The Influence of the Nature of the Polymer Incorporating the Same A3B Multifunctional Porphyrin on the Optical or Electrical Capacity to Recognize Procaine

The multifunctionality of an A3B mixed-substituted porphyrin, namely 5-(4-carboxyphenyl)-10,15,20-tris(4-methylphenyl)porphyrin (5-COOH-3MPP), was proven due to its capacity to detect procaine by different methods, depending on the polymer matrix in which it is incorporated. The hybrid nanomaterial containing k-carrageenan and AuNPs (5-COOH-3MPP-k-carrageenan-AuNPs) was able to optically detect procaine in the concentration range from 5.76 × 10−6 M to 2.75 × 10−7 M, with a limit of detection (LOD) of 1.33 × 10−7 M. This method for the detection of procaine gave complementary results to the potentiometric one, which uses 5-COOH-3MPP as an electroactive material incorporated in a polyvinylchloride (PVC) membrane plasticized with o-NPOE. The detected concentration range by this ion-selective membrane electrode is wider (enlarged in the field of higher concentrations from 10−2 to 10−6 M), linearly dependent with a 53.88 mV/decade slope, possesses a detection limit of 7 × 10−7 M, a response time of 60 s, and has a certified stability for a working period of six weeks.


Introduction
Procaine is a well-known local anesthetic used since its synthesis in 1905 for oral medicine [1] and for veterinary use [2].In addition, procaine has been extensively studied, and it was discovered that this molecule displayed beneficial effects on the functions of cells as an antioxidant, cytoprotective, and anti-inflammatory agent [3].The radioprotective effect of procaine on human lymphocytes after ionizing radiation has been recently documented [4].All these results justify the use of procaine-based drugs for the prophylaxis and treatment of metabolic and degenerative processes that occur in elderly people.Knowing that the administered concentrations of procaine in local anesthesia are 4.23 × 10 −4 M and the highest safety limit is 4.23 × 10 −2 M in general anesthesia [5], the two proposed methods presented in this work are both highly suited for human medical monitoring.Thus, the detection and precise quantitation of procaine are of ongoing research interest.Some of the recently reported detection methods, the detected concentration domain, and the limits of detection are summarized in Table 1.
Table 1.The relevant methods, materials, full concentration range, and limits of detection (LODs) in procaine quantification that have been reported in the last 5 years.

Fully Linear Detected Concentration Range [M] LOD [M]
Ref.
New genosensors based on electrochemical markers made from Co(II/III)-metalloporphyrin-modified DNA attached to AuNPs/AgNPs were able to specifically detect DNA sequences in the femtomolar range [18].Another DNA detection method using AuNPs employs fluorescence microscopy [19], which can discriminate between the processes of DNA immobilization, hybridization, or degradation.
An overview regarding the use of polymer-porphyrin composite materials in sensor design is presented in Table S1.The listed materials are able to detect biologically active compounds through various methods.
In the last few years, our group has focused on finding diverse applications by using the same porphyrin structure.In this respect, a mixed substituted A 3 B porphyrin, namely, 5-(4-carboxyphenyl)-10,15,20-tris(4-methylphenyl)porphyrin (5-COOH-3MPP) presented in Figure 1a, was successfully designed and applied for CO 2 capture [25] as well as a corrosion inhibitor for steel in acid media [26].
An overview regarding the use of polymer-porphyrin composite materials in sensor design is presented in Table S1.The listed materials are able to detect biologically active compounds through various methods.
In the last few years, our group has focused on finding diverse applications by using the same porphyrin structure.In this respect, a mixed substituted A3B porphyrin, namely, 5-(4-carboxyphenyl)-10,15,20-tris(4-methylphenyl)porphyrin (5-COOH-3MPP) presented in Figure 1a, was successfully designed and applied for CO2 capture [25] as well as a corrosion inhibitor for steel in acid media [26].
The aim of this work is to emphasize the response versatility of this A3B porphyrin structure, which contains a carboxylic functional group, in facilitating procaine recognition/detection by means of physical-chemical interactions with NH2 groups present in the molecule of the analyte.The same porphyrin structure was sensitive in both optical and potentiometric detection by changing the polymer in which it was incorporated.Figure 1b,c depict the structures of the used polymers.Figure 1d presents the structure of the investigated analyte, namely procaine.A3B porphyrin, when used as a sensing material, demonstrated to be multifunctional, proving its ability to detect procaine potentiometrically when incorporated in a polyvinylchloride (PVC) membrane as well as optically when involved in a hybrid nanomaterial containing k-carrageenan and AuNPs that amplifies its optical properties.The intended purpose of the reported research is to propose cost-effective and simple methods to detect procaine.
A diagram portraying our main targets: the synthesis of porphyrin, the obtainment of 5-COOH-3MPP-k-carrageenan-AuNPs nanomaterials, and the fabrication of procaine ion-selective membranes, together with their further sensing applications, is drawn in Fig- ure 2. The aim of this work is to emphasize the response versatility of this A 3 B porphyrin structure, which contains a carboxylic functional group, in facilitating procaine recognition/detection by means of physical-chemical interactions with NH 2 groups present in the molecule of the analyte.The same porphyrin structure was sensitive in both optical and potentiometric detection by changing the polymer in which it was incorporated.Figure 1b,c depict the structures of the used polymers.Figure 1d presents the structure of the investigated analyte, namely procaine.
A 3 B porphyrin, when used as a sensing material, demonstrated to be multifunctional, proving its ability to detect procaine potentiometrically when incorporated in a polyvinylchloride (PVC) membrane as well as optically when involved in a hybrid nanomaterial containing k-carrageenan and AuNPs that amplifies its optical properties.The intended purpose of the reported research is to propose cost-effective and simple methods to detect procaine.
A diagram portraying our main targets: the synthesis of porphyrin, the obtainment of 5-COOH-3MPP-k-carrageenan-AuNPs nanomaterials, and the fabrication of procaine ion-selective membranes, together with their further sensing applications, is drawn in Figure 2.
Equation ( 1), used to calculate the value of the LOD, is as follows: where σ is the standard deviation of the blank measurement and K is the slope between the absorbance and the analyte concentration [27].Equation ( 2) was used to obtain the sensitivity value that represents the smallest amount of substance in a sample that can be accurately measured by an assay [28].
where ∆C represents the difference in the procaine concentration in two successive samples expressed in micromolar units, and ∆I is the difference between intensities of absorption in the same two samples.
Equation ( 1), used to calculate the value of the LOD, is as follows: where σ is the standard deviation of the blank measurement and K is the slope between the absorbance and the analyte concentration [27].Equation ( 2) was used to obtain the sensitivity value that represents the smallest amount of substance in a sample that can be accurately measured by an assay [28].
where ∆C represents the difference in the procaine concentration in two successive samples expressed in micromolar units, and ∆I is the difference between intensities of absorption in the same two samples.

The Effects of Interferent Species in the Optical Detection of Procaine
In order to confirm the selectivity of detection for procaine, tests for potential interferent species were performed, selecting NaCl, KI, Ascorbic acid, Lactic acid, Ca lactate, Ca gluconate, Na acetate, glucose, urea, Na salicilate, that are the most probably present in the medical samples.The overlapped UV-vis spectra are depicted in Figure 4a.The control sample (Ref) consists of acidulated 5-COOH-3MPP-k-carrageenan-AuNPs in a DMF-water system in which the concentration of procaine is c = 1 × 10 −6 M. The interferent solutions contain the same concentration of procaine as in Ref and a ten-fold higher concentration of each interferent species.It can be concluded that the only significant interferent species is produced by iodide anion (<5% deviation), which is represented in the 3D plot in Figure 4b.The average percentage errors given by each of the interfering compounds are drawn in Figure 5.

The Effects of Interferent Species in the Optical Detection of Procaine
In order to confirm the selectivity of detection for procaine, tests for potential interferent species were performed, selecting NaCl, KI, Ascorbic acid, Lactic acid, Ca lactate, Ca gluconate, Na acetate, glucose, urea, Na salicilate, that are the most probably present in the medical samples.The overlapped UV-vis spectra are depicted in Figure 4a.The control sample (Ref) consists of acidulated 5-COOH-3MPP-k-carrageenan-AuNPs in a DMF-water system in which the concentration of procaine is c = 1 × 10 −6 M. The interferent solutions contain the same concentration of procaine as in Ref and a ten-fold higher concentration of each interferent species.It can be concluded that the only significant interferent species is produced by iodide anion (<5% deviation), which is represented in the 3D plot in Figure 4b.The average percentage errors given by each of the interfering compounds are drawn in Figure 5.

FT-IR Analysis for Presuming the Mechanism of Detection
The FT-IR spectra for procaine and k-carrageenan are well-known [29,30], and the spectrum for 5-COOH-3MPP was completely presented and characterized in our previous paper [25].The FT-IR spectra of these enumerated compounds are comparatively presented in Figure 6 with the spectrum of the hybrid material 5-COOH-3MPP-kcarrageenan-AuNPs after being exposed to procaine in order to reveal the structural modifications during the detection process.

FT-IR Analysis for Presuming the Mechanism of Detection
The FT-IR spectra for procaine and k-carrageenan are well-known [29,30], and the spectrum for 5-COOH-3MPP was completely presented and characterized in our previous paper [25].The FT-IR spectra of these enumerated compounds are comparatively presented in Figure 6 with the spectrum of the hybrid material 5-COOH-3MPP-kcarrageenan-AuNPs after being exposed to procaine in order to reveal the structural modifications during the detection process.

FT-IR Analysis for Presuming the Mechanism of Detection
The FT-IR spectra for procaine and k-carrageenan are well-known [29,30], and the spectrum for 5-COOH-3MPP was completely presented and characterized in our previous paper [25].The FT-IR spectra of these enumerated compounds are comparatively presented in Figure 6 with the spectrum of the hybrid material 5-COOH-3MPP-k-carrageenan-AuNPs after being exposed to procaine in order to reveal the structural modifications during the detection process.
The composite nanomaterial 5-COOH-3MPP-k-carrageenan-AuNPs, after exposure to procaine, reveals the characteristic peaks for each component and the new ones formed due to interaction with procaine in the FT-IR spectrum.The peak at 462 cm −1 can be presumed to be indicative of the bond between gold and the carbon atom (νC-Au) [31]; the peak located at 856 cm −1 reveals the νC-O-S bond from k-carrageenan; the characteristic peak at 1024 cm −1 indicates a pyran ring in polysaccharides [32,33]; and the signal at 1072 cm −1 is indicative of the νC-O-C glycosidic bond from k-carrageenan [32].The porphyrin also gives specific signals at 1181 cm −1 representing the (δC-Hpyrrole) bond.Another peak at 1267 cm −1 is assigned to the νC-O bond in porphyrin but overlaps with the νO=S=O bond in k-carageenan.Other peaks that confirm the presence of porphyrin are 1467 cm −1 (νC=N).The most intense signal around 1660 cm −1 represents the (νC=C) vibration in porphyrin.
The presence of k-carrageenan is confirmed by the peak at 2780 cm −1 , indicative of the νC-H bond in a polymer [34,35].The abundant C-H bonds present large stretching vibrations at 2988 cm −1 [36], and the many OH groups are confirmed by the widened peak located at 3426 cm −1 , which is typical for intrabackbone H-bonds.The composite nanomaterial 5-COOH-3MPP-k-carrageenan-AuNPs, after exposure to procaine, reveals the characteristic peaks for each component and the new ones formed due to interaction with procaine in the FT-IR spectrum.The peak at 462 cm −1 can be presumed to be indicative of the bond between gold and the carbon atom (νC-Au) [31]; the peak located at 856 cm −1 reveals the νC-O-S bond from k-carrageenan; the characteristic peak at 1024 cm −1 indicates a pyran ring in polysaccharides [32,33]; and the signal at 1072 cm −1 is indicative of the νC-O-C glycosidic bond from k-carrageenan [32].The porphyrin also gives specific signals at 1181 cm −1 representing the (δC-Hpyrrole) bond.Another peak at 1267 cm −1 is assigned to the νC-O bond in porphyrin but overlaps with the νO=S=O bond in k-carageenan.Other peaks that confirm the presence of porphyrin are 1467 cm −1 (νC=N).The most intense signal around 1660 cm −1 represents the (νC=C) vibration in porphyrin.
The presence of k-carrageenan is confirmed by the peak at 2780 cm −1 , indicative of the νC-H bond in a polymer [34,35].The abundant C-H bonds present large stretching vibrations at 2988 cm −1 [36], and the many OH groups are confirmed by the widened peak located at 3426 cm −1 , which is typical for intrabackbone H-bonds.

Presumed Mechanism of Optical Detection
Two new and distinctive peaks were clearly formed after the interaction with procaine at 1626 cm −1 and 1722 cm −1 , as presented in magnified detail in Figure 6.The first peak is assigned to porphyrin diminished νC=O bonding strength after linking to procaine, and the second one represents the signal for negatively charged nitrogen from procaine during electrostatic interaction with positively charged hydrogen from the COOH group grafted on the porphyrin (a chemical relationship between the donating amino group and the accepting carboxyl group) [37].

Presumed Mechanism of Optical Detection
Two new and distinctive peaks were clearly formed after the interaction with procaine at 1626 cm −1 and 1722 cm −1 , as presented in magnified detail in Figure 6.The first peak is assigned to porphyrin diminished νC=O bonding strength after linking to procaine, and the second one represents the signal for negatively charged nitrogen from procaine during electrostatic interaction with positively charged hydrogen from the COOH group grafted on the porphyrin (a chemical relationship between the donating amino group and the accepting carboxyl group) [37].
The surface of the silica plate is unevenly covered with large zig-zag aggregates, surrounded by spherical gold nanoparticles.The high value of the rugosity Sa (5464 nm) of the complex mixture can explain the facilitated access of the procaine molecules to the recognition sites of the 5-COOH-3MPP-k-carrageenan-AuNPs nanomaterial.The surface of the silica plate is unevenly covered with large zig-zag aggregates, surrounded by spherical gold nanoparticles.The high value of the rugosity Sa (5464 nm) of the complex mixture can explain the facilitated access of the procaine molecules to the recognition sites of the 5-COOH-3MPP-k-carrageenan-AuNPs nanomaterial.

AFM of Composite Nanomaterial 5-COOH-3MPP-k-Carrageenan-AuNPs after Exposure to Procaine
The atomic force microscopy images for 5-COOH-3MPP-k-carrageenan-AuNPs after exposure to procaine reveal equilateral triangular-shaped particles with sides ranging narrowly from 19 to 27 nm preponderantly organized into J-type aggregates and unevenly distributed on the surface, as shown in Figure 8.
H-type aggregates are also confirmed by a deflection scan.Large voids are also present, with depths around 14.4 nm and 61.25 nm.

AFM of Composite Nanomaterial 5-COOH-3MPP-k-Carrageenan-AuNPs after Exposure to Procaine
The atomic force microscopy images for 5-COOH-3MPP-k-carrageenan-AuNPs after exposure to procaine reveal equilateral triangular-shaped particles with sides ranging narrowly from 19 to 27 nm preponderantly organized into J-type aggregates and unevenly distributed on the surface, as shown in Figure 8.The surface of the silica plate is unevenly covered with large zig-zag aggregates, surrounded by spherical gold nanoparticles.The high value of the rugosity Sa (5464 nm) of the complex mixture can explain the facilitated access of the procaine molecules to the recognition sites of the 5-COOH-3MPP-k-carrageenan-AuNPs nanomaterial.

AFM of Composite Nanomaterial 5-COOH-3MPP-k-Carrageenan-AuNPs after Exposure to Procaine
The atomic force microscopy images for 5-COOH-3MPP-k-carrageenan-AuNPs after exposure to procaine reveal equilateral triangular-shaped particles with sides ranging narrowly from 19 to 27 nm preponderantly organized into J-type aggregates and unevenly distributed on the surface, as shown in Figure 8.
H-type aggregates are also confirmed by a deflection scan.Large voids are also present, with depths around 14.4 nm and 61.25 nm.
Figure 8.A 2D image of 5-COOH-3MPP-k-carrageenan-AuNPs material after exposure to procaine with 3D detail of the same material confirming both H-and J-type aggregation and the non-uniform surface with large voids.H-type aggregates are also confirmed by a deflection scan.Large voids are also present, with depths around 14.4 nm and 61.25 nm.

Potentiometric Detection of Procaine
The potentiometric response to procaine of the three sensors having the membrane composition presented in Table S2 is shown in Figures S1-S3.
As highlighted in Figures S1-S3, all the sensors have a potentiometric response to procaine in different areas of concentration.
The values of each sensor slope and the linear range are comparatively presented in Figure 9.
The selectivity coefficients, calculated by the separate solution method [38] or 10 −3 M of procaine and interfering solutions, are also presented comparatively in Table 2.The potentiometric response to procaine of the three sensors having the membrane composition presented in Table S2 is shown in Figures S1-S3.
As highlighted in Figures S1-S3, all the sensors have a potentiometric response to procaine in different areas of concentration.
The values of each sensor slope and the linear range are comparatively presented in Figure 9.The selectivity coefficients, calculated by the separate solution method [38] or 10 −3 M of procaine and interfering solutions, are also presented comparatively in Table 2.As shown in Figure 9 and Table 2, the sensors are all procaine-selective, with good values of the selectivity coefficients.However, the best potentiometric results were obtained for sensor 2, with the membrane plasticized with o-NPOE.The sensor has a potentiometric answer to procaine in the range 10 −2 -10 −6 M, with a slope of 53.88 mV/decade, very good values of the selectivity coefficients, and a detection limit of 7 × 10 −7 M.
For the optimum composition of the sensor membrane, the response time of procaine solutions varying from 10 −4 M to 10 −3 M was 60 s, as presented in Figure 10.
The sensor was used for a period of 6 weeks without significant changes in the slope values, as depicted in Figure 11.As shown in Figure 9 and Table 2, the sensors are all procaine-selective, with good values of the selectivity coefficients.However, the best potentiometric results were obtained for sensor 2, with the membrane plasticized with o-NPOE.The sensor has a potentiometric answer to procaine in the range 10 −2 -10 −6 M, with a slope of 53.88 mV/decade, very good values of the selectivity coefficients, and a detection limit of 7 × 10 −7 M.
For the optimum composition of the sensor membrane, the response time of procaine solutions varying from 10 −4 M to 10 −3 M was 60 s, as presented in Figure 10.The sensor was used for a period of 6 weeks without significant changes in the slope values, as depicted in Figure 11.The magnitude of the dielectric constant of each plasticizer (o-NPOE, ε = 24; DOP, ε = 7; DOS, ε = 4) has important effects on membrane behavior.The higher polar o-NPOE plasticizer favors porphyrin aggregation in the membrane due to its -COOH hydrophilic function, and this behavior explains the well-fitted value of the Nernstian slope.The free active centers of the membrane are, in this way, more available for binding procaine by electrostatic interactions.This explanation is also supported by the AFM images (Figure 8) because triangular prismatic aggregation of porphyrins is usually found in more polar environments [39,40].

Analytical Applications
Sensor 2 was applied for the detection of procaine from procaine ampoules (pharmaceutically available) and analytically prepared laboratory synthetic samples, with very well-fitted results.The analytical test results are presented in Table 3. Table 3. Analytical applications of the procaine-selective sensor.

Samples
Potentiometric Detection (mg ± S a ) Amount (mg) Procaine ampoules 98 ± 1 100 Synthetic samples 197 ± 1.4 200 a An average of determinations on three samples of the same origin.Proposed Mechanism for the Potentiometric Detection of Procaine

Materials and Methods
The magnitude of the dielectric constant of each plasticizer (o-NPOE, ε = 24; DOP, ε = 7; DOS, ε = 4) has important effects on membrane behavior.The higher polar o-NPOE plasticizer favors porphyrin aggregation in the membrane due to its -COOH hydrophilic function, and this behavior explains the well-fitted value of the Nernstian slope.The free active centers of the membrane are, in this way, more available for binding procaine by electrostatic interactions.This explanation is also supported by the AFM images (Figure 8) because triangular prismatic aggregation of porphyrins is usually found in more polar environments [39,40].

Analytical Applications
Sensor 2 was applied for the detection of procaine from procaine ampoules (pharmaceutically available) and analytically prepared laboratory synthetic samples, with very well-fitted results.The analytical test results are presented in Table 3.
Table 3. Analytical applications of the procaine-selective sensor.

Samples
Potentiometric Detection (mg ± S a ) Amount (mg) Procaine ampoules 98 ± 1 100 Synthetic samples 197 ± 1.4 200 a An average of determinations on three samples of the same origin.
The purpose of the creation of this nanomaterial is the enlargement of the absorption domain and the amplification of the detection capabilities of the A 3 B porphyrin.

Polymeric Membrane Obtaining and Measurements
Three different procaine-selective membranes, with the composition presented in Table S2, have been prepared.The membrane composition includes porphyrin (5-COOH-3MPP), poly(vinyl)chloride (PVC) of high molecular weight, and either dioctylphtalate (DOP), bis(2-ethylhexyl), sebacate (DOS), or o-nitrophenyloctylether (o-NPOE) as plasticizers having different dielectric constants.Sodium tetraphenylborate (NaTPB) was used in each membrane as an additive (20% mol.relative to the ionophore).Tetrahydrofurane (THF) was used as a solvent for the membrane components.All the reagents were analytically pure.
The ingredients were mixed together and stirred for about 15-20 min to be dissolved.The obtained solutions were transferred to glass plates for the complete evaporation of THF at room temperature until flexible membranes with a thickness of around 15 µm obtained.Afterward, round pieces of membranes 8 mm in diameter were cut and fixed to Fluka electrode bodies.
The potentiometric measurements were conducted using a HI 223 pH/mV at room temperature, and the cell composition is: Hg|Hg 2 Cl 2 |bridge electrolyte|sample|ion-selective membrane|0.01M KCl|AgCl, Ag.
All the sensors were conditioned for 24 h in a 10 −3 M procaine hydrochloride solution.The procaine solutions, from 10 −2 -10 −7 M, were prepared by weighing the proper amount and dissolving it in 2-(N-morpholino)ethanesulfonic acid (MES) buffer of pH = 5.5 (to establish the suitable conditions of water swallowing by the membrane) [43].
All the interfering solutions, 10 −3 M, were prepared in the same way.The selectivity coefficients were calculated by a separate solution method using the theoretical value of the slope of 59.2 mV/decade.The detection limit of the sensor was determined at the intersection of the extrapolated linear range with the lowest concentration level segment of the calibration plot.
For the analytical applications, synthetic samples and pharmaceutical products were prepared as described before.

Apparatus
The recording of UV-vis spectra in 1 cm wide quartz cuvettes was performed on a V-650-JASCO spectrometer (Pfungstadt, Germany).A pH meter, the HI 98,100 Checker Plus from Hanna Instruments (Woonsocket, RI, USA), provided the pH values.Atomic force microscopy (AFM) images were obtained by deposition of samples on pure silica plates and visualization on a Nanosurf ® EasyScan 2 Advanced Research AFM microscope (Liestal, Switzerland) equipped with a piezoelectric ceramic cantilever.All FT-IR spectra were registered from KBr pellets in the range 4000-400 cm −1 on a JASCO 430 FT-IR (Hachioji, Tokyo, Japan) spectrometer.

Conclusions
The same A 3 B porphyrin structure was sensitive in both optical and potentiometric detection, changing the nature of the polymer in which it was incorporated.A hybrid nanomaterial containing 5-COOH-3MPP, k-carrageenan, and AuNPs was capable of optically detecting procaine in the concentration range from 5.76 × 10 −6 M to 2.75 × 10 −7 M, with a limit of detection (LOD) of 1.33 × 10 −7 M, due to a chemical interaction between the donating amino groups from procaine and the accepting carboxyl group from porphyrin.The ion-selective electrode consisting of a PVC membrane plasticized with o-NPOE and the A3B porphyrin gave a complementary wider detected concentration domain in comparison with the optical method, from 10 −2 -10 −6 M, a LOD of 7 × 10 −7 M, a Nernstian slope of 53.88 mV/decade, a response time of 60 s, and stability over six weeks.The higher polar o-NPOE plasticizer favors porphyrin aggregation in the membrane, thus increasing the

Figure 2 .
Figure 2. A diagram detailing the synthesis of porphyrin, formulation of 5-COOH-3MPP-k-carrageenan-AuNPs nanomaterial, fabrication of procaine ion-selective membrane, and final applications in potentiometric and optical sensing.

Figure 2 .
Figure 2. A diagram detailing the synthesis of porphyrin, formulation of 5-COOH-3MPP-kcarrageenan-AuNPs nanomaterial, fabrication of procaine ion-selective membrane, and final applications in potentiometric and optical sensing.

Figure 3 .
Figure 3. (a) The linear dependence between the absorption intensity read at 650 nm and the procaine concentration; (b) The detail of UV-vis spectra during the optical detection of procaine by 5-COOH-3MPP-k-caragenan-AuNPs composite material in the field of trace concentrations.

Figure 3 .
Figure 3. (a) The linear dependence between the absorption intensity read at 650 nm and the procaine concentration; (b) The detail of UV-vis spectra during the optical detection of procaine by 5-COOH-3MPP-k-caragenan-AuNPs composite material in the field of trace concentrations.

Figure 4 .
Figure 4. (a) The overlapped UV-vis spectra showing the insignificant effects of interferent species (excepting the moderate effect of KI) and confirming the selectivity of procaine detection.(b) 3D plot representing the absorption intensity differences induced by interferent compounds at λ = 650 nm.

Figure 5 .
Figure 5.A representation of the average percentage error induced by several interference compounds (in concentrations exceeding 10 times the procaine concentration).

Figure 4 .Figure 4 .
Figure 4. (a) The overlapped UV-vis spectra showing the insignificant effects of interferent species (excepting the moderate effect of KI) and confirming the selectivity of procaine detection.(b) 3D plot representing the absorption intensity differences induced by interferent compounds at λ = 650 nm.

Figure 5 .
Figure 5.A representation of the average percentage error induced by several interference compounds (in concentrations exceeding 10 times the procaine concentration).

Figure 5 .
Figure 5.A representation of the average percentage error induced by several interference compounds (in concentrations exceeding 10 times the procaine concentration).

Figure 8 .
Figure 8.A 2D image of 5-COOH-3MPP-k-carrageenan-AuNPs material after exposure to procaine with 3D detail of the same material confirming both H-and J-type aggregation and the non-uniform surface with large voids.

Figure 8 .
Figure 8.A 2D image of 5-COOH-3MPP-k-carrageenan-AuNPs material after exposure to procaine with 3D detail of the same material confirming both H-and J-type aggregation and the non-uniform surface with large voids.

Figure 9 .
Figure 9.The linear range and slope for the three designed sensors plasticized differently with o-NPOE (purple line), DOS (green line), and DOP (red line).

Figure 9 .
Figure 9.The linear range and slope for the three designed sensors plasticized differently with o-NPOE (purple line), DOS (green line), and DOP (red line).

15 Figure 10 .
Figure 10.The response time of the membrane.Figure 10.The response time of the membrane.

Figure 10 .
Figure 10.The response time of the membrane.Figure 10.The response time of the membrane.

Figure 10 .
Figure 10.The response time of the membrane.

Figure 11 .
Figure 11.Stability in time (weeks) of the best-performing sensor.Proposed Mechanism for the Potentiometric Detection of Procaine

Figure 11 .
Figure 11.Stability in time (weeks) of the best-performing sensor.

Table 2 .
Selectivity coefficients of the sensors.

Table 2 .
Selectivity coefficients of the sensors.