Introduction

The reliable detection of metal ions, particularly trivalent iron (Fe3+), is of critical importance in environmental surveillance, industrial process control, and biomedical diagnostics1,2,3. Elevated Fe3+ levels are implicated in oxidative stress, neurodegenerative diseases, and metabolic disorders, while their accumulation in natural water systems contributes to contamination, infrastructure degradation, and reduced ecological quality4,5,6. Therefore, sensitive, selective, and practical detection of Fe3+ is essential across environmental and healthcare domains to mitigate both biological and ecological risks.

Conventional analytical techniques such as atomic absorption spectroscopy (AAS), inductively coupled plasma mass spectrometry (ICP-MS), inductively coupled plasma optical emission spectroscopy (ICP-OES), X-ray fluorescence (XRF), and various electrochemical methods offer excellent precision, sensitivity, and quantitative capabilities7,8,9,10. However, their widespread application is often hindered by substantial capital and operational costs, bulky instrumentation, labor-intensive sample preparation protocols, and the requirement for highly skilled personnel. Additionally, their reliance on centralized laboratory settings makes them unsuitable for real-time, point-of-need analysis, particularly in remote or resource-constrained environments.

In contrast, chemosensors, especially colorimetric sensors, have emerged as versatile and efficient alternatives11,12. These sensors operate on a simple principle, converting molecular recognition events into visible color changes, thus allowing for naked-eye detection without the need for sophisticated analytical instruments13. Colorimetric chemosensors are highly attractive for point-of-care diagnostics, environmental field testing, and on-site industrial monitoring due to their operational simplicity, fast response time, low energy demands, and minimal infrastructure requirements14,15. They can be easily integrated into flexible formats such as test kits, dipsticks, microfluidic platforms, or paper-based analytical devices, further enhancing their portability and user-friendliness16,17. This feature is particularly advantageous for decentralized testing, where immediate decision-making is necessary. Through careful molecular design, such as incorporating heteroatoms (N, S, O), modulating electronic properties, or introducing conjugated π-systems, these sensors can achieve high degrees of selectivity and sensitivity toward specific metal ions, including Fe3+18.

Among various chemosensor scaffolds, thiazole derivatives offer a particularly promising platform. The thiazole ring contains nitrogen and sulfur atoms capable of bidentate metal ion coordination, enhancing binding specificity19. Additionally, its aromatic, conjugated structure promotes intramolecular charge transfer (ICT), which facilitates a pronounced chromogenic response upon metal interaction20,21. Thiazole-based compounds also exhibit favorable physicochemical properties such as high thermal and photochemical stability, tunable electronic characteristics, and synthetic accessibility22,23. Compared to other heterocyclic frameworks like imidazoles or pyridines, thiazoles allow greater flexibility in ligand design while retaining strong affinity for transition metals, making them excellent candidates for the development of robust and selective colorimetric Fe3+ sensors24.

In this study, we report the design and synthesis of a novel aminothiazole-based colorimetric chemosensor, (4-methyl-2-(phenylamino)thiazol-5-yl)(phenyl)methanone (MPTP), developed via an iodine-catalyzed one-pot strategy. The sensor exhibits a distinct chromogenic shift from pale yellow to brown upon interaction with Fe3+, attributed to selective Fe-N coordination and enhanced ICT. MPTP demonstrates excellent selectivity, broad pH tolerance, and reversibility through EDTA-mediated regeneration. Furthermore, its successful integration into a paper-based platform enables portable, equipment-free detection. These findings establish MPTP as a promising next-generation chromogenic sensor, combining solution and solid-phase adaptability for reliable Fe3+ detection in pharmaceutical, clinical, and environmental settings. Figure 1 shows the schematic representation illustrating the overall workflow and key outcomes of this study.

Fig. 1
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Overview of MPTP colorimetric sensing of Fe3+ ions.

Experimental section

Materials and methods

All chemicals, solvents, and reagents were acquired from Sigma Aldrich, Merck Pvt. Ltd (India) SD fine and used as is, with no additional purification. All reactions and product purity were evaluated with thin-layer chromatography (TLC) on aluminium-backed plates. The pharmaceutical supplement FERYXIA™ (ferric citrate tablets) was purchased from a local medical store in Mysuru, Karnataka, India. The resulting product is characterized using HRMS for structural analysis. The UV-Visible spectrum was acquired using a Shimadzu UV-1900 spectrometer and a quartz cell with a path length of 1.0 cm. The FT-IR spectra were recorded using a Shimadzu IRSpirit FT-IR spectrophotometer. The1H and13C NMR spectra were obtained using a Varian 400 MHz spectrometer, and chemical shifts were measured in ppm. All (Density functional theory) DFT calculations were performed using the B3LYP functional with the 6–311 + + G(d, p) basis set in the gas phase as implemented in Gaussian 09.

Synthesis of MPTP

A 50 mL round-bottom flask was charged with a combination of 1-phenyl butane-1,3-dione (1.0 equiv.), aniline (1.0 equiv.), NaSCN (2.5 equiv.), I2 (1.0 equiv.), and DMSO (10 mL), as illustrated in Fig. 2. The reaction mixture was left to stir at 90 °C until the reaction was complete, which was monitored by TLC. After cooling the reaction mixture to room temperature, sodium thiosulfate was added to stop the reaction, followed by 10 mL of water to dilute the solution. The aqueous layer was extracted with ethyl acetate (3 × 15 mL) and dried on Na2SO425. To attain the highest purity, the product is dried and recrystallized before being characterized using several spectroscopic techniques. FT-IR (ν, cm− 1, KBr): 1775 (C = N), 1628 (C = O), 1373 (CH3), 1282 (C-N), 845 (C-S), 601 (C-H); 1H NMR (400 MHz, DMSO-d6, δ 10.83 (s, 1H, NH), 7.71–7.07 (m, 10 H, Ar-H), 2.36 (s, 3 H, CH3); 13C NMR (400 MHz, DMSO-d6, δ, ppm): 187.6, 159.2, 140.8, 132.4, 128.2, 128.6, 128.6, 129.8, 128.9, 132.1, 140, 129.9, 129.6, 123.4, 118.7, 118.6, 19.2; HRMS: m/z calculated for C17H15N2OS [M + H]⁺ = 294.37, found = 294.1366; base peak at m/z = 293.1330 ([M-H]⁺).

Fig. 2
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Synthetic route of MPTP.

Solvatochromic effect

The solution of MPTP (300 µM) was prepared in different solvents, such as DMSO, DMF, ethanol, methanol, dioxane, chloroform, and acetonitrile26. The UV-Vis absorption spectra were analysed through a UV-vis spectrometer.

Selectivity analysis of MPTP toward metal ions

To assess the selectivity of MPTP as a colorimetric sensor, MPTP was evaluated in the presence of various metal ions under identical conditions. A series of UV-Visible absorption spectra at 361 nm were recorded for MPTP (100 µM in ethanol) upon addition of 100 µM of different cations, including Ferric chloride (Fe3+), Mercury acetate (Hg2+), Ferrous ammonium sulphate (Fe2+), Manganous sulphate (Mn2+), Nickel chloride (Ni2+), Zinc chloride (Zn2+), Chromium (IV) oxide (Cr4+), Thorium nitrate (Th4+), Zirconium nitrate (Zr4+), Magnesium chloride (Mg2+), Aluminium sulphate (Al3+), Cadmium carbonate (Cd2+), Cobaltous chloride (Co2+), Copper sulphate (Cu2+)27,28.

Interference tolerance test

MPTP (100 µM) was dissolved in ethanol, and an amount of 100 µM of Hg2+, Fe2+, Mn2+, Ni2+, Zn2+, Cr4+, Th4+, Zr4+, Mg2+, Al3+, Cd2+, Co2+, Cu2+ was dissolved in ethanol. An amount of 1 mL of each metal (100 µM) was obtained and combined with 1 mL of each MPTP sensor solution (100 µM) prepared previously. Then, 1 mL of the Fe3+ solution was added to the combined solution containing metal ions and MPTP. UV-vis spectra were obtained at room temperature after a brief mixing period29.

Job’s method

To determine the binding stoichiometry between MPTP and Fe3+, Job’s method of continuous variation was employed. MPTP (100 µM) and FeCl3 (100 µM) were prepared in ethanol. A series of mixtures was prepared by varying the mole fractions of MPTP and Fe3+. Specifically, 1.5 mL of MPTP (3.0, 2.7, 2.4, 2.1, 1.8, 1.5, 1.2, 0.9, 0.6, 0.3, 0 mL) were mixed with 1.5 mL of Fe3+ (0, 0.3, 0.6, 0.9, 1.2, 1.5, 1.8, 2.1, 2.4, 2.7, 3.0 mL), respectively. The solutions were thoroughly mixed, equilibrated at room temperature, and the UV-Visible absorption spectra were recorded at 361 nm. The absorbance values were plotted against the mole fraction of Fe3+ to generate the Job plot. The maximum of the plot corresponds to the stoichiometric ratio of complexation30,31.

Results and discussion

The structure of the product was confirmed using FT-IR, 1H NMR, 13C NMR, and HRMS, shown in Supplementary Information as Section S1. FT-IR spectral analysis (Fig. S1a) confirms the presence of a carbonyl (C = N) stretch at 1775 cm− 1, C = O stretch at 1628 cm− 1, and methyl (CH3) vibrations at 1373 cm−132,33,34. The aromatic C-N stretch at 1282 cm− 1, aromatic ring deformation at 907 cm− 1, C-S stretch at 845 cm− 1, and C-H out-of-plane bending at 601 cm− 1 further support the presence of thiazole and aromatic functionalities in the compound35,36. The 1H NMR spectrum of the compound supports its proposed structure (Fig. S1b), the singlet at 10.83 ppm (1H) corresponds to the phenylamino N-H proton37,38. Aromatic signals appear between 7.71 and 7.07 ppm, consistent with protons on substituted phenyl rings showing typical splitting patterns due to neighbouring proton coupling39,40. A singlet at 2.34 ppm (3 H) is assigned to the methyl group on the thiazole ring, confirming its isolated environment41,42. The observed chemical shifts and splitting patterns are in agreement with the expected electronic environments. The C NMR spectrum (Fig. S1c) shows a distinct downfield resonance at 187.6 ppm, corresponding to the carbonyl (C = O) of the benzoyl group. The C = N carbon of the thiazole ring is observed at 159.2 ppm, while the carbon adjacent to the sulfur atom in the thiazole ring appears at 132.4 ppm. The aromatic carbons of the phenyl ring attached to the carbonyl resonate at 128.2, 128.6, 129.8, 128.9, 132.1, and 140.3 ppm. The phenyl ring of the phenylamino group shows signals at 140.8, 129.9, 129.6, 129.8, 123.4, 118.7, and 118.6 consistent with a para-substituted aromatic system. The methyl carbon attached to the thiazole ring is clearly identified at 19.235 ppm32,43,44,45. HRMS analysis revealed a molecular ion peak at m/z = 294.1366 [M + H]+, consistent with the calculated molecular mass of C17H14N2OS (294.37 g/mol), while a base peak at m/z = 293.1330 [M-H]+ further supported the molecular identity (Fig. S1d).

Plausible mechanism

The proposed mechanism for the synthesis of MPTP proceeds via a multistep iodine-mediated pathway, as illustrated in Fig. 3. The process initiates with the activation of 1-phenylbutane-1,3-dione (I), which undergoes keto-enol tautomerism due to the acidity of the methylene proton flanked by two carbonyl groups. This tautomerization generates an enolate species stabilized by resonance. I2 then reacts with the enolate, yielding an α-iodinated intermediate (II) through electrophilic iodination at the activated methylene carbon. Subsequent nucleophilic substitution of the iodine atom by thiocyanate anion (SCN−), generated from sodium thiocyanate (NaSCN), furnishes the thiocyanate intermediate (III). This electrophilic thiocyanate is then attacked by the nucleophilic amino group of aniline via a Michael-type addition, forming the phenylcarbamimidothioate intermediate (IV). Intermediate IV undergoes intramolecular cyclization via a 5-exo-trig mechanism, forming the thiazolidine ring system (V), specifically (4-hydroxy-4-methyl-2-(phenylimino)thiazolidin-5-yl)(phenyl)methanone. Dehydration of the hydroxyl group leads to the elimination of water and formation of the dihydrothiazole intermediate (V). Finally, aromatization of intermediate (V) occurs through spontaneous electron delocalization, yielding the thermodynamically stable aromatic thiazole-fused product (IV), characterized as (4-methyl-2-(phenylamino)thiazol-5-yl)(phenyl)methanone. The aromatization enhances conjugation and provides a rigid, planar structure favorable for metal coordination in sensing applications.

Fig. 3
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Proposed iodine-mediated multistep reaction mechanism for the synthesis of MPTP25.

Solvatochromic effect

The solvatochromic behavior of MPTP was systematically investigated in solvents of varying polarity to evaluate its sensitivity to environmental dielectric properties. The absorption spectra were recorded in seven solvents: DMSO, DMF, ethanol, methanol, dioxane, chloroform, and acetonitrile and are shown in Fig. 4a, while the full spectral range is included in Fig. S2. A distinct bathochromic shift (red shift) in the absorption maxima (λmax) was observed with increasing solvent polarity, characteristic of positive solvatochromism46. This behavior indicates that the excited state of MPTP is more stabilized in polar solvents than the ground state, resulting in a reduced HOMO-LUMO energy gap and, consequently, a red-shifted absorption47,48,49.

To quantify solvent polarity, Reichardt’s empirical polarity scale (ETN) was employed, and the corresponding transition energies (ET) were calculated using the Eq. (1)50:

The calculated ET values and corresponding molar absorptivity (ε) values are summarized in Table 1, where ε varies significantly across solvents, indicating altered transition probabilities linked to electronic reorganization. This systematic solvent-dependent variation in absorption characteristics reaffirms the strong ICT behavior of MPTP and highlights its utility as a potential polarity-sensitive probe in various sensing environments. The variations in λmax and ET across different solvents reflect pronounced solvent-solute interactions, confirming that MPTP undergoes significant electronic reorganization in the excited state51. These results suggest an ICT mechanism, which is common in donor-acceptor systems52,53,54.

In MPTP, the thiazole ring functions as an electron donor, while the adjacent phenyl ketone moiety acts as an electron acceptor. Upon excitation, electron density shifts from the donor to the acceptor, leading to a more polar excited state. This polar excited state is better stabilized in polar solvents, giving rise to the red-shifted absorption maximum27,47,55.

The correlation between ETN and λmax is further illustrated in Fig. 4b. The graph shows a consistent increase in λmax with increasing values ETN, reinforcing the conclusion that MPTP exhibits positive solvatochromism. This observation supports the ICT mechanism and highlights the sensitivity of MPTP to microenvironmental polarity, making it a promising candidate as a polarity-sensitive optical probe.

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(a) Absorption spectra of MPTP (300 µM) in different solvents for solvatochromism at room temperature, and (b) Correlation between maximum absorption wavelength (λₘₐₓ) and solvent polarity (ETN values).

Table 1 ET data of MPTP as calculated from reichardt’s scale48.
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Selectivity analysis of MPTP

UV-Visible spectral response

To substantiate the visually observed selectivity, the UV-Visible absorption spectra of MPTP were recorded in the presence of various metal ions (Fig. S3). The spectrum of free MPTP displayed a well-defined absorbance profile, which remained virtually unchanged upon the addition of all tested metal ions, with the notable exception of Fe3+. Upon addition of Fe3+ ions to the MPTP solution, the λmax undergoes a hypsochromic shift from 363.81 nm (MPTP) to 359.10 nm (MPTP-Fe3+ complex shown in Fig. 5a29. This blue shift of 4.71 nm indicates a change in the electronic environment of the ligand, consistent with metal-ligand complexation and a potential decrease in conjugation or electron delocalization upon Fe3+ binding. Additionally, the absorbance intensity increases significantly, from 0.65 a.u. (free MPTP) to approximately 1.90 a.u. in the presence of Fe3+, highlighting the strong binding affinity and formation of a stable MPTP-Fe3+ complex. This combination of spectral shift and intensity enhancement strongly supports the effective coordination of Fe3+ to the sensor molecule.

Naked-eye detection

The colorimetric response was further validated by visual inspection of MPTP solutions treated with different metal ions. As seen in Fig. 5b, only the vial containing Fe3+ produced an intense brown coloration, readily visible to the naked eye56,57. All other metal ions failed to induce any significant color change, with the solutions retaining their pale-yellow appearance, essentially identical to the control sample containing MPTP alone.

This distinctive color development in the presence of Fe3+, coupled with the spectral evidence, confirms the formation of a specific MPTP-Fe3+ complex. The strong color contrast makes the probe a highly effective candidate for the simple, equipment-free detection of Fe3+ ions.

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(a) Absorption variation of MPTP (100 µM) with cations (100 µM) at 361 nm, and (b) Colour change of MPTP (200 μm in ethanol) in the presence of various cations (200 μm in ethanol).

Confirmation of MPTP-Fe3+ complex formation

Fourier transform infrared (FT-IR) spectral analysis

FT-IR spectroscopy was utilized to elucidate the interaction between MPTP and Fe3+ ions. The comparative FT-IR spectra of free MPTP and the MPTP-Fe3+ complex are presented in Fig. 6, providing compelling evidence for complexation via the nitrogen coordination site. As discussed above, the spectrum of free MPTP displays characteristic bands of the ligand framework, including N-H stretching at 3214 cm− 1, a C = N band at 1775 cm− 1, C = O stretching at 1628 cm− 1, aromatic C-N at 1200 cm− 1, aliphatic C-N at 1071 cm− 1, and C-S at 845 cm− 1. Upon complexation with Fe3+, the FT-IR spectrum of the MPTP-Fe3+ complex exhibits significant changes indicative of coordination. The disappearance of the N-H stretching band at 3214 cm− 1 suggests the involvement of the N-H stretch and possible deprotonation during complex formation. The absence of the C = N stretching band at 1775 cm− 1 implies direct coordination of the imine nitrogen with, while the retention of the C = O stretching band at 1628 cm− 1 indicates that the carbonyl group is not involved in binding. The aliphatic C-N stretch at 1071 cm− 1, initially weak in the free ligand, becomes markedly more intense in the complex, likely due to conformational changes upon coordination. Other characteristic bands, including the aromatic C-N stretch at 1200 cm− 1, and the C-S stretch at 845 cm− 1, remain largely unchanged, reflecting the preservation of the ligand’s aromatic structure. Notably, a new band at 455 cm− 1, assigned to Fe-N stretching, confirms the formation of a coordination bond with a nitrogen donor, supporting the successful complexation of MPTP with Fe3+58.

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FT-IR absorption band of MPTP and MPTP-Fe3+ complex.

HRMS analysis for MPTP-Fe3+ complex

To further confirm the formation and stoichiometry of the MPTP-Fe3+ complex, HRMS analysis was performed, as detailed in Section S4. An ion at m/z = 454.6322 (Fig. S4a) corresponds to the species [MPTP + Fe3+ + 3Cl−]+, confirming a 1:1 metal-ligand complex with three counter ions, supports the proposed coordination model shown in Fig. 7, and provides direct experimental evidence for the presence of this ion and its proposed complex structure. As shown in (Fig. S4b), the Job plot displays a clear maximum at a mole fraction of 0.5, indicating a 1:1 binding stoichiometry (Fig. S5) between MPTP and Fe3+18.

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A proposed complex formed between MPTP-Fe3+.

Competitive interference assay

To examine the selectivity of MPTP in the presence of potential competing metal ions, mixed-ion solutions were prepared by adding Fe3+ (100 µM) to MPTP (100 µM) in the presence of other interfering cations (100 µM each). This unique spectral and visual response remained unchanged even in the presence of metal ions such as Hg2+, Fe2+, Mn2+, Ni2+, Zn2+, Cr4+, Th4+, Zr4+, Mg2+, Al3+, Cd2+, Co2+, Cu2+ (Fig. 8a)27. This robustness against interference further highlights the exceptional selectivity of MPTP for Fe3+. The persistence of the dark brown coloration is visually evident in Fig. 8b, with other metal ions. Additionally, to validate the sensor under more stringent conditions, interference studies were also performed using excess concentrations of competing metal ions (200 µM each), as shown in Fig. S6.

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(a) Bar graph comparing absorbance at the λmax at 361 nm of MPTP (100 µM) with metal ions (100 µM each), and (b) Color changes of MPTP (200 µM) to Fe3+ (200 µM) with diverse cations (200 µM).

Determination of binding constant using the Benesi-Hildebrand method

The binding affinity of MPTP toward Fe3+ was quantitatively evaluated using the Benesi-Hildebrand method59. UV-Vis absorption titrations were performed by incremental addition of 5, 10, 15, 20, 25 µM of Fe3+ to a fixed concentration of MPTP 30 µM, and the resulting absorbance changes were monitored at the characteristic complexation wavelength. The experimental data were fitted to the linearized Benesi-Hildebrand equation, a linear plot of 1/A-A0 versus 1/[Fe3+] (Fig. 9a) with an excellent correlation coefficient (R2 = 0.9969), confirming the validity of the 1:1 binding model. From the slope and intercept, the Binding constant (Ka) was calculated to be 0.81 × 106 M− 1, indicating a strong and stable interaction between MPTP and Fe3+. This high binding affinity can be attributed to the strong electrostatic attraction between the electron-deficient Fe3+ ion and the electron-rich donor sites in MPTP.

Detection limit determination

To quantify the detection capability of MPTP, UV-Visible titrations were performed with increasing concentrations of Fe3+ ranging from 0 to 10 µM. A linear relationship was observed between the absorbance at 361 nm and Fe3+ concentration, as illustrated in Fig. 9b29. The detection limit (LOD) was calculated using the 3.3σ/k method, where σ is the standard deviation of the blank and k is the slope of the calibration curve60. The LOD was determined to be 0.2687 µM, which is significantly lower than the U.S. EPA’s permissible limit for Fe3+ in drinking water (5.37 µM), thereby validating the probe’s environmental relevance61. The MPTP detection limit for Fe3+ is noteworthy since it is similar to the previously published values (Table S1).

Effect of pH

We examined how pH affected the MPTP and MPTP-Fe3+ complex absorption response in a range of pH between 2 and 12 (Fig. 9c). The pH experiments showed that the ligand MPTP was stable across the investigated pH range, since it did not show any discernible absorbance increase62. The MPTP-Fe3+ combination, on the other hand, showed a noticeable pH dependency in its absorption. The absorbance was very moderate at low pH values, but it rose dramatically between pH 6 and pH 10, suggesting that complex formation was improved in this range. The absorbance dropped above pH 10, indicating that the complex’s stability in very alkaline circumstances may be compromised63.

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(a) Linear plot of Benesi-Hildebrand method absorbance at 361 nm, (b) MPTP detection limit for Fe3+ at 50µM absorbance at 361 nm, (c) pH impact on MPTP and MPTP-Fe3+ absorbance at 361 nm, and (d) Visual response of MPTP-loaded test strips upon exposure to increasing concentrations of Fe3+ (50µM, 100µM, 200µM).

Reversibility and reusability via EDTA-mediated regeneration

For practical sensor applications, reversibility and reusability are essential attributes64. To evaluate the recyclability of MPTP as a Fe3+ chemosensor, we investigated its ability to undergo reversible coordination and decoordination cycles using ethylenediaminetetraacetic acid (EDTA) as a competitive chelating agent.

Visual and spectral response

As illustrated in Fig. 10a, the brown-colored solution of the MPTP-Fe3+ complex was treated with EDTA (100 µM), resulting in an immediate color change to pale yellow, resembling the original uncomplexed MPTP. This change indicates the successful extraction of Fe3+ from the complex due to EDTA’s higher chelating affinity. Upon reintroduction of Fe3+, the brown coloration was restored, signifying reformation of the MPTP-Fe3+ complex31,62. To support this observation, UV-Vis absorption measurements were recorded at 361 nm during each cycle. As shown in Fig. 10b, a marked decrease in absorbance was observed upon EDTA treatment, followed by a recovery upon reintroduction of Fe3+. This absorbance switching pattern confirms the reversibility of the complexation process. This suggests that the MPTP molecule remains structurally intact over multiple binding cycles and is not degraded during metal binding or chelator treatment. The sensor’s durability and ease of regeneration position it as an attractive candidate for deployment in disposable test kits or low-cost continuous monitoring systems.

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(a) Reversible color changes of MPTP with Fe3+ after the addition of EDTA, and (b) Reversible UV-Vis response of MPTP-Fe3+ complex (30 µM) with EDTA (30 µM) at 361 nm.

Kinetic study of MPTP-Fe3+ complex formation

To assess the temporal dynamics of complex formation, time-resolved UV-Vis measurements were performed at 361 nm using equimolar concentrations of MPTP and Fe3+ (80 µM each). The absorbance exhibited a minor but highly linear decrease over 300 s, with an initial value of 1.514 and a rate of −0.0015 a.u./min. The data revealed that complexation occurs nearly instantaneously, with the minimal change suggesting a stable, post-equilibrium signal suitable for rapid and real-time Fe3+ sensing applications. Full kinetic trace and regression analysis are provided in the Fig. S7.

Practical significance

Paper-based strip sensor for on-site Fe3+ detection

To enhance the field-deployment ability and user-friendliness of the MPTP sensor, a paper-based colorimetric test strip was developed. This format enables rapid, instrument-free detection of Fe3+ in aqueous environments59.

Fabrication of test strips

Filter paper strips were prepared by immersing in a 200 µM ethanolic solution of MPTP, then air-drying under ambient conditions. The dried strips retained their original pale yellow coloration in the absence of metal ions, indicating the stability of the probe on a solid substrate65,66.

Colorimetric response to Fe3+

Upon exposure to increasing concentrations of Fe3+ (50, 100, and 200 µM), the MPTP-loaded paper strips underwent a gradual and distinct color transition from off-white to progressively deeper shades of brown, as shown in Fig. 9d. This visible response is concentration-dependent and observable to the naked eye, enabling semi-quantitative detection. The observed chromogenic progression is attributed to Fe3+-induced complexation with MPTP immobilized on the cellulose matrix, reproducing the solution-phase behavior in a solid-state system.

Environmental and pharmaceutical sample analysis

The practical applicability of MPTP was validated in a ferric citrate tablet and in simulated water27. In tablet extracts containing 2 µM Fe3+, MPTP (40 µM, λmax = 361 nm) yielded a found concentration of 2.04 µM (102% recovery) based on the calibration curve. Similarly, 2 µM Fe3+ spiked into simulated water was recovered at 1.96 µM (98% recovery), demonstrating the accurate determination of Fe3+ in a representative aqueous matrix, as shown in Table 2. This result indicates that MPTP can reliably detect Fe3+ in complex environmental and pharmaceutical samples. The complete experimental procedure, dilution details are provided in Section S812,29,67,68.

Table 2 Determination of Fe3+ using MPTP.
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Computational validation

To further corroborate the experimental findings and investigate the electronic behaviour of MPTP at a molecular level, DFT calculations were performed using the B3LYP functional with the 6–311 + + G(d, p) basis set. These computations provide detailed insights into the compound’s electronic transitions, frontier molecular orbitals, charge distribution, and donor-acceptor interactions69,70.

The optimized structure of MPTP (Fig. 11a) revealed a planar and conjugated framework that supports extended π-delocalization across the thiazole and aromatic rings, favorable for Fe3+ coordination71. UV-Vis spectrum displayed a prominent π-π* transition centered around 361 nm, in excellent agreement with the experimental maximum absorbance (Section S9)(Fig. S9a)72. The calculated IR spectrum (Fig. S9b) closely replicated the experimental bands, including the imine (C = N) stretch near 1775 cm− 1 and the carbonyl (C = O) stretch at 1628 cm−173,74,75. The electronic circular dichroism (ECD) spectrum showed a distinct bisignate cotton effect, confirming the molecule’s chiral electronic environment (Fig. S9c). Hole electron distribution mapping (Fig. S9d) revealed partial charge separation across the molecule76. A moderate overlap index (0.634) suggested significant ICT, which is crucial for solvatochromism and metal-ion interaction. The HOMO and LUMO distributions (Fig. 11b) showed that the HOMO is primarily localized on the thiazole and adjacent phenyl rings, while the LUMO spans the electron-deficient region, including the carbonyl-bearing phenyl ring77.

This orbital configuration facilitates donor-acceptor interactions during Fe3+ binding. The charge density difference map (Fig. 11c) illustrated electron accumulation and depletion zones, highlighting potential binding sites. The MEP surface (Fig. 11d) revealed electron-rich regions around the nitrogen atoms, indicating their likely involvement in Fe3+ coordination78. This spatial localization of electron density is consistent with the electrophilic nature of Fe3+, which selectively binds to nucleophilic, electron-rich centers. Hence, the electron-rich nitrogen sites on MPTP facilitate strong electrostatic and orbital interactions, underpinning its selective affinity for Fe3+78. Furthermore, the frontier molecular orbital (FMO) analysis and global reactivity descriptors derived from the DFT calculations summarized in Table 3 provide quantitative insight into the molecule’s stability and reactivity. The relatively low energy gap (ΔE = 3.79 eV) and high electrophilicity index (ω = 4.33 eV) suggest that MPTP possesses both good stability and a strong tendency to accept electrons, making it a suitable ligand for transition metal binding80.

Fig. 11
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(a) MPTP structure optimization, (b) The HOMO-LUMO gap of MPTP, (c) Charge density difference, and (d) MEP of MPTP.

Table 3 FMOs and other global reactive parameters of the DFT optimised MPTP molecule.
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Conclusion

In this study, an aminothiazole-based colorimetric sensor, MPTP was synthesized via a simple iodine-catalysed one-pot route and shown to act as an efficient chemosensor for Fe3+. The probe exhibits a rapid and distinct colour/absorbance response at 361 nm, with excellent selectivity over competing metal ions, broad pH tolerance (2–12), and a low detection limit of 0.268 µM. Job’s plot and Benesi-Hildebrand analyses confirm a 1:1 MPTP-Fe3+ complex with a high association constant, while FT-IR (loss of N-H and C = N bands and appearance of an Fe-N vibration) and kinetic studies highlight nitrogen-centred coordination and fast complex formation, respectively. DFT, frontier orbital, hole-electron, and MEP analyses corroborate the experimental findings, revealing a π-π* transition with pronounced ICT, nitrogen-rich coordination sites, and a low HOMO-LUMO gap with high electrophilicity, which together rationalize the strong and selective Fe3+ binding. The sensor is reversible upon EDTA treatment, enabling reuse, and can be translated into a simple paper-based strip for instrument-free detection. Finally, real-sample measurements yielded recoveries close to 100%, demonstrating accurate Fe3+ determination with negligible matrix interference. Overall, MPTP offers a robust, regenerable, and field-deployable platform for routine spectrophotometric and colorimetric monitoring of Fe3+ in pharmaceutical and environmental matrices.