Cylindrical Molecular Brushes Research Articles

A fluorescent sensor for intracellular Zn2+ based on cylindrical molecular brushes of poly(2-oxazoline) through ion-induced emission

Poly(2-oxazoline) molecular brushes bearing enaminitrile receptors in the side chain ends exhibit good biocompatibility, excellent fluorescent selectivity for Zn2+, and possibility in detecting intracellular Zn2+.

Thermal Stabilization of Enzymes with Molecular Brushes

Herein, we report a conjugation strategy, where we utilize a poly(ethylene oxide) cylindrical molecular brush architecture to design a self-assembled structure for thermal stabilization of enzymes. We demonstrate that the proposed architecture of the moderately stiff polymer ligand results in a significant improvement of biocatalytic activity and thermal stability of lysozyme and trypsin that retain their activity, even upon heating to 100 °C and above. The molecular brush is bound via epoxy functional groups to the amino groups of the lysine on the surface of the enzyme globule, promoting the formation of stiff and crowded cages around the enzymes and preventing the water molecules access to the enzyme and enzymes agglomeration. The molecular dynamic simulations show that the high concentration of poly(ethylene oxide) in the vicinity of the enzyme is critical for their stability. Monitoring of lysozyme–molecular brush conjugates for 6 and 12 months in lyophilized form and in solution, respectively, has s...

Synthesis by RAFT polymerization and properties of anionic cylindrical molecular brushes bearing poly(acrylic acid) side chains

RAFT polymerization of acrylic acid (AA) in the presence of low-molecular chain transfer agent (2-(butylthiocarbonothioylthio) propanoic acid and polyacrylate-based backbone bearing multiple butylthiocarbonothioylthio moieties is reported demonstrating successful synthesis of linear pAA with low polydispersity and anionic cylindrical molecular brushes, respectively. Twofold excess of butylthiocarbonothioylthio moieties attached to polyacrylate-based backbone over the initiator was optimal enabling to synthesize graft copolymers with rather low polydispersity (PDI 1.23–1.36) and reasonably high DP of pAA side chains (up to 25). Anionic cylindrical molecular brushes were characterized by SEC with triple detection, DLS, 1H NMR spectroscopy, and potentiometric titration. Thermal transitions and thermal stability of the brush polymers bearing pAA side chains were determined by DSC and TGA.

Molecular Nanoworm with PCL Core and PEO Shell as a Non‐spherical Carrier for Drug Delivery

Core/shell wormlike polymer brushes with densely grafted poly(ϵ-caprolactone)-b-poly(ethylene oxide) (PCL-b-PEO) are synthesized via grafting an alkynyl terminated PCL-b-PEO (ay-PCL(17) -b-PEO(113) ) onto a well-defined azido functionalized polymethacrylate (PGA(940) ) and are evaluated preliminarily as a single molecular cylindrical vehicle for drug delivery. Water soluble molecular worms of ca. 230 nm are obtained and then the anticancer drug doxorubicin (DOX) is loaded into its PCL core by hydrophobic interaction. Compared with spherical micelles from linear PCL(17) -b-PEO(113) , the brushes demonstrate a lower loading efficiency but a faster release rate of DOX. Confocal laser scanning microscopy measurements show that DOX-loaded cylindrical molecular brushes can easily enter into HeLa and HepG2 cells in 1 h.

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.

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.

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

Synthesis of thermally responsive cylindrical molecular brushes via a combination of nitroxide-mediated radical polymerization and “grafting onto” strategy

Loosely grafted amphiphilic molecular brushes consisting of a hydrophobic polystyrene backbone and hydrophilic poly(ethylene glycol) monomethyl ether (MPEG) side chains, PS-MPEG, were synthesized by a novel two step method. In the first step, well-defined linear poly( p-chloromethylstyrene) PCMS with the degree of polymerization DP ≈ 200 and polydispersity index, M w/ M n = 1.4 was prepared by bulk nitroxide (TEMPO)-mediated radical polymerization (NMP). In the second step, pendant p-chloromethyl units were coupled with activated chains of poly(ethylene glycol) monomethyl ether (MPEG) during the course of the Williamson etherification reaction. Using MPEG with M n = 1100 g/mol over 50% repeating units on PCMS underwent nucleophilic substitution yielding a densely grafted brush with theoretical molecular weight M n,th ≈ 123,000 g/mol. The molecular brush PS-MPEG assumed conformation of a stiff cylinder in both dilute toluene (non-selective good solvent for PS backbone and MPEG grafts) and water (selective for MPEG grafts) solutions as determined by small-angle neutron scattering (SANS) and small-angle X-ray scattering (SAXS). The contour length L = 570 Å and L = 694 Å obtained by fitting the scattering data using model of Sharp–Bloomfield, Pedersen–Schurtenberger and Kholodenko worm revealed dimensions corresponding to theoretically estimated size of a single molecular brush. It was found that PS-MPEG molecular brush in dilute aqueous solutions exhibited lower critical solution temperature (LCST) in the physiological range.

Crystallization of Molecular Brushes with Block Copolymer Side Chains

A series of three cylindrical molecular brushes with poly(e-caprolactone)-b-poly(n-butyl acrylate) side chains were investigated with regard to the effect of the intramolecular confinement on the crystallization behavior of the PCL core block. While the length of the PCL block was maintained (nPCL = 50), the degree of polymerization of the PBA corona block, prepared by atom transfer radical polymerization, was varied from nPBA = 0 (PCL brush) to nPBA = 52 and 163. The crystallization behavior of the studied polymers was shown to be different in thin films and bulk samples. In thin films, the brushlike macromolecules were fully extended and remained segregated due to the steric repulsion of the adsorbed PBA corona. Under the constraint of the backbone extension, crystallization of the PCL core led to formation of a characteristic spinelike morphology. In bulk samples, the core−shell confinement did not prohibit breakout crystallization, leading to the formation of a spherulitic morphology similar to linear...

Cylindrical molecular brushes with a loose grafting density

AbstractA cylindrical molecular brush with a low graft density was synthesized by two steps. Firstly, free radical alternating copolymerization of styrene (St) and N‐[2‐(2‐bromoisobutyryloxy)ethyl] maleimide (BiBEMI) gave a macroinitiator where pendant initiating sites for atom transfer radical polymerization (ATRP) being positioned along the backbone with an interval of four CC bonds. The backbone‐to‐be with an alternating sequence was verified by elemental analysis (EA). Secondly, grafting poly(tert‐butyl acrylate) chains from the macroinitiator by ATRP produced the novel molecular brush. Size exclusion chromatography, static light scattering (SLS), and 1H NMR and atomic force microscopy (AFM) were used to characterize the macroinitiator and the molecular brush. The results show that the backbone contains an average 730 repeat units (1 repeat unit = a pair of St and BiBEMI) and the absolute molecular weight of the brush, Mw,SLS, was 4.88 × 106 Da. The brush reveals a number average length Ln to be 96 nm under AFM observation on carbon coated mica, corresponding to the length per main chain monomer unit (Lunit) of 0.066 nm, indicating a less extended conformation due to the low grafting density. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 5527–5533, 2009

Facile syntheses of cylindrical molecular brushes by a sequential RAFT and ROMP “grafting‐through” methodology

The orthogonality of RAFT and ROMP chemistries are exploited for a highly efficient “grafting through” strategy to afford cylindrical molecular brushes. The ROMP of α-norbornenyl-functionalized poly(t-butyl acrylate) macroRAFT chain transfer agents, catalyzed by a modified 2nd generation Grubbs' catalyst, achieved completion in minutes under air. Following hydrolysis, functionalizable water-soluble poly(acrylic acid) molecular brushes were afforded. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]

Cylindrical Molecular Brushes of Poly(2-oxazoline)s from 2-Isopropenyl-2-oxazoline

We report on the synthesis and characterization of cylindrical molecular brushes based on poly(2-oxazoline)s (POx). The dual-functional monomer, 2-isopropenyl-2-oxazoline (IPOx), was first converted to a poly(2-isopropenyl-2-oxazoline), backbone by free radical (PIPOxR) or living anionic polymerization (PIPOxA). Quantitative reaction with methyl triflate yields a macroinitiator salt (PIPOxOTfR/A) for the preparation of molecular brushes via the grafting from approach by living cationic polymerization of 2-oxazolines (2-methyl-, 2-ethyl-, and 2-isopropyl-2-oxazoline). Characterization of the resulting molecular brushes by NMR and FTIR spectroscopy indicates a very high side chain grafting density and quantitative reactions. Visualization of adsorbed molecular brushes by AFM corroborates this assumption. Furthermore, the lower critical solution temperatures of the POx molecular brushes were determined. The transition temperatures were found to be very defined, reversible, and with no noticeable hysteresis.

Tadpole Conformation of Gradient Polymer Brushes

Cylindrical molecular brushes, each with a gradient of grafting density along the backbone, demonstrated a transition from rodlike to tadpole conformations. Using atomic force microscopy (AFM), a coexistence of two conformational phases was observed within individual molecules adsorbed on a mica substrate. These observations were made by compressing monolayers on the surface of water and then transferring a sample of this monolayer to a mica substrate for AFM studies. Upon compression, the rod−globule transition occurs at the end where the brush is densely grafted, leaving a molecule with a globular “head” and an extended “tail”a so-called tadpole conformation. This research demonstrates the asymmetric changes in the molecular conformation, which is one of the prerequisites for directed motion.

Cylindrical molecular brushes under poor solvent conditions: microscopic observation and scaling analysis.

Axial contraction of cylindrical molecular brushes of polymethylmethacrylate was observed by static light scattering and scanning force microscopy. Single brush molecules were visualized as worm-like particles whose length was almost three times shorter than the contour length of the backbone. A somewhat larger length was measured by light scattering in a good solvent. A scaling approach has been used to analyze the driving forces for the axial contraction and the conformation of the molecular brushes.