key: cord-0739658-mn8zo1we
authors: Hareesha, N.; Manjunatha, J. G.
title: Electro-oxidation of formoterol fumarate on the surface of novel poly(thiazole yellow-G) layered multi-walled carbon nanotube paste electrode
date: 2021-06-17
journal: Sci Rep
DOI: 10.1038/s41598-021-92099-x
sha: 4de829b8beded7593d876126a22404f6c84a9a4d
doc_id: 739658
cord_uid: mn8zo1we

The current study explicates the electro-oxidation behavior of formoterol fumarate (FLFT) in the presence of uric acid (UA) on the surface of poly thiazole yellow-G (TY-G) layered multi-walled carbon nanotube paste electrode (MWCNTPE). The modified (Poly(TY-G)LMWCNTPE) and unmodified (MWCNTPE) electrode materials were characterized through electrochemical impedance spectroscopy (EIS), field emission scanning electron microscopy (FE-SEM), and cyclic voltammetry (CV) approaches. The characterization data confirms the good conducting and electrocatalytic nature with more electrochemical active sites on the Poly(TY-G)LMWCNTPE than MWCNTPE towards the FLFT analysis in the presence of UA. Poly(TY-G)LMWCNTPE easily separates the two drugs (FLFT and UA) even though they both have nearer oxidation peak potential. The electro-catalytic activity of the developed electrode is fast and clear for FLFT electro-oxidation in 0.2 M phosphate buffer (PB) of pH 6.5. The Poly(TY-G)LMWCNTPE offered a well-resolved peak with the highest electro-oxidation peak current at the peak potential of 0.538 V than MWCNTPE. The potential scan rate and oxidation peak growth time studies show the electrode reaction towards FLFT electro-oxidation is continued through a diffusion-controlled step. The variation of concentration of FLFT in the range from 0.2 to 1.5 µM (absence of UA) and 3.0 to 8.0 μM (presence of UA) provides a good linear relationship with increased peak current and a lower limit of detection (LOD) values of 0.0128 µM and 0.0129 µM, respectively. The prepared electrode gives a fine recovery for the detection of FLFT in the medicinal sample with acceptable repeatability, stability, and reproducibility.

Chemicals. FLFT (≥ 98%) was purchased from Sigma-Aldrich, India. UA (99%), TY-G (colorant ≥ 98%), MWCNTs (exterior diameter of 30-50 nm and length of 10-30 μm), and silicone oil (binder, 98%) were taken from Molychem, India. Na 2 HPO 4 ·2H 2 O (99.5%), NaH 2 PO 4 ·H 2 O (99%) and K 4 [Fe(CN) 6 ]·3H 2 O (98.5%) were bought from Himedia, India. KCl (99.5%) was procured from Nice Chemicals, India. All the used chemicals were of analytical reagent grade and used with no additional refinement. All the required solutions of known concentration were prepared by suspending them in a known amount of DW. 

60% of MWCNTs with 40% of silicone oil for around 20 min to get a fine paste. The developed paste was sorted into the vacant outlet (3.0 mm diameter) of a Teflon tube and smoothly rubbed on tissue paper to get a smooth surface.

The Poly(TY-G)LMWCNTPE was fabricated through the electro-polymerization process. Here, the electropolymerization of 1.0 mM TY-G in PB (0.2 M and 7.0 pH) was done on the external surface of MWCNTPE by cycling twenty CV segments having the potential range of − 0.60 to 1.40 V at the potential scan rate of 0.1 V/s. Later, the prepared electrode surface was rinsed carefully in DW to eliminate the unreacted monomer content.

Electrochemical setup. Electrochemical measurements were accomplished for 0.01 mM FLFT in 0.2 M PB. The working electrode (MWCNTPE and Poly(TY-G)LMWCNTPE) immersion length was set to 1.0 cm. Each voltammetric cycle was recorded in the potential gap from 0.2 to 0.9 V against Hg 2 Cl 2 at the potential scan rate of 0.1 V/s. This analysis was performed at 25 ± 2 °C.

Electrode material characterization. FE-SEM study. The electrode surface morphological study was carried out through the FE-SEM technique. FE-SEM pictures show the surface morphology of MWCNTPE and Poly(TY-G)LMWCNTPE. Figure 1a picturizes the arbitrarily fused thin and long root-shaped tubes with erratically distributed gaps on the exterior of the electrode. Also, those tubes and gaps didn't show any of the roofed films on their exterior (picture having 100 nm magnification), represents the surface of unmodified MWC-NTPE. Furthermore, Fig. 1b displays the FE-SEM morphology of modified Poly(TY-G)LMWCNTPE. Here, each MWCNTs and erratically distributed gaps are roofed by thin deposition of an electro-polymerized film of TY-G. Moreover, the width of Poly(TY-G)LMWCNTPE is improved with sufficient porosity after the electropolymerization of TY-G associate with MWCNT alone.

EIS study. EIS is the significant tool for the measurement of the interfacial charge transmission character of the electrode material components at the interface of the supporting electrolyte. The achieved results of EIS corresponding to MWCNTPE (Line 'b') and Poly(TY-G)LMWCNTPE (Line 'a') are presented using Nyquist plots (Inset Fig. 2 ). EIS experimentation was conducted in the supporting electrolyte KCl (0.1 M) having K 4 [Fe(CN) 6 ]·3H 2 O (1.0 mM) at 0.06 V of working potential and 0.005 V of amplitude in the frequency range of 1.0 Hz to 100 kHz. As from the Nyquist plots, MWCNTPE affords a larger semicircle as compared to Poly(TY-G) LMWCNTPE, which specifies that the electron transfer nature of the MWCNTs is substantially enhanced by the deposition of electro-polymerized TY-G. Figure 3 shows the cyclic voltammograms (CVs, at the potential scan rate of 0.1 V/s and potential width of − 0.2 to 0.6 V) for K 4 [Fe(CN) 6 ]·3H 2 O at the surface of MWCNTPE (Line 'a') and Poly(TY-G)LMWCNTPE (Line 'b') in optimum conditions. It can be displayed that, the Poly(TY-G)LMWCNTPE reveals a greater redox peak current in association with unmodified MWCNTPE. The electro-active area of MWCNTPE and Poly(TY-G)LMWCNTPE surfaces was computed on the application of following Randles-Sevcik's equation 29, 32 , Figure 4a displays the plot of oxidation peak current versus the number of electro-polymerization cycles. Here we observed the amplified oxidation peak current of FLFT from 5 to 10 cycles, on the other hand from 10 to 25 cycles the FLFT oxidation peak current gradually decreased, which is most feasibly due to the sufficient coverage of poly(TY-G) film on the accessible surface area of the MWCNTPE. Here, ten polymerization cycles show sufficient coverage on the surface of MWCNTPE and provide a faster rate of electron transfer with optimum peak current and the reduction of background current. As a result, ten polymerization cycles were chosen as optimum cycles for this experimentation. Figure 5b espied that the electro-oxidation peak potential of FLFT was transferred towards a shorter potential zone (negative shift) as the intensification of PB pH from 6.0 to 8.5. This incident specified that on the surface of Poly(TY-G)LMWCNTPE the electro-oxidation process of FLFT was a protonated electron transfer. Hence, the smaller number of protons participation supports the process of electro-oxidation with less current sensitivity at elevated PB pH (6.5 to 8.5). Fine linearity is observed between peak potential and PB pH values (plot of E pa v/s pH) and the fitted linear regression equation is as follows, where, 'R 2 ' is the regression coefficient. Here, the slope value 0.055 V/pH is most nearer to the theoretic value (0.059 V/pH), signifying that the electro-oxidation of FLFT associates with an alike number of protons and electrons on the surface of Poly(TY-G)LMWCNTPE. Supporting this, the number of protons that participated in the electro-oxidation reaction of FLFT was determined using the following Nernst relation, where, 'B' is the slope of Eq. (2), 'm' is the number of protons that participated in the FLFT oxidation reaction, 'n' is the number of electrons participating in the FLFT oxidation reaction and other terms (R, T and F) represents their standard physical values. The calculated value of the number of protons was found to be 1.86 ≈ 2. Furthermore, the pKa value of FLFT after the electro-oxidation was detected from the intersection point displayed in the plot of E pa v/s pH (Fig. 5b) . FLFT displays the pKa value of 7.0, indicating that the oxidation process most probably has taken place at the phenolic group of FLFT. From Fig. 5c , the electro-oxidation peak current of FLFT was very high at acidic pH of 6.5. These data are resolute that acidic pH (6.5) is most appropriate for the highly sensitive sensing of FLFT due to the strong interaction between Poly(TY-G)LMWCNTPE surface and FLFT. Therefore, the pH value of 6.5 was chosen as the optimal pH for this investigation.

Scan rate impact on peak potential and current of FLFT at Poly(TY-G)LMWCNTPE. The potential scan rate impact on the peak potential and current of FLFT at Poly(TY-G)LMWCNTPE deliver a key evi- www.nature.com/scientificreports/ dence for the electro-oxidation mechanism and the kinetic behaviors of the equipped electrode. The CV executions were documented and shown in Fig. 6a for 0.005 mM FLFT in PB (0.2 M and 6.5 pH) on Poly(TY-G) LMWCNTPE at variable potential scan rate in the range between 0.05 and 0.25 V/s, which displays the increased electro-oxidation peak currents and potentials of FLFT. The kinetic nature and dependability of the modified electrode towards the oxidation reaction of FLFT were verified based on acceptable linear plots of the log value of the electro-oxidation peak current versus log value of the potential scan rate (Fig. 6b) and electro-oxidation peak current versus square root value of the potential scan rate (Fig. 6c) . The obtained results are fitted in the following linear relations are as follows,

The slope (0.412 ± 0.023) of Eq. (4) and the R 2 value of Eq. (5) are very adjacent to the required theoretical values suggesting that the kinetic behavior of the electro-oxidation of FLFT on Poly(TY-G)LMWCNTPE has proceeded through a diffusion-controlled pathway 26 . The plot of electro-oxidation peak potential versus log value of the potential scan rate (Fig. 6d) provides fine linearity and the results are fitted in the following linear relation is as follows,

The number of electrons that participated in the electro-oxidation reaction of FLFT was confirmed using the slope value (0.045 ± 0.002) of Eq. (6) www.nature.com/scientificreports/ where, 'E pa/2 ' is the electro-oxidation peak potential at the half peak current of FLFT, 'α' is the electrochemical charge transfer coefficient, 'n' is the number of involved electrons, 'υ' is the applied potential scan rate, 'k 0' is the electrochemical heterogeneous rate constant, and other terms (R, T, and F) represents their standard physical values. The premeditated value of a number of electrons was found to be 2.26 ≈ 2. The possible electro-oxidation reaction of FLFT is shown in Scheme 2. The electrochemical heterogeneous rate constant for the oxidation of FLFT was calculated by deducing Eq. (7) and the premeditated value of 'k 0 ' was found to be 1.818 s −1 .

The electrochemical surface coverage concentration (Г) of FLFT at the surface of MWCNTPE and Poly(TY-G)LMWCNTPE is calculated using the following relation 36 , where, 'Q' is the integrated electrical charge of the oxidation peak. The calculated value of electrochemical surface coverage concentration of FLFT for the MWCNTPE was 1.286 ÅM/cm 2 and for the Poly(TY-G)LMWCNTPE was 2.802 ÅM/cm 2 . This consequence is the other key factor for the high electro-oxidation peak current of FLFT at Poly(TY-G)LMWCNTPE.

Oxidation peak growth time. The influence of peak growth time is the prominent tool to disclose the maximum accumulation point (higher peak current) of FLFT on the surface of Poly(TY-G)LMWCNTPE with its kinetic behavior at the variable growth time. The peak growth time has been optimized using the DPV experimentation by altering the growth time within the range from 0 to 100 s for 0.005 mM FLFT in PB (0.2 M and 6.5 pH) and the outcomes are presented in Fig. 7 . Here the observation suggests that the growth time of 20 s (exists at the second position) provides the maximum peak current than other growth times (0 s, 40 s, 60 s, 80 s, and 100 s). This consequence is most probably due to the effect of saturation followed by diffusion kinetic behavior In the presence of FLFT, a fine electro-oxidation peak is viewed at the potential of 0.514 V as compared to bare MWC-NTPE, which shows a less enhanced electro-oxidation peak at the potential of 0.569 V. Furthermore, modified electrode provides elevated electro-oxidation peak current and lesser electro-oxidation peak potential for FLFT than the bare MWCNTPE delivers an exceptional electro-catalytic potential. This shift in both the current and potential at the modified electrode is most conceivably due to the various interactions between FLFT molecules and poly(TY-G), such as π-π covalent, hydrogen bonding, electrostatic, and dipole-dipole interactions, shown in Scheme 3 37 . Furthermore, in the absence of FLFT in PB (0.2 M and 6.5 pH), the surface of Poly(TY-G)LMWC-NTPE didn't show any electro-catalytic oxidation response.

Calibration plot for FLFT with and without UA. The detection capability of the prepared Poly(TY-G) LMWCNTPE towards FLFT was verified based on the concentration variation method in the presence and absence of UA using the DPV technique (Inset Fig. 9 ). Figure 9a shows the documented differential pulse voltammograms (DPVs) of different concentrations of FLFT in the range from 0.2 to 3.0 μM in PB (0.2 M and pH 6.5) at the surface of Poly(TY-G)LMWCNTPE. Here, the electro-oxidation peak current of FLFT enhanced as the concentration of FLFT increased (Fig. 9b) ; also, the preliminary concentration range 0.2 to 1.5 μM gives a finer linear correlation and the achieved results are fitted in the following linear relation is as follows, Table 1 11, 12, 14, 26, 27 , proposing that the Poly(TY-G)LMWCNTPE provides the lowest/very nearer LOD.

The simultaneous examination of FLFT and UA in PB (0.2 M and pH 6.5) was performed using the DPV technique on the surface of Poly(TY-G)LMWCNTPE (Line 'b') and MWCNTPE (Line 'a') (Fig. 9c) . The line 'b' discloses well and distinctive electro-oxidation peaks resultant to UA and FLFT at the electro-oxidation peak www.nature.com/scientificreports/ The determined LOD value was found to be 0.0129 µM, suggesting that the Poly(TY-G)LMWCNTPE delivers almost nearer LOD value even in the presence of interfering UA molecule. Hence, the prepared electrode is almost free from interference.

towards the electro-oxidation of FLFT was examined via the DPV method in the presence of some biologically available species (metal ions and organic molecules, each having a concentration of 1.0 mM). Figure 10 shows the graph of different chemical species (such as Ag + , Ba 2+ , Hg 2+ , Ca 2+ , Fe 2+ , K + , Na + , dopamine (DA), tryptophan (THR), tyrosine (TY), and curcumin (CU)) versus the % of electro-oxidation potential variation of FLFT. Here we observe only ± 5.0% of potential variation at the oxidation of FLFT, suggesting that Poly(TY-G)LMWCNTPE shows acceptable compatibility in presence of the above-mentioned chemical species. But in the case of electrooxidation peak current, the compatibility was little vary compared to the base peak current.

In supplement to the aforesaid studies, the Poly(TY-G)LMWC-NTPE sensing capability towards FLFT was determined in a medicinal sample based on the standard addition approach. As from Table 2 www.nature.com/scientificreports/ pH 6.5) via the DPV method by quantifying the current response at the Poly(TY-G)LMWCNTPE (initial current and current after one day). The calculated value of the percentage of degradation gives 90.72% of retained peak current affords a first-class electrode storage stability.

In this effort, the Poly(TY-G)LMWCNTPE and MWCNTPE were prepared simplistically and economically for the detection of FLFT in PB using the CV and DPV methodologies. The modification of poly(TY-G) on MWCNTPE was confirmed by FE-SEM, EIS, CV, electro-active surface area, and surface concentration measurements. The enhanced active surface area of the Poly(TY-G)LMWCNTPE improves the rate of electron and proton transfer during the electro-oxidation of FLFT. The CV outcomes validate different interactions between FLFT molecules and Poly(TY-G)LMWCNTPE, which significantly shifts the peak current to a higher level and peak potential to a lower level in the oxidation of FLFT. The impact of the potential scan rate study reveals the heterogeneous rate constant and diffusion kinetics (also supported by the effect of accumulation) with the transfer of 2 e − and 2 H + in the electro-oxidation of FLFT. The supporting electrolyte pH study shows that the proportion of electron and proton transfer in the electro-oxidation of FLFT is equivalent (1:1). The Poly(TY-G)LMWCNTPE implicates better electrochemical behavior (in presence and absence of UA) with fine linear response, superior sensitivity with lower LOD, first-class selectivity (in the presence of different chemical species), reproducibility, repeatability, and good storage stability. Additionally, the modified Poly(TY-G)LMWCNTPE provides excellent recovery (90.64 to 96.70%) for FLFT in a medicinal sample. All these results concluded that the Poly(TY-G) LMWCNTPE is a more optimistic and potent sensing tool in the analysis of many other electro-active molecules and medicinal samples in vision of its superior active surface area and electrocatalytic activity. 

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We thankfully acknowledge the financial support from the Department of Science and Technology (DST), India for the INSPIRE Fellowship (Registration Number: IF180479).

N.H.: Conceive and designed the work, contributed to the data collection and performed the data analysis, interpretation and graphical presentation, contributed to critically review the article, contributed to the literature survey, contributed to the drafting of the article and the final approval of the submitted version. J.G.M.: Conceive and designed the work, contributed to the data collection and performed the data analysis, and interpretation, contributed to critically review the article, contributed to the drafting of the article and the final approval of the submitted version.

The authors declare no competing interests.

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