Chelating Polymer Research Articles

Hexavalent Chromium Removal and Reduction to Cr (III) by Polystyrene Tris(2-aminoethyl)amine

A commercially available chelating polymer, polystyrene tris(2-aminoethyl)amine, was used for the removal of chromium from aqueous solution. The influence of pH, contact time, adsorbent dosage and initial Cr (VI) concentration on adsorption was studied. The optimum pH for the removal of Cr (VI) was at pH 5, while optimum contact time and adsorbent dosage were 120 minutes and 10 g/L, respectively. Total chromium and Cr (VI) concentrations were analyzed by ICP-MS and UV-Visible. Adsorption isotherms using Langmuir and Freundlich isotherm models revealed that the data fitted Langmuir isotherm model better than Freundlich with a maximum adsorption capacity of 312.27 mg/g. FTIR spectroscopy, Scanning electron microscopy (SEM) and Energy Dispersive Spectrometry (EDS) analyses were performed on the adsorbent before and after binding Cr (VI). All analyses confirmed the complexation of Cr (VI) to the adsorbent. Desorption experiments using KCl solution indicated 89.3% release of chromium, rendering this method of high potential for adsorbent regeneration.

Preconcentration and Determination of Traces of Heavy Metals with Polymer Chelating Sorbents in the Analysis of Natural and Waste Water

Monitoring the concentrations of heavy metals in natural and waste water at and below the level of their maximum permissible concentrations is an urgent environmental problem. Hence, new procedures for the preconcentration of heavy metals with their subsequent determination by different methods are required. Along with other sorbents, significant attention is attracted to polymer chelating sorbents, which provide individual or group extraction of trace elements, eliminate matrix effects, and provide high concentration factors. The effect of the various parameters such as electrochemically and chemically synthesis methods, physical oxidation state of the polymer, polymer thickness, solution pH and metal ion concentration on the adsorption, kinetics and efficiency were investigated. The results showed a vary broad concentration range of the heavy metals from (0.05 to 10 mg/L) can be adsorbed on different kinds of polymers at different pH values and different efficiently. The adsorption capacity of the polymer to different concentrations of heavy metals was evaluated as the milligram of metal ions by one gram of various forms of the polymer. The DC conductivity measurements were also employed on the solid polymer before and after adsorption of metal ions. The experimental adsorption date was fitted to different mathematical isotherms to estimate the binding constant of heavy metals with the polymer in both single and mixed ion solutions. The method provides the extraction of analytes from natural water of complex composition containing high concentrations of alkali, alkaline-earth and other elements and is characterized by rapidly, selectivity, low detection limits, and a high reproducibility of the results. The relative standard deviation is 2-4%. The technique was test with real waste water samples.

Azo resorcin[4]calixpyrrole grafted Amberlite XAD-2 polymer: an efficient solid phase extractant for separation and preconcentration of La(III) and Ce(III) from natural geological samples

The impregnation of new azocalixpyrroles obtained from resorcinol derivative into a polymeric chelating resin, Amberlite XAD-2. A simple and effective method is presented for the separation and preconcentration of U(VI)] and Thorium Th(IV) by solid phase extraction on synthesized modified polymeric chelating resin. The synthesized chelating polymeric sorbent showed superior binding affinity towards U(VI) and Th(IV) under selective pH conditions. The optimum pH range was established and the flow rates for U(VI) and Th(IV) were studied respectively. U(VI) and Th(IV) are quantitatively eluted with suitable eluants like HCl and HNO3 and determined by inductively coupled plasma-atomic emission spectrometry (ICP-AES). Other parameters such as total sorption capacity, exchange kinetics, preconcentration factor, distribution coefficient, breakthrough capacity and resin stability. The uptake and stripping of these metal ions on the resin were fast, indicating a better accessibility of the metal ions towards the chelating sites. Chromatographic separation of Th(IV) and U(VI) was accomplished by adjustment of pH in the range of 3.0–9.0 pH, respectively. Separation of Th(IV) and U(VI) from other metal cations, in synthetic solution was achieved. The synthesized resins were recycled at least 14–16 times without much affecting column sorption capacity.

Water-soluble anhydride containing alternating copolymers as scale inhibitors

Scale can be defined as adherent deposit of inorganic compounds which is formed by precipitation of salts from water and crystal growth on the surfaces. Scale formation can be inhibited by adding sequestering or chelating polymers to the water treatment system. Water-soluble or dispersible copolymers of ethylenically unsaturated monomers with sulphate, phosphate or carboxylic terminated are useful as deposit control and corrosion inhibition agents in water treatment, pulp and paper manufacturing processes and as rheology modifiers for concrete and cement additives and as hydrophilic modifier components in personal care, cosmetic and pharmaceutical formulations. Anhydride groups containing poly(maleic anhydride-alt-acrylic acid) are expected to show considerably high inhibition activity due to the anionic character formed after their hydrolysis. The structural properties of copolymer were identified by viscosity, acid number (AN) experiments FTIR, GPC, and DSC analyses. The inhibitory behavior of the polymer was determined by using EDTA titration standard method. Also the assessment of effectiveness soluble calcium ion using of copolymer tested with respect to inhibition crystal growth calcium carbonate was followed by XRD and SEM.

Photocatalytic property of strontium–niobium mixed oxide prepared by utilizing organic mediators to the overall splitting of H2O

The effects of the polymer precursor in polymerizable complex (PC) method for the preparation of a Sr–Nb mixed oxide photocatalyst were studied. A polymer made of citric acid and ethylene glycol, which is generally applied in the PC method, as well as that made of succinic acid and 2-(2-aminoethylamino)ethanol (AEEA) were used as polymer chelating ligands. The photocatalytic activity of prepared mixed oxides for the overall H2O splitting depended on the oxide crystal structure, which was affected by the chelating complex polymer precursors and the calcination temperature. In particular, the Sr–Nb mixed oxide prepared from succinic acid and AEEA precursors showed the significantly high photocatalytic activity for the overall splitting of H2O after calcination at 973K. The influences of the origin of polymer precursors to the crystal structure and the composition of the Sr–Nb mixed oxide and its photocatalytic performance to the overall H2O splitting are discussed.

Separation of AsV from aqueous solutions using chelating polymers containing FeIII -loaded phosphorus groups

Abstract AsV ions were removed by batch equilibrium with FeIII-loaded chelating polymers containing aminophosphinic or aminophosphonic groups. It was effectively removed AsV from a synthetic wastewater as well as from a real drinking water containing 40 μg As per liter. Sorption is best described by pseudo-second order kinetics and a Langmuir isotherm.

Synthesis and performance of Li4Ti5O12 anode materials using the PVP-assisted combustion method

Abstract Li4Ti5O12 was synthesized by a facile gel-combustion method (GCM) with polyvinylpyrrolidone (PVP) as the polymer chelating agent and fuel. The structural and electrochemical properties of the sample were compared with the one prepared by the conventional solid-state reaction (SSR) through X-ray diffraction (XRD), scanning electron microscopy (SEM), cyclic voltammetry (CV), charge–discharge measurements, and electrochemical impedance spectroscopy (EIS), respectively. The sub-microscale Li4Ti5O12 oxides, with a high phase purity and good stoichiometry, can be obtained by annealing at 800 °C. The grain size is smaller than that of the samples that were power prepared by SSR. Lithium-ion batteries with a GCM Li4Ti5O12 anode exhibit excellent reversible capacities of 167.6, 160.7, 152.9, and 144.2 mAh/g, at the current densities of 0.5 C, 1 C, 3 C and 5 C, respectively. The excellent cycling and rate performance can be attributed to the smaller particle size, lower charge-transfer resistance and larger lithium ion diffusion coefficient. It is therefore concluded that GCM Li4Ti5O12 is a promising candidate for applications in high-rate lithium ion batteries.

Removal of heavy metal ions with the use of chelating polymers obtained by grafting pyridine–pyrazole ligands onto polymethylhydrosiloxane

Abstract New chelating polymers soluble in organic non-polar solvents were synthesized by hydrosilylation reaction of polymethylhydrosiloxane with pyridine–pyrazole ligands. Two types of linkers were used to graft pyridine–pyrazole ligands onto polymethylhydrosiloxane. The composition and properties of the polymers obtained were studied by NMR spectroscopy, Fourier transform infrared spectroscopy, elemental analysis, thermogravimetric analysis and derivative scanning calorimetry. The effects of various parameters such as initial metal ion concentration, contact time, temperature and pH were examined in the processes of extraction of Cu 2+ , Cd 2+ , Cr 3+ , Ni 2+ and Co 2+ . The equilibrium data were best represented by Langmuir isotherm and the uptake capacities of polymers obtained varied between 0.24 mmol (for Co 2+ ) and 1.48 mmol (for Cu 2+ ) per 1 g of polymer. The adsorption kinetics was found to follow the pseudo-second-order kinetic model. The polymers adsorption capacity was more than 90% level after five cycles of adsorption–desorption. Treatment of real wastewater samples showed good ability of the polymers to absorb metal ions.

Preparation and characterization of hydroquinone based polyoxalate and its application in the removal of heavy metals from water

Hydroquinone based polyoxalate was synthesized from oxalyl chloride and hydroquinone. The polymer was characterized with FTIR, 1H-NMR, 13C-NMR, PXRD, SEM and thermal analysis. The chelation behaviour of the polymer towards Pb(II), Cd(II), and Hg(II) in aqueous solutions was studied by batch technique as a function of contact time and pH. The polymer showed high metal uptake toward Pb(II) and Cd(II) and moderate metal uptake toward Hg(II). The adsorption capacity was not affected by the pH of solution. The adsorption data were fitted with second order kinetic model and the isotherms models of Langmuir and Freundlich. Thermodynamics measurements showed that sorption process was spontaneous. Furthermore, the chelating polymer was loaded with metal ions using fixed bed column. For regenerating the loaded polymer, different eluting agents include HNO3, H2SO4, and EDTA was investigated. The highest recovery of metal ions was achieved using HNO3, indicating that desorption process was governed by the solubility factor and cation exchange mechanism.

Biomimetic design of chelating interfaces

ABSTRACTSiderophores are naturally occurring small molecules with metal binding constants greater than many synthetic chelators. Herein, we report a two‐step process to graft a siderophore‐mimetic metal chelating polymer from a polypropylene (PP) surface. Poly(methyl acrylate) was first grafted from the PP surface by photoinitiated graft polymerization, followed by the conversion into poly(hydroxamic acid) (PHA) to obtain PP‐g‐PHA films. ATR/FTIR, contact angle, SEM, and AFM were performed to characterize surface properties of films. Iron binding kinetics and the influence of pH (3.0–5.0) on the chelating ability of films were determined. PP‐g‐PHA exhibited significant iron chelating activity (∼80 nmol/cm2) with an equilibration time of 24 h. The materials retained 50% chelating ability at pH 3.0 compared with pH 5.0, almost double the retention of previously reported polycarboxylate chelating interfaces. By using siderophore‐mimetic surface chemistry, such effective metal chelating interfaces can extend the applications of metal chelating polymers in environmental remediation, water purification, and active packaging areas. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41231.

Polymer chelates of fe, co, and ni based on 5-ethynyl-2H-tetrazole

Electrochemical preparation of chelates based on 5-ethynyl-2H-tetrazole on the surface of iron, cobalt, and nickel results in colored polymer film at low current density. At higher current density the polymer chelate is transferred into the solution. The composition and structure of the polymer chelates has been studied by infrared spectroscopy, elemental analysis, and thermogravimetric analysis. The mechanism of the chelates formation in various solvents has been suggested.

Chelating polymer modified P84 nanofiltration (NF) hollow fiber membranes for high efficient heavy metal removal

High performance nanofiltration (NF) membranes for heavy metal removal have been molecularly designed by adsorption of chelating polymers containing negatively charged functional groups such as poly (acrylic acid-co-maleic acid) (PAM), poly (acrylic acid) (PAA) and poly (dimethylamine-co-epichlorohydrin-co-ethylenediamine) (PDMED) on the positively charged polyethyleneimine (PEI) cross-linked P84 hollow fiber substrates. Not only do these chelating polymers change the membrane surface charge and pore size, but also provide an extra mean to remove heavy metal ions through adsorption in addition to traditional steric effect and Donnan exclusion. The adsorbed membranes have comparable water permeability and superior rejections to heavy metals, for instance, Pb(NO3)2, CuSO4, NiCl2, CdCl2, ZnCl2, Na2Cr2O7 and Na2HAsO4, with rejections higher than 98%. The membranes also display excellent rejections to mixed ions with rejections more than 99%. The newly developed membranes show reasonably stability during 60-h tests as well as multiple washes.

Synthesis of polyamidoxime chelating ligand from polymer‐grafted corn‐cob cellulose for metal extraction

ABSTRACTA conventional free‐radical initiating process was used to prepare graft copolymers from acrylonitrile (AN) with corn‐cob cellulose with ceric ammonium nitrate (CAN) as an initiator. The optimum grafting was achieved with corn‐cob cellulose (anhydroglucose unit, AGU), mineral acid (H2SO4), CAN, and AN at concentrations of 0.133, 0.081, 0.0145, and 1.056 mol/L, respectively. Furthermore, the nitrile functional groups of the grafted copolymers were converted to amidoxime ligands with hydroxylamine under basic conditions of pH 11 with 4 h of stirring at 70°C. The purified acrylic polymer‐grafted cellulose and polyamidoxime ligand were characterized by Fourier transform infrared spectroscopy and field emission scanning electron microscopy analysis. The ligand showed an excellent copper binding capacity (4.14 mmol/g) with a faster rate of adsorption (average exchange rate = 7 min), and it showed a good adsorption capacity for other metal ions as well. The metal‐ion adsorption capacities of the ligand were pH‐dependent in the following order: Cu2+ > Co2+ > Mn2+ > Cr3+ > Fe3+ > Zn2+ > Ni2+. The metal‐ion removal efficiency was very high; up to 99% was removed from the aqueous media at a low concentration. These new polymeric chelating ligands could be used to remove aforementioned toxic metal ions from industrial wastewater. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40833.

Lanthanide-Containing Polycations for Monitoring Polyplex Dynamics via Lanthanide Resonance Energy Transfer

Theranostic nanomaterials have emerged in the past decade that combine therapeutic delivery and diagnostic imaging into one package. Such materials offer the opportunity to aid diagnosis, track therapeutic biodistribution, and monitor drug release. We have developed a series of nucleic acid delivery polymers containing oligoethylene amines that are able to be protonated at physiological pH (for binding/compacting pDNA) and a lanthanide-chelating domain, which imparts diagnostic functionality. Diamine monomers (containing between 3 and 6 Boc-protected ethyleneamines) were prepared via a multistep procedure involving the selective protection and deprotection of primary and secondary amines. The polymer structures were then synthesized by step-growth polymerization of the oligoethylene diamines with a bisanhydride of diethylenetriamine pentaacetic acid (DTPA-BA), yielding degrees of polymerization between 18 and 24. Chelation of the polymers with gadolinium and terbium was performed to offer MRI contrast agent and luminescence properties, respectively. All of the polymer chelates were found to house approximately one water coordination site, as calculated by the Horrock's equation and possess longitudinal relaxivities (r1, on a per Gd basis) at least twice that of Magnevist, a clinical contrast agent. All the structures formed polyplexes with pDNA with highly positive zeta potentials and hydrodynamic diameters around 50-80 nm. Lanthanide resonance energy transfer (LRET) was used to monitor polyplex association and dissociation. Polyplexes were formed using the donor-acceptor pair comprising of terbium-chelated polymer with five ethyleneamines within the repeat unit (6c-Tb) and tetramethyl rhodamine (TMR)-labeled pDNA. Association/dissociation in the presence of heparin and NaCl was monitored. The effect of amine number along the polymer backbone on transfection efficiency and cytotoxicity was also investigated. None of the polymers revealed cytotoxic effects with cultured cells; however, the polymer with six ethyleneamines clearly offered the highest transfection efficiency. This preliminary study offers insight into the development of materials with the ability to monitor polyplex unpackaging over time within the cellular environment.

Manganese sequestration and improved high-temperature cycling of Li-ion batteries by polymeric aza-15-crown-5

Mn cation trapping by polymeric aza-15-crown-5 ethers is an effective means for mitigating the consequences of Mn dissolution in Li-ion batteries. Mn cations trapping was investigated in lithium manganese oxide (LMO) spinel–graphite (GR) cells containing 1 M LiPF6 in ethylene carbonate (EC):diethyl carbonate (DEC) 1:2 v/v. A commercial polyolefin separator membrane coated with poly[divinylbenzene-(vinylbenzyl-aza-15-crown-5)-vinylbenzylchloride)] effected a 39% reduction in capacity loss rate during cycling at 50 °C with 100% depth of discharge (DOD) at C/5 rate. Simultaneously, a 50–60% reduction in the Mn deposited at the negative electrode, and a 6× to 10× increase in the Mn on the coated separator were observed for cells with coated separators, over baseline cells with plain separators. X-ray absorption near-edge spectroscopy (XANES) yielded average oxidation states near +3 for Mn cations in graphite electrodes and separators from cycled cells, suggesting that Mn metal or in oxidation state +2 can only be minor fractions of the Mn existing outside the positive electrode. We discuss the implications of these results for choosing an optimal chelating agent. We also show that the cation chelating polymer reported here is compatible with existing manufacturing processes for Li-ion battery separators.

Synthesis, characterization and cyclic voltammetric study of copper(II) and nickel(II) polymer chelates

Graft copolymers based on dextran (Dx) and 2-acrylamido-2-methyl-1-propane sulphonic acid (AMPS) were synthesized by free radical initiated solution polymerization technique using ceric ammonium nitrate as initiator. These graft copolymers were used to prepare Cu(II) and Ni(II) chelates by reactions with Cu(II) and Ni(II) metal ions respectively. Graft copolymer and metal chelates were characterized by elemental analysis, intrinsic viscosity, FT-IR, scanning electron microscopy (SEM), atomic force microscopy (AFM), thermogravimetric analysis (TGA) and powder X-ray diffraction (XRD). Elemental analysis, intrinsic viscosity and FT-IR studies revealed the incorporation of metal ions to form metal chelates. SEM studies showed the change in morphology due to metal incorporation. From AFM studies it was observed that there was increase in Root mean square (RMS) roughness values in case of metal complexes. Metal chelates were observed to be thermally more stable than graft copolymer from TGA. UV–vis spectroscopy study revealed increase in absorbance values and cyclic voltammetric (CV) studies showed more than tenfold increase in redox current due to formation of Cu(II) and Ni(II) metal chelates. The binding constants of each complex determined by using UV–visible spectroscopy revealed that Cu(II) has more binding ability than Ni(II).

Chitosan and Ionic Liquid Based Solid Polymer Electrolytes: The Anion Alkyl Chain Length Effect

It has been long recognized that polymer electrolytes (PEs) are potentially interesting as electrolytes for solid-state electrochemical devices 1-3 . It is also recognized that the most important properties of electrolyte solutions are non-volatility and high ionic conductivity. If the former property is easily fulfilled because polymers do not vaporize, only decompose at higher temperatures, the latter one is the major drawback that is delaying their application in commercial devices. To overcome this, the solvent-free polymer electrolytes (SPEs) community has been paying great attention to ionic liquids (ILs). Since ILs are composed only of ions, and show very high ionic conductivity, non-volatility and non-flammability 4 .Nowadays, safety, environmental issues also pose a significant concern. Because of that, some research groups have been turning their attention to natural polymers, due to their biodegradability, low toxicity and extraction from renewable sources, as fast growing plants and animals 5 . Among the extensive range of the existing natural polymers is chitosan. Chitosan is obtained by deacetylation of its parent polymer chitin, a polysaccharide widely distributed in nature (e.g. crustaceans, insects and certain fungi) 6 .This work describes the results of the characterization of polymer electrolytes using chitosan matrix doped with ionic liquids series 1-ethyl-3-methylimidazolium dialkylphosphate [C2mim][CnPO4], 1-ethyl-3-methylimidazolium alkylsulfonate [C2mim][CnSO3] and 1-ethyl-3-methylimidazolium alkylsulfate [C2mim][CnSO4]. This work studies the effect of increasing the alkyl chain length of the anion on the thermal, morphological and electrochemical properties of these SPEs.The samples have been characterized by thermal analysis (TGA and DSC), X-ray diffraction (XRD), scanning electron microscopy (SEM), polarized optical microscopy (POM), complex impedance spectroscopy and cyclic voltammetry. Acknowledgements This work was supported by FEDER through the COMPETE Program and by the Portuguese Foundation for Science and Technology (FCT) in the framework of the Strategic Project PEST-C/QUI/UI0686/2011 and PEST-OE/EQB/LA0004/2011, projects PTDC/CTM-NAN/121274/2010 and PTDC/QUI-QUI/117340/2010, grant SRFH/BD/90366/2012 (R.L.) and Investigador FCT grant (J.M.S.S.E.). References 1P.V. Wright, Br. Poly. J. 7 (1975) 319–327. 2 M. Armand, M. T. Duclot, J.M. Chabagno, In Proceedings of the Second International Meeting on Solid State Electrolytes; St. Andrews, Scotland, Sept 20_22, 1978; 1978; Extended 6.5. 3F.M. Gray, in Solid Polymer Electrolytes: Fundamentals and Technological Applications, VCH Publishers, Inc., New York, 1991. 4 H. Ohno, Electrochemical Aspects of Ionic Liquids, 2nd ed. John Wiley & Sons, Inc., New Jersey, 2011. 5R. Leones, F. Sentanin, L.C. Rodrigues, I.M. Marrucho, J.M.S.S. Esperança, A. Pawlicka, M.M. Silva, eXPRESS Polymer Letters 6 (12) (2012) 1007. 6 R.A.A. Muzzarelli, Natural chelating polymers: alginic acid, chitin and chitosan, Pergamon Press Oxford, New York, 1973.

Electrochemical mediated preparation of chelating polymer brushes at paraffin-impregnated graphite electrode for Pb2+ sensing

In this work, two-dimension iminodiacetic acid functional gclycidyl methacrylate polymer brushes were prepared at paraffin-impregnated electrode for Pb2+ sensing. Gclycidyl methacrylate polymer brushes were prepared using electrochemical mediated atom transfer radical polymerization, ring-opening reaction of the epoxy groups was enforced using iminodiacetic acid to form chelating polymer brushes (IGMA/WGE). The electrode was carefully examined by fourier transform infrared spectroscopy, field emission scanning electronmicroscope and electrochemistry techniques. Abundant chelating polymer brushes evenly coated at WGE with an average size of 0.1×2μm. Further IGMA/WGE was successfully used for the determination of Pb2+ by differential pulse adsorptive anodic stripping voltammetry. The current responses (-0.58V) were linearly increased depending on the concentration from 3 to 90nM (i(μA)=-1.12+0.82 c (nM), limit 0.79nM, 3σ). The present electrode is potentially useful for real sample analysis.

A high-sensitivity lanthanide nanoparticle reporter for mass cytometry: tests on microgels as a proxy for cells.

This paper addresses the question of whether one can use lanthanide nanoparticles (e.g., NaHoF4) to detect surface biomarkers expressed at low levels by mass cytometry. To avoid many of the complications of experiments on live or fixed cells, we carried out proof-of-concept experiments using aqueous microgels with a diameter on the order of 700 nm as a proxy for cells. These microgels were used to test whether nanoparticle (NP) reagents would allow the detection of as few as 100 proteins per “cell” in cell-by-cell assays. Streptavidin (SAv), which served as the model biomarker, was attached to the microgel in two different ways. Covalent coupling to surface carboxyls of the microgel led to large numbers (>104) of proteins per microgel, whereas biotinylation of the microgel followed by exposure to SAv led to much smaller numbers of SAv per microgel. Using mass cytometry, we compared two biotin-containing reagents, which recognized and bound to the SAvs on the microgel. One was a metal chelating polymer (MCP), a biotin end-capped polyaspartamide containing 50 Tb3+ ions per probe. The other was a biotinylated NaHoF4 NP containing 15 000 Ho atoms per probe. Nonspecific binding was determined with bovine serum albumin (BSA) conjugated microgels. The MCP was effective at detecting and quantifying SAvs on the microgel with covalently bound SAv (20 000 SAvs per microgel) but was unable to give a meaningful signal above that of the BSA-coated microgel for the samples with low levels of SAv. Here the NP reagent gave a signal 2 orders of magnitude stronger than that of the MCP and allowed detection of NPs ranging from 100 to 500 per microgel. Sensitivity was limited by the level of nonspecific adsorption. This proof of concept experiment demonstrates the enhanced sensitivity possible with NP reagents in cell-by-cell assays by mass cytometry.

Intracellular Routing in Breast Cancer Cells of Streptavidin-Conjugated Trastuzumab Fab Fragments Linked to Biotinylated Doxorubicin-Functionalized Metal Chelating Polymers

We describe the synthesis of a heterotelechelic metal-chelating polymer (Bi-MCP-Dox), a polyacrylamide with a number average degree of polymerization DPn = 50 (PDI = 1.2), with biotin (Bi) and doxorubicin (Dox) as functional chain ends and diethylenetriaminepentaacetic acid (DTPA) pendant groups as the binding sites for metal ions. We compared its behavior in cell-uptake experiments with a similar polymer (Bi-MCP) without Dox. These MCPs were complexed with trastuzumab Fab (tmFab) fragments covalently linked to streptavidin (SAv) to form tmFab-SAv-Bi-MCP-Dox and tmFab-SAv-Bi-MCP via the strong affinity between Bi and SAv. tmFab targets human epidermal growth factor receptor-2 (HER2), which is overexpressed on certain human breast cancer cells. Surface plasmon resonance (SPR) experiments with the extracellular domain (ECD) of HER2 showed that incorporation of the MCPs in these complexes had no significant effect on the association or dissociation rate with the HER2 ECD and the dissociation constants. The tmFab-complexed MCPs were subsequently labeled with (111)In (an Auger electron emitting radionuclide). Auger electrons can cause lethal DNA double strand breaks (DSBs) but only if they are emitted intracellularly and especially, in close proximity to the nucleus. To evaluate the cellular and nuclear uptake of tmFab-SAv-Bi-MCP-Dox, we incubated HER2+ SK-BR-3 human breast cancer cells with the complexes saturated with stable In(3+) and visualized their distribution by confocal fluorescence microscopy, monitoring the fluorescence of Dox. In parallel, we carried out cell fractionation studies on tmFab-SAv-Bi-MCP-Dox and on tmFab-SAv-Bi-MCP labeled with (111)In. Both radiolabeled complexes showed cell internalization and nuclear localization. We conclude that metal-chelating polymers with this composition appear to encourage internalization, nuclear uptake, and chromatin (DNA) binding of trastuzumab fragments modified with streptavidin in human breast cancer cells expressing HER2. Further study is needed to understand the impact of polymer charge on cellular uptake and distribution to intracellular compartments.