The central challenge the team addressed is a familiar one in analytical electrochemistry. Thiocyanate and sulfide ions are both difficult to oxidize directly at electrode surfaces, because the heterogeneous electron transfer between the electrode and these anions is intrinsically slow and often accompanied by fouling of the surface by oxidation products such as elemental sulfur. Direct anodic oxidation of sulfide, for example, has long been known to deposit sulfur films on electrodes, degrading their performance over time. Mediated electrocatalysis offers an elegant workaround: instead of forcing the analyte to surrender electrons directly to the solid electrode, a dissolved redox-active mediator is first oxidized at the electrode and then chemically oxidizes the analyte in solution, regenerating the reduced form of the mediator and completing a catalytic cycle. In electrochemical notation this is the classic EC′ mechanism, where an electrode reaction (E) is followed by a homogeneous chemical reaction (C′) that consumes the electrogenerated species.

Chlorpromazine is exceptionally well suited to this role. The phenothiazine core undergoes a well-defined, reversible one-electron oxidation in aqueous media, converting the parent compound into a stable radical cation that is a potent chemical oxidant. Because the redox couple sits at a potential that is accessible on many electrode materials, the oxidized form can be generated cleanly and reproducibly. The Iranian team chose boron-doped diamond as the working electrode, a material prized in electrochemistry for its extraordinary chemical inertness, wide potential window in water, and resistance to fouling. These properties make BDD an ideal substrate for studying mediated oxidation reactions without the complicating background chemistry that plagues more reactive carbon or metal surfaces. Using cyclic voltammetry, the researchers first characterized the redox behavior of chlorpromazine itself in aqueous buffer, establishing the standard potential and the kinetic parameters that govern the electron transfer at the diamond surface.

The crucial methodological innovation of the study lies in its use of digital simulation software, specifically DigiSim 3, to fit simulated cyclic voltammograms to the experimental curves. Digital simulation works by numerically solving the coupled partial differential equations that describe mass transport, electron transfer, and homogeneous chemical kinetics in the diffusion layer adjacent to the electrode. The researcher proposes a mechanism, assigns plausible values for the diffusion coefficients, heterogeneous electron-transfer rate constants, charge-transfer coefficients, and catalytic rate constants, and the software generates a predicted voltammogram. By iteratively adjusting these parameters until the simulated curve overlays the experimental data, the team could extract quantitative kinetic information that would be nearly impossible to obtain from peak currents and peak potentials alone. The quality of the fit then becomes a stringent test of the proposed mechanism: if the assumed reaction scheme is wrong, no reasonable parameter set will reproduce the observed peak shapes, positions, and scan-rate dependence.

When thiocyanate was added to the solution containing chlorpromazine, the cyclic voltammograms changed in a manner diagnostic of electrocatalysis. The anodic peak current for the oxidation of the mediator increased substantially, while the corresponding cathodic peak on the reverse scan diminished, exactly the signature expected when the electrochemically generated oxidized chlorpromazine is consumed by a fast chemical reaction with thiocyanate in the diffusion layer. The same behavior appeared with sulfide. The team systematically varied the analyte concentration and the potential scan rate, mapping out how the catalytic response evolved across both dimensions. At slow scan rates, the chemical step has more time to consume the oxidized mediator, amplifying the catalytic enhancement; at fast scan rates, the voltammetry increasingly reflects the intrinsic kinetics of the mediator redox couple itself. This scan-rate dependence, combined with concentration dependence, provided the experimental scaffolding on which the digital simulations were built.

The fitted parameters tell a quantitative story. The diffusion coefficient of thiocyanate was determined to be (2.08 ± 0.05) × 10⁻⁵ cm² s⁻¹, while sulfide diffused somewhat faster at (5.08 ± 0.16) × 10⁻⁵ cm² s⁻¹, consistent with the smaller hydrodynamic radius of the hydrated sulfide species. The heterogeneous electron-transfer rate constant for the chlorpromazine couple on boron-doped diamond came out at 0.0066 cm s⁻¹ for both analyte systems, indicating a moderately fast but not diffusion-limited surface reaction. The charge-transfer coefficients, which describe the symmetry of the energy barrier for electron transfer, were 0.605 ± 0.037 for the thiocyanate system and 0.550 ± 0.025 for sulfide, values close to the idealized 0.5 that characterizes a well-behaved outer-sphere electron transfer. Most strikingly, the catalytic rate constants, which quantify how rapidly the oxidized mediator attacks the analyte in solution, reached (4.05 ± 0.42) × 10⁴ M⁻¹ s⁻¹ for thiocyanate and (5.34 ± 1.92) × 10⁴ M⁻¹ s⁻¹ for sulfide, confirming that the homogeneous chemical steps are genuinely fast and efficient.

The satisfactory agreement between simulated and experimental voltammograms across the full range of conditions gives the authors confidence that the EC′ mechanism they propose is the correct description of the chemistry. In other words, the oxidized chlorpromazine radical cation formed at the diamond surface diffuses into the solution, transfers oxygen-equivalent oxidizing power to thiocyanate or sulfide, and is reduced back to its parent form, ready to be re-oxidized at the electrode. This catalytic turnover is what produces the amplified anodic currents that underpin potential analytical applications. The study builds on the group’s earlier work, including a 2017 investigation of chlorpromazine-mediated oxidation of arsenic(III) and iron(II) and a 2024 study that revealed more complex EEC and EC′EC mechanisms when the mediator operates in the presence of the amino acid L-cysteine. Together, these papers sketch a versatile mediator chemistry whose mechanism shifts depending on the identity and reactivity of the target analyte.

Why does this matter beyond the electrochemistry community? Thiocyanate is a clinically and forensically significant biomarker. It is the principal metabolite of cyanide exposure, and elevated salivary thiocyanate levels are associated with tobacco smoking, making it a target for noninvasive screening methods ranging from ion-selective electrodes to colorimetric assays. Sulfide, meanwhile, occupies a dual identity: hydrogen sulfide is a notorious toxic gas and an environmental pollutant in wastewater and food spoilage, yet it is also increasingly recognized as a biologically produced signaling molecule, or gasotransmitter, whose concentration in living cells is actively regulated. Analytical methods for sulfide therefore span environmental monitoring, food safety, and biomedical research, employing everything from nanoporous gold electrodes to fluorescent probes and smartphone-based colorimetry. A robust, mechanistically understood electrocatalytic route to oxidizing both species could feed into the design of simpler, cheaper electrochemical sensors that do not suffer from the fouling problems of direct oxidation.

The study also contributes to a broader renaissance of interest in the electrochemistry of phenothiazines. Recent work has mapped the surprisingly complex three-electron oxidation pathway of chlorpromazine, and other groups have developed nanostructured electrodes, from nickel phosphate to antimony vanadate nanospheres, for detecting the drug itself in biological samples. The Ionics paper inverts that perspective: rather than detecting chlorpromazine, it deploys the drug as an active catalytic agent. The combination of a fouling-resistant diamond electrode, a cheap and commercially available mediator, and the mechanistic rigor of digital simulation offers a template for how mediated electrocatalysis can be characterized quantitatively rather than merely demonstrated. As sensor developers seek mediators whose kinetics are fully understood and whose behavior can be predicted computationally, this fusion of experiment and simulation may prove to be the study’s most lasting contribution, turning a vintage antipsychotic into a precision tool for environmental and analytical chemistry.

Subject of Research: Electrocatalytic oxidation mechanisms of thiocyanate and sulfide mediated by chlorpromazine at boron-doped diamond electrodes, characterized by digital electrochemical simulation

Article Title: A comprehensive experimental and theoretical elucidation of the electrocatalytic oxidation mechanisms of thiocyanate and sulfide mediated by chlorpromazine: supported by digital electrochemical simulations

Article References: Salimi, A., Amini, N., & Naderi, K. (2026). A comprehensive experimental and theoretical elucidation of the electrocatalytic oxidation mechanisms of thiocyanate and sulfide mediated by chlorpromazine: supported by digital electrochemical simulations. Ionics. https://doi.org/10.1007/s11581-026-07571-3

Image Credits: AI Generated

DOI: 10.1007/s11581-026-07571-3

Keywords: chlorpromazine, thiocyanate, sulfide, electrocatalysis, boron-doped diamond electrode, cyclic voltammetry, digital simulation, EC′ mechanism, reaction kinetics, phenothiazine, electrochemical sensing, redox mediator