Molecular Brushes Research Articles

Strategies Toward Well-Defined Polymer Nanoparticles Inspired by Nature: Chemistry versus Versatility.

Polymeric nanoparticles are promising delivery platforms for various biomedical applications. One of the main challenges toward the development of therapeutic nanoparticles is the premature disassembly and release of the encapsulated drug. Among the different strategies to enhance the kinetic stability of polymeric nanoparticles, shell- and core-crosslinking have been shown to provide robust character, while creating a suitable environment for encapsulation of a wide range of therapeutics, including hydrophilic, hydrophobic, metallic, and small and large biomolecules, with gating of their release as well. The versatility of shell- and core-crosslinked nanoparticles is driven from the ease by which the structures of the shell- and core-forming polymers and crosslinkers can be modified. In addition, postmodification with cell-recognition moieties, grafting of antibiofouling polymers, or chemical degradation of the core to yield nanocages allow the use of these robust nanostructures as "smart" nanocarriers. The building principles of these multifunctional nanoparticles borrow analogy from the synthesis, supramolecular assembly, stabilization, and dynamic activity of the naturally driven biological nanoparticles such as proteins, lipoproteins, and viruses. In this review, the chemistry involved during the buildup from small molecules to polymers to covalently stabilized nanoscopic objects is detailed, with contrast of the strategies of the supramolecular assembly of polymer building blocks followed by intramicellar stabilization into shell-, core-, or core-shell-crosslinked knedel-like nanoparticles versus polymerization of polymers into nanoscopic molecular brushes followed by further intramolecular covalent stabilization events. The rational design of shell-crosslinked knedel-like nanoparticles is then elaborated for therapeutic packaging and delivery, with emphasis on the polymer chemistry aspects to accomplish the synthesis of such nanoparticulate systems.

One‐pot, facile synthesis of well‐defined molecular brush copolymers by a tandem RAFT and ROMP, “Grafting‐through” strategy

Two well-defined brush copolymers, PNB-g-PMMA, were synthesized by a one-pot, RAFT/ROMP, “grafting-through” method, without intermediate steps of isolation or purification. The controlled dimensions of the brushes were verified by atomic force microscopy. This strategy significantly simplified the synthesis of brush copolymers when compared with conventional methods.

Synthesis and characterization of organic–inorganic macrocyclic molecular brushes with poly(ε-caprolactone) side chains

In this work, we reported the synthesis of a dodecahydroxyl-functionalized macrocyclic oligomeric silsesquioxane (MOSS). The novel 24-membered hydroxyl-functionalized MOSS was employed as a macroinitiator for the ring-opening polymerization of ε-caprolactone (CL) and the organic–inorganic macrocyclic molecular brushes with poly(ε-caprolactone) (PCL) side chains were successfully synthesized. The organic–inorganic macrocyclic molecular brushes were characterized by means of nuclear magnetic resonance spectroscopy (NMR) and gel permeation chromatography (GPC). The results of wide angle X-ray diffraction (XRD) indicate that the architecture of the organic–inorganic macrocyclic molecular brushes did not alter the structure of PCL crystals. Differential scanning calorimetry (DSC) shows that the architecture of organic–inorganic macrocyclic molecular brushes significantly affected the rearrangement of PCL crystals. Compared to linear PCL, the organic–inorganic macrocyclic molecular brushes possessed the improved thermal stability in terms of the temperatures at the maximum of degradation rate and the yields of degradation residues.

Synthesis and Characterization of Brush-Shaped Hybrid Inorganic/Organic Polymers Based on Polyphosphazenes

A series of densely grafted star- and comb-shaped molecular brushes composed of polystyrene, poly(tert-butyl acrylate), and poly(N-isopropylacrylamide) were prepared by atom transfer radical polymerization (ATRP) using either cyclotriphosphazenes or polyphosphazenes as initiators. The initiators were prepared by the introduction of a free hydroxyl group into the side chains of a phosphazene cyclic trimer and polymer, followed by esterification with 2-bromopropionyl bromide. The grafting conditions were optimized for various monomers. The kinetics of the reaction were first-order with respect to the monomer concentration in both cyclotriphosphazene and polyphosphazene systems. The molecular weights of the resulting polymers were estimated by gel permeation chromatography (GPC). The side chains of the brush polymers were cleaved from the backbone and analyzed by GPC to confirm the synthesis of well-defined polymer brushes. Brushes based on poly(tert-butyl acrylate) were subjected to hydrolysis to yield nega...

Formation of nanophases in epoxy thermosets containing an organic–inorganic macrocyclic molecular brush with poly(ε-caprolactone)-block-polystyrene side chains

In this contribution, we report the synthesis of organic–inorganic macrocyclic molecular brushes with a 24-membered macrocyclic oligomeric silsesquioxane (MOSS) backbone and with poly(e-caprolactone) (PCL) (or poly(e-caprolactone)-block-polystyrene (PCL-b-PS) diblock copolymer) side chains. The macrocyclic molecular brushes were incorporated into epoxy to access the nanostructured thermosets. The nanostructures in the thermosets were investigated by means of atomic force microscopy (AFM), small angle X-ray scattering (SAXS) and dynamic mechanical thermal analysis (DMTA). It is judged that the formation of the nanophases in the thermosets containing the macrocyclic molecular brush with PCL side chains (MOSS[PCL]12) follows the self-assembly mechanism in terms of the immiscibility of the MOSS backbone with epoxy after and before the curing reaction. It was found that the spherical, vesicular and lamellar nanophases were formed in the epoxy thermosets containing the macrocyclic molecular brush with PCL-b-PS side chains (MOSS[PCL-b-PS]12). In contrast to the thermosets containing MOSS[PCL]12 the formation of the nanophases in the thermosets containing MOSS[PCL-b-PS]12 was ascribed to the self-assembly-directed reaction-induced microphase separation mechanism.

Preparation of quaternized organic–inorganic hybrid brush polyphosphazene-co-poly[2-(dimethylamino)ethyl methacrylate] electrospun fibers and their antibacterial properties

Densely grafted star- and comb-shaped molecular brushes composed of poly[2-(dimethylamino)ethyl methacrylate] were prepared via atom transfer radical polymerization (ATRP) using either cyclotriphosphazenes or polyphosphazenes as initiators. The grafting conditions were optimized in order to obtain well controlled brush structures. The kinetics of the reactions were first-order with respect to the monomer concentration in both cyclotriphosphazene and polyphosphazene systems. The resultant star- and comb-shaped brushes were quaternized with iodomethane, iodobutane, iodoheptane, iododecane and iodododecane, and the products were characterized by NMR, gel permeation chromatography (GPC) and differential scanning calorimetry (DSC). Electrospinning of the quaternized brushes gave rise to microfibers with diameters in range of 700 nm to 1.1 μm, evidenced by scanning electron microscopy (SEM). The antibacterial activity of the quaternized brush species in both aqueous solution and as fibrous solids against Escherichia coli (E. coli) has been evaluated. In aqueous solution, star-shaped brushes quaternized with iodoheptane showed the best antibacterial effect, with a minimum inhibitory concentration (MIC) as low as 250 μg mL−1. In the fibrous solid state, more than 99% of E. coli were killed within 2 h after contacting 100 mg of microfibers electrospun from the star-shaped brush polymers quaternized with either iododecane or iodododecane.

Synthesis and Direct Visualization of Dumbbell-Shaped Molecular Brushes.

Dumbbell-shaped triblock molecular brushes were synthesized by ring-opening metathesis polymerization (ROMP) of poly(lactide) macromonomers with terminal norbornene groups (NB-PLA) in a sequential addition manner. By changing the macromonomer size and the feed ratio of Grubbs' catalyst to macromonomer, the dimensions of the "ball" and "bar" of the dumbbell-shaped molecular brushes were controlled. The growth and production of well-defined structures were verified by gel permeation chromatography (GPC), and the final dumbbell-shaped architectures were visualized by atomic force microscopy (AFM). This synthetic methodology represents a rapid and convenient route to unique macromolecular topologies.

Straightforward Access to Amphiphilic Dual Bottle Brushes by Combining RAFT, ATRP, and NMP Polymerization in One Sequence

Molecular brush diblock copolymers were synthesized by the orthogonal overlay of the RAFT (reversible addition–fragmentation chain transfer), the ATRP (atom transfer radical polymerization), and the NMP (nitroxide-mediated polymerization) techniques. This unique combination enabled the synthesis of the complex amphiphilic polymers without the need of postpolymerization modifications, using a diblock copolymer intermediate made from two selectively addressable inimers and applying a sequence of four controlled free radical polymerization steps in total. The resulting polymers are composed of a thermosensitive poly(N-isopropylacrylamide) brush as hydrophilic block and a polystyrene brush as hydrophobic block, thus translating the structure of the established amphiphilic diblock copolymers known as macro surfactants to the higher size level of “giant surfactants”. The dual molecular brushes and the aggregates formed on ultra flat solid substrates were visualized by scanning force microscopy (SFM).

Computer simulation of bottle-brush polymers with flexible backbone: Good solvent versus theta solvent conditions

By molecular dynamics simulation of a coarse-grained bead-spring-type model for a cylindrical molecular brush with a backbone chain of N(b) effective monomers to which with grafting density σ side chains with N effective monomers are tethered, several characteristic length scales are studied for variable solvent quality. Side chain lengths are in the range 5 ≤ N ≤ 40, backbone chain lengths are in the range 50 ≤ N(b) ≤ 200, and we perform a comparison to results for the bond fluctuation model on the simple cubic lattice (for which much longer chains are accessible, N(b) ≤ 1027, and which corresponds to an athermal, very good, solvent). We obtain linear dimensions of the side chains and the backbone chain and discuss their N-dependence in terms of power laws and the associated effective exponents. We show that even at the theta point the side chains are considerably stretched, their linear dimension depending on the solvent quality only weakly. Effective persistence lengths are extracted both from the orientational correlations and from the backbone end-to-end distance; it is shown that different measures of the persistence length (which would all agree for Gaussian chains) are not mutually consistent with each other and depend distinctly both on N(b) and the solvent quality. A brief discussion of pertinent experiments is given.

Click-chemistry for surface modification of monodisperse-macroporous particles

In this study, click chemistry was proposed as a tool for tuning the surface hydrophilicity of monodisperse-macroporous particles in micron-size range. The monodisperse-porous particles carrying hydrophobic or hydrophilic molecular brushes on their surfaces were obtained by the proposed modification. Hydrophilic poly(glycidyl methacrylate-co-ethylene dimethacrylate), poly(GMA-co-EDM) particles were hydrophobized by the covalent attachment of poly(octadecyl acrylate-co-propargyl acrylate), poly(ODA-co-PA) copolymer onto the particle surface via triazole formation by click chemistry. In the second part, Hydrophobic poly(4-chloromethylstyrene-co-divinylbenzene), poly(CMS-co-DVB) particles were hydrophilized by the covalent attachment of poly(vinyl alcohol), PVA onto their surface also via triazole formation by click chemistry. The presence of PVA and poly(ODA-co-PA) copolymer on the corresponding particles was shown by FTIR-DRS. After click-coupling reactions applied for both hydrophobic poly(CMS-co-DVB) and hydrophilic poly(GMA-co-EDM) particles, the marked changes in surface polarity were shown by contact angle measurements. Protein adsorption characteristics of plain and modified particles were investigated for both materials. In the isoelectric point of albumin, the non-specific albumin adsorption decreased from 225 to 80 mg/g by grafting PVA onto the poly(CMS-co-DVB) beads. On the other hand, the non-specific albumin adsorption onto the plain poly(GMA-co-EDM) beads increased from 50 to 400 mg/g by the covalent attachment of poly(ODA-co-PA) copolymer onto the bead-surface via click chemistry. The protein adsorption behavior was efficiently regulated by the covalent attachment of appropriate molecular brushes onto the surfaces of selected particles. The results indicated that “click chemistry” was an efficient tool for controlling the polarity of monodisperse-macroporous particles.

Heavy Metal Ion Removal Characteristics of Monodisperse Macroporous Beads with Anion-Exchanger Molecular Brushes

Polyethyleneimine-functionalized poly(VBC- co-DVB) beads were prepared and their adsorption/desorption properties towards Cd(II), Co(II) and Cu(II) ions were studied. The amounts of metal ions adsorbed increased only a little on changing the pH of the associated solution within the range 2–6 for Cd(II) and Co(II) ions, especially after pH 5. However, the amount of Cu(II) ions adsorbed at pH 6 was significantly higher than that adsorbed within the above pH range. The equilibrium adsorption capacities obtained for Cu(II), Cd(II) and Co(II) ions were 26.6, 30.8 and 32.2 mg metal ion/g sorbent, respectively. The equilibrium adsorption data for all the metal ions could be fitted by the monolayer Langmuir model. The data for Cu(II) ions exhibited the highest correlation coefficient and highest affinity constant of all the metal ions studied. According to kinetic studies, 80% of the maximum adsorption capacities were achieved for all the heavy metal ions within 2 h, after which the extent of adsorption attained a plateau value. The kinetic data revealed that adsorption was rapid over the first 30 min for Cd(II) and Cu(II) ions compared to Co(II) ions. The kinetic data for the adsorption of all the metal ions studied obeyed the pseudo-second-order kinetic model.

Linear Rheological Response of a Series of Densely Branched Brush Polymers

We have examined the linear rheological responses of a series of well-defined, dense, regularly branched brush polymers. These narrow molecular weight distribution brush polymers had polynorobornene backbones with degrees of polymerization (DP) of 200, 400, and 800 and polylactide side chains with molecular weight of 1.4 kDa, 4.4 kDa, and 8.7 kDa. The master curves for these brush polymers were obtained by time temperature superposition (TTS) of the dynamic moduli over the range from the glassy region to the terminal flow region. Similar to other long chain branched polymers, these densely branched brush polymers show a sequence of relaxation. Subsequent to the glassy relaxation, two different relaxation processes can be observed for samples with the high molecular weight (4.4 and 8.7 kDa) side chains, corresponding to the relaxation of the side chains and the brush polymer backbone. Influenced by the large volume fraction of high molecular weight side chains, these brush polymers are unentangled. The lowest plateau observed in the dynamic response is not the rubbery entanglement plateau but is instead associated with the steady state recoverable compliance. Side chain properties affect the rheological responses of these densely branched brush polymers and determine their glassy behaviors.

Structure of Bottle Brush Polymers on Surfaces: Weak versus Strong Adsorption

Large-scale Monte Carlo simulations are presented for a coarse-grained model of cylindrical molecular brushes adsorbed on a flat structureless substrate, varying both the chain length N of the side chains and the backbone chain length N(b). For the case of good solvent conditions, both the cases of weak adsorption (only 10 to 15% of the monomers being bound to the surface) and strong adsorption (~40% of the monomers being bound to the surface, forcing the bottle brush into an almost 2D conformation) are studied. We focus on the scaling of the total linear dimensions of the cylindrical brush with both chain lengths N and N(b), demonstrating a crossover from rod-like behavior (for not very large N(b)) to the scaling of 2D self-avoiding walks. Despite the fact that snapshot pictures suggest a "worm-like" picture as a coarse-grained description of such cylindrical brushes, the Kratky-Porod worm-like chain model fails because there is no regime where Gaussian statistics applies. We compare the stiffness (orientational correlations of backbone bonds, persistence length estimates, etc.) of the adsorbed bottle brush polymers with their corresponding 3D nonadsorbed counterparts. Consequences for the discussion of pertinent experiments are briefly discussed.

Synthesis and Direct Imaging of Ultrahigh Molecular Weight Cyclic Brush Polymers

Convenient route to cyclic polymers: Ultrahigh molecular weight cyclic brush polymers were synthesized through ring-expansion metathesis polymerization of various macromonomers. Atomic force microscopy was used to visualize toroidal shapes and large opening pores, along with linear chains, which may result from high sensitivity of brush polymers to mechanical degradation.

Synthesis of low grafting density molecular brush from a poly(N‐alkyl urea peptoid) backbone

AbstractThe synthesis of a molecular brush was accomplished by combining step‐growth polymerization and reversible addition fragmentation chain transfer (RAFT) polymerization in a “grafting from” methodology. A symmetrical N‐alkyl urea peptoid sixmer containing alkyne functional groups was prepared using a divergent strategy, and the structure of the product was confirmed using NMR spectroscopy and mass spectrometry. A step‐growth process was used to prepare a linear poly(N‐alkyl urea peptoid) by reacting the diamine‐functionalized N‐alkyl urea peptoid sixmer with a diisocyanate. RAFT chain transfer agents were coupled to the poly(N‐alkyl urea peptoid) backbone through a copper‐catalyzed azide/alkyne cycloaddition reaction. The afforded macro‐RAFT agent was used to sequentially polymerize styrene and tert‐butyl acrylate block copolymer arms from the poly(N‐alkyl urea peptoid) backbone. The tert‐butyl groups were removed using dilute trifluoroacetic acid affording hydrophilic polyacrylic acid segments. The molecular brushes were observed to generate micelles in aqueous solution. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011

Analysis of the cluster formation in two-component cylindrical bottle-brush polymers under poor solvent conditions. A simulation study

Two-component bottle-brush polymers, where flexible side chains containing N = 20, 35 and 50 effective monomers are grafted alternatingly to a rigid backbone, are studied by Molecular Dynamics simulations, varying the grafting density [Formula: see text] and the solvent quality. Whereas for poor solvents and large enough [Formula: see text] the molecular brush is a cylindrical object with monomers of different type occupying locally the two different halves of the cylinder, for intermediate values of [Formula: see text] an axially inhomogeneous structure of "pearl-necklace" type is formed, where microphase separation between monomers of different type within a cluster takes place. These "pearls" have a strongly non-spherical ellipsoidal shape, due to the fact that several side chains cluster together in one "pearl". We discuss the resulting structures in detail and we present a comparison with the single-component bottle-brush case.

Understanding the Multiple Length Scales Describing the Structure of Bottle‐brush Polymers by Monte Carlo Simulation Methods

AbstractBottle‐brush polymers contain a long flexible macromolecule as a backbone to which flexible side chains are grafted. Through the choice of the grafting density and the length of the side chains the local stiffness of this cylindrical molecular brush can be controlled, but a quantitative understanding of these phenomena is lacking. Monte Carlo simulation results are presented and discussed which address this issue, extracting mesoscopic length scales (such as the cross‐sectional radius, persistence length, and contour length of these objects). Large‐scale simulations of the bond fluctuation model are combined with simulations of the simple self‐avoiding walk (SAW) model with flexibility controlled by a bond‐angle potential, using the pruned‐enriched Rosenbluth algorithm. It is shown that under good solvent conditions the bottle‐brush polymers never display a pre‐asymptotic Gaussian regime that would be described by the Kratky–Porod worm‐like chain model, unlike the semiflexible SAW model. Implications of these results for the proper interpretation of experiments are discussed.magnified image

Core−Shell Molecular Bottlebrushes with Helical Polypeptide Backbone: Synthesis, Characterization, and Solution Conformations

A series of core−shell molecular bottlebrushes with helical polypeptide backbone and polylactide-b-poly(ethylene glycol) block copolymer side chains [PPLG-g-(PLA-b-PEG)] have been synthesized via a grafting-to method. The structurally well-defined side chains with low molecular weight distribution (PDI < 1.03) have been synthesized by ring-opening polymerization (ROP) of dl-lactides using PEG-OH macroinitiator and AlEt3 catalyst. Postpolymerization modification by esterification enables the quantitative installation of an alkynyl functionality at the block polymer chain ends. Grafting of alkynyl-terminated PLA-b-PEG onto poly(γ-azidopropyl-l-glutamate) (PAPLG) via copper-mediated [2 + 3] alkyne−azide 1,3-dipolar cycloaddition yields the targeted molecular bottlebrushes with high grafting density under mild conditions. A combination of the Langmuir−Blodgett (LB) technique with atomic force microscopy (AFM) has allowed for direct imaging of the synthesized molecular brushes and characterization of their mol...

Effect of residual copper on stability of molecular brushes prepared by atom transfer radical polymerization

Effect of residual copper on stability of molecular brushes with poly(n-butyl acrylate) (PBA) side chains was studied. The brushes were prepared by atom transfer radical polymerization (ATRP) using the grafting-from approach. Although the copper concentration was decreased down to below ten ppm levels by passing through alumina column, further removal was required to prevent crosslinking reactions. Further removal was performed by dialysis or precipitation.

Synthesis of macrocyclic molecular brushes with amphiphilic block copolymers as side chains

AbstractMacrocyclic molecular brushes c‐PHEMA‐g‐(PS‐b‐PEO) consisting of macrocyclic poly(2‐hydroxylethyl methacrylate) (c‐PHEMA) as backbone and polystyrene‐b‐poly(ethylene oxide) (PS‐b‐PEO) amphiphilic block copolymers as side chains were synthesized by the combination of atom transfer radical polymerization (ATRP), click chemistry, and single‐electron transfer nitroxide radical coupling (SET‐NRC). First, a linear α‐alkyne‐ω‐azido heterodifunctional PHEMA (l‐HCC‐PHEMA‐N3) was prepared by ATRP of HEMA using 3‐(trimethylsilyl)propargyl 2‐bromoisobutyrate as initiator, and then chlorine end groups were transformed to N3 group by nucleophilic substitution reaction in DMF in the presence of an excess of NaN3. The 3‐trimethylsilyl groups could be removed in the presence of tetrabutylammonium fluoride, and the product was cyclized by “click” chemistry in high dilution conditions. The hydroxyl groups on c‐PHEMA were transferred into bromine groups by esterification with 2‐bromoisobutyryl bromide and then initiate the ATRP of styrene. The formed macrocyclic molecular brushes c‐PHEMA‐g‐PS were coupled with the TEMPO‐PEO to afford the target macrocyclic molecular brushes c‐PHEMA‐g‐(PS‐b‐PEO) by SET‐NRC, and the efficiency is as high as 80∼85%. All of the intermediates and final product were characterized with 1H NMR, Fourier transform infrared (FTIR), and gel permeation chromatography in details © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011