Next Article in Journal
Microfluidic Gastrointestinal Cell Culture Technologies—Improvements in the Past Decade
Previous Article in Journal
Editorial to the Special Issue “Advances in Optical Biosensors and Chemical Sensors”
Previous Article in Special Issue
Ti3C2 Nanosheets Functionalized with Ferritin–Biomimetic Platinum Nanoparticles for Electrochemical Biosensors of Nitrite
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Biosensors
Volume 14
Issue 9
10.3390/bios14090448
biosensors-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

A Novel Ferrocene-Linked Thionine as a Dual Redox Mediator for the Electrochemical Detection of Dopamine and Hydrogen Peroxide

by
Manikandan Palinci Nagarajan
1,2,
Manikandan Ramalingam
1,
Ilakeya Subbiah Arivuthilagam
1,
Vishwa Paramaguru
1,
Md. Mahbubur Rahman
3,
Jongdeok Park
1,
Francis Kwaku Asiam
1,
Byungjik Lee
1,
Kwang Pyo Kim
2,* and
Jae-Joon Lee
1,*
1
Research Center for Photoenergy Harvesting & Conversion Technology (phct), Department of Energy & Materials Engineering, Dongguk University, 26 Phil-dong, 3-ga, Jung-gu, Seoul 04620, Republic of Korea
2
Department of Applied Chemistry, Kyung Hee University, 1732 Deokyoung-daero, Giheung-gu, Yongin-si 17104, Republic of Korea
3
Department of Energy Materials Science and Engineering, Konkuk University, Chungju 27478, Republic of Korea
*
Authors to whom correspondence should be addressed.
Biosensors 2024, 14(9), 448; https://doi.org/10.3390/bios14090448
Submission received: 13 May 2024 / Revised: 14 September 2024 / Accepted: 16 September 2024 / Published: 19 September 2024
(This article belongs to the Special Issue Nanomaterial-Based Biosensors to Support the One Health Concept)
Browse Figures
Versions Notes

Abstract

:
We introduce a novel dual redox mediator synthesized by covalently linking ferrocene dicarboxylic acid (FcDA) and thionine (TH) onto a pre-treated glassy carbon electrode. This unique structure significantly enhances the electro-oxidation of dopamine (DA) and the reduction of hydrogen peroxide (H2O2), offering a sensitive detection method for both analytes. The electrode exhibits exceptional sensitivity, selectivity, and stability, demonstrating potential for practical applications in biosensing. It facilitates rapid electron transfer between the analyte and the electrode surface, detecting H2O2 concentrations ranging from 1.5 to 60 µM with a limit of detection (LoD) of 0.49 µM and DA concentrations from 0.3 to 230 µM with an LoD of 0.07 µM. The electrode’s performance was validated through real-sample analyses, yielding satisfactory results.

1. Introduction

The advancement of modern analytical techniques for human health management is driven by the need to develop sustainable, reliable, and user-friendly systems for monitoring analytes in various matrices, including environmental samples, food commodities, and biological fluids [1,2]. These techniques emphasize using environmentally friendly materials and reduced reagent quantities to minimize chemical waste production.
Hydrogen peroxide (H2O2) is not only industrially significant but also a well-known byproduct of numerous enzymatic reactions, making its accurate quantification critical in food industries, environmental monitoring, and clinical applications [3]. As a typical reactive oxygen species, H2O2 can induce oxidative stress damage to cells, including neurons. The brain, with its high oxygen consumption, elevated polyunsaturated fatty acid content, and relatively low antioxidant defenses, is particularly susceptible to oxidative stress. Evidence suggests that oxidative stress may play a role in neurodegenerative disorders characterized by the loss of dopamine (DA)-producing neurons [4]. Abnormal DA levels are linked to diseases such as Parkinson’s, Alzheimer’s, senile dementia, and schizophrenia [5,6]. Understanding the relevance or interplay between DA and oxidative stress levels correlated with H2O2 levels is of significant interest [7].
Direct electrochemical detection of DA [8,9,10,11,12,13,14,15,16] and H2O2 [17,18,19,20,21,22,23] is well-known but typically requires sophisticated electrode design for optimization, stability, and reproducibility over a wide concentration range. This is often achieved using nanomaterials, including conducting polymers [24,25], graphene [26,27,28,29], and redox mediators [30,31,32,33,34]. Early detection of DA and nitrophenol utilizing thionine (TH) as a redox mediator immobilized on glassy carbon (GC) electrodes has been reported [35,36,37,38]. Recent studies have highlighted the use of bi-mediators capable of detecting dual analytes. The complex form of nickel hexacyanoferrate and TH on GC electrodes were used for the oxidation of gallic acid and reduction of H2O2 [12,39], respectively, while the concept of bi- or dual-mediators for electrochemical sensors has been rarely explored.
In this study, we developed a novel electrode with a complex dual redox mediator consisting of ferrocene dicarboxylic acid (FcDA) directly linked to a TH unit. The dual mediator was synthesized by covalently linking FcDA and TH, followed by immobilization onto a pre-treated GC surface via hydrogen bonding interactions, resulting in the formation of GC/TH−FcDA for electrochemical sensor applications, as shown in Scheme 1. We investigated the electrochemical behavior of GC/TH−FcDA for the electrocatalytic detection of both DA and H2O2 by each electrochemically active moiety of FcDA and TH over a wide potential range at a single electrode. GC/TH−FcDA exhibited stable and reproducible sensing capabilities for dual analytes and can be extended for simultaneous detection of multiple analytes through simple electrode design.

2. Materials and Methods

2.1. Reagents and Materials

All reagents used in this study were of analytical grade and purchased from Sigma-Aldrich (St.Louis, MO, USA) without further purification. Double-distilled water (18.2 MΩ∙cm), obtained from a Millipore Milli-Q bio cell A10 water purification system (Merck, Darmstadt, Germany), was employed throughout the experiments. TH, FcDA, N-ethyl-N’-(3-dimethylaminopropyl)-carbodiimide hydrochloride (EDC.HCl), hydroxybenzotriazole (HOBt), DA, ascorbic acid (AA), uric acid (UA), disodium hydrogen phosphate, sodium dihydrogen phosphate, and H2O2 were used as received. A phosphate-buffer solution (PBS, 0.1 M, pH 7) was prepared by mixing aqueous solutions of disodium hydrogen phosphate and sodium dihydrogen phosphate. All electrochemical measurements were conducted at ambient temperature. Before measurements, the electrolyte was purged with inert nitrogen gas for 5 min to eliminate active oxygen interference.

2.2. Instrumentation

Electrochemical experiments were conducted using a CHI-430A potentiostat (CH Instruments, Austin, TX, USA) with a standard three-electrode setup. The reference and auxiliary electrodes consisted of an Ag/AgCl electrode saturated with KCl and a platinum wire. The working electrodes were GC electrodes with a diameter of 3 mm, modified with TH-FcDA to obtain GC/TH−FcDA. Fourier-transform infrared (FT-IR) measurements were performed in AT-IR mode using a JASCO FT-IR-4600 instrument (Tokyo, Japan). The surface morphology of materials was characterized by scanning electron microscopy (SEM, JEOL JSM-7100, Tokyo, Japan).

2.3. Preparation of TH-FcDA

TH was covalently linked to FcDA in a 2:1 molar ratio using EDC.HCl and HOBt as cross-linking reagents [12], as depicted in Figure 1. FcDA (1 mM) and 2 mmol of EDC.HCl were stirred for 2 h to activate the carboxylic acid (-COOH) groups of ferrocenes for o–acylurea formation. Subsequently, 2 mM of HOBt was added to the reaction mixture and stirred vigorously for another 2 h to facilitate ester formation. Then, 2 mmol of TH was introduced, and the reaction mixture was stirred vigorously to promote the reaction of the amine (-NH2) group in TH with the ester group, resulting in an amide bond formation. The covalently bonded TH-FcDA material was precipitated, washed with ethanol to remove unreacted precursors, and dried in a vacuum oven at 80 °C for 6 h and used for further electrochemical measurements.

2.4. Modification of GC with TH-FcDA

The GC was surface-cleaned and polished prior to modification. The GC’s surface was pre-treated using a chronoamperometric technique previously reported by our group [15,33,34]. The GC was immersed in 0.1 M PBS (pH 7) and subjected to a constant potential of +1.8 V for 300 s. The TH-FcDA solution (5 mg/mL in dimethyl sulfoxide, 3 µL) was then drop-casted onto the pre-treated GC surface and dried at ambient temperature. The modified electrode (GC/TH−FcDA) was subsequently washed with water to remove any unbonded material and dried under an inert atmosphere.

3. Results and Discussions

3.1. FT-IR and Morphology Studies

The chemical groups of FcDA, TH, and TH-FcDA were characterized via FT-IR, as shown in Figure 2A. The spectra revealed the presence of the -COOH group in FcDA, the NH2 group in TH, and the amide group in TH-FcDA. The IR bands at 758 and 897 cm−1 correspond to the aromatic C-H bending in all three materials. In FcDA, the bands at 1300 and 1672 cm−1 confirmed the presence of C-O and C=O stretching vibrations of the -COOH group, respectively [40]. In addition, the IR band at 2926 cm−1 corresponds to the C-H stretching in TH [41]. Furthermore, the peaks at 3130 and 3323 cm−1 verified the existence of -NH2 group in TH. Conversely, the C=O stretching vibration shifted to 1606 cm−1 with slight broadening owing to the at -CO-NH- bond formation in TH-FcDA. Therefore, the FT-IR analysis confirmed the formation of the TH-FcDA complex. The morphologies of these materials were analyzed using SEM measurements. The FcDA showed an aggregated and interconnected nanoparticle structure (Figure S1A). In addition, the TH revealed the aggregated nanonetwork-like morphology (Figure S1B). As shown in Figure 2B, the TH-FcDA exhibited a mixed structure with the combination of the interconnected and cluster type of nanoparticle structure and cubic type structure. These structural variations between the materials suggest the formation of TH-FcDA.

3.2. Electrochemical Measurements

The cyclic voltammetric (CV) behaviors of GC, GC/FcDA, GC/TH, and GC/TH−FcDA were investigated in a 0.1 M PBS at pH 7 with a scan rate of 50 mV/s, and the results are presented in Figure 3. The ferrocene oxidation and reduction peaks (Epa and Epc, respectively) were observed at 0.28 and 0.21 V, respectively, with a ∆Ep of 70 mV for GC/FcDA. In comparison, the redox peaks for the formation of TH to leuco–TH were located with Epa and Epc of −0.21 and −0.18 V, respectively, with ∆Ep of 30 mV for GC/TH. In the redox complex of the TH-FcDA-modified GC, the ferrocene redox peak shifted negatively, and the current also increased, indicating the TH-mediated redox reaction of FcDA. The TH redox peak current increased in the GC/TH−FcDA electrode compared to the GC/TH electrode (ΔEp = 10 mV) with the ΔEp of 40 mV. This can be attributed to the improved charge transfer properties of the linked moieties resulting from the hydrogen bonding interactions between the -NH2 groups of TH and –COOH functionalities of GC, as schematically presented in Figure 1.
Figure 4A illustrates the CV response of GC/TH−FcDA in 0.1 M PBS at pH 7, with DA concentrations varying from 0.3 to 4.5 mM and H2O2 concentrations from 3 to 22 µM. The results demonstrate a linear increase in the anodic peak current density (Jpa) within the redox potential of FcDA (0.16 V) upon adding DA, with a linear regression equation of Jp (mA/cm2) = 9.40 [DA] (mM) + 7.01 and a correlation coefficient, R2 = 0.9983 (Figure S2A1). The reduction peak current of TH also increases as the concentration of DA increases in successive CV measurements. This is likely due to the polymerization of DA onto the electrode surface. Additionally, a linear increase in cathodic peak current density (Jpc) was observed at −0.2 V with increasing H2O2 concentrations, corresponding to a linear regression equation of Jp (µA/cm2) = 2.07 [H2O2] (µM) + 14.08 (R2 = 0.9993) (Figure S2A2). These demonstrate the low LoDs of 2.77 and 1.37 µM for DA and H2O2, respectively. [12,38] These CV findings suggest that the oxidation of DA to dopamine-o-quinone occurs at FcDA moieties, while the reduction of H2O2 to H2O and ½O2 occurs at TH moieties (Scheme 1). This was further confirmed using density functional theory (DFT), as detailed in Section 3.5.
Moreover, the different pulse voltammetry (DPV) response of GC/TH−FcDA in 0.1 M PBS at pH 7 with DA concentrations ranging from 0.3 to 230 μM and H2O2 from 1.5 to 60 μM is shown in Figure 4B. The calibration curve for the electrochemical detection of DA and H2O2 using the GC/TH−FcDA demonstrated a good linear relationship between the peak currents and the concentrations, spanning 0.3 to 230 µM for DA and 1.5 to 60 µM for H2O2 (Figure S2B). The electrode exhibited a linear regression equation of Jpa (µA/cm2) = 0.59 [DA] (µM) + 29.84 with an R2 of 0.9997 and an estimated sensitivity of 0.59 µA/µM/cm2, indicating the high electrocatalytic activity towards the oxidation of DA at 0.16 V. The LoD was determined to be 0.07 µM, which is lower than previously reported values for similar electrodes (Table S1A) [12,13,14,15,16,17,18,19]. Furthermore, for H2O2 detection, the electrode demonstrated a sensitivity of 0.68 µA/µM/cm2 with a linear regression equation of Jpc (µA/cm2) = 0.68 [H2O2] + 57.23 with R2 = 0.9996 and an LoD (S/N = 3) of 0.49 µM, exceeding earlier findings (Table S1B) [12,21,22,23,24,25,26,27].
Figure 5(A1,A2) presents the CV response of GC/TH−FcDA in 0.1 M PBS at pH 7, featuring both 10 µM of DA and H2O2, with scan rates ranging from 10 to 300 mV/s. The voltammograms reveal that both the Jpa and Jpc, corresponding to the redox potential of FcDA moieties at 0.15 V, indicative of DA oxidation, increase with the square root of the scan rate. These observations suggest that the DA oxidation process is diffusion-controlled, consistent with findings reported in an earlier study [38]. Similarly, the Jpc for the reduction of H2O2 increased with the scan rate, which showed linear behavior between Jpc and the square root of the scan rate, indicating a diffusion-controlled reduction reaction of H2O2, aligning with previous reports [19].
DPV measurements were conducted on GC/TH−FcDA to evaluate the influence of supporting electrolyte pH on DA oxidation and H2O2 reduction, as depicted in Figure 5(B1,B2). The Jpa for DA oxidation increased gradually from pH 5 to 7, followed by a decline from pH 7 to 9 (Figure 5(B1)). The Epa shifted negatively with increasing pH from 5 to 9, described by the linear regression equation Epa = -0.065pH + 0.595 (R2 = 0.995) (Figure S3A). This result suggests that the stoichiometry for the DA oxidation reaction involved two electrons and two protons [42]. Again, the Jpc for H2O2 reduction increased with increasing pH from 5 to 7, then decreased from pH 7 to 9 (Figure 5(B2)). The Epc also shifted negatively with rising pH from 5 to 9, quantified by the linear regression equation Epc = -0.078pH + 0.078 (R2 = 0.993) (Figure S3B). The number of electrons and protons involved in the H2O2 reduction was determined to be two [19]. The Jpa for DA oxidation and Jpc for H2O2 reduction reached their maximum at pH 7 (0.1 M PBS), establishing pH 7 (0.1 M PBS) as the optimal supporting electrolyte pH for sensing DA and H2O2.

3.3. Interference Study

The detection of DA (10 µM) and H2O2 (10 µM) in the presence of a 100-fold excess of various analytes, including UA, AA, glucose, lysine, cysteine, and catechol, was investigated, and the obtained DPV results are displayed in Figure 6. An additional oxidation peak at 0.21 V was noted, signifying the oxidation of UA. Importantly, this peak did not interfere with the DA oxidation, attributed to a potential difference of 0.05 V between the oxidation processes of DA and UA. These findings confirm that excess concentrations of other analytes did not affect the detection of DA, and none of the above analytes interferes with the detection of H2O2, demonstrating the good selectivity of the GC/TH−FcDA sensor.

3.4. Real-Sample Analysis, Reproducibility, and Stability

To examine the practical applicability of the proposed GC/TH−FcDA sensor, a real-sample analysis was conducted. Human urine samples were pre-treated and stored at 4 °C prior to analysis [38]. H2O2 was detected in commercial milk samples. Both DA and H2O2 detections were performed using the standard addition method [39]. Five repetitive experiments were conducted for each sample, and recovery measurements were also performed using the standard addition method. The recovery results for DA ranged from 99.8% to 100.08%, while for H2O2, recoveries ranged from 99.2% to 101.0%, as delineated in Table 1. These results substantiate the excellent recovery performance and practical applicability of the developed electrode material.
As depicted in Figure S4, the GC/TH−FcDA demonstrated excellent reproducibility with a relative standard deviation (RSD%) of 0.35% and 0.07%, estimated from 30 consecutive CV scans performed in 10 µM H2O2 and DA 0.1 M PBS pH 7, respectively. For a long-term stability study, the GC/TH−FcDA sensor was stored in an airtight container when not in use for 20 days and retained 90% of its initial response. These findings confirm the stability of the electrode and its capacity to resist interference from repeated use cycles.

3.5. Density Functional Theory (DFT) Studies

The geometries and corresponding properties of the computed structures were analyzed using the B3LYP/6-31G (d,p) [43] level of theory with the GAUSSIAN 09 software and visualized with GaussView (5). No imaginary modes were observed in the frequency analysis, confirming that all structures are stationary points. The corresponding geometric coordinates are tabulated in Table S2 [44]. Figure 7 presents the electrostatic potential (ESP) map of TH-FcDA and its interactions with DA and H2O2. The DA molecule interacts with TH-FcDA through a potential π-π interaction site on both DA and FcDA molecules. The ESP map of the two materials reveals that the net positive density of TH-FcDA is localized on one side of the FcDA, while the net negative density on DA is oriented towards the aromatic ring, suggesting possible repulsion of DA on the TH side due to the positive charge density at the edges. Additionally, H2O2 demonstrates an electrostatic interaction with TH, primarily utilizing the oxygen groups at the positive end of TH.

4. Conclusions

This research successfully developed a highly stable dual redox mediator by covalently linking FcDA and TH onto a GC electrode. The electrochemical investigations elucidated the roles of FcDA and TH moieties in facilitating the oxidation of DA and reduction of H2O2, respectively. Carboxylation of the GC surface enhanced the immobilization of the redox mediator, resulting in high stability and a reproducible sensing response under neutral pH conditions. The electrode exhibited a notable sensing performance for DA, with a detection range from 0.3 to 230 µM, a sensitivity of 0.59 µA/µM/cm2, and a LoD of 0.07 µM (S/N = 3). Additionally, the electrode enabled effective sensing of H2O2, displaying in a range from 1.5 to 60 µM, with a sensitivity of 0.68 µA/µM/cm2 and an LoD of 0.49 µM (S/N = 3). Notably, the sensor was validated by detecting DA and H2O2 in diluted urine and milk samples, demonstrating its potential for practical applications in biosensing.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/bios14090448/s1. Figure S1. SEM images of (A) FcDA, and (B) TH. Figure S2. Linear plot for different concentrations of DA (A1, B1) and H2O2 (A2, B2) measured from Figure 4. Figure S3. Linear plot for different pH in the detection of DA (A) and H2O2 (B) measured from Figure 5(B1,B2). Figure S4. Reproducibility and Stability of GC/TH−FcDA electrode in the presence of H2O2 (A1,A2) and DA (B1,B2). Table S1. A. Comparison of analytical parameters for DA detection at GC/TH−FcDA. B. Comparison of analytical parameters for H2O2 detection at GC/TH−FcDA. Table S2. Cartesian coordinates of the molecules.

Author Contributions

Conceptualization, M.P.N. and J.-J.L.; methodology, M.P.N., M.R., J.P., F.K.A., V.P., I.S.A. and B.L.; software, M.P.N. and F.K.A.; formal analysis, M.P.N. and M.R.; validation, M.P.N., M.R., J.P., F.K.A., V.P., I.S.A. and B.L.; writing—original draft preparation, M.P.N.; writing—review and editing, M.M.R., M.R., J.P., F.K.A., V.P., I.S.A., B.L., K.P.K. and J.-J.L.; supervision, K.P.K. and J.-J.L.; project administration, J.-J.L.; funding acquisition, K.P.K. and J.-J.L. All authors have read and agreed to the published version of the manuscript.

Funding

This research was supported by the Korean National Research Foundation, funded by the Ministry of Science, ICT & Future Planning (grant NRF-2021R1A2C2094554).

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

The original contributions presented in the study are included in the article; further inquiries can be directed to the corresponding authors.

Conflicts of Interest

The authors declare no conflicts of interest.

References

  1. Pena-Pereira, F.; Bendicho, C.; Pavlović, D.M.; Martín-Esteban, A.; Díaz-Álvarez, M.; Pan, Y.; Cooper, J.; Yang, Z.; Safarik, I.; Pospiskova, K.; et al. Miniaturized Analytical Methods for Determination of Environmental Contaminants of Emerging Concern—A Review. Anal. Chim. Acta 2021, 1158, 238108. [Google Scholar] [PubMed]
  2. Dincer, C.; Bruch, R.; Costa-Rama, E.; Fernández-Abedul, M.T.; Merkoçi, A.; Manz, A.; Urban, G.A.; Güder, F. Disposable Sensors in Diagnostics, Food, and Environmental Monitoring. Adv. Mater. 2019, 31, e1806739. [Google Scholar] [CrossRef] [PubMed]
  3. Armenta, S.; Esteve-Turrillas, F.A.; Garrigues, S.; Guardia, M. de la Smart Materials for Sample Preparation in Bioanalysis: A Green Overview. Sustain. Chem. Pharm. 2021, 21, 100411. [Google Scholar] [CrossRef]
  4. Anastas, P.T. Green Chemistry and the Role of Analytical Methodology Development. Crit. Rev. Anal. Chem. 1999, 29, 167–175. [Google Scholar] [CrossRef]
  5. Heli, H.; Pishahang, J.; Amiri, H.B. Synthesis of Hexagonal CoAl-Layered Double Hydroxide Nanoshales/Carbon Nanotubes Composite for the Non-Enzymatic Detection of Hydrogen Peroxide. J. Electroanal. Chem. 2016, 768, 134–144. [Google Scholar] [CrossRef]
  6. Giorgio, M.; Trinei, M.; Migliaccio, E.; Pelicci, P.G. Hydrogen Peroxide: A Metabolic by-Product or a Common Mediator of Ageing Signals? Nat. Rev. Mol. Cell Biol. 2007, 8, 722–728. [Google Scholar] [CrossRef]
  7. Dias, V.; Junn, E.; Mouradian, M.M. The Role of Oxidative Stress in Parkinson’s Disease. J. Parkinsons Dis. 2013, 3, 461–491. [Google Scholar] [CrossRef]
  8. Drábková, M.; Admiraal, W.; Maršálek, B. Combined Exposure to Hydrogen Peroxide and LightSelective Effects on Cyanobacteria, Green Algae, and Diatoms. Environ. Sci. Technol. 2007, 41, 309–314. [Google Scholar] [CrossRef]
  9. Mahbubur Rahman, M.; Liu, D.; Siraj Lopa, N.; Baek, J.-B.; Nam, C.-H.; Lee, J.-J. Effect of the Carboxyl Functional Group at the Edges of Graphene on the Signal Sensitivity of Dopamine Detection. J. Electroanal. Chem. 2021, 898, 115628. [Google Scholar] [CrossRef]
  10. Ahammad, A.J.S.; Nath, N.C.D.; Xu, G.-R.; Kim, S.; Lee, J.-J. Interference-Free Determination of Dopamine at the Poly(Thionine)-Modified Glassy Carbon Electrode. J. Electrochem. Soc. 2011, 158, F106–F110. [Google Scholar] [CrossRef]
  11. Xi, X.; Tang, W.; Wu, D.; Shen, C.; Ji, W.; Li, J.; Su, Y.; Guo, X.; Liu, R.; Yan, F. All-Carbon Solution-Gated Transistor with Low Operating Voltages for Highly Selective and Stable Dopamine Sensing. ACS Sens. 2023, 8, 1211–1219. [Google Scholar] [CrossRef] [PubMed]
  12. Devendiran, M.; Krishna Kumar, K.; Sriman Narayanan, S. Fabrication of a Novel Ferrocene/Thionin Bimediator Modified Electrode for the Electrochemical Determination of Dopamine and Hydrogen Peroxide. J. Electroanal. Chem. 2017, 802, 78–88. [Google Scholar] [CrossRef]
  13. Ognjanović, M.; Stanković, D.M.; Jaćimović, Ž.K.; Kosović-Perutović, M.; Dojčinović, B.; Antić, B. The Effect of Surface-Modifier of Magnetite Nanoparticles on Electrochemical Detection of Dopamine and Heating Efficiency in Magnetic Hyperthermia. J. Alloys Compd. 2021, 884, 161075. [Google Scholar] [CrossRef]
  14. Shafi, P.M.; Joseph, N.; Karthik, R.; Shim, J.-J.; Bose, A.C.; Ganesh, V. Lemon Juice-Assisted Synthesis of LaMnO3 Perovskite Nanoparticles for Electrochemical Detection of Dopamine. Microchem. J. 2021, 164, 105945. [Google Scholar] [CrossRef]
  15. Bahrami, E.; Amini, R.; Vardak, S. Electrochemical Detection of Dopamine via Pencil Graphite Electrodes Modified by Cu/CuxO Nanoparticles. J. Alloys Compd. 2021, 855, 157292. [Google Scholar] [CrossRef]
  16. Anbumannan, V.; Kumar, R.T.R.; Suresh, K. Enhanced Electrochemical Detection of Dopamine by Graphene Oxide/Tungsten Trioxide Nanocomposite. Mater. Sci. Semicond. Process. 2021, 127, 105696. [Google Scholar] [CrossRef]
  17. Tian, J.; Wu, W. A Novel Preparation of Water-Dispersed Graphene and Their Application to Electrochemical Detection of Dopamine. Adv. Powder Technol. 2021, 32, 619–629. [Google Scholar] [CrossRef]
  18. Mathiarasu, R.R.; Manikandan, A.; Baby, J.N.; Panneerselvam, K.; Subashchandrabose, R.; George, M.; Slimani, Y.; Almessiere, M.A.; Baykal, A. Hexagonal Basalt-like Ceramics LaxMg1-XTiO3 (x = 0 and 0.5) Contrived via Deep Eutectic Solvent for Selective Electrochemical Detection of Dopamine. Physica B Condens. Matter 2021, 615, 413068. [Google Scholar] [CrossRef]
  19. Atta, N.F.; Abdel Gawad, S.A.; Galal, A.; Razik, A.A.; El-Gohary, A.R.M. Efficient Electrochemical Sensor for Determination of H2O2 in Human Serum Based on Nano Iron-nickel Alloy/Carbon Nanotubes/Ionic Liquid Crystal Composite. J. Electroanal. Chem. 2021, 881, 114953. [Google Scholar] [CrossRef]
  20. Sajjan, V.A.; Mohammed, I.; Nemakal, M.; Aralekallu, S.; Kumar, K.H.; Swamy, S.; Sannegowda, L.K. Hemantha Kumar, Sreenivasa Swamy, Lokesh Koodlur Sannegowda, Synthesis and electropolymerization of cobalt tetraaminebenzamidephthalocyanine macrocycle for the amperometric sensing of dopamine. J. Electroanal. Chem. 2019, 838, 33–40. [Google Scholar] [CrossRef]
  21. Molodtsova, T.; Gorshenkov, M.; Saliev, A.; Vanyushin, V.; Goncharov, I.; Smirnova, N. One-Step Synthesis of γ-Fe2O3/Fe3O4 Nanocomposite for Sensitive Electrochemical Detection of Hydrogen Peroxide. Electrochim. Acta 2021, 370, 137723. [Google Scholar] [CrossRef]
  22. Zhao, J.; Yang, H.; Wu, W.; Shui, Z.; Dong, J.; Wen, L.; Wang, X.; Yang, M.; Hou, C.; Huo, D. Flexible Nickel–Cobalt Double Hydroxides Micro-Nano Arrays for Cellular Secreted Hydrogen Peroxide in-Situ Electrochemical Detection. Anal. Chim. Acta 2021, 1143, 135–143. [Google Scholar] [CrossRef] [PubMed]
  23. Atacan, K.; Özacar, M. Construction of a Non-Enzymatic Electrochemical Sensor Based on CuO/g-C3N4 Composite for Selective Detection of Hydrogen Peroxide. Mater. Chem. Phys. 2021, 266, 124527. [Google Scholar] [CrossRef]
  24. Zhao, F.; Zhou, S.; Zhang, Y. Ultrasensitive Detection of Hydrogen Peroxide Using Bi 2 Te 3 Electrochemical Sensors. ACS Appl. Mater. Interfaces 2021, 13, 4761–4767. [Google Scholar] [CrossRef]
  25. Liu, X.; Zhang, X.; Zheng, J. One-Pot Fabrication of AuNPs-Prussian Blue-Graphene Oxide Hybrid Nanomaterials for Non-Enzymatic Hydrogen Peroxide Electrochemical Detection. Microchem. J. 2021, 160, 105595. [Google Scholar] [CrossRef]
  26. Qiao, X.; Arsalan, M.; Ma, X.; Wang, Y.; Yang, S.; Wang, Y.; Sheng, Q.; Yue, T. A Hybrid of Ultrathin Metal-Organic Framework Sheet and Ultrasmall Copper Nanoparticles for Detection of Hydrogen Peroxide with Enhanced Activity. Anal. Bioanal. Chem. 2021, 413, 839–851. [Google Scholar] [CrossRef]
  27. Rashed, M.A.; Harraz, F.A.; Faisal, M.; El-Toni, A.M.; Alsaiari, M.; Al-Assiri, M.S. Gold Nanoparticles Plated Porous Silicon Nanopowder for Nonenzymatic Voltammetric Detection of Hydrogen Peroxide. Anal. Biochem. 2021, 615, 114065. [Google Scholar] [CrossRef]
  28. Ghanbari, K.; Bonyadi, S. Modified Glassy Carbon Electrode with Polypyrrole Nanocomposite for the Simultaneous Determination of Ascorbic Acid, Dopamine, Uric Acid, and Folic Acid. J. Electrochem. Sci. Technol. 2020, 11, 68–83. [Google Scholar] [CrossRef]
  29. Peng, J.; Li, X.; Liu, Y.; Zhuge, W.; Zhang, C.; Huang, Y. Photoelectrochemical Sensor Based on Zinc Phthalocyanine Semiconducting Polymer Dots for Ultrasensitive Detection of Dopamine. Sens. Actuators B Chem. 2022, 360, 131619. [Google Scholar] [CrossRef]
  30. Sai Iswarya Bakavaty, T.; Gurunathan, K. Graphene-Wrapped WO3/Mo Derivatives for the Simultaneous Electrochemical Detection of Dopamine and Uric Acid. Mater. Sci. Eng. B 2024, 299, 116967. [Google Scholar] [CrossRef]
  31. Barber, R.; Davis, J.; Papakonstantinou, P. Stable Chitosan and Prussian Blue-Coated Laser-Induced Graphene Skin Sensor for the Electrochemical Detection of Hydrogen Peroxide in Sweat. ACS Appl. Nano Mater. 2023, 6, 10290–10302. [Google Scholar] [CrossRef]
  32. Rahman, M.M.; Lee, J.J. Electrochemical Dopamine Sensors Based on Graphene. J. Electrochem. Sci. Technol. 2019, 10, 185–195. [Google Scholar]
  33. Nankya, R.; Opar, D.O.; Jung, H. Mesoporous Graphene-Modified Electrode for Independent and Selective Detection of Dopamine in the Presence of High Concentration of Ascorbic Acid. Bull. Korean Chem. Soc. 2020, 41, 170–175. [Google Scholar] [CrossRef]
  34. Wang, Z.; Zhang, L.; Tian, Y. A Durable Non-Enzymatic Electrochemical Sensor for Monitoring H 2 O 2 in Rat Brain Microdialysates Based on One-Step Fabrication of Hydrogels. Analyst 2015, 140, 3788–3793. [Google Scholar] [CrossRef]
  35. Mahbubur Rahman, M.; Lee, J.-J. Sensitivity Control of Dopamine Detection by Conducting Poly(Thionine). Electrochem. Commun 2021, 125, 107005. [Google Scholar] [CrossRef]
  36. Rahman, M.M.; Lopa, N.S.; Kim, K.; Lee, J.-J. Selective Detection of L-Tyrosine in the Presence of Ascorbic Acid, Dopamine, and Uric Acid at Poly(Thionine)-Modified Glassy Carbon Electrode. J. Electroanal. Chem. 2015, 754, 87–93. [Google Scholar] [CrossRef]
  37. Sree, V.G.; Sohn, J.I.; Im, H. Pre-Anodized Graphite Pencil Electrode Coated with a Poly(Thionine) Film for Simultaneous Sensing of 3-Nitrophenol and 4-Nitrophenol in Environmental Water Samples. Sensors 2022, 22, 1151. [Google Scholar] [CrossRef]
  38. Rahman, M.M.; Lopa, N.S.; Ju, M.J.; Lee, J.-J. Highly Sensitive and Simultaneous Detection of Dopamine and Uric Acid at Graphene Nanoplatelet-Modified Fluorine-Doped Tin Oxide Electrode in the Presence of Ascorbic Acid. J. Electroanal. Chem. 2017, 792, 54–60. [Google Scholar] [CrossRef]
  39. Sangeetha, N.S.; Narayanan, S.S. A Novel Bimediator Amperometric Sensor for Electrocatalytic Oxidation of Gallic Acid and Reduction of Hydrogen Peroxide. Anal. Chim. Acta 2014, 828, 34–45. [Google Scholar] [CrossRef]
  40. Kumar, T.N.; Sivabalan, S.; Chandrasekaran, N.; Phani, K.L.N. Ferrocene-functionalized polydopamine as a novel redox matrix for H2O2 oxidation. J. Mater. Chem. B 2014, 2, 6081–6088. [Google Scholar] [CrossRef]
  41. Thenmozhi, K.; Narayanan, S.S. Carbon paste electrode with covalently immobilized thionine for electrochemical sensing of hydrogen peroxide. IOP Conf. Ser. Mater. Sci. Eng. 2017, 263, 022031. [Google Scholar] [CrossRef]
  42. Manikandan, P.N.; Dharuman, V. Electrochemical Simultaneous Sensing of Melatonin, Dopamine and Acetaminophen at Platinum Doped and Decorated Alpha Iron Oxide. Electroanalysis 2017, 29, 1524–1531. [Google Scholar] [CrossRef]
  43. Stephens, P.J.; Devlin, F.J.; Ashvar, C.S.; Bak, K.L.; Taylor, P.R.; Frisch, M.J. Comparison of Local, Nonlocal, and Hybrid Density Functionals Using Vibrational Absorption and Circular Dichroism Spectroscopy; American Chemical Society: Washington, DC, USA, 1996; pp. 105–113. [Google Scholar]
  44. Frisch, M.J.; Trucks, G.W.; Schlegel, H.B.; Scuseria, G.E.; Robb, M.A.; Cheeseman, J.R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G.A.; et al. Gaussian 09, Revision B.01; Gaussian, Inc.: Wallingford, CT, USA, 2013. [Google Scholar]
Biosensors 14 00448 sch001
Scheme 1. Electrochemical oxidation of DA and reduction of H2O2 on GC/TH−FcDA.
Scheme 1. Electrochemical oxidation of DA and reduction of H2O2 on GC/TH−FcDA.
Biosensors 14 00448 sch001
Biosensors 14 00448 g001
Figure 1. Schematic illustration of the preparation process of the thionine-linked ferrocene dicarboxylic acid-modified GC electrode.
Figure 1. Schematic illustration of the preparation process of the thionine-linked ferrocene dicarboxylic acid-modified GC electrode.
Biosensors 14 00448 g001
Biosensors 14 00448 g002
Figure 2. (A) FT-IR spectra of FcDA, TH, and TH-FcDA. (B) SEM images of TH-FcDA.
Figure 2. (A) FT-IR spectra of FcDA, TH, and TH-FcDA. (B) SEM images of TH-FcDA.
Biosensors 14 00448 g002
Biosensors 14 00448 g003
Figure 3. CV behavior of the GC (curve A), GC/FcDA (curve B), GC/TH (curve C), and GC/TH−FcDA (curve D) measured in 0.1 M PBS of pH 7.
Figure 3. CV behavior of the GC (curve A), GC/FcDA (curve B), GC/TH (curve C), and GC/TH−FcDA (curve D) measured in 0.1 M PBS of pH 7.
Biosensors 14 00448 g003
Biosensors 14 00448 g004
Figure 4. (A) CV and (B) DPV responses of GC/TH−FcDA in 0.1 M PBS (pH 7) at different concentrations of DA (A1 and B1) and H2O2 (A2 and B2).
Figure 4. (A) CV and (B) DPV responses of GC/TH−FcDA in 0.1 M PBS (pH 7) at different concentrations of DA (A1 and B1) and H2O2 (A2 and B2).
Biosensors 14 00448 g004
Biosensors 14 00448 g005
Figure 5. CV response of GC/TH−FcDA in 0.1 M PBS (pH 7) in the presence of (A1) 10 μM DA and (A2) 10 μM H2O2 at different scan rates (10–300 mV/s). DPV response of GC/TH−FcDA in 0.1 M PBS at different pHs (5–9) in the presence of (B1) 10 μM DA and (B2) 10 μM H2O2.
Figure 5. CV response of GC/TH−FcDA in 0.1 M PBS (pH 7) in the presence of (A1) 10 μM DA and (A2) 10 μM H2O2 at different scan rates (10–300 mV/s). DPV response of GC/TH−FcDA in 0.1 M PBS at different pHs (5–9) in the presence of (B1) 10 μM DA and (B2) 10 μM H2O2.
Biosensors 14 00448 g005
Biosensors 14 00448 g006
Figure 6. DPV response of 10 µM DA and H2O2 with 300 µM of different interference species in 0.1 M PBS pH 7.
Figure 6. DPV response of 10 µM DA and H2O2 with 300 µM of different interference species in 0.1 M PBS pH 7.
Biosensors 14 00448 g006
Biosensors 14 00448 g007
Figure 7. Electrostatic potential (ESP) map for TH-FcDA with DA and H2O2.
Figure 7. Electrostatic potential (ESP) map for TH-FcDA with DA and H2O2.
Biosensors 14 00448 g007
Table 1. Estimation of DA in diluted human urine samples. Estimation of H2O2 in milk samples.
Table 1. Estimation of DA in diluted human urine samples. Estimation of H2O2 in milk samples.
Sample
No		Spiked
(µM)		Found
(µM) *		Recovery (%) RSD
(%)
1109.98 ± 0.0299.80.2
25050.04 ± 0.04100.080.08
310099.89 ± 0.1199.890.11
Sample NoSpiked (µM)Found (µM) *Recovery (%)RSD (%)
154.96 ± 0.0499.20.8
21010.10 ± 0.101010.99
32020.09 ± 0.09100.450.44
* Average three-replicate measurements.
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Palinci Nagarajan, M.; Ramalingam, M.; Subbiah Arivuthilagam, I.; Paramaguru, V.; Rahman, M.M.; Park, J.; Asiam, F.K.; Lee, B.; Kim, K.P.; Lee, J.-J. A Novel Ferrocene-Linked Thionine as a Dual Redox Mediator for the Electrochemical Detection of Dopamine and Hydrogen Peroxide. Biosensors 2024, 14, 448. https://doi.org/10.3390/bios14090448

AMA Style

Palinci Nagarajan M, Ramalingam M, Subbiah Arivuthilagam I, Paramaguru V, Rahman MM, Park J, Asiam FK, Lee B, Kim KP, Lee J-J. A Novel Ferrocene-Linked Thionine as a Dual Redox Mediator for the Electrochemical Detection of Dopamine and Hydrogen Peroxide. Biosensors. 2024; 14(9):448. https://doi.org/10.3390/bios14090448

Chicago/Turabian Style

Palinci Nagarajan, Manikandan, Manikandan Ramalingam, Ilakeya Subbiah Arivuthilagam, Vishwa Paramaguru, Md. Mahbubur Rahman, Jongdeok Park, Francis Kwaku Asiam, Byungjik Lee, Kwang Pyo Kim, and Jae-Joon Lee. 2024. "A Novel Ferrocene-Linked Thionine as a Dual Redox Mediator for the Electrochemical Detection of Dopamine and Hydrogen Peroxide" Biosensors 14, no. 9: 448. https://doi.org/10.3390/bios14090448

APA Style

Palinci Nagarajan, M., Ramalingam, M., Subbiah Arivuthilagam, I., Paramaguru, V., Rahman, M. M., Park, J., Asiam, F. K., Lee, B., Kim, K. P., & Lee, J. -J. (2024). A Novel Ferrocene-Linked Thionine as a Dual Redox Mediator for the Electrochemical Detection of Dopamine and Hydrogen Peroxide. Biosensors, 14(9), 448. https://doi.org/10.3390/bios14090448

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop