Heterotelechelic Polymers Research Articles

Preparation of α,ω‐telechelic hexyl acrylate polymers with OH, COOH, and NH2 functional groups by RAFT

AbstractThe design, synthesis, and use of two new, stable, functionalized chain transfer agents (CTA's) containing OH and amine end groups for the RAFT polymerization is reported: 2‐hydroxyethoxy‐carbonylphenylmethyl dithiobenzoate and 2‐(2‐(tert‐butoxycarbonyl)ethylamino)‐2‐oxo‐1‐phenylethyl benzodithioate, respectively. The RAFT polymerization of n‐hexyl acrylate (HA) using those CTA's, were compared to several other functionalized dithiobenzoate esters reported in the literature containing COOH and Ester groups. The performances of the dithiobenzoates were compared in terms of kinetics and molecular weight distribution control. Good control in polymerization of n‐hexyl acrylate with a linear increase of Mn with conversion mantaining polydispersity indices (PDI) below 1.1 was obtained by use of the new functionalized CTA's developed and also by use of some other CTA's tested, to produce well‐defined linear polymers with one specific chain‐end functionality: OH, COOH or Amine. Using a postpolymerization reaction with functionalized azocompounds in a 5 to 1 ratio, α,ω‐telechelic polymers, with OH or COOH as functional group at the second end were obtained. By using this synthetic strategy α,ω‐homotelechelic and heterotelechelic polymers were readily prepared. The chemical availability of functional end‐groups in the telechelics was demonstrated by reaction with methacrylic anhydride. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 3033–3051, 2010

Heterotelechelic Polymers for Capture and Release of Protein-Polymer Conjugates.

A heterotelechelic biotin-maleimide polymer containing a cleavable disulfide bond was synthesized by RAFT polymerization and used to reversibly modify surfaces with proteins.

Facile Synthesis of Functional Periodic Copolymers: A Step toward Polymer-Based Molecular Arrays.

A step-growth strategy was investigated for preparing functional periodic copolymers. Functional heterotelechelic α-alkyne, ω-azido poly(styrene-co-N-substituted maleimide) precursors (Mn ≈ 2500 g·mol−1) have been prepared and subsequently polymerized by copper-catalyzed azide−alkyne cycloaddition (CuAAC). These precursors have been first synthesized by sequential atom transfer radical copolymerization of styrene and a N-substituted maleimide (i.e., benzyl maleimide, N-(2-(amino-tBOC)-ethylen)-maleimide, or benzyl N,N-maleoylglycinate) initiated by 3-(1,1,1-trimethylsilyl)-2-propynyl 2-bromo-2-methylpropanoate. In this approach, styrene homopolymerization was first started, and a discrete amount of the maleimide comonomer (e.g., 1 equiv as compared to initiator) was added when styrene half-conversion was reached. This controlled maleimide addition resulted in the formation of well-defined polystyrene segments containing a functional maleimide in the middle of their chains (i.e., in average 1 unit per chain). Subsequently, the sequence-controlled copolymers poly(styrene-co-N-substituted maleimide) have been transformed into reactive heterotelechelic polymers. Various synthetic pathways have been compared for preparing these reactive intermediates. Ultimately, these heterotelechelic precursors were polymerized by CuAAC. 1H NMR and SEC evidenced the formation of high-molecular-weight periodic copolymers.

Heterotelechelic Ring-Opening Metathesis Polymers

By combining sacrificial synthesis with the vinyl lactone termination technique, heterotelechelic polymers were synthesized. The nonterminating nature of sacrificial synthesis was utilized to introduce a hydroxyl group at the start of the polymer chain. Lactone termination was used to functionalize the chain ends with aldehydes or carboxylic acids. The synthesis of well-defined heterotelechelic polymers was thus accomplished employing the Grubbs’ first generation catalyst as the initiator. The living nature of this polymerization allowed for precise control over the molecular weight and guaranteed full functionalization of both polymer chain ends. The presence of the functional groups is shown by MALDI-ToF and NMR measurements. Also, labeling experiments with chromophores were conducted to demonstrate the utility of such heterotelechelic polymer chains.

Supramolecular ABC Triblock Copolymers

Just add it! Ruthenium initiators functionalized with hydrogen-bonding sites were utilized in ring-opening metathesis polymerization to prepare heterotelechelic polymers with hydrogen-bonding and metal-coordination units in a single step. Supramolecular ABC triblock copolymers were then self-assembled in one pot by simply adding complementary telechelic polymers to a solution of the heterotelechelic polymer (see picture).

Synthesis of Heterotelechelic Polymers for Conjugation of Two Different Proteins.

In this report we describe a straightforward approach to synthesize polymers with end-groups that bind site-specifically to two different proteins. Telechelic biotin, maleimide poly(N-isopropylacrylamide) (pNIPAAm) was synthesized for the formation of streptavidin (SAv)-bovine serum albumin (BSA) polymer conjugates. Reversible addition-fragmentation chain transfer (RAFT) polymerization of NIPAAm was conducted in the presence of biotinylated chain transfer agents (CTAs) with either ester or amide linkages, and the resultant α-biotinylated pNIPAAm were formed with low polydispersity indices (PDI ≤ 1.09). UV-Vis analysis of the trithiocarbonate chain-ends indicated 88% or greater retention of the group. A maleimide was introduced to the ω chain-end via a radical cross-coupling reaction with a functionalized azo-initiator. The polymer structures were characterized by 1H NMR spectroscopy and gel permeation chromatography (GPC). The resultant biotin-maleimide heterotelechelic polymer was used to form a SAv-BSA heterodimer conjugate. Bioconjugate formation was confirmed by gel electrophoresis.

The stabilization and bio-functionalization of iron oxide nanoparticles using heterotelechelic polymers

Iron oxide nanoparticles (IONPs) are important tools for nanobiotechnology applications. However, aqueous instability and non-specific biodistribution problems limit the applications of IONPs. Considering this, α-phosphonic acid, ω-dithiopyridine functionalized polymers were synthesized via the reversible addition–fragmentation chain transfer (RAFT) polymerization and used for stabilizing and biofunctionalizing IONPs. A new trithiocarbonate RAFT agent bearing dimethyl phosphonate group was utilized in the synthesis of well-defined telechelic polymers of styrene, oligoethylene glycol acrylate (OEG-A) and N-isopropylacrylamide (NIPAAm). IONPs were grafted with α-phosphonic acid, ω-dithiopyridine functionalized poly(OEG-A) through the α-chain end of the polymer, as evidenced by FTIR-ATR, XPS and zeta potential measurements. Using TGA results, the grafting density of the polymer chains was calculated between 0.12 and 0.23 chains/nm2 particle depending on the molecular weight of the polymer. DLS measurements indicated that the particles grafted with poly(OEG-A) larger than 10 000 g/mol were stable in water for several days and the mean diameter of the particles was between 40 and 130 nm depending on the molecular weight of the polymer. Moreover, particles stabilized with poly(OEG-A) with a Mn = 62 000 g/mol were stable in phosphate buffer (pH 6.5, 0.1 M) containing varying concentrations of BSA. Polymer-stabilized IONPs were successfully functionalized with two different peptides, i.e. reduced glutathione as a model peptide and NGR motif as a tumor-targeting peptide through the ω-dithiopyridine functionality of the polymer, as measured by XPS and zeta potential analysis. Poly(OEG-A)-stabilized IONPs were also found to be resistant to protein adsorption.

Advanced supramolecular initiator for nitroxide-mediated polymerizations containing both metal-ion coordination and hydrogen-bonding sites

The synthesis of a new difunctional nitroxide initiator combining two orthogonal supramolecular entities is reported; controlled radical polymerization of styrene using this initiator is demonstrated to generate well-defined heterotelechelic polymers in a one-step procedure.

Direct Synthesis of Well-Defined Heterotelechelic Polymers for Bioconjugations

Direct synthesis of well-defined heterotelechelic polymers having functional groups allowing the chemoselective bioconjugations would be desirable to enhance the versatility of polymers for bioconjugations and bio-related applications. Considering this, well-defined α-azide, ω-dithiopyridine polymers were synthesized in one step via the reversible addition−fragmentation chain transfer (RAFT) polymerization. The telechelic functionality (i.e., mole ratio of the ω-dithiopyridine to the α-azide end group) of polymers was above 0.90, indicating the efficient generation of well-defined heterotelechelic polymers. The heterotelechelic functionality for chemoselective bioconjugations was tested by reacting α-azide, ω-dithiopyridine poly(NIPAAm) with model biomolecules, i.e., biotin/avidin, glutathione, and bovine serum albumin, via click and thiol−disulfide exchange chemistries. Near-stoichiometric conjugation with biomolecules indicated high functionality of the polymer end groups.

Film thickness effects on the distribution of high-molecular-weight heterotelechelic polymers.

High-molecular-weight heterotelechelic deuteriopolystyrene, NDPSF, possessing an amine functional group at one end of the chain and a fluorocarbon group at the other was tethered to a silicon substrate by its amine functional group. These layers were coated with an unfunctionalised polystyrene matrix, HPS, such that the total film thickness covered a range from 2.2 to 9 times the radius of gyration of NDPSF. The detailed distribution of the polymers after annealing for times much greater than the reptation period of either of the components, was obtained using neutron reflectometry. No evidence for bridging of the two interfaces was found for the thicker films, but the finite concentration of the NDPSF polymer observed for the thinnest films may be due to bridging since the energy gain of the fluorocarbon end is just greater than the loss due to configurational entropy losses. A linear increase in the ellipsometric thickness of the excess of NDPSF at the substrate was discovered and we attribute this to the NDPSF slowly being leached out of the layer initially at the substrate followed by diffusion into the bulk of the film. The concentration profiles obtained are consistent with hindered relaxation of the large NDPSF molecules, when they are tethered at the substrate or at the vacuum surface.

Synthesis of hyperbranched poly(tert-butyl acrylate) by self-condensing atom transfer radical polymerization of a macroinimer

Using 2-hydroxyethyl α-bromoisobutyrate as initiator, atom transfer radical polymerization (ATRP) of tert-butyl acrylate leads to poly(tert-butyl acrylate) (PtBA) with a hydroxyl group at one and a bromine atom at the other end. Esterification of the hydroxyl group of these heterotelechelic polymers with acryloyl chloride yields PtBA (Mn = 3 060) with a polymerizable double bond at one end and a bromine atom at the other end which can act as an initiator in ATRP (“macroinimer”). Self-condensing ATRP of such a macroinimer leads to hyperbranched or highly branched PtBA. The polymer was characterized by GPC viscosity measurements. Even at Mw = 78 800, a rather low polydispersity index of Mw/Mn = 2.6 was obtained. A significantly lower value for the Mark-Houwink exponent (α = 0.47 compared to α = 0.80 for linear PtBA) indicates the compact nature of the branched macromolecules.

Synthesis of heterotelechelic polymers by free radical addition-fragmentation chain transfer

Telechelic polymers are polymers, generally of moderate molar masses, carrying functional groups at both chain ends. A telechelic polymer is therefore characterized by the nature and the length of the polymer chain and the nature of the functional groups. Classical telechelic polymers are linear macromolecules carrying two identical functional end-groups. When the polymer contains two different functional groups, it is called “heterotelechelic”. During the past decade, a large number of new synthetic methods for the preparation of telechelic polymers have been proposed in the literature. Free radical addition-fragmentation reaction has not only been reported to be a new method allowing chain-length control, because of schematic analogy with chain transfer reaction, but has also been identified as an effective means for generating functional polymers. This review describes new developments in the radical synthesis of heterotelechelic poly(vinyl monomer)s through the use of addition-fragmentation chain transfer agents.

End-functionalized polymers by living cationic polymerization with EtAlCl2. 2. Synthesis of homo- and heterotelechelic poly(isobutyl vinyl ether)

Homo- and heterotelechelic polymers [X-CH 2 CH 2 OCH(CH 3 )(iBVE) n CH(COOEt) 2 (X = OCOCH 3 , N(COOtBU) 2 , CH(COOtBu) 2 and X-CH 2 CH 2 OCH(Ch 3 )(iBVE) n Ph (X = CH(COOEt) 2 of isobutyl vinyl ether (iBVE) were prepared by living cationic polymerization. The α-end function X was introduced bu use of initiating systems where functional trifluoroacetate initiators were coupled with EtAlCl 2 and excess 1,4-dioxane in hexane solvent. These polymers could be converted to telechelic polymers with a hydroxy, amino or carboxy group at the α-end?