Metallo‐supramolecular micelles: Studies by analytical ultracentrifugation and electron microscopy

In aqueous solutions, amphiphilic block copolymers in which a polystyrene (PS) segment is connected to a poly(ethylene oxide) (PEO) block via a bis(2,2′:6′,2″‐ terpyridine ruthenium) complex can form micelles. Such micelles of the protomer type PS₂₀‐[Ru]‐PEO₇₀, according to the preparation procedure representing frozen micelles, were studied by sedimentation velocity and sedimentation equilibrium analysis in an analytical ultracentrifuge and by transmission electron microscopy, with different techniques applied for the sample preparation. The particles obtained were surprisingly multifarious in size. In ultracentrifugation experiments performed at relatively low salt concentrations, the distributions of the sedimentation coefficient s_20,w showed a pronounced peak at 9.6 S and a broad, only partly separated second peak around 14 S. The molar mass of the particles at the peak was around 430,000 g/mol, corresponding to an aggregation number of approximately 85. The average hydrodynamic diameter of the particles in the peak fraction was approximately 13 nm. In electron micrographs of negatively stained samples, spheres of diameters between 10 and 25 nm were the most abundant particles, but larger ones with a wide size range were also visible. The latter particles apparently were composed of smaller ones. The data from both sedimentation analysis and electron microscopy showed that (1) the studied compound formed primary micelles of diameters around 20 nm and (2) the primary micelles had a tendency toward aggregation. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 3159–3168, 2003     

Reversible Metallo‐Supramolecular Block Copolymer Micelles Containing a Soft Core

An amphiphilic metallo‐supramolecular poly(ethylene‐co‐butylene)‐block‐poly(ethylene oxide) diblock copolymer containing a bis(2,2′:6′,2″‐terpyridine)ruthenium(II) complex as a supramolecular connection between the two constituting blocks was used to prepare stable aqueous micelles. The micelles were characterized by dynamic light scattering and atomic force microscopy. Individual micelles were observed together with aggregates of micelles. Only the addition of a large excess of competitive ligand caused the cleavage of the very stable ruthenium complex.     

Metallo‐Supramolecular Graft Copolymers: A Novel Approach Toward Polymer‐Analogous Reactions

A copolymer of poly(methyl methacrylate) with terpyridine units in the side chains was synthesized utilizing free‐radical polymerization. The free terpyridine units were complexed with several different terpyridineruthenium mono‐complexes, yielding metallo‐supramolecular graft copolymers. The materials obtained were characterized by means of NMR and UV‐vis spectroscopy as well as GPC. Characterization by thermal analysis revealed distinct differences between these new materials and the initial copolymer.     

Metallo‐supramolecular Crosslinked Polyurethanes

The effects of incorporating metal‐binding ligands as chain extenders in polyurethane elastomers were investigated. Segmented polyurethanes based on 2 kDa poly(tetramethylene oxide) (PTMO) and 4,4‐methylenebis(cyclohexyl isocyanate) were polymerized using a two‐step process in which 2,6‐bis(1‐ethyl‐5‐(methoxymethyl)‐1H‐benzo[d]imidazol‐2‐yl)pyridine was added as a chain extender. The resulting polyurethanes were then metallated using stoichiometric amounts of Zn(II) metal salts with different counterions. The resulting metallopolymers have substantially improved Young's moduli, increased failure stress, and improved thermomechanical behavior. The materials were microphase‐separated into anisotropic hard domains within a PTMO matrix. Simultaneous small‐angle X‐ray scattering and tensile testing revealed the minority hard segment domains remain relatively intact during elongation, likely due to the strength of the metal–ligand complex. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2019 , 57, 1744–1757     

Molecule-responsive block copolymer micelles

Ring-opening metathesis polymerization was used to generate an ABC triblock copolymer, containing complementary diamidopyridine (DAP) and thymine (THY) outer blocks, which assembles into spherical aggregates held together by DAP-THY noncovalent interactions. Addition of THY-containing small guest molecules results in complete opening and deaggregation of the block copolymer micelle. This molecular recognition and macroscopic response shows high selectivity to the guest structure, and tolerates only a small amount of conformational mobility in the THY guest. On the other hand, addition of a small DAP-containing guest does not break the aggregates, but instead, results in new micelles which show a different selectivity profile from the parent morphology. We have examined the effect of a number of structural features in the block copolymers, on both the extent and selectivity of their macroscopic response to guests (that is, opening of the micelle). This study has resulted in a set of structural guidelines, which help in the design of effective molecule-responsive micelles for applications in selective drug delivery, sensing, and surface patterning.     

From supramolecular block copolymers to advanced nano-objects

The formation of asymmetric bis-complexes, based on terpyridine ligands and ruthenium ions, is described as a powerful tool for the self-assembly of polymer blocks end-functionalized with terpyridine units. This is illustrated in this contribution for the synthesis of amphiphilic metallo-supramolecular block copolymers, which are further used to produce aqueous micelles. Finally, the reversibility of the supramolecular bond opens new avenues for the preparation and manipulation of these nano-objects.     

Novel pH sensitive block copolymer micelles for solvent free drug loading

Novel pH sensitive biodegradable block copolymers (MPEG-PDLLA-OSM) composed of mono-methoxy poly(ethylene glycol) (MPEG), poly (D,L-lactide) (PDLLA) and sulfamethazine oligomer (OSM) were synthesized via ring-opening polymerization and a dicyclohexyl carboimide (DCC) coupling reaction. These copolymers had a relatively low critical micelle concentration (CMC) due to the strong hydrophobic properties of non-ionized OSM at pH 7.0. Also, the pH sensitive block copolymers showed the micelle-unimer transition due to the ionization-non-ionization of OSM in the pH range (pH 7.2-8.4) above the CMC. Due to the pH sensitive properties of the block copolymer, the hydrophobic drug paclitaxel (PTX) was incorporated into a pH sensitive block copolymer micelle by the pH induced micellization method, without using an organic solvent. The block copolymer micelle prepared by pH induced micellization showed a relatively high PTX loading efficiency, and good stability for 2 d at 37 degrees C. Furthermore, the PTX loaded micelle showed a sustained release of PTX with a small burst in vitro over 2 d. The present results suggest that the pH induced micellization method due to the micelle-unimer transition of the pH sensitive block copolymer would be a novel and valuable drug incorporation tool for hydrophobic and protein drugs, since no organic solvent is involved in the formulation.     

星形PLA-PEG嵌段共聚物胶束的制备与表征

以胆酸为引发剂,用辛酸亚锡催化丙交酯开环聚合合成星型CA-PLA。利用DCC为脱水剂,将不同分子量的端羧基化PEG与星型CA-PLA偶联,合成一系列以胆酸为核的星形两亲性嵌段共聚物,用透析法制备共聚物胶束,并用TEM和DLS研究胶束的性质。合成了分子量为6000和12000的两种CA-PLA,其分子量可以通过胆酸羟基与丙交酯的比例进行控制。将分子量2000和5000的PEG分别与两种CA-PLA偶联,合成了四种星型CA-PLA-PEG嵌段共聚物。共聚物胶束形貌为均匀的球形,粒径为20-40nm,且随共聚物中PLA链段分子量的增加而增大,随PEG链段分子量的增加而减小。临界胶束浓度(CMC)低于同等链段长度的线型PLA-PEG嵌段共聚物胶束。     

Micelles and reverse micelles with a photo and thermo double‐responsive block copolymer

A novel photo and thermo double‐responsive block copolymer was developed to fabricate micelles and reverse micelles in aqueous solution. The block copolymer was synthesized by ATRP block copolymerization of a spiropyran‐ containing methacrylate (SPMA) with di(ethylene glycol) methyl ether methacrylate (DEGMMA). By facile control of the photo irradiation and solution temperature, PSPMA‐core and PDEGMMA‐core micelles can be obtained, respectively. The thermo‐ and photo‐responsive micelles were used as smart polymeric nanocarriers for controlled encapsulation, triggered release, and re‐encapsulation of model drug coumarin 102. The double‐responsive self‐assembly and disassembly were tracked by dynamic light scattering, transmission electron microscopy, and fluorescence spectroscopy. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 2855–2861, 2010     

Cylindrical micelles from the aqueous self-assembly of an amphiphilic poly(ethylene oxide)-b-poly(ferrocenylsilane) (PEO-b-PFS) block copolymer with a metallo-supramolecular linker at the block junction

A supramolecular AB diblock copolymer has been prepared by the sequential self-assembly of terpyridine end-functionalized polymer blocks by using Ru(III)/Ru(II) chemistry. By this synthetic strategy a hydrophobic poly(ferrocenylsilane) (PFS) was attached to a hydrophilic poly(ethylene oxide) (PEO) block to give an amphiphilic metallo-supramolecular diblock copolymer (PEO/PFS block ratio 6:1). This compound was used to form micelles in water that were characterized by a combination of dynamic and static light scattering, transmission electron microscopy, and atomic force microscopy. These complementary techniques showed that the copolymers investigated form rod-like micelles in water; the micelles have a constant diameter but are rather polydisperse in length, and light scattering measurements indicate that they are flexible. Crystallization of the PFS in these micelles was observed by differential scanning calorimetry, and is thought to be the key behind the formation of rod-like structures. The cylindrical micelles can be cleaved into smaller rods whenever the temperature of the solution is increased or they are exposed to ultrasound.     

Temperature‐based fluorescence measurements of pyrene in block copolymer micelles: Probing micelle core glass transition breadths

Glass transition temperature (T_g) breadths are reported for polystyrene (PS) micelle cores in two series of micelle‐forming block copolymers [PS‐poly(ethylene oxide) and PS‐poly(methyl methacrylate)] with an ionic liquid solvent (1‐ethyl‐3‐methylimidazolium bis(trifluoromethylsulfonyl)amide). An increased level of fluorescent molecules was induced within the cores upon rapid cooling followed by aging. Using fluorescence to monitor dye release with relaxation of this state upon heating, transition onset and end‐point temperatures were defined. The system with the lowest PS‐block molecular weight showed no evidence of a transition above 25 °C; however, in every other case, transitions were observed beginning at ～40‐45 °C and ending at ～60‐85 °C. These temperatures closely match PS‐block T_g results measured by differential scanning calorimetry in semidilute solutions of the same materials, suggesting that the transition temperature range correlates strongly to the transition of the cores from fully glassy to fully rubbery. Differences in transition end‐points were related to PS‐block molecular weights and relative copolymer fractions of PS. © 2011 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2012     

Synthesis of core‐crosslinked carbosilane block copolymer micelles and their thermal transformation to silicon‐based ceramics nanoparticles

Carbosilane fine particles were synthesized by core‐crosslinking of carbosilane block copolymer micelles and they were pyrolytically transformed into silica nanoparticles. The carbosilane block copolymer, poly(1‐(3‐butenyl)‐1‐methylsilacyclobutane)‐block‐polystyrene, (polyBMSB‐b‐polySt), [(m, n) = (31, 16), (54, 30), and (75, 28)], was synthesized by anionic polymerization of BMSB and St, where m and n represent polymerization degrees of BMSB and St segments, respectively. The block copolymer formed micelles in N,N‐dimethylformamide (DMF). The hydrodynamic diameters (D_h) of the micelles evaluated by dynamic light scattering ranged from 40 to 158 nm depending on the copolymer molecular weight. The core of the micelle was cross‐linked by Pt‐catalyzed hydrosilation with 1,2‐bis(dimethylsilylethane). The D_h of the core‐cross‐linked micelles in THF ranged from 56 to 164 nm. These precursor particles were pyrolyzed at 850 °C under N₂ to give ceramic nanoparticles. The diameters of the spherical ceramic particles estimated by AFM ranged from 25 to 60 nm. X‐ray fluorescence analysis of the ceramic products revealed that it consisted of mainly SiO₂ rather than SiC. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 3778–3787, 2005     

Formation of thermo‐sensitive and cross‐linkable micelles by self‐assembly of poly(pentafluorophenyl acrylate)‐containing block copolymer

Poly(pentafluorophenyl acrylate)‐block‐poly(N‐isopropylacrylamide) (PPFPA‐b‐PNIPAM) is synthesized by reversible addition‐fragmentation chain transfer (RAFT) polymerization. Light‐responsive moieties of ortho‐nitrobenzyl (ONB)‐protected diamine are partially introduced to the PFPA moieties via postpolymerization modification. The amphiphilic block copolymers are assembled into micelles in water. The ONB‐protected diamine group in the micelle core is released upon UV irradiation, which subsequently induces an in situ cross‐linking by a spontaneous reaction with the remaining PFPA groups in the core and yields stable cross‐linked micelles. Micellization of the copolymers is confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). 4‐Nitro‐7‐piperazino‐2,1,3‐benzoxadiazole (NBD) and pyrene are loaded in the core of cross‐linked micelles to demonstrate the possibility for additional post‐functionalization of residual PFPA moieties and hydrophobic molecule encapsulation, respectively. It is anticipated that these micelles can be alternative cargos for incorporating active compounds that may be useful for advanced applications. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 1103–1113     

A Homotelechelic bis‐terpyridine macroligand: One‐step synthesis and its metallo‐supramolecular self‐assembly

A homotelechelic macroligand bearing two 2,2′:6′,2″‐terpyridin‐4′‐yl units, as chain ends, is used as building block for the preparation of a linear metallo‐supramolecular chain‐extended polymer. The macroligand has been prepared by nitroxide‐mediated polymerization (NMP) of styrene using a bis‐terpyridine‐functionalized NMP initiator. The controlled character of the NMP process has been confirmed by detailed characterization of the polymer by size‐exclusion chromatography, nuclear magnetic resonance spectroscopy as well as mass spectrometry. Subsequently, the self‐assembly with Fe^II ions into the chain‐extended metallopolymer and the disassembly thereof, in the presence of a strong competitive ligand, has been studied by UV–vis absorption spectroscopy and diffusion‐ordered NMR spectroscopy. The reversibility of the formation of the metallo‐supramolecular material, when addressed by external stimuli, could be proven. © 2013 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013     

Polymeric micelles and nanoparticles from block and statistical poly((RS)-3,3-dimethylmalic acid) derivatives: preparation and characterization

Amphiphilic and biodegradable micelles and nanoparticles designed as potential drug carriers were prepared from biodegradable statistical and block copolyesters obtained by a living anionic ring-opening process. These novel materials display amphiphilic properties arising from the joint presence of hydrophilic poly((RS)-3,3-dimethylmalic acid) and hydrophobic poly(hexyl (RS)-3,3-dimethylmalate) segments. Micelles obtained from a well-defined block copolymer have been characterized by their critical aggregation concentration, and nanoparticles derived from statistical copolymer have been analyzed by transmission electron microscopy (TEM).     

UV‐induced crosslinking of ring opening metathesis block copolymer micelles

Statistical and amphiphilic block copolymers bearing cinnamoyl groups were prepared by ring opening metathesis polymerization (ROMP). The UV‐induced [2 + 2] cycloaddition reaction of polymer bound cinnamic acid groups was studied in polymer thin films as well as in block copolymer micelles. In both cases, exposure to UV‐light for 10 min led to a crosslinking conversion of about 60%, as determined by FT‐IR spectroscopy and UV–vis absorption measurements. Time based IR‐spectroscopy revealed a maximum conversion of 78% reached after an irradiation time of about 16 min. For micelles obtained from polymers bearing 5 mol % or more cinnamoyl groups, the crosslinking reaction proceeded smoothly, yielding in crosslinked particles which were stable in a non‐selective solvent (CHCl₃). Diameters determined by dynamic light scattering in the selective solvent (MeOH) were similar for both, non‐crosslinked and crosslinked micelles, whereas diameters of crosslinked micelles in the non‐selective solvent (CHCl₃) were significantly larger compared to MeOH samples. This strategy of direct self assembly of block‐copolymers in a selective solvent followed by “clean” crosslinking, without the need for additional crosslinking reagents or crosslinking initiators, provides a straight forward approach toward ROMP‐based polymeric nano‐particles. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 2402–2413, 2008     

Metallo‐Supramolecular Diethylene Glycol: Water‐Soluble Reversible Polymers

Bis(2,2′:6′,2″‐terpyrid‐4′‐yl) diethylene glycol was synthesized as a monomer unit and further utilized for polymerization with FeCl₂ in order to form water‐soluble coordination polymers. Viscosity measurements and film‐forming properties indicate the formation of linear coordination polymers or larger ring structures. The terpyridine/iron(II) complexes are stable up to temperatures of 210 °C, but can be uncomplexed by the addition of an excess of a strong competitive ligand (HEDTA) under mild conditions.