Supramolecular Polymeric Materials Research Articles

Methods for Synthesizing the Macromolecular Constituents of Smart Nanosized Carriers for Controlled Drug Delivery

Smart multifunctional polymeric nanocarriers able to respond to physicochemical changes in their environment or to external stimuli represent a new paradigm in the field of pharmaceutical formulations for controlled drug delivery. The introductory part of the present review deals with this new concept and presents the main advantages resulting from the use of such nanovehicles instead of conventional, much larger drug delivery systems. The access to drug nanocarriers based on smart supramolecular polymeric materials is primarily limited by the available polymerization methods capable to produce polymers with low polydispersity index, as well as much more complex macromolecular architectures with strictly controlled chemical composition, such as block copolymers and star or graft polymers or copolymers. This article reviews the state-of-the art in controlled/"living" free radical polymerization techniques as well as ring opening polymerization methods. Nitroxide mediated free radical polymerization (NMP), atom transfer radical polymerization (ATRP), reversible addition-fragmentation chain-transfer polymerization (RAFT), single electron transfer-living radical polymerization (SET-LRP), single electron transfer-nitroxide radical coupling reaction (SET-NRC), cationic ring opening polymerization (CROP), anionic ring opening polymerization (AROP), and metal catalyzed ring opening polymerization are described, highlighting their mechanistic details and their synthetic potential as well as their limitations. The final part of the article is dedicated to a special type of unimolecular, monodisperse nanocarriers - the dendrimers. Both divergent and convergent approaches to dendrimer synthesis are described along with the therapeutic applications taking advantage of the unique branched tree-like globular structure of dendrimers to treat cancer.

Depolymerizable, adaptive supramolecular polymer nanoparticles and networks

Depolymerizable polymers are appended with supramolecular cross-linking motifs to enable preparation of tunable single-chain polymeric nanoparticles and degradable polymer networks.

Aggregation-induced emission encoding supramolecular polymers based on controllable sulfonatocalixarene recognition in aqueous solution

A pH-responsive supramolecular polymer based on a homoditopic bis-p-sulfonatocalixarene host and a tetraphenylethylene derivative guest as building blocks with aggregation-induced emission (AIE) property is fabricated in aqueous solution. Quite different from usual supramolecular polymers constructed before, this novel supramolecular polymer has high luminescence efficiency rather than becoming low-luminescent after polymerization. Interestingly, the AIE signals are switchable between two alternative emission wavelengths in H2O or with ON and OFF switching in the mixing H2O–THF = 1 : 1 solution, which are realized by controllable and reversible supramolecular interactions. This strategy to design supramolecular polymers with switchable AIE property overcomes the common problem of aggregation-caused quenching (ACQ) in usual supramolecular polymers and provides a new concept to develop smart supramolecular polymeric materials.

Synthesis, self‐assembly and reversible healing of supramolecular perfluoropolyethers

ABSTRACTThe synthesis and thermomechanical properties of a novel class of self‐healing perfluoropolyethers (PFPEs) is reported. By decoration of 2‐ureido‐4[1H]‐pyrimidone end groups on the termini of low molar mass PFPE, the formation of supramolecular polymers and networks held together via hydrogen bonding associations was achieved. These novel supramolecular polymer materials exhibit a combination of enhanced modulus and elasticity, along with self‐healing properties, where rapid self‐healing time was demonstrated using dynamic rheological measurements. These types of supramolecular PFPEs are anticipated to be useful for a number of emerging areas in lubrication. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 3598–3606

PH-Controlled Reversible Formation of a Supramolecular Hyperbranched Polymer Showing Fluorescence Switching

A π-conjugated AB2 monomer 1 with a dibenzo[24]crown-8 (DB24C8) ring and two secondary amine centres has been synthesised. Treatment of a solution of 1 in dichloromethane with trifluoroacetic acid (TFA) leads to protonation of the amine groups, and then the DB24C8 rings are threaded by the dialkylammonium ion centres of other monomer molecules, leading to the formation of a supramolecular hyperbranched polymer, TFA-1. Rather strong π-π stacking interactions between the conjugated cores are evident in this polymer. The supramolecular hyperbranched polymer (SHP) can be completely depolymerised by adding a slight excess of N-tert-butyl-N',N',N'',N'',N''',N'''-hexamethylphosphorimidic triamide, tetrabutylammonium fluoride, or tetrabutylammonium acetate. The acid-base-controlled process induces a reversible change in the fluorescence intensities of the solutions due to the controllable presence of the π-π stacking interactions between the conjugated cores. This dynamic behaviour is significant with respect to "smart" supramolecular polymer materials.

ChemInform Abstract: Stimuli‐Responsive Supramolecular Polymeric Materials

AbstractReview: 303 refs.

Stimuli-responsive supramolecular polymeric materials

Supramolecular materials, dynamic materials by nature, are defined as materials whose components are bridged via reversible connections and undergo spontaneous and continuous assembly/disassembly processes under specific conditions. On account of the dynamic and reversible nature of noncovalent interactions, supramolecular polymers have the ability to adapt to their environment and possess a wide range of intriguing properties, such as degradability, shape-memory, and self-healing, making them unique candidates for supramolecular materials. In this critical review, we address recent developments in supramolecular polymeric materials, which can respond to appropriate external stimuli at the fundamental level due to the existence of noncovalent interactions of the building blocks.

TOF-Secondary Ion Mass Spectrometry Imaging of Polymeric Scaffolds with Surrounding Tissue after in Vivo Implantation

Supramolecular polymeric materials are of increasing interest for the use as drug delivery carriers. A thorough insight in the biocompatibility and the degradation of these materials in vivo are of fundamental importance to further their development and application in medical practice. Molecular imaging techniques are powerful tools that enable the elucidation of molecular distributions in and around such polymer implants. A supramolecular polymeric hydrogel was implanted under the renal capsule to study its biocompatibility with TOF-SIMS. This results in a molecular cartography of the polymer implant combined with the cellular signature of the implantation environment. In this experiment, molecular signals are observed from cells that are involved in the biological response to the implant, e.g., macrophages. These molecular signatures are compared with macrophage standards cultured in different polarization environments. On the basis of this comparison, information can be acquired on the various macrophage differentiations that are connected to different stages in the foreign body response. Mass spectrometric imaging techniques offer the opportunity to visualize different histological phenomena in a single experiment without the need for specific immunohistochemical markers. Cellular infiltration into the polymer is visualized, offering a clear view on both biological and polymer features in a single imaging experiment.

Self-assembly constructed by perylene bisimide derivatives bearing complementary hydrogen-bonding moieties

An intermediate compound 2, 4-bis(laurylamino)-6-(1-(2-aminoethyl)-piperazine)-1, 3, 5-triazine was prepared by stepwise nucleophilic substitution on triazine ring by lauryl amine and subsequently 1-(2-aminoethyl)-piperazine. Then imidization of perylene-3, 4, 9, 10-tetracarboxylic acid dianhydride with 2,4-bis(laurylamino)-6-(1-(2-aminoethyl)-piperazine)-1, 3, 5-triazine was carried out to afford a novel perylene derivative bearing two melamine blocks (S2) and 1, 6, 7, 12-tetra(4-tert-butyl phenoxy)-perylene-3, 4, 9, 10-tetracarboxylic acid bisimide (S1). The hydrogen-bonding interactions between S1 and S2 were investigated by 1H NMR spectrum, UV/Vis spectrum and fluorescence spectrum. The influences on the morphologies of S1·S2 aggregates were investigated. The results show that well-defined nanofibers with a diameter of about 100 nm can be obtained by self-assembly between S1 and S2 only in CH2Cl2 solution. Based on these results, guidelines for the molecular design and self-assembly of supramolecular polymer materials are presented.

Supramolecular Biomaterials. A Modular Approach towards Tissue Engineering

Abstract Supramolecular chemistry is an exciting area of science that plays a central role in bringing different disciplines together, ranging from molecular medicine to nanotechnology. Materials science based on supramolecular interactions is an emerging field, which has made important steps forward in the past ten years. The self-assembly of small synthetic molecules into long-chain architectures gives rise to the careful design of supramolecular polymers or fibers based on highly directional, reversible, non-covalent interactions. Much afford is put into the development of supramolecular (polymeric) materials with true materials properties, both in solution and in the solid state. These supramolecular materials are beginning to reach the market in all kind of applications. The field of regenerative medicine in general and that of tissue engineering in particular is one of the most challenging areas in which supramolecular materials might have a high potential. In tissue engineering, the biological environment and the interactions of cells with the artificial biomaterial is of utmost importance for the functioning of the implant, i.e. the engineered tissue. Ideal biomaterials do not only have to fulfil the biomaterials trinity of tuneable mechanical properties, regulation of the degradability and the ease for bioactivity incorporation, but also have to mimic the natural environment where the materials are brought into. Therefore, a modular, self-assembly approach using several supramolecular building blocks is an exquisite way to produce such “responsive” biomaterials. It is proposed that the artificial materials described in this account have the same type of dynamic ability to adapt its biofunctionality as is so well known for the living cells in the host tissue. This account will highlight two systems, i.e. self-assembling oligopeptide fibers as pioneered by Stupp et al. and Zhang et al., and our hydrogen-bonded supramolecular polymers, to show the potential of a modular approach to dynamic biomaterials for tissue engineering.

Perspectives on main‐chain hydrogen bonded supramolecular polymers

AbstractSupramolecular polymers are assembled from monomeric units held together by reversible non‐covalent interactions. These supramolecular materials display polymeric properties and may soon have important industrial applications. This mini review focuses on the advances in main‐chain supramolecular polymers whose assembly is guided primarily by hydrogen bonding interactions. The design constraints of these new systems discussed include assembly motifs, the strength and directionality of the non‐covalent interactions, association versus reversibility, and environmental effects on the degree of polymerization. Selected literature examples including Meijer's ureidopyrimidinone system are used to highlight the challenges and potential of these supramolecular polymeric materials. Copyright © 2007 Society of Chemical Industry

Synthesis and assembly behavior of nucleobase‐functionalized block copolymers

The use of oligonucleobase moieties in materials science has experienced growing interest in recent years. Several researchers have elegantly shown the application of oligonucleotides as versatile building blocks for the synthesis of, for example, controlled nanoscaled structures and molecular machines. Also, in polymer science, oligonucleobases have become a topic of investigation. Nucleobase-functionalized polymers have been applied in various applications such as template polymerizations and supramolecular materials, in which the noncovalent anchors are based on oligonucleotides. Lutz et al. found that the incorporation of a complementary nucleobase functionality into synthetic copolymers leads to materials that can exhibit a DNAlike melting behavior. In addition, Rowan and coworkers prepared thermoresponsive supramolecular polymer materials, in which the noncovalent interactions are based on single nucleobase moieties. Recent advances in controlled (radical) polymerization techniques such as atom transfer radical polymerization (ATRP) have further increased activity in the polymer chemistry field. These methods allow the formation of well-defined polymer architectures in which a large variety of biological functionalities, such as nucleobases, can be included. It is well known that amphiphilic block copolymers have the ability to assemble into multiple morphologies in solution. Depending on a number of parameters, such as the ratio of the hydrophilic and hydrophobic blocks, the morphology can vary from spherical micelles, rods, and vesicles to large compound micelles (LCMs). Even more structural control is possible when block copolymers are used that are built up out of a synthetic part and a biomolecular part. Another method was developed by Rotello and coworkers, who prepared plug and play polymers that facilitated recognition through hydrogen-bonding interactions to change the morphology of the polymers or even direct self-assembly of patterned surfaces. Several examples in which peptide sequences are incorporated into polymer chains have been shown to control the material properties and enable self-assembly into well-defined nanoscale architectures. Besides proteins, this could also apply to nucleobase block copolymers. In previous investigations, it already has been demonstrated that the incorporation of small oligonucleotide strands has vast potential to influence the aggregation of block copolymers. Often the incorporation of these biofunctional moieties into the polymer chain facilitates some form of aggregation. Either the aggregation of the biological functionality is enhanced by the polymer chain or aggregation of the polymer chains is increased via specific interactions between the biological functionalities. In addition, the nanocompartmentalization by block copolyCorrespondence to: J. C. M. van Hest (E-mail: j.vanhest@ science.ru.nl)

Utilization of a Combination of Weak Hydrogen-Bonding Interactions and Phase Segregation to Yield Highly Thermosensitive Supramolecular Polymers

Supramolecular polymerization, i.e., the self-assembly of polymer-like materials through the utilization of the noncovalent bond, is a developing area of research. In this paper, we report the synthesis and investigation of nucleobase-terminated (N6-anisoyl-adenine and N4-(4-tert-butylbenzoyl)cytosine) low molecular weight poly(THF) macromonomers (<2000 g mol(-1)). Even though the degree of interaction between the nucleobase derivatives is very low (<5 M(-1)) these macromonomers self-assemble in the solid state to yield materials with film and fiber-forming capability. While the mechanical properties of films of both materials show extreme temperature sensitivity, resulting in the formation of very low viscosity melts, they do behave differently, which is attributed to the nature of the self-assembly controlled by the nucleobase. A combination of FT-IR, WAXD, and rheological experiments was carried out to further investigate the nature of the self-assembly in these systems. The studies demonstrate that a combination of phase segregation between the hard nucleobase chain ends and the soft poly(THF) core combined with aromatic amide hydrogen bonding is utilized to yield the highly thermosensitive supramolecular polymeric materials. In addition, analysis of the data suggests that the rheological properties of these supramolecular materials is controlled by the disengagement rate of the nucleobase chain ends from the "hard" phase, which, if shown to be general, provides a design criteria in the development of more thermally responsive materials.

Polymer science with transition metals and main group elements: Towards functional, supramolecular inorganic polymeric materials

AbstractInorganic polymers are relatively unexplored because the efficient formation of macromolecular chains from atoms of transition metals and main group elements has presented a synthetic challenge. Nevertheless, these materials offer exciting opportunities for accessing properties that are significantly different from and which therefore complement those available with the well‐established organic systems. Inorganic block copolymers are of particular interest for the generation of functional, nanoscale supramolecular architectures and hierarchical assemblies using self‐assembly processes. This article focuses on research in my group over the past decade, which has targeted the development of new and controlled routes to inorganic polymers and their subsequent use in forming supramolecular materials as well as studies of their properties and applications. The use of ring‐opening polymerization (ROP) and transition‐metal‐catalyzed polycondensation approaches are illustrated. Controlled ROP procedures have been developed that allow access to polyferrocene block copolymers that self‐assemble into interesting nanoscopic architectures such as cylinders and superstructures such as flowers. The future prospects for inorganic polymer science are discussed, and a growing emphasis on the study of supramolecular inorganic polymeric materials is predicted. © 2001 John Wiley &amp; Sons, Inc. J Polym Sci Part A: Polym Chem 40: 179–191, 2002

Orientation of Supramolecular Self-Organized Polymeric Nanostructures by Oscillatory Shear Flow

Macroscopic orientation of self-organized supramolecular polymeric materials has been demonstrated by oscillatory shear flow using in-situ small-angle X-ray scattering (SAXS). In the case when a homopolymer poly(4-vinylpyridine) and pentadecylphenol molecules are stoichiometrically complexed to form comb copolymer-like supermolecules, the self-organized lamellar local structures align parallel when sheared below the order-disorder transition temperature at 56 °C using 0.5 Hz frequency and 100% strain amplitude. Therefore, the hydrogen bonds between the phenolic and pyridine groups are strong enough to withstand the applied flow. In the case of a diblock copolymer of polystyrene and poly(4-vinylpyridine) stoichiometrically complexed with pentadecylphenol molecules to form the supermolecules, the self-organization yields lamellar-within-lamellar local structure near room temperature. The larger lamellar diblock copolymer structure showed a parallel orientation relative to the shearing plates upon shearing at 125 °C (i.e., above the order-disorder transition of the short length scale comb copolymer-like structure) with initially 0.5 Hz and finally 1 Hz, both at 50% strain amplitude. On cooling, the short length scale lamellar structure, consisting of poly(4-vinylpyridine) block and pentadecylphenol, is formed inside the layers of the comb copolymer-like material in perpendicular orientation.