Extraction or adsorption? Voltammetric assessment of protamine transfer at ionophore-based polymeric membranes.

Cation-exchange extraction of polypeptide protamine from water into an ionophore-based polymeric membrane has been hypothesized as the origin of a potentiometric sensor response to this important heparin antidote. Here, we apply ion-transfer voltammetry not only to confirm protamine extraction into ionophore-doped polymeric membranes but also to reveal protamine adsorption at the membrane/water interface. Protamine adsorption is thermodynamically more favorable than protamine extraction as shown by cyclic voltammetry at plasticized poly(vinyl chloride) membranes containing dinonylnaphthalenesulfonate as a protamine-selective ionophore. Reversible adsorption of protamine at low concentrations down to 0.038 µg/mL is demonstrated by stripping voltammetry. Adsorptive preconcentration of protamine at the membrane/water interface is quantitatively modeled by using the Frumkin adsorption isotherm. We apply this model to ensure that stripping voltammograms are based on desorption of all protamine molecules that are transferred across the interface during a preconcentration step. In comparison to adsorption, voltammetric extraction of protamine requires ∼0.2 V more negative potentials, where a potentiometric super-Nernstian response to protamine is also observed. This agreement confirms that the potentiometric protamine response is based on protamine extraction. The voltammetrically reversible protamine extraction results in an apparently irreversible potentiometric response to protamine because back-extraction of protamine from the membrane extremely slows down at the mixed potential based on cation-exchange extraction of protamine. Significantly, this study demonstrates the advantages of ion-transfer voltammetry over potentiometry to quantitatively and mechanistically assess protamine transfer at ionophore-based polymeric membranes as foundation for reversible, selective, and sensitive detection of protamine.

Ion-transfer voltammetry of perfluoroalkanesulfonates and perfluoroalkanecarboxylates: picomolar detection limit and high lipophilicity.

Here we report on ion-transfer voltammetry of perfluoroalkanesulfonates and perfluoroalkanecarboxylates at the interface between a plasticized polymer membrane and water to enable the ultrasensitive detection of these persistent environmental contaminants with adverse health effects. The ion-transfer cyclic voltammograms of the perfluoroalkyl oxoanions are obtained by using a ∼1 µm thick poly(vinyl chloride) membrane plasticized with 2-nitrophenyl octyl ether. The cyclic voltammograms are numerically analyzed to determine formal ion-transfer potentials as a measure of ion lipophilicity. The fragmental analysis of the formal potentials reveals that the 10(4) times higher lipophilicity of a perfluoroalkanesulfonate in comparison to the alkanesulfonate with the same chain length is due to the inductive effect of perfluorination on lowering the electron density of the adjacent sulfonate group, thereby weakening its hydration. The fragmental analysis also demonstrates that the lipophilicities of perfluoroalkyl and alkyl groups with the same length are nearly identical and vary with the length. Advantageously, the high lipophilicity of perfluorooctanesulfonate allows for its stripping voltammetric detection at 50 pM in the presence of 1 mM aqueous supporting electrolytes, a ∼10(7) times higher concentration. Significantly, this detection limit for perfluorooctanesulfonate is unprecedentedly low for electrochemical sensors and is lower than its minimum reporting level in drinking water set by the U.S. Environmental Protection Agency. In comparison, the voltammetric detection of perfluoroalkanecarboxylates is compromised not only by the lower lipophilicity of the carboxylate group but also by its oxidative decarboxylation at the underlying poly(3-octylthiophene)-modified gold electrode during voltammetric ion-to-electron transduction.

Subnanomolar detection limit of stripping voltammetric Ca²âº-selective electrode: effects of analyte charge and sample contamination.

Ultrasensitive ion-selective electrode measurements based on stripping voltammetry are an emerging sensor technology with low- and subnanomolar detection limits. Here, we report on stripping voltammetry of down to 0.1 nM Ca(2+) by using a thin-polymer-coated electrode and demonstrate the advantageous effects of the divalent charge on sensitivity. A simple theory predicts that the maximum concentration of an analyte ion preconcentrated in the thin membrane depends exponentially on the charge and that the current response based on exhaustive ion stripping from the thin membrane is proportional to the square of the charge. The theoretical predictions are quantitatively confirmed by using a thin ionophore-doped polymer membrane spin-coated on a conducting-polymer-modified electrode. The potentiostatic transfer of hydrophilic Ca(2+) from an aqueous sample into the hydrophobic double-polymer membrane is facilitated by an ionophore with high Ca(2+) affinity and selectivity. The resultant concentration of the Ca(2+)-ionophore complex in the ~1 µm-thick membrane can be at least 5 × 10(6) times higher than the aqueous Ca(2+) concentration. The stripping voltammetric current response to the divalent ion is enhanced to achieve a subnanomolar detection limit under the condition where a low-nanomolar detection limit is expected for a monovalent ion. Significantly, charge-dependent sensitivity is attractive for the ultrasensitive detection of multivalent ions with environmental and biomedical importance such as heavy metal ions and polyionic drugs. Importantly, this stripping voltammetric approach enables the absolute determination of subnanomolar Ca(2+) contamination in ultrapure water containing 10 mM supporting electrolytes, i.e., an 8 orders of magnitude higher background concentration.

Electrochemical Sensing and Imaging Based on Ion Transfer at Liquid/Liquid Interfaces.

Here we review the recent applications of ion transfer (IT) at the interface between two immiscible electrolyte solutions (ITIES) for electrochemical sensing and imaging. In particular, we focus on the development and recent applications of the nanopipet-supported ITIES and double-polymer-modified electrode, which enable the dynamic electrochemical measurements of IT at nanoscopic and macroscopic ITIES, respectively. High-quality IT voltammograms are obtainable using either technique to quantitatively assess the kinetics and dynamic mechanism of IT at the ITIES. Nanopipet-supported ITIES serves as an amperometric tip for scanning electrochemical microscopy to allow for unprecedentedly high-resolution electrochemical imaging. Voltammetric ion sensing at double-polymer-modified electrodes offers high sensitivity and unique multiple-ion selectivity. The promising future applications of these dynamic approaches for bioanalysis and electrochemical imaging are also discussed.

Stripping voltammetry of nanomolar potassium and ammonium ions using a valinomycin-doped double-polymer electrode.

Here, we report on the first application of an ionophore-doped double-polymer electrode for ion-transfer stripping voltammetry (ITSV) to explore the nanomolar limit of detection (LOD) and multiple-ion detectability. We developed a theoretical model for ITSV at a thin ionophore-doped membrane on the solid supporting electrode to demonstrate that its LOD is controlled by the equilibrium preconcentration of an aqueous analyte ion as an ionophore complex into the thin polymer membrane and is lowered by the formation of a more stable ion-ionophore complex. The theoretical predictions were confirmed using valinomycin as a K(+)-selective ionophore, which forms a ∼60 times more stable complex with K(+) than with NH(4)(+), as confirmed by cyclic voltammetry. A LOD of 0.6 nM K(+) was achieved by ITSV using commercial ultrapure water as a K(+)-free media, where NH(4)(+) contamination at a higher concentration was also detected by ITSV. The dependence of the ITSV response on the preconcentration time was monitored under the rotating-electrode configuration and analyzed theoretically to directly determine ∼100 nM NH(4)(+) and ∼5 nM K(+) contaminations in commercial ultrapure water and laboratory-purified water, respectively, without the background ITSV measurement of an analyte-free blank solution.

Electrochemical mechanism of ion-ionophore recognition at plasticized polymer membrane/water interfaces.

Here, we report on the first electrochemical study that reveals the kinetics and molecular level mechanism of heterogeneous ion-ionophore recognition at plasticized polymer membrane/water interfaces. The new kinetic data provide greater understanding of this important ion-transfer (IT) process, which determines various dynamic characteristics of the current technologies that enable highly selective ion sensing and separation. The theoretical assessment of the reliable voltammetric data confirms that the dynamics of the ionophore-facilitated IT follows the one-step electrochemical (E) mechanism controlled by ion-ionophore complexation at the very interface in contrast to the thermodynamically equivalent two-step electrochemical-chemical (EC) mechanism based on the simple transfer of an aqueous ion followed by its complexation in the bulk membrane. Specifically, cyclic voltammograms of Ag(+), K(+), Ca(2+), Ba(2+), and Pb(2+) transfers facilitated by highly selective ionophores are measured and analyzed numerically using the E mechanism to obtain standard IT rate constants in the range of 10(-2) to 10(-3) cm/s at both plasticized poly(vinyl chloride) membrane/water and 1,2-dichloroethane/water interfaces. We demonstrate that these strongly facilitated IT processes are too fast to be ascribed to the EC mechanism. Moreover, the little effect of the viscosity of nonaqueous media on the IT kinetics excludes the EC mechanism, where the kinetics of simple IT is viscosity-dependent. Finally, we employ molecular level models for the E mechanism to propose three-dimensional ion-ionophore complexation at the two-dimensional interface as the unique kinetic requirement for the thermodynamically facilitated IT.

Electrochemical heparin sensing at liquid/liquid interfaces and polymeric membranes.

The monitoring of heparin and its derivatives in blood samples is important for the safe usage of these anticoagulants and antithrombotics in many medical procedures. Such an analytical task is, however, highly challenging due to their low therapeutic levels in the complex blood matrix, and it still relies on classical, indirect, clot-based assays. Here we review recent progress in the direct electrochemical sensing of heparin and its analogs at liquid/liquid interfaces and polymeric membranes. This progress has been made by utilizing the principle of electrochemical ion transfer at the interface between two immiscible electrolyte solutions (ITIES) to voltammetrically drive the interfacial transfer of polyanionic heparin and monitoring the resulting ionic current as a direct measure of heparin concentration. The sensitivity, selectivity, and reproducibility of the ion-transfer voltammetry of heparin are dramatically enhanced compared to those of traditional potentiometry. This voltammetric principle was successfully applied for the detection of heparin in undiluted blood samples, and was used to develop highly sensitive ion-selective electrodes based on thin polymeric membranes that are intended for analytical applications beyond heparin detection. The mechanism of heparin recognition and transfer at liquid/liquid interfaces was assessed quantitatively via sophisticated micropipet techniques, which aided the development of a powerful ionophore that can extract large heparin molecules into nonpolar organic media. Moreover, the reversible potentiometric detection of a lethal heparin-like contaminant in commercial heparin preparations was achieved through the use of a PVC membrane doped with methyltridodecylammonium chloride, which enables charge density dependent polyanion selectivity.