Surface Patterning of Porphyrin Trimers via Self-Assembly and Dewetting

The use of bottom-up approaches to construct patterned surfaces for technological applications is appealing, but to date is applicable to only relatively small areas (∼10 square micrometers). We constructed highly periodic patterns at macroscopic length scales, in the range of square millimeters, by combining self-assembly of disk-like porphyrin dyes with physical dewetting phenomena. The patterns consisted of equidistant 5-nanometer-wide lines spaced 0.5 to 1 micrometers apart, forming single porphyrin stacks containing millions of molecules, and were formed spontaneously upon drop-casting a solution of the molecules onto a mica surface. On glass, thicker lines are formed, which can be used to align liquid crystals in large domains of square millimeter size.

Virus-based nanocarriers for drug delivery

New nanocarrier platforms based on natural biological building blocks offer great promises in revolutionalizing medicine. The usage of specific protein cage structures: virus-like particles (VLPs) for drug packaging and targetted delivery is summarized here. Versatile chemical and genetic modifications on the outer surfaces and inner cavities of VLPs facilitate the preparation of new materials that could meet the biocompatibility, solubility and high uptake efficiency requirements for drug delivery. A full evaluation on the toxicity, bio-distribution and immunology of these materials are envisaged to boost their application potentials.

Metal-Free Triazole Formation as a Tool for Bioconjugation

The development of selective and site-specific bio-orthogonal conjugation methods is an important topic in chemical biology. A wide range of methods, such as the Staudinger ligation, native chemical ligation, genetic incorporation, expressed-protein ligation, Huisgen azide–alkyne cycloaddition, and the Diels–Alder ligation are currently employed in the selective modification of proteins and other biomolecules. In recent years, the Cu-catalyzed variant of the Huisgen 1,3-dipolar cycloaddition, also referred to as “click reaction”, has been increasingly applied in various fields of chemistry as a versatile and mild ligation method. This method allows for the synthesis of complex materials, which include bioconjugates, glycopeptides, functionalized polymers, virus particles, and therapeutics. However, due to the toxicity of the copper catalyst to both bacterial and mammalian cells applications that involve in vivo ligation are limited. In order to circumvent the use of copper ions, Bertozzi and co-workers have devised a strain-promoted [3+2] cycloaddition reaction that involves azides and a strained cyclooctyne derivative. Recent reports by Ju et al. have also shown successful applications of copper-free 1,3-dipolar cycloaddition by using either elevated temperatures or electron-deficient alkynes. We envisioned that the combination of ring strain and electron deficiency, as occurs in oxa-bridged bicyclic systems 2a and 2b, could also lead to an increased reactivity toward [3+2] cycloaddition reactions. Here, we report a spontaneous tandem [3+2] cycloaddition–retro-Diels–Alder ligation method that results in a stable 1,2,3-triazole linkage. This methodology can be applied to biomacromolecules that contain various functional groups under physiological conditions. The oxabridged bicyclic systems 2a and 2b were prepared by a Diels– Alder reaction of substituted propiolates with furan (Scheme 1). Subsequent hydrolysis provided the desired carboxylic acid derivatives 3a and 3b, in excellent yield. To compare the reactivity of Diels–Alder products 2a and b with the corresponding alkynes, [3+2] cycloaddition reactions were performed under ambient conditions by using benzyl azide, and monitored over time with H NMR spectroscopy (Figure 1). The oxanorbornadienes 2a and 2b and their respective alkynes provided identical 1,4,5-substituted triazoles to the products.

Molecular materials based on crown ether functionalized phthalocyanines

This micro-review presents an overview of molecular materials derived from phthalocyanines which are substituted with crown ether rings. These flat disk-like molecules can self-assemble into ordered, well-defined structures with or without the aid of alkali metal ions. Highly ordered assemblies of crown ether phthalocyanines are capable of transporting electrons and ions, which is of interest for sensor applications.