Active Ester Groups Research Articles

Nanoparticles based on star polymers as theranostic vectors: endosomal-triggered drug release combined with MRI sensitivity.

Dual-functional star polymers (diameters 15 nm) are synthesized producing nanoparticles with excellent colloidal stability in both water and serum. The nanoparticles are built with aldehyde groups in the core and activated esters in the arms. The different reactivity of the two functional groups to sequentially react with different amino compounds is exploited; doxorubicin (DOX) and 1-(5-amino-3-aza-2-oxypentyl)-4,7,10-tris(tert-butoxycarbonylmethyl)-1,4,7,10-tetraazacyclododecane (DO3A-tBu-NH2 )-a chelating agent effective for the complexation of Gadolinium ions (Gd). The activated ester group is employed to attach the DO3A chelating agent, while the aldehyde groups are exploited for DOX conjugation, providing a controlled release mechanism for DOX in acidic environments. DOX/Gd-loaded nanoparticles are rapidly taken up by MCF-7 breast cancer cells, subsequently releasing DOX as demonstrated using in vitro fluorescence lifetime imaging microscopy (FLIM). Endosomal, DOX release is observed, using a phasor plot representation of the fluorescence lifetime data, showing an increase of native DOX with time. The MRI properties of the stars are assessed and the relaxivity of Gd loaded in stars is three times higher than conventional organic Gd/DO3A complexes. The DOX/Gd-conjugated nanoparticles yield a similar IC50 to native DOX for breast cancer cell lines, confirming that DOX integrity is conserved during nanoparticle attachment and release.

Binding of Functionalized Polymers to Surface-Attached Polymer Networks Containing Reactive Groups

To study diffusion and binding of polymers into surface-attached networks containing reactive groups, surface-attached polymer networks bound to oxidized silicon surfaces are generated, which contain succinimide ester groups. The surface-attached polymer layers are brought into contact with poly(ethylene glycol)s (PEG), which carry terminal amine end groups and which have systematically varied molecular weights. The coupling reaction between the active ester groups in the polymer networks and the amine groups in the incoming chains are studied by ellipsometry, surface plasmon spectroscopy, AFM, and Fourier transform infrared spectroscopy (FTIR). The degree of functionalization of the reactive layers by the PEG-NH2 depends strongly on the cross-link density of the network, the active ester content, and the molecular weight of the amine-terminated polymer. A model for the attachment reaction is proposed which suggests that the incoming polymer chains bind only at the outer periphery of the network in a narrow penetration zone. According to this model, when the incoming polymers are rather short, penetration into the layer and binding are prohibited by the high segment density and the anisotropic stretching of the surface-attached networks (“entropic shielding”). For incoming chains with a higher molecular weight and/or networks with a small mesh sizes, size exclusion effects determine diffusion and binding.

Selective Postmodification of Copolymer Backbones Bearing Different Activated Esters with Disparate Reactivities.

In this communication, we report an easy method for introducing functional groups into polymer structures by successively reacting two different activated ester functionalities (pentafluorophenyl (PFP) ester and azlactone (AZ)) with different functional amine compounds. By exploiting the difference in reactivity of the two activated esters (PFP and AZ) toward different amino compounds, we demonstrate, for the first time, a selective modification of the different activated ester groups, thereby introducing functional groups to the polymer backbone in a controlled manner. Statistical and block copolymers of vinyl dimethyl azlactone (VDM) and pentafluorophenyl acrylate (PFPA), i.e.,(p(VDM-stat-PFPA)) and (p(VDM-block-PFPA)), were prepared using reversible addition-fragmentation transfer (RAFT) polymerization and subsequently modified using a library of amino compounds, yielding macromolecules with bespoke functionality. In additional work, the functional macromolecules were self-assembled into nanoparticles.

Enhanced Sensitivity Employing Zwitterionic and pI Balancing Dyes (Z-CyDyes) Optimized for 2D-Gel Electrophoresis Based on Side Chain Modifications of CyDye Fluorophores. New Tools For Use in Proteomics and Diagnostics

The CyDye family of fluorescent dyes is currently the overwhelming choice for applications in proteomic analysis, using two-dimensional difference gel electrophoresis (2D-DIGE). Protein labeling with CyDyes is hampered by protein precipitation and gel smearing when used above minimal labeling. The solubility of labeled protein may be improved by introducing water solubilizing groups on the dye such as cysteic acids. However, addition of a negatively charged functionality will have the undesired effect of shifting the pI in relation to the unlabeled protein. These limitations have been addressed through the synthesis of highly water-soluble and pI balancing zwitterionic CyDye fluorophores (Z-CyDyes). The new dyes feature a cysteic acid motif, a titratable amine functionality and a NHS activated ester group. In side by side 2D-DIGE comparisons of Z-CyDyes and CyDyes, the new dyes significantly enhanced protein spot volume and the number of spots that were detected. Z-CyDyes have the potential to enhance the depth of proteome coverage and provide a general strategy for improving the performance of protein tagging reagents.

Promotion of initial cell adhesion on trisuccinimidyl citrate-modified nickel-free high-nitrogen stainless steel

The surface of nickel-free high-nitrogen stainless steel (HNS) was modified with a citric acid-based cross-linker, trisuccinimidyl citrate (TSC), to promote initial cell adhesion in external skeletal fixation pins. The remaining active ester groups on TSC-immobilized HNS reacted with the amino groups of serum proteins. The immobilized serum proteins formed cell recognition sites to promote the initial cell adhesion immediately after cell seeding. The amount of fibronectin, which is a typical cell adhesion protein, immobilized on the TSC-immobilized HNS surface was threefold greater than on the original HNS after only 15 min. The fibroblastic cell culture experiments showed that the initial cell adhesion was significantly enhanced on the TSC-immobilized HNS compared with the original HNS at 3 h. Furthermore, the cell adhesion activity of the TSC-immobilized HNS continued to promote cell proliferation even at 7 days. Therefore, TSC-immobilized HNS may enable the rapid integration of soft tissues through its reaction with the patient's serum proteins and extracellular proteins around the surgical site.

Tamibarotene-loaded citric acid-crosslinked alkali-treated collagen matrix as a coating material for a drug-eluting stent

Tamibarotene-loaded biodegradable matrices with antithrombogenic and drug-releasing properties were prepared in a crosslinking reaction between amino groups of alkali-treated collagen (AlCol) and active ester groups of trisuccinimidyl citrate. The resulting matrices were characterized by their residual amino group concentrations, swelling ratios and thermal, antithrombogenic and drug-releasing properties. It was clarified that the addition of tamibarotene does not inhibit matrix formation. After immersion in water, the swelling ratio of a matrix became lower than that prior to immersion. Thermal analysis indicated that AlCol interacted with tamibarotene. The addition of tamibarotene to the matrix did not influence the antithrombogenic property of the resulting matrix. A matrix with a high crosslinking density had a prolonged tamibarotene elution time. These results demonstrate that tamibarotene-loaded matrices have great potential as a coating material for drug-eluting stents.

Azide photochemistry for facile modification of graphitic surfaces: preparation of DNA-coated carbon nanotubes for biosensing

A facile, two-step method for chemically attaching single-stranded DNA to graphitic surfaces, represented here by carbon nanotubes, is reported. In the first step, an azide-containing compound, N-5-azido-nitrobenzoyloxy succinimide (ANB-NOS), is used to form photo-adducts on the graphitic surfaces in a solid-state photochemical reaction, resulting in active ester groups being oriented for the subsequent reactions. In the second step, pre-synthesized DNA strands bearing a terminal amine group are coupled in an aqueous solution with the active esters on the photo-adducts. The versatility of the method is demonstrated by attaching pre-synthesized DNA to surfaces of carbon nanotubes in two platforms—as vertically-aligned multi-walled carbon nanotubes on a solid support and as tangled single-walled carbon nanotubes in mats. The reaction products at various stages were characterized by x-ray photoelectron spectroscopy. Two different assays were used to check that the DNA strands attached to the carbon nanotubes were able to bind their partner strands with complementary base sequences. The first assay, using partner DNA strands tethered to gold nanoparticles, enabled the sites of DNA attachment to the carbon nanotubes to be identified in TEM images. The second assay, using radioactively labelled partner DNA strands, quantified the density of functional DNA strands attached to the carbon nanotubes. The diversity of potential applications for these DNA-modified carbon-nanotube platforms is exemplified here by the successful use of a DNA-modified single-walled carbon-nanotube mat as an electrode for the specific detection of metal ions.

An Antithrombogenic Citric Acid‐Crosslinked Gelatin with Endothelialization Activity

A novel citric acid-crosslinked gelatin matrix with endothelialization activity and anti-adhesive properties for platelets is prepared. The matrix is characterized using an endothelial cell culture and an antithrombogenic activity test. The number of endothelial cells cultured on the surface of the trisuccinimidyl citrate (TSC)-crosslinked gelatin increases as the concentration of TSC increases to 20 mM, and then decreases with further increases in TSC concentration. Compared with glutaraldehyde-crosslinked gelatin, platelet number and fibrin network formation on the TSC-crosslinked gelatin are minimal at high TSC concentration. The biocompatibility of the matrix is evaluated by bioluminescence imaging. This indicates that the inflammation reaction of the TSC-crosslinked gelatin is lower than that of glutaraldehyde-crosslinked gelatin. Physicochemical analysis of TSC-crosslinked gelatin with different TSC concentrations shows that the high concentration of the cell adhesion sequence, arginine-glycine-aspartic acid, contributes to the promotion of endothelial cell adhesion and subsequent endothelial cell growth. Analysis of the carboxyl groups in the TSC-crosslinked gelatin showed that the antithrombogenic activity is due to the increased negative charge derived from the hydrolyzed active ester groups of TSC. These findings show that TSC-crosslinked gelatin has the potential for use in biomedical devices in contact with blood, such as stents, artificial blood vessels, and artificial heart valves.

Direct observation of selective protein capturing on molecular imprinting substrates

A sensing interface for specific protein capture was fabricated using a novel molecular imprinting (MIP) process. Bovine serum albumin (BSA) and ovalbumin (OVA) were imprinted on a quartz substrate with modified alkyl groups, and target protein capture was detected using a deep-UV fluorescence image microscope (UVFLIM). The imprinted protein was immobilized to silica beads (diameter: 15μm) using a phospholipid polymer containing both active ester groups and silane coupling groups, which were used as protein stamps to prepare the imprinting surface. Protein recognition sites were constructed by integrating sodium dodecyl sulfate (SDS) as the ligand, which was immobilized with a biocompatible photoreactive phospholipid polymer. When BSA solution was added to the BSA-based MIP substrate, strong fluorescence was observed from the tryptophan residue of BSA. In contrast, for the OVA-based MIP substrate and non-MIP substrate, no fluorescence was observed. The surface showed good selectivity of BSA against OVA. The phospholipid polymer layer prevented non-specific protein adsorption, resulting in highly selective protein recognition. Further, when the protein-imprinted substrate was constructed without ligands, neither protein was captured on the substrate. We demonstrated the importance of ligand integration for capturing target proteins at specific positions. UVFLIM can be used to detect biomolecules at the single-molecule level by using intrinsic fluorescence without molecular labeling. Our new protein-imprinted surface used with UVFLIM is a versatile tool for capturing biomolecules.

Electrospun phospholipid polymer substrate for enhanced performance in immunoassay system

A functional polymer bearing both phosphorylcholine and active ester groups, poly[2-methacryloyloxyethyl phosphorylcholine (MPC)-co-n-butyl methacrylate (BMA)-co-N-succinimidyloxycarbonyl di(ethylene glycol) methacrylate (PENHS)] (PMBS), provided a highly biomolecule-friendly platform for immunoassays. The nonbiofouling property of the PMBS remarkably reduces the background noise from nonspecific adsorption of proteins in the analyte in an enzyme-linked immunosorbent assay (ELISA), which improves the specificity and signal-to-noise ratio. Electrospinning deposition, a versatile and cost-effective technique, was employed to fabricate nanofibrous PMBS. This nanostructure increased the surface area of the polymer, allowing more antibodies to bind to the polymer interface and enhancing the sensitivity of the biosensing system. The electrospun PMBS fibers were stable and retained their unique morphologies after contact with an aqueous solution for 4.0h. The ability of PMBS to reduce background noise without blocking by protein-based reagents was verified by comparison with an immunoassay conducted on a polystyrene substrate. The ELISA of human immunoglobulin-G with the electrospun PMBS substrate showed a good sigmoidal relationship with a linear detection range from 1.0 to 100ng/mL. The detection time was 25% shorter than the conventional assay as the blocking step was omitted. The immobilized primary antibodies exhibited high stability on the electrospun PMBS; 60% and 25% of the residual bioactivity remained after storage in dry conditions for 2 and 4 weeks, respectively. Thus, for further development of biosensors, nanostructured PMBS can improve lifetime of immobilized biomolecules, and also contribute to an enhanced reliability and signal-to-noise ratio of immunoassay.

Polynuclear Copper(I) Clusters Supported by Carboxylate Ligands with Coordinatively Active Ester Group

Two new copper(I) complexes with polynuclear cores bridged by 4-(ethoxycarbonyl)benzoate ligands, [Cu6(O2CC6H4CO2C2H5)4(O2CCF3)2] (1) and [Cu4(O2CC6H4CO2C2H5)4] (2), have been prepared by ligand exchange method in high yield and fully characterized by X-ray diffraction and spectroscopic techniques. The important role of intermolecular interactions between the polynuclear copper(I) clusters imposed through the coordinatively active dangling ester groups of bridging carboxylate ligands on the solid-state packing and photoluminescent behavior of 1 and 2 has been revealed.

Structural Analysis of High Performance Ion-Gel Comprising Tetra-PEG Network

The structure of Tetra-PEG ion gel, which is tetra-arm poly(ethylene glycol) (Tetra-PEG) network in ionic liquid (IL) and has recently established in our group and possesses high ion conductivity and high mechanical properties, was investigated as functions of polymer concentration (ϕ) and molecular weight (Mw) by using small-angle neutron scattering (SANS) measurements. The results were compared with those of Tetra-PEG hydrogel. The macromer solutions of tetra-amine terminated PEG (TAPEG) macromers, which is one of the two constituents forming Tetra-PEG network, were found to interpenetrate each other in IL and exhibited a scaling relationship, ξ ∼ ϕ–3/4, where ξ is the correlation length. The SANS functions, I(q), for the ion gels made by cross-end-coupling of TAPEG and TNPEG (tetra-arm PEG with active ester groups) were represented by the so-called Ornstein–Zernike equation, suggesting absence of frozen inhomogeneites. The same scaling relationship to the macromer solutions, ξ ∼ ϕ–3/4, was also obtaine...

Water-soluble polymeric derivatives of β-cyclodextrin

On the basis of hydrophilic copolymers of N-vinylamides—N-vinylpyrrolidone and N-methyl-N-vinylacetamide—that contain carboxylic or activated ester groups, new polymeric β-cyclodextrin derivatives are synthesized via polymer-analogous transformations. Their solubility in water depends on the content of β-cyclodextrin and the types of hydrophilic and reactive comonomers.

Refractive Index Changes in Polymers Bearing Pendant Active Ester Groups by Thermal Rearrangement Reaction

Abstract Linear and branched polymers bearing S-(2-benzoxazolyl) thioester groups were selectively synthesized by free radical and photoinitiated radical polymerization, respectively, of S-(2-benzoxazolyl)-4-vinylthiobenzoate. Upon heating, the pendant S-(2-benzoxazolyl) thioester groups were converted to 3-acylbenzoxazoline-2-thione groups, accompanied with a change of refractive index (Δn) of about +0.01 in both cases. The structural conversion was confirmed by UV–vis and IR spectroscopy, as well as comparison with authentic polymers bearing 3-acylbenzoxazoline-2-thione groups (similarly synthesized from 3-(4-vinylbenzoyl)benzoxazoline-2-thione). Application of such thermally induced rearrangement reactions may provide a new approach for obtaining materials whose refractive index can be changed by heat (e.g., generated by a laser beam).

High PEGylation efficiency of pentaethylenehexamine-end poly(ethylene glycol) (mPEG-N6) for active-ester surface

The chemical surface-modification of carboxylated polystyrene submicroparticles (sMPs) with α-methoxy-poly(ethylene glycol)-pentaethylenehexamine (mPEG-N6), which possesses multiple amino end-groups at one end, was explored with respect to modification efficiency. As a control, a PEG mono-aminated at one end (mPEG-N1) was employed in parallel experiments. Dynamic light scattering (DLS), electrophoretic mobility (μe), Fourier transform infra-red (FT-IR) absorption, and 3-(p-carboxybenzoyl)quinoline-2-caboxaldehyde (CBQCA) assays were carried out. From reported pKa values of the amino groups, about 25% of the amino groups were protonated at pH9.5 for pentaethylenehexamine (N6), in other words, 1.5 amino groups were protonated and 4.5 amino groups were non-protonated on average for each mPEG-N6 molecule under the conditions. The multiple amino end-groups of mPEG-N6 played two different roles in modifying the sMPs: the protonated part offered electrostatic attraction between mPEG-N6 and the negatively charged sMPs; the non-protonated part covalently reacted with the active ester groups on the sMP surface after EDC-activation treatments. During the PEG-modification process, the former attractive force increased the local mPEG-N6 concentration surrounding the sMPs, which facilitated covalent conjugation to the sMPs. In contrast, protonated mPEG-N1 (80% under the same conditions) tends to cover the negatively charged sMPs, which retards the reaction of non-protonated mPEG-N1. These collaborative actions within each mPEG-N6 chain improved the PEG-modification efficiency, rending mPEG-N6 an ideal PEGylation agent relative to mPEG-N1.

Construction of a densely poly(ethylene glycol)-chain-tethered surface and its performance

Non-biofouling surfaces constitute one of the most important subjects in sensitively and selectively detecting biomolecular events. Poly(ethylene glycol) (PEG) chains tethered on substrate surfaces are well known to reduce non-biofouling characteristics. Protein adsorption onto a PEG-chain-tethered surface is strongly influenced by the density of the PEG chain and is almost completely suppressed by the successive treatment of longer PEG chains (5 kDa) followed by the treatment of PEG (2 kDa; mixed-PEG-chain-tethered surface) because of a significant increase in PEG chain density. To modify versatile substrate surface, PEG possessing pentaethylenehexamine at one end (N6-PEG) was prepared via a reductive amination reaction of aldehyde-ended PEG with pentaethylenehexamine. Using N6-PEG, antibody/PEG co-immobilization was conducted on a substrate possessing active ester groups. After the antibody was immobilized on the surface, PEG tethered chains were constructed surrounding the immobilized antibody. It is interesting to note that the PEG-chain-tethered functions not only as a non-fouling agent but also improves immune response. The hybrid surface was also applied to oligo DNA immobilization. The oligo DNA/PEG hybrid surface improved hybridization, retaining its non-fouling ability. Densely packed PEG tethered chains surrounding antibodies and/or oligo DNA improved their orientation on the surface. Thus, this material is promising as a high-performance biointerface for versatile applications. Protein adsorption on the poly(ethylene glycol) (PEG)-tethered-chain surface was almost completely suppressed by successive treatment of longer PEG chain followed by treatment of PEG (2 kDa; mixed-PEG tethered-chain surface) because of significant increase in PEG chain density. Using pentaethylenehexamine-ended PEG, which was newly designed by ourselves, antibody/PEG and oligoDNA/PEG co-immobilizations were carried out. The PEG tethered chain was found to work not only as a non-fouling character but also as an improvement in orientation of biomolecules. Thus, it is promising as a high-performance biointerface for versatile applications.

Characterization of the dielectric properties of covalently attached organic films on silicon surfaces

Monolayers of methyl-undecanoate were constructed on silicon surfaces via a covalent Si–C bond. The molecular monolayers were characterized by high resolution electrical impedance spectroscopy (EIS), X-ray photoelectron spectroscopy (XPS) and ellipsometry and displayed a densely packed monolayer. After formation of the monolayer, the methyl ester was hydrolyzed without noticeable change in the integrity of the monolayer. The carboxyl terminated organic layer was then reacted with (1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide to form active N-hydroxy succinimide ester groups. The activation chemistry was confirmed by XPS and the substructure of the methyl-undecanoate carboxylic acid and the N-hydroxy succinimide ester terminated films were characterized using EIS. XPS and EIS spectra provided information on the chemical composition and substructure of the monolayers for each step in the chemical modification of the surface.

Abstract 3223: Active enhancement of anti-tumor effect by NF-κB inhibitor DHMEQ using PMBN conjugated with anti-EGFR antibody in human pancreatic adenocarcinoma cells in vivo and in vitro

Abstract Background and Objective: The NF-kB/Rel family of transcription factors is involved in the development of cancer. This family is constitutively activated in many human pancreatic cancers and pancreatic cell lines. DHMEQ inhibits NF-κB activity by preventing nuclear translocation and has been shown anti-tumor effect. However, because of its hydrophobic property, DHMEQ has to be administered intraperitoneally or subcutaneously every day. Therefore, it is necessary to develop effective drug delivery system (DDS) of DHMEQ for clinical application. In this study, we have used PMBN polymer, which forms a stable polymer aggregate in water that can enhance the solubility of hydrophobic substance such as DHMEQ. The active ester group of PMBN can be replaced by proteins such as anti-epidermal growth factor receptor (EGFR) antibody. It is expected that a selective increased accumulation of PMBN-DHMEQ antibody conjugate could lead to a reduction of its dose and/or numbers of administration. The aim of this study is that investigate active enhancement of anti-cancer effect by DHMEQ using PMBN. Methods: The human pancreas adenocarcinoma cell lines, AsPC-1, BxPC-3, MIAPaCa-2, which showed high expression level of EGFR were used in vitro study. DHMEQ, PMBN and mouse monoclonal anti-human EGFR antibody (528) were mixed at the weight ratio of 1:25:5 and sonicated to prepare PMBN-DHMEQ antibody conjugate in advance. Control DHMEQ was dissolved in 0.5% chrolomethylcellulose (CMC-DHMEQ). The effect of cell growth inhibition by each preparation was evaluated by WST assay in vitro. AsPC-1 cells which expressing Gaussia luciferase (AsPC-1-Luc) was used to investigate anti-tumor effect in vivo. 5×105 of AsPC-1-Luc was injected into nice portal vein to develop liver metastases model of pancreatic cancer. Mice were given PMBN-DHMEQ antibody conjugate (intravenously) or CMC-DHMEQ (intraperitoneally) every three days at a dose of 12mg/kg DHMEQ. Metastases level of each group was compared by measuring luciferase activity of mice whole liver homogenate using Renilla Luciferase Assay System (Promega). Result: PMBN-DHMEQ antibody conjugate showed higher cell growth inhibition than CMC-DHMEQ in vitro WST assay. Also it showed stronger growth inhibition effect than CMC-DHMEQ in vivo. Quantitative luciferase assay showed that PMBN-DHMEQ antibody conjugate have 49.2 times higher effect compare to CMC-DHMEQ. Conclusion: Our results demonstrate that the PMBN-DHMEQ-anti-EGFR antibody conjugate can efficiently decrease cancer development of cells overexpressing EGFR by an active enhancement effect. This result suggest that increased accumulation of PMBN-DHMEQ anti-EGFR antibody conjugate increased tumor concentration of DHMEQ and the therapeutic response. PMBN-mediated DDS, which in turn reduce its dose and/or numbers of administration of DHMEQ. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3223. doi:10.1158/1538-7445.AM2011-3223

Penetration of Polymer Brushes by Chemical Nonidentical Free Polymers

We report on the reaction of surface-attached polymer brushes with polymer molecules, which are present in a contacting solution. More specifically, we synthesize copolymer brushes containing N-hydroxysuccinimide active ester groups and study their reaction with poly(ethylene glycol) molecules, which carry an amino group at one end. Qualitatively, highly “pegylated” surfaces are obtained with an equivalent thickness of the PEG layers of up to 200 nm. Yield and kinetics of the grafting reaction are studied as a function of size and concentration of the incoming molecules, brush graft density, and brush molecular weight. It is observed that the completion of the grafting reaction is surprisingly fast, the molecular weight of the incoming molecules has a strong, while graft density and molecular weight of the brush have only a weak influence on the extent of functionalization. We develop a model for the grafting reaction, where due to limited penetration of the brush by the incoming chains the reaction occurs only at the outer periphery of the surface-attached layer. Reactive groups present in the inner parts of the brush do not take part in the attachment reaction. In the outer parts of the brush, however, partial penetration is possible so that the attachment reaction is fast and essentially only governed by the details of the shape of the segment density distribution and the size of the incoming chains.

Synthesis and characterization of a naphthalimide–dye end-labeled copolymer by reversible addition–fragmentation chain transfer (RAFT) polymerization

We describe the synthesis of an end-functionalized copolymer of N-(2-hydroxypropyl)methacrylamide (HPMA) and N-hydroxysuccinimide methacrylate (NMS) by reversible addition–fragmentation chain transfer (RAFT) polymerization. To control the polymer composition, the faster reacting monomer (NMS) was added slowly to the reaction mixture beginning 30 min after initating the polymerization (ca. 16% HPMA conversion). One RAFT agent, based on azocyanopentanoic acid, introduced a –COOH group to the chain at one end. Use of a different RAFT agent containing a 4-amino-1,8-naphthalimide dye introduced a UV–vis absorbing and fluorescent group at this chain end. The polymers obtained had molecular weights of 30 000 and 20 000, respectively, and contained about 30 mol% NMS active ester groups.