Electroanalysis of Fentanyl and Its New Analogs: A Review.

The review describes fentanyl and its analogs as new synthetic opioids and the possibilities of their identification and determination using electrochemical methods (e.g., voltammetry, potentiometry, electrochemiluminescence) and electrochemical methods combined with various separation methods. The review also covers the analysis of new synthetic opioids, their parent compounds, and corresponding metabolites in body fluids, such as urine, blood, serum, and plasma, necessary for a fast and accurate diagnosis of intoxication. Identifying and quantifying these addictive and illicit substances and their metabolites is necessary for clinical, toxicological, and forensic purposes. As a reaction to the growing number of new synthetic opioid intoxications and increasing fatalities observed over the past ten years, we provide thorough background for developing new biosensors, screen-printed electrodes, or other point-of-care devices.

Extreme Basicity of Biguanide Drugs in Aqueous Solutions: Ion Transfer Voltammetry and DFT Calculations.

Ion transfer voltammetry is used to estimate the acid dissociation constants Ka1 and Ka2 of the mono- and diprotonated forms of the biguanide drugs metformin (MF), phenformin (PF), and 1-phenylbiguanide (PB) in an aqueous solution. Measurements gave the pKa1 values for MFH(+), PFH(+), and PBH(+) characterizing the basicity of MF, PF, and PB, which are significantly higher than those reported in the literature. As a result, the monoprotonated forms of these biguanides should prevail in a considerably broader range of pH 1-15 (MFH(+), PFH(+)) and 2-13 (PBH(+)). DFT calculations with solvent correction were performed for possible tautomeric forms of neutral, monoprotonated, and diprotonated species. Extreme basicity of all drugs is confirmed by DFT calculations of pKa1 for the most stable tautomers of the neutral and protonated forms with explicit water molecules in the first solvation sphere included.

Inhibitory effect of water on the oxygen reduction catalyzed by cobalt(II) tetraphenylporphyrin.

Stopped-flow kinetic measurements, UV-vis spectroscopy, rotating disk voltammetry, and quantum chemical calculations are used to clarify the role of water in the homogeneous two-electron reduction of O2 to H2O2 in 1,2-dichloroethane (DCE) using ferrocene (Fc) as an electron donor, tetrakis(pentafluorophenyl)boric acid (HTB) as a proton donor, and [5,10,15,20-tetraphenyl-21H,23H-porphine]cobalt(II) (Co(II)TTP) as a catalyst. Kinetic analysis suggests that the reaction is controlled by the intramolecular proton coupled electron transfer to the O2 molecule coordinated to the metal center producing the O2H(•) radical. This rate-determining step is common to both the O2 reduction by Fc catalyzed by Co(II)TPP and the O2 reduction by Co(II)TPP itself. Experimental data point to the competitive coordination of water to the metal center leading to a strong inhibition of the catalytic reaction. In agreement with this finding, quantum chemical calculations indicate that water is bound to the metal center much more strongly than triplet O2. A similar effect is demonstrated also for the O2 reduction catalyzed by the porphyrin free base (H2TPP), though its rate is lower by 2 orders of magnitude.

A comparative study of the redox and excited state properties of (nBu4N)2[Mo6X14] and (nBu4N)2[Mo6X8(CF3COO)6] (X = Cl, Br, or I).

The excited-state dynamics, luminescence, and redox properties of a series of hexanuclear molybdenum cluster complexes, (nBu4N)2[Mo6X14] and (nBu4N)2[Mo6X8(CF3COO)6] (X = Cl, Br, or I), were investigated. Substitution of the apical halogen ligands for the trifluoroacetate ligands increased the oxidation potentials and induced a blue shift in the absorption and luminescence bands as well as a considerable increase in the luminescence quantum yields for heavy inner ligands. Time-resolved transient absorption measurements showed that the intersystem crossing from the excited singlet states is ultrafast with time constants ranging between <120 fs and 1.68 ps and leads to hot triplet states. The following cooling occurred at a ps time scale and was assigned to electronic redistribution within the emissive triplet state sublevels. The formation of singlet oxygen, O2((1)Δg), suggested earlier on the basis of photooxidation experiments for some complexes, was revised by direct measurements of O2((1)Δg) phosphorescence. We showed the effects of the attached ligands on key physico-chemical and photophysical parameters of the title complexes. The synthesis and structural characterisation of a new cluster complex, (nBu4N)2[Mo6Br8(CF3COO)6], completed the series. Our results demonstrated that the complexes with heavy inner ligands (Br, I) and apical trifluoroacetate ligands were photochemically and electrochemically stable, highly luminescent, and good sensitisers of O2((1)Δg).

Competitive inhibition of a metal-free porphyrin oxygen-reduction catalyst by water.

A stopped-flow method is used to study the effects of water and reactant acid anion TB(-) = tetrakis(pentafluorophenyl)borate on the homogeneous oxygen reduction catalyzed by the protonated tetraphenylporphyrin. Observed competitive inhibition of the catalyst is linked to the DFT free energy of extraction of O(2), water, and TB(-) from the porphyrin complex.

Electrochemical quantification of 2,6-diisopropylphenol (propofol).

2,6-Diisopropylphenol (propofol) is a potent anesthetic drug with fast onset of the anesthetic effect and short recovery time for the patients. Outside of the United States, propofol is widely used in performing target controlled infusion anesthesia. With the long term vision of an electrochemical sensor for in vivo monitoring and feedback controlled dosing of propofol in blood, different alternatives for the electrochemical quantification of propofol using diverse working electrodes and experimental conditions are presented in this contribution. When the electrochemical oxidation of propofol takes place on a glassy carbon working electrode, an electrochemically active film grows on the electrode surface. The reduction current of the film is proportional to the propofol concentration and the accumulation time. Based on these findings a stripping analytical method was developed for the detection of propofol in acidic solutions between 0 and 30 µM, with a detection limit of 5.5±0.4 µM. By restricting the scanned potential window between 0.5 V and 1.0 V in cyclic voltammetric experiments, the formation of the electrochemically active polymer can be prevented. This allowed the development of a direct voltammetric method for assessing propofol in acidic solutions between 0 and 30 µM, with a 3.2±0.1 µM (n=3) detection limit. The stripping method has a better sensitivity but somewhat worse reproducibility because the electrode surface has to be renewed between each experiment. The direct method does not require the renewal of the electrode surface between measurements but has no adequate selectivity towards the common interfering compounds.

Fine tuning of the catalytic effect of a metal-free porphyrin on the homogeneous oxygen reduction.

The catalytic effect of tetraphenylporphyrin on the oxygen reduction with ferrocene in 1,2-dichloroethane can be finely tuned by varying the molar ratio of the acid to the catalyst present in the solution. The mechanism involves binding of molecular oxygen to the protonated free porphyrin base, in competition with ion pairing between the protonated base and the acid anion present.

Charge transfer in porphyrin-calixarene complexes: ultrafast kinetics, cyclic voltammetry, and DFT calculations.

Transient absorption spectroscopy, cyclic voltammetry, and DFT calculations were used to describe charge transfer processes in a series of 5,10,15,20-tetrakis(N-methylpyridinium-n-yl) porphyrins (TMPyPn, n = 4,3,2) and TMPyPn/p-sulfonatocalix[m]arene (clxm, m = 4,6,8) complexes. Excitation of TMPyPn is accompanied by an increasing electron density at the methylpyridinium substituents in the order TMPyP2 < TMPyP3 < TMPyP4. The quenching of the excited singlet states of the complexes increases with the number of ionized phenolic groups of clxm and can be correlated with the partial transfer of the electron density from O(-) to the peripheral methylpyridinium substituents rather than to the porphyrin ring.

Voltammetry of ion transfer across a polarized room-temperature ionic liquid membrane facilitated by valinomycin: theoretical aspects and application.

Cyclic voltammetry is used to investigate the transfer of alkali-metal cations, protons, and ammonium ions facilitated by the complex formation with valinomycin at the interface between an aqueous electrolyte solution and a room-temperature ionic liquid (RTIL) membrane. The membrane is made of a thin (approximately 112 microm) microporous filter impregnated with an RTIL that is composed of tridodecylmethylammonium cations and tetrakis[3,5-bis(trifluoromethyl)phenyl]borate anions. An extension of the existing theory of voltammetry of ion transfer across polarized liquid membranes makes it possible to evaluate the standard ion-transfer potentials for the hydrophilic cations studied, as well as the stability constants (K(i)) of their 1:1 complexes with valinomycin, as log K(i) = 9.0 (H(+)), 11.1 (Li(+)), 12.8 (Na(+)), 17.2 (K(+)), 15.7 (Rb(+)), 15.1 (Cs(+)), and 14.7 (NH(4)(+)). These data point to the remarkably enhanced stability of the valinomycin complexes within RTIL, and to the enhanced selectivity of valinomycin for K(+) over all other univalent ions studied, compared to the conventional K(+) ion-selective liquid-membrane electrodes. Selective complex formation allows one to resolve voltammetric responses of K(+) and Na(+) in the presence of an excess of Mg(2+) or Ca(2+), which is demonstrated by determination of K(+) and Na(+) in the table and tap water samples.

Current-polarized ion-selective membranes: The influence of plasticizer and lipophilic background electrolyte on concentration profiles, resistance, and voltage transients.

Lipophilic background electrolytes consisting of a lipophilic cation and a lipophilic anion, such as tetradodecylammonium tetrakis(4-chlorophenyl) borate (ETH 500), or bis(triphenylphosphoranylidene) ammonium tetrakis[3,5bis(trifluoromethyl) phenyl] borate (BTPPATFPB) are incorporated into the membranes of ion-selective electrodes (ISEs) to improve the detection limit and selectivity of the electrodes and decrease the resistance of the sensing membrane. In this work, spectroelectrochemical microscopy (SpECM) is used in conjunction with chronopotentiometry to quantify the effects of a lipophilic background electrolyte on the concentration profiles induced inside current-polarized membranes and on the measured voltage transients in chronopotentiometric experiments. In agreement with the theoretical model, the lipophilic background electrolyte incorporated into o-NPOE or DOS plasticized membranes decreases the membrane resistance and thus the contribution of migration in the overall transport across ion-selective membranes. Consequently, it has a significant influence on the changing concentration profiles of the ion-ionophore complex during chronopotentiometric experiments.

Mathematical model of current-polarized ionophore-based ion-selective membranes.

A mathematical model is presented to describe the effects of constant current on ion-selective membranes using theta functions. The model provides exact analytic solutions for calculating the concentration polarization of the ionophore, the ion-ionophore complex, and the charged mobile sites in space and time within the membrane. It also predicts the time course of the membrane potential and the electric field inside the membrane following the application of constant current. This analytic solution is faster to compute than numerical simulations and provides the solution for any given time or position directly. The simulated concentration profiles compare favorably with concentration profiles recorded experimentally using spectro-electrochemical microscopy.

Potentiometric sensor for heparin polyion: transient behavior and response mechanism.

Chronopotentiometry and electrochemical impedance spectroscopy were used to study the transient behavior and the potentiometric response mechanism of the polymer membrane-based sensor for heparin. Membrane with a composition of 66 wt % poly(vinyl chloride), 33 wt % o-nitrophenyl octyl ether (plasticizer), and 0.05 M tridodecylmethylammonium chloride (ion exchanger) was deposited on the surface of a silver or a glassy carbon (GC) electrode. In the latter case, the membrane contained also 0.1 M 1,1'-dimethylferrocene/1,1'-dimethylferricenium+ couple ensuring the electronic contact between the membrane and GC. The sensor was dipped in an aqueous solution of 0.1 M LiCl, which was stirred with a magnetic stirrer (2-18.2 Hz), and eventually spiked with heparin (0.05-5 U mL-1). Chronopotentiometric measurements were carried out using either the Ag supported membrane with a thickness>100 microm or the GC supported membrane with a defined thickness of 2-30 microm, which was also used in impedance measurements. Remarkable features of the potentiometric response include the linear dependence of the initial slope of the potential transient on the heparin concentration in the aqueous phase and on the square root of the stirring frequency, and the absence of the effect of the membrane thickness. Impedance measurements (0.1 Hz-10 kHz) made it possible to identify and to evaluate the geometric capacitance and the capacitance of the electric double layer at the membrane/solution interface, the bulk membrane and charge-transfer resistances, and the Warburg impedance of the chloride transport. Changes in the membrane bulk and charge-transfer resistances and the Warburg impedance upon spiking the aqueous solution with heparin were found to be consistent with the steady-state response of approximately -25 mV, indicating that the bulk chloride concentration in the membrane decreased to about half of its initial value. A novel theoretical model of the transient behavior was developed based on the balance of the charging and the faradic currents of chloride and heparin, in accordance with the ion-exchange mechanism that has been proposed previously. It was concluded that the initial slope of the potential transient is linked to the charging of the double layer coupled to the chloride ion transfer across the membrane/solution interface and to the diffusion-limited transport of heparin in the solution. The potentiometric assay of heparin could be based on measurements of the initial slope of the potential transient or the potential at a fixed time shortly after the heparin injection.

How to assess the limits of ion-selective electrodes: method for the determination of the ultimate span, response range, and selectivity coefficients of neutral carrier-based cation selective electrodes.

The span and range of an ion-selective electrode (ISE) has been identified by IUPAC as a potential or activity difference between the upper and lower detection limits of the electrode. Once the span is known, the ultimately attainable detection limit of the ISE can be calculated using its theoretical response slope. In this paper, we propose an original method for the determination of the ultimate span and response range of ISEs. The simple measurement of span is recommended to aid the fast screening of novel ionophores and help to focus optimization processes to the most promising candidates. The measurement of span is combined with a generally applicable procedure for the determination of the three seminal parameters of ISEs: the response slope, the ultimate selectivity coefficients, and detection limit. In the proposed procedure, following the span measurement, two subsequent exponential dilution experiments are completed in which the responses of the electrode for the primary and the interfering ions are tested using a solution of a discriminated ion and deionized water as diluting electrolytes in consecution. The advantages and the practical usefulness of the proposed methods and procedures are demonstrated through the evaluation of the performance characteristics of novel and well-characterized ionophore-based potassium and calcium sensors.