Carboxylic Acid Side Groups Research Articles

Phenylboronic acid-modified nanoscale multi-arm polymers for tumor-targeted therapy.

Unimolecular polymer nanomaterials (UPNs) have well-defined structures, desirable stability and designable functional groups, and hence exhibit great application potential in drug delivery. However, the syntheses of UPNs are generally time-consuming and tedious, which greatly limit their applications. In this paper, we present the preparation of a β-cyclodextrin-cored star-shaped polymer with 21 poly(tert-butyl acrylate) arms. This polymer was facilely synthesized by one-step atom transfer radical polymerization (ATRP). After cleaving the tert-butyl ester protecting groups, the abundant carboxylic acid side groups were used to incorporate doxorubicin (DOX), phenylboronic acid (PBA) groups and poly(ethylene glycol) (PEG) to achieve drug loading and tumor drug delivery. Due to the tumor-targeting ability of the PBA groups, this UPN-based nanomedicine showed high tumor accumulation, penetration and therapeutic efficacy.

Responsive Polyesters with Alkene and Carboxylic Acid Side-Groups for Tissue Engineering Applications.

Main chain polyesters have been extensively used in the biomedical field. Despite their many advantages, including biocompatibility, biodegradability, and others, these materials are rather inert and lack specific functionalities which will endow them with additional biological and responsive properties. In this work, novel pH-responsive main chain polyesters have been prepared by a conventional condensation polymerization of a vinyl functionalized diol with a diacid chloride, followed by a photo-induced thiol-ene click reaction to attach functional carboxylic acid side-groups along the polymer chains. Two different mercaptocarboxylic acids were employed, allowing to vary the alkyl chain length of the polymer pendant groups. Moreover, the degree of modification, and as a result, the carboxylic acid content of the polymers, was easily tuned by varying the irradiation time during the click reaction. Both these parameters, were shown to strongly influence the responsive behavior of the polyesters, which presented adjustable pKα values and water solubilities. Finally, the difunctional polyesters bearing the alkene and carboxylic acid functionalities enabled the preparation of cross-linked polyester films by chemically linking the pendant vinyl bonds on the polymer side groups. The biocompatibility of the cross-linked polymers films was assessed in L929 fibroblast cultures and showed that the cell viability, proliferation, and attachment were greatly promoted on the polyester surface, bearing the shorter alkyl chain length side groups and the higher fraction of carboxylic acid functionalities.

Redox-Active Micelle-Based Reaction Platforms for In Situ Preparation of Noble Metal Nanocomposites with Photothermal Conversion Capability.

Polyferrocenylsilane (PFS)-based polymers are an attractive family of organometallic polymers with unique redox-active properties. Herein, we report a novel amphiphilic redox-active PFS-based homopolymer, poly(ferrocenylmethylethylthiocarboxypropylsilane) (PFC), with a hydrophobic backbone chain and hydrophilic carboxylic acid side groups in each repeating unit. Self-assembly was induced by addition of water to a molecularly dispersed solution of PFC in DMSO. Spherical PFC micelles with controllable hydrodynamic diameters (60-180 nm) were obtained under various conditions. These PFC micelles could be readily endocytosed by A549 cells and HUVEC cells and show no significant cytotoxicity toward them at the concentration of 200 μg/mL. On this basis, Au nanoparticles (AuNPs) were prepared through in situ reduction of HAuCl4 by PFC micelles as nanoreactors without requiring any other reductants. The PFC/Au nanocomposites (NCs) were found to exhibit significant photothermal behavior. Moreover, PFC micelles could also act as nanoreactors for other noble metals such as Ag, Pd, and Pt. By taking advantage of properties of the nanostructures and noble metal nanoparticles comprising these materials, the PFC micelles and PFC/noble metal NCs may have great potential in biomedical or catalytic applications.

Synthesis, Tumor Specificity, and Photosensitizing Efficacy of Erlotinib-Conjugated Chlorins and Bacteriochlorins: Identification of a Highly Effective Candidate for Photodynamic Therapy of Cancer.

Erlotinib was covalently linked to 3-(1'-hexyloxy)ethyl-3-devinylpyropheophorbide-a (HPPH) and structurally related chlorins and bacteriochlorins at different positions of the tetrapyrrole ring. The functional consequence of each modification was determined by quantifying the uptake and subcellular deposition of the erlotinib conjugates, cellular response to therapeutic light treatment in tissue cultures, and in eliminating of corresponding tumors grown as a xenograft in SCID mice. The experimental human cancer models the established cell lines UMUC3 (bladder), FaDu (hypopharynx), and primary cultures of head and neck tumor cells. The effectiveness of the compounds was compared to that of HPPH. Furthermore, specific functional contribution of the carboxylic acid side group at position 172 and the chiral methyl group at 3(1') to the overall activity of the chimeric compounds was assessed. Among the conjugates investigated, the PS 10 was identified as the most effective candidate for achieving tumor cell-specific accumulation and yielding improved long-term tumor control.

PH-Responsive Copolymer Films Prepared by Surface-Initiated Polymerization and Simple Modification.

We report the preparation of pH-responsive, ester/carboxylic acid random copolymer films via simple modification of poly(norbornene diacyl chloride) (pNBDAC), prepared via surface-initiated ring-opening metathesis polymerization, with mixtures of water and ethanol to form carboxylic acid and ethyl ester side groups. The pNBDAC film serves as a compositionally versatile platform to controllably obtain copolymers with multiple functionalities. In modifying the pNBDAC to form the copolymer film, ethanol exhibits a significantly higher reactivity with acyl chloride groups within the film than does water. The magnitude and range of the pH-responsive performance are highly dependent on the carboxylic acid content in the copolymer films, which demonstrates the effect of film hydrophilicity on the pH-responsive switching of ionic barrier properties. The resistance of the film against ion transfer can be decreased by a factor of 104 through pH change, demonstrating pH-induced switching from hydrophobic and insulating to swollen and ion-permeable films. The interactions of the copolymer films with water at different pH values were also explored. When the copolymer contains 34% carboxylic acids, a 4× greater film thickness is obtained in high pH solution than in low pH solution due to ionically driven water swelling. The reversibility of the pH-responsive performance of these copolymer films is high based on measurements using quartz crystal microbalance with dissipation (QCM-D).

Alendronate-Functionalized Poly(2-oxazoline)s with Tunable Affinity for Calcium Cations

A library of poly(2-oxazoline)s functionalized with controllable amounts of alendronate, hydroxyl, and carboxylic acid side groups was successfully synthesized to create novel polymers with tunable affinity for calcium cations. The affinity of alendronate-containing polymers for calcium cations was quantified using isothermal titration calorimetry. Thermodynamic measurements revealed that the Ca2+-binding affinity of these polymers increased linearly with the amount of alendronate functionalization, up to values (KCa2+ = 2.4 × 105 M–1) that were about 120-fold higher than those for previously reported polymers. The calcium-binding capacity of alendronate-functionalized poly(2-oxazoline)s was exploited to form robust hydrogel networks cross-linked using reversible physical bonds. Oscillatory rheology showed that these hydrogels recovered more than 100% of their initial storage modulus after severe network destruction. The versatile synthesis of alendronate-functionalized polymers and their strong and tunable affinity for calcium cations render these polymers promising candidates for various biomedical applications.

Preparation and Characterization of Transparent Polyimide⁻Silica Composite Films Using Polyimide with Carboxylic Acid Groups.

Polyimide (PI) composite films with thicknesses of approximately 100 µm were prepared via a sol–gel reaction of 3-aminopropyltrimethoxysilane (APTMS) with poly(amic acid) (PAA) composite solutions using a thermal imidization process. PAA was synthesized by a conventional condensation reaction of two diamines, 3,5-diaminobenzoic acid (DABA), which has a carboxylic acid side group, and 2,2′-bis(trifluoromethyl)benzidine (TFMB), with 4,4′-(hexafluoroisopropylidene)diphthalic anhydride (6FDA) in N,N-dimethylacetamide (DMAc). The PAA–silica composite solutions were prepared by mixing PAA with carboxylic acid side groups and various amounts of APTMS in a sol–gel process in DMAc using hydrochloric acid as a catalyst. The obtained PI–silica composite films showed relatively good thermal stability, and the thermal stability increased with increasing APTMS content. The optical properties and in-plane coefficient of thermal expansion (CTE) values of the PI–silica composite films were investigated. The CTE of the PI–silica composite films changed from 52.0 to 42.1 ppm/°C as the initial content of APTMS varied. The haze values and yellowness indices of the composite films increased as a function of the APTMS content.

Interaction of pH-responsive polyanions with phospholipid membranes

The behavior of two acrylate polymers, with carboxylic acid side groups, was investigated with regard to their pH-responsive interaction with phospholipid membranes.

Water-Stable Nanoporous Polymer Films with Excellent Proton Conductivity.

Achieving high values for proton conductivity in a material critically depends on providing hopping sites arranged in a regular fashion. Record values reported for regular, molecular crystals cannot yet be reached by technologically relevant systems, and the best values measured for polymer membranes suited for integration into devices are almost two orders of magnitude lower. Here, an alternative polymer membrane synthesis strategy based on the chemical modification of surface-mounted, monolithic, crystalline metal-organic framework thin films is demonstrated. Due to chemical crosslinking and subsequent removal of metal ions, these surface-mounted gels (SURGELs) are found to exhibit high proton conductivity (0.1 S cm-1 at 30 °C and 100% RH (relative humidity). These record values are attributed to the highly ordered polymer network structure containing regularly spaced carboxylic acid side groups. These covalently bound organic frameworks outperform conventional, ion-conductive polymers with regard to ion conductivity and water stability. Pronounced water-induced swelling, which causes severe mechanical instabilities in commercial membranes, is not observed.

Two-dimensional (2D) infrared correlation study of the structural characterization of a surface immobilized polypeptide film stimulated by pH

The pH-induced structural changes to surface immobilized poly (l-glutamic acid) (PLGA) films were examined by Fourier transform infrared (FTIR) spectroscopy and two-dimensional (2D) correlation analysis. Significant spectral changes were observed in the FTIR spectra of the surface immobilized PLGA film between pH 6 and 7. The 2D correlation spectra constructed from the pH-dependent FTIR spectra of the surface immobilized PLGA films revealed the spectral changes induced by the alternations of the protonation state of the carboxylic acid group in the PLGA side chain. When the pH was increased from 6 to 8, weak spectral changes in the secondary structure of the PLGA main chain were induced by deprotonation of the carboxylic acid side group.

Ultrafiltration membranes with markedly different pH- and ion-responsivity by photografted zwitterionic polysulfobetain or polycarbobetain

Stimuli-responsive ultrafiltration (UF) membranes were synthesized via photo-initiated “grafting from” of the zwitterionic monomers N-(3-sulfopropyl)-N-methacroyl-oxyethyl-N,N-dimethyl-ammonium betaine (sulfobetaine methacrylate, SPE) and 2-carboxy-N,N-dimethyl-N-(2′-(methacryl-oyloxy)ethyl)ethan-aminium inner salt (carbobetaine methacrylate, CBMA) onto commercial polyethersulfone UF membranes. The effects of kosmotropic and chaotropic potassium salts and pH on flux were determined in order to investigate the stimuli-responsive behavior of the polyzwitterion-grafted membranes. PolySPE showed the expected stimuli-responsiveness based on the “anti-polyelectrolyte” effect. The degree of swelling of grafted sulfobetaine polymer increased and water permeability decreased with increasing salt concentration; and the results can be related to the “Hofmeister series”, i.e. the magnitude of the effect increased with increasing chaotropic character of the anion, in the order: SO42−<H2PO4−<Cl−<ClO4−. However, the carbobetaine polymer (polyCBMA) did not show such anti-polyelectrolyte behavior at pH values in neutral and basic range. In contrast to the “strong–strong” type zwitterionic material polySPE, the swelling behavior of the “strong-weak” polyCBMA was significantly influenced by pH value because protonation of carboxylic acid side groups changes the grafted chains from net neutral zwitterionic into polycationic with ordinary polyelectrolyte properties. Hence, permeability of polyCBMA-grafted membranes increased with increasing salt concentration at pH=3. Furthermore, the rejection of dextrans as a function of electrolyte concentration and pH was determined and all results were in agreement with changes of water fluxes. For specific salt conditions, large and reversible changes of dextran rejection were found, confirming the possibilities of adjusting the sieving properties of the responsive zwitterionic membranes. Detailed studies by zetapotential measurements were also performed to investigate the specific effects of ion type, electrolyte concentration and pH onto the stimuli-responsive changes of surface charge of grafted membranes. All results support that the effects of the grafted zwitterionic polymers on the barrier properties of the UF membranes can be described with a pore-opening/-closing mechanism based on reversible deswelling/swelling of grafted chains on the pore walls in response to composition changes with respect to salt (for polySPE) or salt and pH value (polyCBMA).

Injectable supramolecular hydrogels via inclusion complexation of mPEG-grafted copolyglutamate with α-cyclodextrin

A series of monomethoxy poly(ethylene glycol) (mPEG) grafted copolyglutamates (PmPEGs) were synthesized through ring-opening polymerization (ROP) followed by click chemistry. Supramolecular hydrogels based on polymer inclusion complexes (ICs) between PmPEG and α-cyclodextrin (α-CD) were prepared in aqueous solution. The rheological measurements indicated their gelation properties were affected by several factors including the mPEG length, graft density and the sample concentration. These hydrogels displayed thermo-sensitive gel-sol transition under appropriate conditions due to the reversible mPEG and α-CD inclusion complexation. These hydrogels also showed pH-sensitive behavior due to the deprotonate of carboxylic acid side groups. The ICs formation of a channel-type crystalline structure induced gelation mechanism was verified by various techniques. In vitro cytotoxicity assays demonstrated that the supramolecular hydrogels are nontoxic and cytocompatible.

Synthesis and Characterizations of Novel Proton-Conducting Fluoropolymer Electrolyte Membranes Based on Poly(vinylidene fluoride-ter-hexafluoropropylene-ter-α-trifluoromethacrylic acid) Terpolymers Grafted by Aryl Sulfonic Acids

The synthesis and the characterization of new polymer electrolyte membranes made of fluorinated copolymers based on vinylidene fluoride (VDF) and hexafluoropropylene (HFP) and grafted by aryl sulfonic acids are presented. They were obtained in a three-step process. First, the conventional batch radical terpolymerization of α-trifluoromethacrylic acid (TFMAA), VDF and HFP, initiated by 2,5-bis(tert-butylperoxy)-2,5-dimethylhexane led to original fluorinated functional terpolymers bearing carboxylic acid side groups in fair to good yields (>55%). The microstructure and the thermal properties of these macromolecules were studied. Interestingly, poly[(VDF-alt-TFMAA)-co-HFP)] random terpolymers that contained alternated microblock structures based on VDF and TFMAA units separated by one HFP unit were evidenced by 19F nuclear magnetic resonance (NMR) spectroscopy. That technique also enabled us to assess the termonomer contents. Average molecular weights, glass transition temperatures, and decomposition tempera...

Photoluminescent Color Tuning in Fluorene Derivative/Copolymer Composite Films Based on H-Bonds

Reversible addition-fragmentation chain transfer (RAFT) polymerization is used to synthesize diblock and random copolymers of poly[(2-trifluoroethyl methacrylate)-co-(methacrylic acid)]. Copolymer films doped with fluorene derivatives comprised of pyridine groups exhibit reversible photoluminescent (PL) color tuning by adjusting the location of fluorene derivatives in H-bonds or non-H-bonds environments. The composite films exhibit green and blue photoluminescence with and without effective H-bonding between the pyridine ring in the fluorene derivative and the carboxylic acid side group, respectively. At elevated temperatures, the H-bonded structure dissociates and the fluorene derivative migrates to the hydrophobic block in the diblock polymer, and they do not form H-bonds upon cooling. However, re-formation of H-bonds also occurs upon cooling random copolymers. Moreover, adjusting the annealing temperature and the solvent annealing reversibly tunes the PL color in the diblock copolymer composite films.

Low-Bandgap Donor−Acceptor Conjugated Polymer Sensitizers for Dye-Sensitized Solar Cells

A set of two donor-acceptor type conjugated polymers with carboxylic acid side groups have been synthesized and utilized as active materials for dye-sensitized solar cells (DSSCs). The polymers feature a π-conjugated backbone consisting of an electron-poor 2,1,3-benzothiadiazole (BTD, acceptor) unit, alternating with either a thiophene-fluorene-thiophene triad (2a) or a terthiophene (3a) segment as the donor. The donor-acceptor polymers absorb broadly throughout the visible region, with terthiophene-BTD polymer 3a exhibiting an absorption onset at approximately 625 nm corresponding to a ∼1.9 eV bandgap. The polymers adsorb onto the surface of nanostructured TiO(2) due to interaction of the polar carboxylic acid units with the metal oxide surface. The resulting films absorb visible light strongly, and their spectra approximately mirror the polymers' solution absorption. Interestingly, a series of samples of 3a with different molecular weight (M(n)) adsorb to TiO(2) to an extent that varies inversely with M(n). DSSCs that utilize the donor-acceptor polymers as sensitizers were tested using an I(-)/I(3)(-) electrolyte. Importantly, for the set of polymer sensitizers 3a with varying M(n), the DSSC efficiency varies inversely with M(n), a result that reflects the difference in adsorption efficiency observed in the film absorption experiments. The best DSSC cell tested is based on a sample of 3a with M(n) ∼ 4000, and it exhibits a ∼65% peak IPCE with J(sc) ∼12.6 mA cm(-2) under AM1.5 illumination and an overall power conversion efficiency of ∼3%.

Polysialic Acid-Based Micelles for Encapsulation of Hydrophobic Drugs

Despite improvements relative to unmodified counterparts, poly(ethylene glycol) (PEG) conjugation may not be the ideal solution for improving circulatory stability of current nanoparticle carriers or free drugs. Polysialic acid (PSA), a natural polymer for which the body possesses no receptors, has been conjugated directly to biologically active molecules to prevent premature clearance; however, this concept has not yet been applied to nanoparticle drug carrier systems. In the current study, PSA was modified with a long-chain hydrocarbon through reaction of the carboxylic acid side groups with N-decylamine (DA). The resultant PSA-DA conjugates self-assembled into micelles for encapsulation of hydrophobic drug molecules, as demonstrated with Cyclosporine A. Cytotoxicty was dependent on the degree of substitution with DA. On the basis of size and zeta potential, the micelles are capable of passively targeting diseased regions, such as cancer and inflammatory tissue. Further investigations are necessary to explore whether the PSA-based micelles possess stealth properties similar to those of PEG and to establish in vitro and in vivo efficacy.

Polyaniline nanofibres as templates for the covalent immobilisation of biomolecules

The attachment of antibodies onto polyaniline nanofibres using covalent chemistry was investigated for the first time. Polyaniline nanofibres were functionalised post-polymerisation to attach either amide or carboxylic acid side-groups. These templates could then be further modified to attach antibodies, specifically in this instance mouse immunoglobulin G (IgG). The resultant conjugates were characterised using a variety of techniques including infrared, UV–vis and Raman spectroscopy. Conjugates were then used to detect secondary antibodies (anti-IgG). Results from enzyme-linked immunoassay studies indicate successful binding of the antibody to the polyaniline nanofibres. Carboxyl functionalised polyaniline nanofibres are shown in particular to decrease non-specific binding in the immunoassay. Direct electrical communication between polyaniline nanofibres covalently linked to peroxidase-labelled antibodies was observed during cyclic voltammetry, which demonstrates their potential for further development as nano-dimensional immunosensors.

Effects of Pairwise, Self-Associating Functional Side Groups on Polymer Solubility, Solution Viscosity, and Mist Control

Solution properties are reported for homologous series of narrowly distributed polymers with systematically varied content of self-associating groups. Anionically polymerized polybutadienes of two lengths (510 and 1250 kg/mol) serve as prepolymers that are modified by incorporation of carboxylic acid side groups using thiol−ene coupling to pendant vinyl groups. Carboxylic acid groups strongly reduce polymer solubility in hydrocarbon solvents, restricting the extent of functionalization that can be examined in single-phase solutions (e.g., in chlorododecane, functionalization must be kept <1.8 mol % even for the shorter of the two backbones). In the single-phase regime, addition of hydrogen bond “stickers” weakly affects solution viscosity. Even at concentrations that produce overlap at the scale of strand length between stickers, viscosity increases are less than 1 order of magnitude. These controlled studies (using functionalized and unmodified polymer homologues of matched, well-defined length) challenge the pre-existing understanding of the rheology of self-associating polymers. The results indicate that effects of intrachain pairing are important beyond the dilute regimebehavior unaccounted for in earlier experimental and theoretical studies. The implications for mist control of aviation fuel are that self-associating polymers of acceptable solubility in the fuel are not superior to nonassociating polymers even at concentrations several times above overlap.

Variable-Band-Gap Poly(arylene ethynylene) Conjugated Polyelectrolytes Adsorbed on Nanocrystalline TiO2: Photocurrent Efficiency as a Function of the Band Gap

A series of poly(arylene ethynylene) conjugated polyelectrolytes (CPEs) substituted with carboxylic acid side groups have been synthesized and characterized. The polymers feature a backbone consisting of a carboxylated dialkoxyphenylene-1,4-ethynylene unit alternating with a second arylene ethynylene moiety of variable electron demand. The HOMO-LUMO gap is varied across the series, giving rise to a set of four polymers that have absorption maxima ranging from 404 to 495 nm. The CPEs adsorb effectively from solution onto nanostructured TiO(2) films, giving rise to TiO(2)/CPE films that absorb approximately 90% of the incident light at the absorption band maximum. The photocurrent generation efficiency of the TiO(2)/CPE films was examined in a solar cell configuration using an I(3)(-)/I(-) propylene carbonate electrolyte and a Pt/fluorine-doped tin oxide counter electrode. Most of the films exhibit good photocurrent generation efficiency with a peak quantum efficiency of approximately 50% at wavelengths corresponding to the polymers' absorption band maximum. Interestingly, the photocurrent generation efficiency for the lowest-band-gap polymer is substantially lower compared to the other three systems. This effect is attributed to efficient nonradiative decay of excitons at trap sites arising from interchain contacts distal from the TiO(2)/CPE interface.

Synthesis and Characterizations of Positive-Working Photosensitive Polyimides Having 4,5-Dimethoxy-o-Nitrobenzyl Side Group

To synthesize a new positive-working photosensitive polyimide, alkali-soluble polyimide containing carbox-ylic acid side group was synthesized, and parts of its carboxylic acid groups were esterified with 4,5-dimethoxy-2-nitrobenzyl bromide. The chemical structure of the resulting polymer was characterized by