Grafting-to Method Research Articles

Thermally responsive porous membranes with both switching wettability and permeability prepared via grafting-to and grafting-from methods

Pre-synthesized amino-functional poly(N-isopropylacrylamide) (PNIPAm, grafting-to) and monomer (NIPAm, grafting-from) were grafted on with polydopamine pre-functionalized porous polyvinylidene difluoride (PVDF) membrane to fabricate thermally responsive membranes. Scanning electron microscopy revealed irregular particles and more homogeneous spherical particles on the surface of membranes fabricated by grafting-to and grafting-from, respectively. Grafting yield and chemical analyses further indicated higher grafting density for membranes prepared by grafting-from method. The lower grafting density of PNIPAm obtained by grafting-to method resulted in poor switching wettability and permeability; water contact angle and water permeance of the membrane increased from 41° to 49° and from 270 to 440 L m−2h−1bar−1 when temperature. was enhanced from 25 to 45 °C and thereby passed through the lower critical solution temperature (33 °C) of PNIPAm. The membrane obtained by grafting-from method showed a switching wettability between superhydrophilic and hydrophobic properties (0° at 25 °C to 117° at 45 °C) with a higher thermal responsive factor in water permeance (200 L m−2h−1bar−1 at 25 °C and 480 L m−2h−1bar−1 at 45 °C). From the results it can be concluded that the grafting-from approach is better suitable to fabricate thermally responsive membranes, and the membranes can be further tuned and applied to separate mixtures containing particles of various sizes while maintaining good antifouling and thermally induced cleaning properties.

Thiol-selective native grafting from polymerization for the generation of protein-polymer conjugates.

Protein-polymer conjugates combine properties of biopolymers and synthetic polymers, such as specific bioactivity and increased stability, with great benefits for various applications from catalysis to biomedicine. Furthermore, polymer conjugation can mimic important posttranslational modifications of proteins such as glycosylation. There are typically two approaches to create protein-polymer conjugates: the protein is functionalized in advance with an initiator for a grafting-from method or a previously produced polymer is conjugated to the protein via a grafting-to method. In this study, we present a new approach that uses native proteins and allows for direct grafting-from using a thiol-induced, light-activated controlled radical polymerization (TIRP) that is initiated at thiols from specific cysteine residues of the protein. This straightforward method is employed to introduce polymers onto proteins and enzymes without any prior protein modifications, it works in aqueous buffer and maintains the protein's native structure and activity. The resulting protein-polymer conjugates exhibit high molar masses and low dispersities. We demonstrate the versatility of this approach by introducing different types of polymers such as hydrophilic poly(2-hydroxyethyl acrylate) (pHEAA), temperature-responsive poly(N-isopropylacrylamide) (pNIPAM) as well as glycopolymers mimicking the natural protein glycosylation and enabling selective interactions. We present successful combinations of the protein and polymer functions e.g., temperature-induced aggregation leading to an increase in enzyme activity and the introduction of artificial glycosylation inducing specific protein-protein cluster formation and giving straightforward access to glycosurfaces. Based on this straightforward, potentially scalable yet highly controlled synthesis of protein-polymer conjugates, various areas of applications are envisioned ranging from biomedicine to material sciences.

Grafting-To and From for Multiplexed Chemical-Warfare-Agent Responsive Polymer Brushes

Surface-tethered polymers have important applications in functional polymer coatings, particularly for the development of chemically responsive surfaces. Here, we combined the traditional grafting-to and grafting-from methods to create a new surface grafting strategy, termed grafting-to and from, using surface-initiated ring-opening metathesis polymerization (SI-ROMP). In this method, poly(pentafluorophenyl methacrylate) is grafted to an amine terminated surface. Surplus reactive esters after reaction with surface amines render this polymer a connecting or tie layer that can be further reacted to provide dense ROMP initiation sites. This amplification of grafting sites results in thick and environmentally stable polymer brushes upon SI-ROMP. With the goal of developing polymer-grafted breathable membranes that autonomously react to multiple chemical warfare agents (CWAs), we demonstrate the benefit of this method by employing amine reactive monomers in the grafting-from step. This enables diverse postsynthetic functionalization for the facile screening of chemical motifs to enhance response capabilities to mustard blister agents. Surface-tethered triarylmethanol-containing polymers with four distinct functional groups are prepared and challenged with the vapor of 2-chloroethyl ethyl sulfide (CEES), a simulant of mustard agent, in humid air. Importantly, hydroxyl groups effectively improve CWA response and the resulting polymer brushes show chain collapse after both CEES and diethylchlorophosphate (DCP) treatment. Our results illustrate that the grafting-to and from method can be used to grow functional and robust polymer coatings for various applications.

Grafting density and antifouling properties of poly[N-(2-hydroxypropyl) methacrylamide] brushes prepared by “grafting to” and “grafting from”

Poly(HPMA) brushes prepared by a grafting-from method suppress fouling from blood plasma by an order of magnitude better than the polymer brushes of the same molecular weight prepared by a grafting-to method.

Preparation of nanoparticles of shellac and shellac-oligomer conjugates

Shellac is a natural biodegradable oligoester produced by lac insects, containing reactive functional groups such as hydroxyl, carboxylic acid, ester, aldehyde, and alkene groups, which can be used for chemical functionalization. Herein, shellac is functionalized with poly(ethylene glycol) (PEG) or poly(N-isopropylacrylamide) (PNIPAM) via grafting-to and grafting-from methods. The functional polymer conjugates are then processed as nanoparticles by the miniemulsion-solvent evaporation process. Shellac-PEG nanoparticles are enriched with apolipoprotein AI after incubation in fetal bovine serum at 37 °C. Moreover, shellac-PNIPAM nanoparticles adsorb specifically prothrombin at 37 °C (T > volume phase transition temperature, VPTT).

Graft-Then-Shrink: Simultaneous Generation of Antifouling Polymeric Interfaces and Localized Surface Plasmon Resonance Biosensors.

Antifouling polymer coatings that are simple to manufacture are crucial for the performance of medical devices such as biosensors. "Grafting-to", a simple technique where presynthesized polymers are immobilized onto surfaces, is commonly employed but suffers from nonideal polymer packing leading to increased biofouling. Herein, we present a material prepared via the grafting-to method with improved antifouling surface properties and intrinsic localized surface plasmon resonance (LSPR) sensor capabilities. A new substrate shrinking fabrication method, Graft-then-Shrink, improved the antifouling properties of polymer-coated Au surfaces by altering graft-to polymer packing while simultaneously generating wrinkled Au structures for LSPR biosensing. Thiol-terminated, antifouling, hydrophilic polymers were grafted to Au-coated prestressed polystyrene (PS) followed by shrinking upon heating above the PS glass transition temperature. Interestingly, the polymer molecular weight and hydration influenced Au wrinkling patterns. Compared to Shrink-then-Graft controls, where polymers are immobilized post shrinking, Graft-then-Shrink increased the polymer content by 76% in defined footprints and improved the antifouling properties as demonstrated by 84 and 72% reduction in macrophage adhesion and protein adsorption, respectively. Wrinkled Au LSPR sensors had sensitivities of ∼200-1000 Δλ/ΔRIU, comparing favorably to commercial LSPR sensors, and detected biotin-avidin and desthiobiotin-avidin complexation in a concentration-dependent manner using a standard plate reader and a 96-well format.

Autonomous Nanoscale Chemomechanical Oscillation on the Self-Oscillating Polymer Brush Surface by Precise Control of Graft Density.

As a novel functional surface, a self-oscillating polymer brush that undergoes autonomous, periodic swelling/deswelling during the Belousov-Zhabotinsky (BZ) reaction has been developed. Although extensive research has revealed how the fundamental aspects of the BZ reaction can be regulated based on the surface design of the self-oscillating polymer brush, design strategies for the induction of mechanical oscillation remain unexplored. Herein, we investigated the graft density effects on the phase transition behavior, which is an important design parameter for the mechanical oscillation of the modified polymer. The self-oscillating polymer-modified substrates with controlled graft densities were prepared by immobilizing various compositions of an initiator and a noninitiator followed by surface-initiated atom transfer radical polymerization of the self-oscillating polymer chains. In addition to the characterization of each prepared substrate, atomic force microscopy (AFM) and digital holographic microscopy (DHM) were employed to evaluate the density effects on the static and dynamic surface structures. AFM revealed that equilibrium swelling as well as thermoresponsive behavior is profoundly affected by the graft density. Moreover, using DHM, autonomous mechanical oscillation was captured only on the self-oscillating polymer brush with adequate graft density. Notably, the oscillation amplitude (150 nm) and the period (20 s) in this study were superior to those in a previous report on the self-oscillating polymer modified through the grafting-to method by 10- and 3-fold, respectively. This study presents design guidelines for future applications, such as autonomous transport devices.

Surface-Initiated Passing-through Zwitterionic Polymer Brushes for Salt-Selective and Antifouling Materials

The use of the traditional growing-from approach to prepare surface-initiated polymer brushes is widespread as it produces polymer brushes with higher grafting densities than grafting-to methods. I...

Fabrication of 2D Block Copolymer Brushes via a Polymer-Single-Crystal-Assisted-Grafting-to Method.

Block copolymer brushes are of great interest due to their rich phase behavior and value-added properties compared to homopolymer brushes. Traditional synthesis involves grafting-to and grafting-from methods. In this work, a recently developed "polymer-single-crystal-assisted-grafting-to" method is applied for the preparation of block copolymer brushes on flat glass surfaces. Triblock copolymer poly(ethylene oxide)-b-poly(l-lactide)-b-poly(3-(triethoxysilyl)propyl methacrylate) (PEO-b-PLLA-b-PTESPMA) is synthesized with PLLA as the brush morphology-directing component and PTESPMA as the anchoring block. PEO-b-PLLA block copolymer brushes are obtained by chemical grafting of the triblock copolymer single crystals onto a glass surface. The tethering point and overall brush pattern are determined by the single crystal morphology. The grafting density is calculated to be ≈0.36 nm-2 from the atomic force microscopy results and is consistent with the theoretic calculation based on the PLLA crystalline lattice. This work provides a new strategy to synthesize well-defined block copolymer brushes.

Influence of anchoring segments on methacrylate-based comb-type hydrophilic polymer segments coated on silica surfaces using the grafting-to method

Owing to development of controlled radical polymerization, a coating of substrates with (meth)acrylate-based hydrophilic polymers has been widely utilized to construct a biocompatible interface. The polymer layers impart a non-fouling effect against proteins correlated to conformations of the polymer segments. For (meth)acrylate-based polymer coating, it is speculated that interaction between polymers and substrates cannot be negligible when describing the conformation because their main chains have a hydrophobic nature derived from the alkyl structure. Herein, we performed coating of silica nanoparticles (SiNPs) with poly(olygoethylenglycolmethacrylate) (pOEGMA) and observed the coated pOEGMA likely lied flat on the silica surface in aqueous milieu. Block copolymerization with an anchoring segment facilitated the pOEGMA domains to be free from the surface and promoted non-fouling property likely due to anchoring segments occupying adsorption sites for pOEGMA. These results indicated the anchoring segment plays an important role in the construction of the methacrylate-based polymer layers for a bio-interface.

Terraced and Smooth Gradient Polymer Brushes via a Polymer Single-Crystal Assisted Grafting-To Method.

Gradient polymer brushes provide a spatial gradient change in molecular characteristics of the brush, and such a change can be utilized to study structure-property relationships in a combinatorial fashion. In this study, a bottom-up method was used to synthesize gradient polymer brushes with a predesigned and precisely controlled grafting density gradient and brush pattern. A polymer single-crystal assisted grafting-to (PSCAGT) method was employed where end-functionalized polymers were grown into two-dimensional polymer single crystals. The latter were chemically coupled to a solid substrate to form well-defined polymer brushes. To tune the grafting density, end-dissimilar polymers were used to co-crystallize into one single crystal. Programmed single-crystal growth was introduced to synthesize brushes with two different gradient architectures, that is, terraced and smooth gradient with pyramid patterns. This work demonstrates that the PSCAGT method offers a unique means to tune polymer brush nanostructure.

Grafting strategies for the synthesis of active DNase I polymer biohybrids

Protein polymer hybrids play an increasingly important role in therapeutics and biocatalysis. Synthesis of these biohybrids can be achieved by either the grafting-from or grafting-to strategy and are generally thought to be interchangeable. Therefore, when choosing between these two strategies the decision is usually based on polymer accessibility and purification preference. However, in this study, we demonstrated that the choice of the polymer ligation strategy played a significant role in the stability and bioactivity of the final hybrid. Our goal was to prepare a thermally stable DNase I polymer hybrid by utilizing either synthetic strategies. We found that the grafting-from strategy using reversible addition-fragmentation chain transfer polymerization (RAFT) or atom transfer radical polymerization (ATRP) yielded DNase I biohybrids with no activity. Control reactions were used to demonstrate inherent protein deactivation caused by the grafting-from conditions for either ATRP or RAFT polymerization. The grafting-to method yielded active and thermally stable DNase I biohybrids.

Salt-Induced Control of the Grafting Density in Poly(ethylene glycol) Brush Layers by a Grafting-to Approach.

In this work, a method to obtain control of the grafting density during the formation of polymer brush layers by the grafting-to method of thiolated poly(ethylene glycol) onto gold is presented. The grafting density of the polymer chains was adjusted by adding Na2SO4 in concentrations between 0.2 and 0.9 M to the aqueous polymer solution during the grafting process. The obtained grafting densities ranged from 0.26 to 1.60 chains nm-2, as determined by surface plasmon resonance. The kinetics of the grafting process were studied in situ by a quartz crystal microbalance with dissipation, and a mushroom to brush conformational transition was observed when the polymer was grafted in the presence of Na2SO4. The transition from mushroom to brush was only observed for long periods of grafting, highlighting the importance of time to obtain high grafting densities. Finally, the prepared brush layer with the highest grafting density showed high resistance to the adsorption of bovine serum albumin, while layers with a lower grafting density showed only limited resistance.

Velcro-mimicking surface based on polymer loop brushes.

We herein report the fabrication of a Velcro-mimicking surface based on polymer brushes. Using poly(ε-caprolactone) (PCL) as the model polymer, polymer loop brushes (PLBs) and singly tethered polymer brushes (STPBs) with nearly identical tethering point density and brush heights were synthesized using a polymer single crystal (PSC)-assisted grafting-to method. Atomic force microscopy-based single molecular force spectroscopy (AFM-SMFS) and macroscale lap-shear experiments both demonstrated that the PLBs led to strong adhesion that is up to ∼10 times greater than the STPBs, which is attributed to the enriched chain entanglement between the probing polymer and the brushes. We envisage that our results will pave the way towards a new materials design for strong adhesives and nanocomposites.

Serum Protein-Resistant Behavior of Multisite-Bound Poly(ethylene glycol) Chains on Iron Oxide Surfaces.

Recent surveys have shown that the number of nanoparticle-based formulations actually used at a clinical level is significantly lower than that expected a decade ago. One reason for this is that the physicochemical properties of nanoparticles fall short for handling the complexity of biological environments and preventing nonspecific protein adsorption. In this study, we address the issue of the interactions of plasma proteins with polymer-coated surfaces. With this aim, we use a noncovalent grafting-to method to functionalize iron oxide sub-10 nm nanoparticles and iron oxide flat substrates and compare their protein responses. The functionalized copolymers consist of alternating poly(ethylene glycol) (PEG) chains and phosphonic acid grafted on the same backbone. Quartz crystal microbalance with dissipation was used to monitor polymer adsorption kinetics and evaluate the resistance to protein adsorption. On flat substrates, functionalized PEG copolymers adsorb and form a brush in moderate or highly stretched regimes, with densities between 0.15 and 1.5 nm–2. PEG layers using phosphonic acid as linkers exhibit excellent protein resistance. In contrast, layers prepared with carboxylic acid as the grafting agent exhibit mitigated protein responses and layer destructuration. The present study establishes a correlation between the long-term stability of PEG-coated particles in biofluids and the protein resistance of surfaces coated with the same polymers.

Engineering a Tunnel to a More Versatile Lipoic Acid Ligase

Protein‐polymer conjugates have become a rapidly expanding area of research. As a result of broad utility in a range of disciplines, protein‐polymer conjugates can now be applied to therapeutics, biofuels, and even protein tags. Grafting‐to and Grafting‐from methods have been successful in creating these conjugates but have limitations on the specificity of attachment (Lele et al. 2005). Lipoic acid ligase (LplA) has been demonstrated to be convenient tool for attaching small molecule precursors that can enable subsequent attachment of a polymer to specific sites of target proteins containing a lipoic acid ligase acceptor peptide (LAP) sequence. Studies on LplA have demonstrated that mutation of tryptophan 37 to valine allows LplA to accommodate 10‐azidodecanoic acid (Plaks et al., 2015). Paired with an alkyne‐bearing polymer this enables the use of click chemistry to attach a polymer to the protein‐ligated 10‐azidodecanoic acid. While useful, attachment of a pre‐clicked polymer would enable for more rapid exploration of protein‐polymer conjugates with a wide library of polymers. In this study, we describe structure‐guided, activity‐based efforts to engineer a tunnel within LplA to further open the binding pocket and allow LplA to accept pre‐clicked polymers.Support or Funding InformationThe authors acknowledge financial support from the US National Science Foundation (Award No. MCB 1552113 to RCP), the Burroughs Wellcome Fund (Award No. 1014031 to RCP), and institutional support from Miami University through the Robert H. and Nancy J. Blayney Professorship (to RCP).

Synthesis of Polystyrene and Poly(4-vinylpyridine) Mixed Grafted Silica Nanoparticles via a Combination of ATRP and CuI -Catalyzed Azide-Alkyne Click Chemistry.

Binary polystyrene and poly(4-vinylpyridine) mixed grafted silica nanoparticles (PSt/P4VP-g-SNPs) are fabricated using CuI -catalyzed azide-alkyne Huisgen cycloaddition (CuAAC) via grafting-to method. Azide-terminated PSt and P4VP are synthesized via post- and pre-atom transfer radical polymerization modification, respectively. Then, the polymers are simultaneously anchored onto alkyne-modified SNPs by CuAAC yielding mixed brushes as shown by Raman spectroscopy, dynamic light scattering, and thermogravimetric analysis. To the best of our knowledge, this is the first report of simultaneously grafting two distinct polymer chains to synthesize mixed grafted silica nanoparticles using CuAAC technique via grafting-to method.

Submicrometer-Encapsulation of NaBH4 by Dopamine End-Functionalized Polystyrene: Gas Generation at Oil–Water Interfaces

We present a single-step, grafting-to synthetic method for the encapsulation of particulate NaBH4 by dopamine end-functionalized polymer chains. Metal–catechol coordination chemistry is used to produce core–shell capsules, which generate H2 gas exclusively upon adsorption to an oil–water interface. Significantly, the synthetic process enables facile control of core diameter, shell thickness, and the chemistry of both shell and core. The interfacial reactivity of these stimuli-responsive capsules may be engineered for various applications such as medical diagnostics, therapeutics, and subsurface imaging. In addition to their triggered reactivity, the capsules react in a manner independent of pressure and are thus well-suited for high pressure subsurface environments.

The Importance of Excess Poly(N-isopropylacrylamide) for the Aggregation of Poly(N-isopropylacrylamide)-Coated Gold Nanoparticles.

Thermoresponsive materials are generating significant interest on account of the sharp and tunable temperature deswelling transition of the polymer chain. Such materials have shown promise in drug delivery devices, sensing systems, and self-assembly. Incorporation of nanoparticles (NPs), typically through covalent attachment of the polymer chains to the NP surface, can add additional functionality and tunability to such hybrid materials. The versatility of these thermoresponsive polymer/nanoparticle materials has been shown previously; however, significant and important differences exist in the published literature between virtually identical materials. Here we use poly(N-isopropylacrylamide) (PNIPAm)-AuNPs as a model system to understand the aggregation behavior of thermoresponsive polymer-coated nanoparticles in pure water, made by either grafting-to or grafting-from methods. We show that, contrary to popular belief, the aggregation of PNIPAm-coated AuNPs, and likely other such materials, relies on the size and concentration of unbound “free” PNIPAm in solution. It is this unbound polymer that also leads to an increase in solution turbidity, a characteristic that is typically used to prove nanoparticle aggregation. The size of PNIPAm used to coat the AuNPs, as well as the concentration of the resultant polymer–AuNP composites, is shown to have little effect on aggregation. Without free PNIPAm, contraction of the polymer corona in response to increasing temperature is observed, instead of nanoparticle aggregation, and is accompanied by no change in solution turbidity or color. We develop an alternative method for removing all traces of excess free polymer and develop an approach for analyzing the aggregation behavior of such materials, which truly allows for heat-triggered aggregation to be studied.

Hybrid Mesoporous Silica Based on Hyperbranch-Substrate Nanonetwork as Highly Efficient Adsorbent for Water Treatment

Hybrid mesoporous silica based on a hyperbranch-substrate nanonetwork as highly efficient adsorbent was explored by an efficient and facile approach combined with one-pot condensation and grafting-to methodology, including a terminated amino hyperbranched polymer (HBP) modification. The specific synthesis procedure involves the following steps: (i) premodification of SBA-15 via a co-condensation-hydrolysis route, obtaining carboxyl functionalized SBA-15 (SBA-CAR), and (ii) grafting HBP onto SBA-CAR by a grafting-to method, obtaining hybrid mesoporous silica (SBA-HBP). The main structural characteristics of SBA-15 are preserved in the resultant SBA-HBP, which exhibits high surface area, large pore volume, and well-ordered porosity made up of uniform mesopores. Due to its reusability and with a three-dimensional hyperbranch-substrate nanonetwork with substantial functional groups, the as-synthesized SBA-HBP is considered a versatile and sustainable adsorbent for dyes (i.e., methylene blue and congo red) and...