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Article Cite This: ACS Omega 2019, 4, 7723−7733
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Development of Nitrobenzoxadiazole-Appended Calix[4]arene Conjugate (L) for Selective Sensing of Trivalent Cr3+, Fe3+, and Al3+ Ions in Solution and in the Solid State and Imaging MCF7 cells by {L + Al3+} Subrata Kumar Dinda, Aekta Upadhyay, Sirilata Polepalli, Mohammed Althaf Hussain, and Chebrolu Pulla Rao* Downloaded via 79.110.17.95 on April 28, 2019 at 14:26:31 (UTC). See https://pubs.acs.org/sharingguidelines for options on how to legitimately share published articles.
Bioinorganic Laboratory, Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai 400 076, India S Supporting Information *
ABSTRACT: A nitrobenzoxadiazole (NBD)-appended calix[4]arene conjugate (L) possessing a cyclic core formed by connecting the 1,3-positions at the lower rim has been designed. The L has been developed as a receptor for the selective recognition of biologically and ecologically relevant trivalent metal ions, viz., Cr3+, Fe3+, and Al3+. The interaction and region of binding of these metal ions by the receptor L have been explored by isothermal titration calorimetry, spectroscopy, microscopy, and density functional theory (DFT) computational studies. The probe L itself exhibits weak fluorescence emission intensity, and the quantum yield is enhanced by ∼4-fold upon addition of the M3+ ion due to the chelate enhanced fluorescence effect. Fluorescence enhancement also takes place in L when it interacts with M3+ even in the solid state and in the MCF7 cancer cells. The binding constant (Kb) for M3+ by L is ∼104 M−1, supporting that these ions bind to L with moderate strength. The detection limit for all the three metal ions is as low as 4−5 μM. The 1H NMR data reflects the region of binding of the M3+ ion to L. The binding is further supported by DFT studies where the space filling structures evidently shows the binding core in L, and the M3+ ion is buried in this core. As a result of this, the microscopy features are almost the same for L and {L + M3+}. The reversible utility of the sensor has been achieved by the addition of H2PO−4 . Based on the input−output information, a molecular logic circuit (INHIBIT logic gate) has been built, which will provide an electronic basis for designing a memory device by the concerned experts.
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using ion binding groups and fluorophoric moieties. Connecting the 1,3-arms derivatized with appropriate binding centers at the lower rim of calix[4]arene would provide a cyclic and preformed binding core. When the species binds to such a core, it will elicit a signal when appended to a fluorophoric group. In this paper, we have designed (Figure 1) a 1,3-lower rim-closo-di-derivative of calix[4]arene in order to provide a preformed binding core. This has been attached to nitrobenzoxadiazole (NBD) moiety in order to respond accordingly and elicit an appropriate fluorescence signal when the species binds in the core. Recognition of trivalent metal ions has been reported in the literature26−38 by using different fluorophores but not with the NBD moiety. Using this strategy, a molecular receptor system L has been developed and demonstrated its recyclable sensing behavior with three trivalent metal ions, viz., Cr3+, Fe3+, and Al3+, which are important in biology and the environment. The demonstrations were based on isothermal
INTRODUCTION The recognition followed by the sensing of the biologically and environmentally important metal ions has emerged as a significant challenge in the field of chemosensors.1−6 Conventional analytical approaches are inefficient when the analytes are present together, and this necessitates the development of selective receptors. In addition, the sensitivity of the response is a major issue and is important in designing selective molecular receptors. Therefore, the thrust continues to develop highly sensitive and selective chemosensors particularly for the ions of importance in biology and ecology. It would be beneficial if the sensor molecule has selective features for specific interaction and binding and further possess the moieties useful in producing sensitive response. The latter is possible with fluorescent groups. Among the fluorescent sensors, a “turn-on” response is more preferred over the “turn-of f ” because the turn-off results in fluorescence quenching, and the quenching is in turn influenced by a variety of processes. It has been demonstrated in the literature by our group7−12 and others13−25 that the calix[4]arene platform provides an excellent scaffold for modifying these ions © 2019 American Chemical Society
Received: March 1, 2019 Accepted: April 17, 2019 Published: April 26, 2019 7723
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Selective Sensing of Trivalent Ions, viz., Cr3+, Fe3+, and Al3+ by L. The receptor molecule L shows three absorption bands positioned at 285, 335, and 470 nm. The receptor L was titrated with metal ions, viz., Na+, K+, Mg2+, Ca2+, Al3+, Cr3+, Mn2+, Fe2+, Fe3+, Co2+, Ni2+, Cu2+, and Zn2+. Among all the 13 metal ions studied, the molecule L showed significant changes in the absorption spectra only in the case of the trivalent ions, viz., Cr3+, Fe3+, and Al3+, and the rest of the metal ions showed no significant changes in their spectra. In the presence of Cr3+, Fe3+, and Al3+ ions, the absorbance at 470 nm band decreases gradually to an extent of ∼30%, and the band shows a blue shift by 12−16 nm (Figure 2a−c). The absorption band at 335 nm also shows a decrease in its absorbance by 30−40% with a blue shift of ∼9 nm (Figure 2d−f).
Figure 1. Design of L.
titration calorimetry (ITC), spectroscopy, microscopy, and computational studies. The outcome of all these led to the development of a logic gate. As L possesses a cyclic core at the lower rim that provides a preorganized binding core with the presence of six O-ligating centers, the sensitivity is expected to be high toward M3+ ions because of their interaction followed by binding in this core. Since this is a cyclic core, this will have much less flexibility, hence suited to accommodate the demands of M3+ ion coordination geometry better.
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RESULTS AND DISCUSSION The receptor molecule (L) was synthesized starting from calix[4]arene (P1) as per the steps given in Scheme 1. P1 was Scheme 1. Scheme for the Synthesis of La
Figure 2. Absorption spectra obtained during the titration of L with (a) Cr3+, (b) Fe3+, and (c) Al3+. In all the cases, [L] = 10 μM and [M3+] = 0 to 100 μM in chloroform/methanol (1:59). Plot of absorbance (scale on the left) and λmax (scale on the right) versus mole ratio, viz., [M3+]/[L] for (d) Cr3+, (e) Fe3+, and (f) Al3+. ESIMS spectra of (g) {L + Cr3+}, (h) {L + Fe3+}, and (i) {L + Al3+} complexes. In (g)−(i), the black line and red line correspond to the experimental pattern and the simulated pattern, respectively.
The absorption spectra for all the other metal ion titrations are given in Figure S01. The Job plots obtained based on the absorption data for Cr3+, Fe3+ and Al3+ yielded a 1:1 complex in the case of all the three ions (Figure S02), and the formation of such complexes have been established based on ESI-MS studies. In ESI-MS, the molecule L resulted in a molecular ion peak at m/z = 1038.56 corresponding to [M + H]+. The complexes {L + Cr3+}, {L + Fe3+}, and {L + Al3+} show ESIMS peaks at m/z of 1213.47, 1091.48, and 1262.44 corresponding to {L + Cr3++2NO−3 }+, {L + Fe3+−2H+}+, and {L + Al3++2ClO−4 }+, respectively, supporting the formation of the corresponding 1:1 complexes (Figure 2g−i). The isotopic peak patterns observed in all these cases agree well with the simulated one, supporting the presence of the corresponding metal ion. Similarly, the fluorescence titrations were also carried out with all the 13 metal ions. The receptor L exhibits a weak
a
(a) Ethyl bromoacetate, K2CO3, reflux, 24 h. (b) Tris(2-aminoethyl) amine, toluene and methanol (1:1), stirring at room temperature (RT), 3 days. (c) NBD-Cl, stirring at RT, 48 h.
functionalized to give 1,3-alternate diester derivative P2. The two ester terminals of P2 were cyclized via two amide bonds resulting in the precursor molecule P3, which, upon reaction with NBD-Cl, results in the binding of the NBD moiety as a pendant and thereby yields the desired receptor molecule L. 7724
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fluorescence emission band at 550 nm. During the titrations, the fluorescence emission spectra showed changes only in the case of the three trivalent metal ions, viz., Cr3+, Fe3+, and Al3+, and not with all the other metal ions studied (Figure 3a and
in Figure 3d). Thus, the lifetime data clearly supports a 4-fold increase in the life span of the excited state of the complexed species as compared to the uncomplexed L. This result further supports that, in the excited state, the closo-binding core present at the lower rim of L exhibits rigidity upon complexation by the M3+ ion. Thermodynamics of the Binding of M3+ by L. Isothermal titration calorimetry experiments were carried out in order to derive the thermodynamic parameters of binding of Fe3+ and Al3+ by L (Figure 4a,b). The interaction of the
Figure 3. (a) Emission spectra obtained during the titration of L with Cr3+ in chloroform/methanol (1:59) and λex = 470 nm. The inset in (a) shows the plot of relative fluorescence intensity (I/I0) as a function of mole ratio, viz., [Cr3+]/[L]. Similar plots for [Fe3+]/[L] and [Al3+]/[L] are in (b) and (c), respectively. In all the cases, [L] = 10 μM and [M3+] = 0−100 μM. (d) Histogram showing the relative fluorescence intensity (I/I0) of L at 550 nm in the presence of different metal ions. Inset in (d) on the right shows the photograph of vials containing L and {L + M3+} under UV light. Inset on the left shows the decay curves for L (black line), {L + Cr3+} (red line), {L + Fe3+} (blue line), and {L + Al3+} (olive green line).
Figure S03). The competitive titration of {L + Mn+}, where Mn+ is Na+, K+, Mg2+, Ca2+, Mn2+, Fe2+, Co2+, Ni2+, Cu2+, and Zn2+ with a mixture of trivalent metal ion M3+, that is, {Cr3++Fe3++Al3+}, showed a 4-fold enhancement in each of the case (Figure S04), thus supporting that there is no interference of any of the Mn+ ions in the sensing of M3+ by L. The plots of fluorescence intensity ratio versus [M3+]/[L] mole ratio are sigmoidal, supporting the binding followed by the complexation of these trivalent ions by L (Figure 3b,c). In the case of all these three M3+ ions, the fluorescence emission of L was enhanced by 4-fold due to the chelate enhanced fluorescence emission (CHEF) resulting from the formation of the complex. The corresponding results are given in Figure 3d in comparison with all the ions studied. Based on the fluorescence titration data, the ion binding constants by L were evaluated by fitting the data (Figure S05) using Benesi−Hildebrand equation to give (2.9 ± 0.2) × 104, (1.60 ± 0.02) × 104, and (5.3 ± 0.2) × 104 M−1 for Cr3+, Fe3+, and Al3+, respectively. Thus, the binding constants in all these three cases are in the same order of magnitude. The quantum yield of L and its complexes were measured in CHCl3/ methanol (1:99) using Rhodamine 6G (ϕ = 0.94) as the standard. While the L exhibited a ϕ value of 0.06, its complexes exhibited 0.32, 0.35, and 0.45, respectively for Cr3+, Fe3+, and Al3+ complexes (Figure S06). Thus, the quantum yield of the complexes increases by 5 to 7 times to that of the L in accordance with the fluorescence enhancement observed. The limits of detection (LODs) for Cr3+, Fe3+, and Al3+ were determined using fluorescence titration data by the 3σ/K method (Figure S07), and this resulted in values of (1.8 ± 0.1), (1.7 ± 0.2), and (2.3 ± 0.2) ppm, respectively, where these are in the 4.6−4.8 μM range. The fluorescence excited state lifetime measurements of L and its {L + M3+} complexes were carried out at λex = 400 nm and λem = 550 nm using the time-correlated single photon counting (TCSPC) method. The data (Table S01) primarily exhibits a biexponential decay behavior. The average lifetime (τav) observed for L is 0.99 ns, and those for its Cr3+, Fe3+, and Al3+ complexes are 4.07, 3.97, and 3.93 ns, respectively (inset
Figure 4. Isothermal titration calorimetry plots of L with (a) Fe3+ and (b) Al3+ in CH3CN at 20 °C. The interaction of M3+ with CH3CN was subtracted.
corresponding M3+ titration with acetonitrile was subtracted. In the case of Fe3+, the best fit for the data is with three sequential binding, while the data for Al3+ corresponds to the one site fit. The ΔG value is negative for both the titrations, supporting that the binding of M3+ by L is feasible. However, the overall heat of the complexation is exothermic with a ΔH value of −(2.6 ± 0.6) × 104 cal mol−1 in the case of Fe3+ and is endothermic in the case of Al3+ with a ΔH value of (3.9 ± 0.2) × 104 cal mol−1. The ΔS value is −31 and +148 cal mol−1 deg−1 for Fe3+ and Al3+ titrations, respectively. The association constants (Ka) obtained from the ITC data are (7.5 ± 3.5) × 104 and (1.6 ± 0.1) × 103 M−1 for Fe3+ and Al3+, respectively, supporting that Fe3+ binds strongly to L by an order magnitude greater than that of Al3+. Even the complexation energy obtained from the DFT computational study is greater in the case of Fe3+ when compared to the Al3+ complex as given in this paper. Evidence for the Binding Site in L for M3+ by 1H NMR Spectroscopy. In order to support the formation of the complex between L and Al3+ and to identify the region of interaction, 1H NMR titrations were carried out (Figure 5). With the addition of Al3+ to L, the protons correponding to the amide (labeled as “k”), benzofurazan ring (labeled as “g” and “f”), −OH (labeled as “l”), CH2 in the chain region of the lower rim moiety (labeled as “a”, “b”, “c”, “d”, “e”), and bridging −CH2 protons (labeled as “h” and “i”) are affected the most. At the lower mole ratios of Al3+ (∼0.1 equiv), the amide protons are split into two signals, and at higher mole ratio of Al3+ (∼0.6 equiv), these merge to give one set of signal along with an upfield shift of ∼0.1 ppm. One of the benzofurazan ring protons (labeled as “g”) showed an upfield shift of ∼0.05 ppm, and the second proton (labeled as “f”) showed a 7725
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Figure 6. DFT-optimized structures for (i) L and (ii) {L + M3+} complex. The hydrogen bonding region in L and the coordination sphere for M3+ to L are expanded for clarity.
Figure 5. 1H NMR spectra obtained during the titration of L with increasing concentration of Al3+ ((i)−(xii)) in CDCl3/CD3CN (1:3 volume ratio). The concentration of L is 8.5 mM, and that of Al3+ is 0−5 mM. Different protons in L are labeled.
The frontier molecular orbital analysis for L given in Figure S11 helps to predict its nucleophilicity so as to form the metal ion coordination. From the highest occupied molecular orbital (HOMO), the nucleophilic regions are identified to be at the calixarene aromatic region including the lower rim oxygens, and hence this is expected to be the coordinating region for a metal ion. The DFT-optimized structure obtained for the M3+ complex of L clearly showed the binding of the ion in the core formed at the lower rim by connecting the 1- and 3-arms (Figure 6(ii)). The complexation energies (CEs) are −908, −1011, and − 886 kcal/mol for the complexes of Cr3+, Fe3+, and Al3+, respectively, suggesting that Fe3+ forms a stronger complex with L among these three trivalent ions. The energies of HOMO and lowest unoccupied molecular orbital (LUMO) of L and those of the [L + Fe3+] complex were calculated using the frontier MO analysis of L and its Fe3+ complex at the M062X/6-31G(d,p),SDD// B3LYP/6-31G(d,p),SDD level of theory. The HOMO−LUMO energy gap is 4.6 eV for L. Upon complexation with Fe3+, the energy of both the HOMO and LUMO were lowered, and the energy gap is reduced to 4.43 eV as can be noticed from Figure 7. This has been supported by the observed fluorescence enhancement. The DFT-optimized structures in all the three complexes exhibit six O coordination atoms about the metal ion that is locked in the cyclic core present at the lower rim. Analysis of the M···O distances (Table S03) clearly supports the presence of two very long distances (2.597 and 2.974 Å) in the case of Cr3+, two moderately long distances (2.387 & 2.230 Å) in the case of Fe3+, and one unusually long distance (2.773 Å) in the case of the Al3+ complex. Comparison of the O···M···O bond angle data (Table S04) of the coordination core reveals that the cis-angles span in the range of 56 to 132°, while the transangles span in the range of 121 to 168°, supporting that all these complexes exhibit highly distorted octahedral geometry about the metal center. The space filling model structure for the DFT-optimized L shown in Figure 8a clearly supports the formation of the 1,3closo-binding core at the lower rim that is surrounded by six O centers. Similar structures given for the complexes in Figure 8b−d support the fact that the corresponding metal ion binds in this core at the lower rim. Comparison of these cores further reveals that each of these metal ions is buried to different extents into this core. In the lower rim cyclic core, several of the dihedral angles show large changes on going from the
downfield shift of 0.24 ppm at lower mole ratios of Al3+. Beyond 0.2 equiv of Al3+, these signals remain unaltered in the chemical shift but sharpened at ∼1.0 equiv. The 1H NMR titration data reveals that the protons of the bridged CH2 (labeled as “h” and “i”) of the calixarene present at 4.20 and 3.52 ppm shift to upfield by ∼0.06 and ∼0.07 ppm, respectively. The presence of the bridged CH2 doublets in L and {L + Al3+} in the 1H NMR spectra suggests that the L continue to be in the cone conformation even after complexation with Al3+. In the aliphatic region, there is an upfield shift in −OCH2 protons (labeled as “a”) and all other −CH2 protons (labeled as “b”, “c”, “d”, and “e”) are shifted to downfield. Both the −CH3 type of protons are also shifted upfield by ∼0.02 ppm. This suggests that Al3+ interacts with the benzafuran ring proton of L at lower equivalents (∼0.1) of Al3+, and when the mole ratio increases, a stable complexation is observed when M3+ is in the cyclic ring at the lower rim. The binding is further supported by the DFT studies reported in this paper. Similar results were obtained with the 1H NMR titration of L against Fe3+/Cr3+ given in Figure S08. The major differences being that some of the peaks are broadened, while some are shifted due to the paramagnetic nature of Fe3+/Cr3+ (Figure S09), suggesting that the binding region for Fe3+/Cr3+ is same as that of Al3+. The spectral differences of L observed in the case of Fe3+/Cr3+ can be easily appreciated when these are compared with that observed for Al3+ as given in Figure S09. The binding of M3+ by the lower rim cyclic core is also evident from the DFT studies. Details of the Complexation of L by M3+ from the Computational Studies. The optimized structures for the NBD conjugate of calixarene (L) and for its complex with the trivalent metal ion {L+ M3+} are given in Figure 6 and Figure S10. The optimized structure of L exhibits three intramolecular hydrogen bonds where both the lower rim phenolic O−H groups act as hydrogen donors, while both the ether-O’s (Oa− H···Ob and Oc−H···Od) and the amide-O (Oc−H···Oe) of the arm act as hydrogen acceptors as can be noticed from the structure for L given in Figure 6i. Among these three hydrogen bonds, the Oc−H···Oe is strong, while the other two are weak as can be understood from the data given in Table S02. 7726
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as revealed by the DFT studies (Figure 8). The elemental mapping in the case of the Cr3+ complex also shows the presence of this M3+ ion in the particles along with C, N, and O from L (Figure 9m−r). The energy-dispersive X-ray spectroscopy (EDAX) provides 7.95 wt % of Cr3+. Similar data for the Fe3+ and Al3+ complexes given in Figures S12 and S13 also supports the presence of the corresponding ions in their complexes. Reversible Sensing by L. The reversible sensing of Cr3+, Fe3+, and Al3+ by L has been demonstrated by titrating the complex with (n-Bu)4NH2PO4. The fluorescence emission intensity of L is enhanced upon the addition of the selective M3+ (switch “ON”), and the same is quenched (switch “OFF”) upon the addition of (n-Bu)4NH2PO4 (Figure 10a and Figure S14). This completes one cycle. Addition of the corresponding M3+ restores the fluorescence intensity (again switches “ON”) and is further quenched (again switches “OFF”) upon the addition of (n-Bu)4NH2PO4, and that completes the second cycle. Thus, the reversible sensing of M3+ by L has been demonstrated for four consecutive cycles without losing the sensitivity of L as can be noticed from Figure 10b−d. Molecular Logic Gate. In this ion-selective sensing experiments, there are four inputs, viz., Cr3+, Fe3+, Al3+, and H2PO−4 , and only one output, that is, the fluorescence intensity at 550 nm (Figure S15). The system has been considered to be either as the “ON” state if the fluorescence emission intensity at 500 nm (FI550) is >5.0 × 105 (a.u.) or as the “OFF” state if otherwise. The presence of any one or more of the metal ion(s) only results in the fluorescence “ON” (value of “1”) situation, and if any one of this combination is fed with H2PO−4 , the system is “OFF” (value of “0”). Using this information, a group of basic logic functions, viz., “OR” (presence of any one or more of the cations) and “NOT” (presence of H2PO−4 ), are constructed as per that given in the logic circuit (Figure 11) and the data given in the truth table (Table 1). A combination of “OR” and “NOT” from this table results in the logic gate “AND”. Thus, this molecular logic gate is basically termed as INHIBIT logic gate. Fluorescence Emission of L and {L + M3+} in the Solid State. The ligand L shows the selective sensing for trivalent metal ions (Al3+, Cr3+, and Fe3+) by showing around 4-fold enhancement in its fluorescence intensity in the solution state. Therefore, the response of L for Al3+ in the solid state was analyzed by fluorescence microscopy. The ligand L itself shows weak fluorescence as observed under a green filter (Figure 12a−c). However, the fluorescence is appreciably enhanced upon addition of M3+ as can be seen in Figure 12d−f and Figure S16. The histogram plot for the mean intensity in all the cases shows ∼3−4-fold enhancement (Figure 12g) in the fluorescence intensity of L, which is consistent with the solution studies. Fluorescence Emission of L and {L + Al3+} in Biological Cells and Cell Imaging. The cell viability assay was performed for L to test its cytotoxicity in MCF7 cells. Upon treatment of varying concentrations (0−80 μM) of L to MCF7 and incubation for 24 h, the cells show a high cell viability of >85% (Figure 13). Therefore, the ligand L does not induce any toxicity to cells and can be used for cellular imaging. In order to understand the sensing of Al3+ in live cells using L by fluorescence enhancement, MCF7 cell lines were initially treated with L followed by Al3+, and the cells were imaged by fluorescence microscopy at every stage. As seen from Figure
Figure 7. Energy level diagram representing the HOMO and LUMO of L and {L + Fe3+} complex.
Figure 8. Space filling model of DFT-optimized structures: (a) L, (b) {L + Cr3+}, (c) {L + Fe3+}, and (d) {L + Al3+} complexes. (e) Atom labeling for the binding core present at the lower rim.
uncomplexed L to its M3+ bound complex, suggesting that the core is reorganized in order to accommodate the M3+ resulting in distorted octahedral binding (Table S05). However, a gross comparison of these space filling structures reveals that the NBD pendant shows a bent structure in the complexes as compared to the uncomplexed L, where the curvature is greatest in the case of the Al3+ complex. This is vivid when the dihedral angle of 14−17 (Figure 8e) in the case of L is compared with its M3+ complexes. The change in this dihedral angle (Table S05) is about twice in the case of the Al3+ complex as compared to that observed with the Fe3+ and Cr3+ complexes. The overall shape of the complex is reminiscent of an elephant trunk in the case of the Al3+ complex. Microstructural Features of L and Its Complexes. The DFT study reveals the binding of M3+ in the preorganized cyclic core present at the lower rim of the receptor L. Therefore, one would expect that the binding of metal ion will not induce any appreciable topological changes in the morphology of the particles. The ligand L shows discrete spherical particles of 300−400 nm as can be observed from SEM micrographs (Figure 9a). This is also in accordance with TEM and AFM micrographs (Figure 8e,i). Thus, the shape and size of the particles formed in the case of all these metal ions (Cr3+, Fe3+, and Al3+) are almost the same (Figure 9a−l). This is possible only when the binding of the M3+ ion is by the lower rim binding core of L. Added to this is the buried nature of the metal ion in the core, 7727
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Figure 9. SEM micrographs of (a) L, (b) {L + Cr3+}, (c) {L + Fe3+}, and (d) {L + Al3+}. In (a)−(d), the scale bars are 100 nm. AFM micrographs of (e) L, (f) {L + Cr3+}, (g) {L + Fe3+}, and (h) {L + Al3+}. Area in (e)−(h) is 10 μm × 10 μm. TEM micrographs of (i) L (scale bar = 200 nm), (j) {L + Cr3+} (scale bar = 1 μm), (k) {L + Fe3+} (scale bar = 200 nm), and (l) {L + Al3+} (scale bar = 200 nm). (m) Elemental analysis of the {L + Cr3+} complex from EDAX. The inset shows the quantification of all the elements present in the complex. (n) Merged image of the mapped elements (C, N, O, and Cr) in the {L + Cr3+} complex. (o−r Mapping of C, N, O, and Cr in the {L + Cr3+} complex, respectively.
there is a 4-fold increase in the fluorescence as quantified using a large number of cells present in the micrograph, and the comparative intensity plot is given in Figure 14g. Comparison of L with the Literature Reported Calix[4]Arene-Based Molecular Systems. There are only
14, feeble green fluorescence was observed when MCF7 cells were treated with only L (Figure 14a−c), and the extent of fluorescence emission is similar to that exhibited by L alone in the powder or in the solution. After the treatment with Al3+, very bright fluorescence was observed (Figure 14d,e). In effect, 7728
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Figure 10. (a) Fluorescence spectra obtained in the titration of {L + Cr3+} with increasing concentration of H2PO−4 (0−3 equiv). Reversible sensing of (b) Cr3+, (c) Fe3+, and (d) Al3+ up to four cycles in which the Y axis shows the fluorescence intensity. Here, an increase in fluorescence stands for the “ON” state, and a decrease in fluorescence stands for the “OFF” state.
Figure 11. Schematic representation of the INHIBIT molecular logic circuit. Here, “INx” refers to the input, and “FI550” refers to the fluorescence intensity as the output. Figure 13. MTT assay of MCF7 cells treated with increasing concentrations of L and incubated for 24 h.
Table 1. Truth Table for the INHIBIT Logic Gate IN1 (Al3+)
IN2 (Fe3+)
IN3 (Cr3+)
IN4 (H2PO−4 )
0 0 0 0 0 0 0 0 1 1 1 1 1 1
0 0 0 0 1 1 1 1 0 1 0 1 0 1
0 1 1 0 1 0 1 0 0 1 1 0 0 1
0 1 0 1 0 0 1 1 0 0 0 0 1 1
output FI550 0 0 1 0 1 1 0 0 1 1 1 1 0 0
(low) (low) (high) (low) (high) (high) (low) (low) (high) (high) (high) (high) (low) (low)
Fe3+, and only two each for Cr3+ and Al3+ are known, wherein the studies were primarily carried out in non-aqueous systems. Therefore, the quest for developing calix[4]arene-based receptors for M3+, particularly for Cr3+ and Al3+ ions, continues. The LOD observed in the case of the present receptor L toward Cr3+ and Al3+ is comparable to those reported in the literature works through fluorescence enhancement. Though one molecular system each for Fe3+ and Cr3+ has been reported earlier in the nanomolar range, these ions exhibit fluorescence quenching and not the enhancement.
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DETAILED HIGHLIGHTS The NBD-appended calix[4]arene conjugate (L) having a cyclic ring structure at the lower rim has been synthesized and characterized thoroughly by analytical and spectroscopy techniques. The L showed “turn on” fluorescence enhancement by 4-fold upon complexation with three trivalent metal ions, viz., Cr3+, Fe3+, and Al3+, due to CHEF. The ligand L exhibited high selectivity toward the recognition of these M3+ ions over the other mono- and divalent ones among the 13 ions studied. The binding of M3+ by L was supported by a decrease in the absorbance accompanied by a blue shift of the absorption band observed at 470 nm. The interaction of M3+ by L resulted in the formation of a 1:1 complex as derived based on the Job plots and was further confirmed by the molecular ion peak observed in ESI-MS in conjunction with the isotope peak pattern authenticating the presence of the corresponding metal ion. All these three M3+ ions bind to almost the same extent with the binding constant being in the range of 104 M−1, also supporting that their binding region is the same. The complexes exhibit a 6-fold increase in its quantum yield as compared to its uncomplexed counterpart, which reflects in the higher sensitivity of their detection, and this is in line with the 4-fold increase observed in the average life time (τav) of the excited species in the case of the complexes. The lowest detection limit of these three M3+ ions by L is in the micromolar range that spans across 1.7 to 2.3 ppm.
Figure 12. Fluorescence microscopy images: (a−c) L and (d−f) {L + Cr3+} in the solid powder. (g) Histogram showing the relative fluorescence intensities (I/I0) of L and {L + M3+} in the solid state where the mole ratio of {L/M3+} is 1:15.
a limited number of calix[4]arene-based conjugates being reported in order to show the M3+ ion sensing, and all these 10 cases are listed in Table 2. Most of these receptors primarily show the sensing of only one M3+ ion. No single calix[4]arenebased conjugate has been reported till now that acts as a receptor for all the three M3+ ions, viz., Fe3+, Cr3+, and Al3+, while the present molecule L acts as a receptor for all these three ions. Seven of these receptors were demonstrated for 7729
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Figure 14. Fluorescence microscopy images of MCF7 cells: (a−c) treated with L (50 μM); (d−f) treated with 250 μM Al3+ to L. (g) Histogram showing the fluorescence intensity of L- and {L + Al3+}-treated MCF7 cells.
Table 2. Sensor Details of Calix[4]arene-Based Systems from the Literature in Comparison with the Present Study M3+
probe
LOD
Tb-calixarene benzimidazole-modified calix[4]arene 3-alkoxy-2-naphthoic acid calix[4]arene pyridyl-appended calix[4]arene anthraquinone-appended calix[4] arene
Fe3+ Fe3+ Fe3+ Fe3+ Cr3+
190 μM 0.027 μM NIL 125 μM 0.004 μM
quinoline-appended calix[4]arene benzoazole calix[4]arene carbohydrazide bis-calix[4]arene cyclohexyl-diamine di-derivatized calix[4] arene tetrasulfonated calix[4]bis-aza-crown nitrobenzoxadiazole-appended calix[4] arene
Fe3+ Fe3+, Cr3+ Fe3+ Al3+ Al3+ Cr3+ , Al3+, Fe3+
solvent
fluorescence response
ref
quenching quenching quenching quenching quenching
19 20 23 24 25
0.334 μM NIL 0.3 μM 9 μM
H2O Tris-HCl buffer (1 mM, pH 7.0) H2O/CH3OH (1:1 (v/v), pH = 6.9) CH3CN CH3CN/aq. phosphate buffer (6:4 (v/v), pH = 7.2) CH3CN CH2Cl2/MeOH (1:1, v/v) DMSO CH3CN
enhancement enhancement enhancement enhancement
11 21 14 9
1.8 μM 4.6−4.8 μM
lutidine buffer solution (pH = 6.0, 10 mM) CHCl3/MeOH (1:59)
enhancement enhancement
22 present work
The complex formation between L with M3+ was further confirmed by isothermal titration calorimetry (ITC) and 1H NMR titration data. The calorimetric data supported the feasibility of the formation of the complex of L by M3+. The shifts observed in the 1H NMR spectra when titrated with Al3+ clearly support the binding of this ion in the cyclic core present at the lower rim. The paramagnetic 1H NMR spectra observed for L in the case of Fe3+ and Cr3+ also confirmed the binding of these ions in the same binding core. The binding core present at the lower rim is evident when one observes the DFToptimized structure of L using the space filling model. This also indicated the orientation of −O ligating centers into this core. The ligating ability of this core was further supported by analyzing the corresponding HOMO in L. Indeed, the inspection of the corresponding structures of their M3+ complexes reveals the binding of these ions in this core. However, a closer look further reveals that each of these ions is penetrated to different extents into the core at the lower rim. This resulted in one or more of long M3+···O distances in the primary coordination sphere. Overall, the analysis of the DFT results support the formation of six-coordinated MO6 core possessing a highly distorted octahedral geometry in the complexes. The NBD pendant takes a bent structure when M3+ is bound to L as evidenced from the dihedral angles exhibited in this region. In the case of Al3+, this takes a twist reminiscent of the trunk of an elephant. All this, invokes the initial
interaction of the metal ion with the NBD moiety followed by complexing L by binding through the lower rim cyclic core. The microscopy (SEM, TEM, and AFM) studies showed that the morphological features, such as shape and size of the complexes, are the same both for the L and its complexes. This is expected when the cyclic core present at the lower rim acts as the binding core for the M3+ ion. This was already deduced based on the experimental and computational data given in this paper. The sensor (L) exhibits a reversible behavior toward M3+ when titrated alternatively with H2PO−4 followed by the M3+ ion, and this has been demonstrated for four cycles by fluorescence spectral measurements. Even in the solid state, the fluorescence emission of {L + M3+} is enhanced by ∼3−4-fold, just like that observed in the case of the solution study. The MCF7 cells also exhibit a 4-fold increase in the fluorescence emission when these cells are incubated with L followed by Al3+. Thus, the fluorescence enhancement in L by the interaction of M3+ is observed not only in the solution but also in the solid state and even in the biological cells. All these support the fact that the utility of L goes even to the biological context. Using the input−output criteria, an INHIBIT logic gate has been demonstrated where the inputs are Cr3+, Fe3+, Al3+, and H2PO−4 , and the output is the variation in the fluorescence intensity FI550 and thus provides an avenue for future development of an appropriate memory device. 7730
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give a final concentration of L of 10 μM, and the [Mn+]/[L] mole ratio was varied from 0 to 10. The bulk concentration of each metal ion solution used was 6 × 10−4 M and prepared in methanol. Sensor Reversibility. The reversible use of the sensor L in the detection of M3+ ions was demonstrated by titrating with H2PO4− and measuring the fluorescence. The emission intensities of all the solutions were recorded in the range of 480−800 nm by using λex = 470 nm. The stock solution of L (0.6 mM) was prepared in CHCl3 and that of M3+ salts (100 mM) and (n-Bu)4NH2PO4 (300 mM) in CH3OH. The cuvette concentration of L was 10 μM in CHCl3/CH3OH (1:59, v/v) using a quartz cuvette with a total volume of 3.0 mL. The solutions of M3+ (3 μL) and H2PO−4 (3 μL) from the stock solutions were consecutively added to the cuvette in order to complete one cycle. Four cycles were repeated for each case. Microscopy Studies. In order to prepare the samples for microscopy studies, the concentrations of L (50 μM, 1.0 equiv) and M3+ salts (Cr3+, Fe3+, and Al3+) (500 μM, 10.0 equiv) were prepared in chloroform/methanol (1:9, v/v). For AFM studies, 15 μL of the solution was dropcasted on the silicon wafer. For SEM studies, the same amount of the solution was dropcasted on the alumina foil in the case of {L + Cr3+} and {L + Fe3+}, whereas the solution of {L + Al3+} was dropcasted on the silicon wafer. For TEM studies, the same amount of solutions was dropcasted on a copper grid. All these samples were dried under IR lamp and then stored in a vacuum desiccator. The L and {L + M3+} solids are ground together in a mortar by pestle, and the solid mixture was analyzed under fluorescence microscopy by using the green filter, and the fluorescence intensity is measured using NIS elements imaging software. Isothermal Titration Calorimetry Study. All the ITC experiments were carried out on a MicroCal isothermal microcalorimeter (Northampton, USA). The molecule L dissolved in acetonitrile (300 μL, 1 mM) was taken in the reaction cell with acetonitrile in the reference cell. The perchlorate salts of M3+ (M = Fe and Al) were taken in the syringe at a concentration of 10 mM. The titration was performed for 20 injections with 2 μL per injection at a time interval of 150−200 s at 20 °C. The data were fitted using the built-in software. NMR Titration of L with M3+. 1H NMR titration studies were carried out on a Bruker Avance III 400 instrument working at 400 MHz. The solution of 8.5 mM L was prepared in a mixture of CD3CN/CDCl3 (4:1, v/v) with a total volume of 600 μL. On each addition, 3 μL of Al3+ solution (100 mM) prepared in CD3CN was gradually added to L, and the spectra were measured until the ratio of [Al3+]/[L] is 0.6 equiv. Similar 1H NMR titrations of L were carried out with Fe3+ and Cr3+ salts. Computational Studies. All the computations are performed using Gaussian 09 software packages.41−43 The model structure for L possessing NBD as the fluorophore was prepared starting from a known crystal structure44 as given in Figure S20 optimized at the B3LYP/6-31G(d,p) level of theory from the already known crystal structure.44 In the subsequent step, the Al3+ ion was placed wrt. L as per that given in Figure S21, and the resultant complex was optimized at the B3LYP level. The complexation of the paramagnetic Cr3+ and Fe3+ ions with L were optimized with unrestricted open-shell formalism using the UB3LYP method where the starting model was prepared by placing the M3+ ion as given in Figure S05. While the metal ions studied here were treated with SDD, all
EXPERIMENTAL SECTION Materials and Methods. All the materials used were of standard analytical grade procured either from Merck or from Sigma-Aldrich and used without further purification. All the reactions were performed under a dinitrogen atmosphere, unless mentioned. The 1H and 13C NMR spectra were measured on a Bruker Avance III 400 and 500 NMR instruments working at 400 and 500 MHz, respectively. The ESI-MS spectra were recorded on a Bruker maXis Impact instrument using electrospray ionization (ESI) in a positive mode method. The steady-state fluorescence spectra were measured on a Horiba Scientific Instrument/Fluoromax-4. The absorption spectra were measured on a Shimadzu UV-NIR3600. Elemental analyses were measured on a Thermo Finnigan FLASH EA 1112 series CHNS instrument. The SEM micrographs of the samples were measured on JSM7600F working at an accelerating voltage of 0.1−30 kV. The TEM micrographs of the samples were measured on TECHNAI G2 F30 TEM working at an accelerating voltage of 200 kV. AFM images of the samples were measured on NanoSurf Flex AFM. Cell images and micrographs of the solidstate fluorescence of samples were measured on a Nikon Eclipse fluorescence microscope. All the solvents used were of HPLC grade and dried by following the routine procedures immediately before use. All the salts used were perchlorates except for Cr3+, which was a nitrate salt. Synthesis and Characterization of Receptor (L). The precursors P 2 and P 3 are synthesized using known procedures,39,40 and the characterization data is given in Figures S17 and S18. A mixture of precursor P3 (500 mg, 0.572 mmol, 1.0 equiv) and 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) (136 mg, 0.686 mmol, 1.2 equiv) was dissolved in 50 mL of dichloromethane, and triethylamine (237 μL, 1.716 mmol, 3.0 equiv) was added to it. The mixture was stirred at room temperature for 48 h. The completion of the reaction was checked by TLC using 50% ethyl acetate in petroleum ether. The crude product was purified by column chromatography filled with neutral alumina (mesh size, 70−290 μm) wherein the elution was carried out using ethyl acetate and petroleum ether in the ratio starting from 10:90 to 40:60 gradually changing in order to give rise to an orange-yellow solid product (L). Yield: 380 mg (64%). 1H NMR (DMSO-d6, 400 MHz) δ (ppm): 9.26 (s, 1H), 8.49 (s, 2H), 8.29 (d, J = 8.4 Hz, 1H), 8.07 (s, 2H), 7.09 (s, 4H), 7.07 (s, 4H), 6.44 (d, J = 9.2 Hz, 1H), 4.49 (s, 4H), 4.19 (d, J = 12.8 Hz, 4H), 3.70 (s, 2H), 3.45 (s, 4H), 3.39 (d, J = 13.2 Hz, 4H), 2.90 (t, J = 7.2 Hz, 2H), 2.84 (s, 4H), 1.14 (s, 18H), 1.08 (s, 18H); 13C NMR(CDCl3, 125 MHz) δ (ppm): 170.1, 149.6, 148.8, 148.8, 144.4, 143.8, 136.8, 132.3, 127.5, 126.3, 125.8, 74.9, 54.5, 40.2, 34.3, 34.1, 32.0, 31.7, 31.1. ESI-MS (HRMS) m/z calculated for C60H76N7O9 [M + H]+ is 1038.5699 and observed is 1038.5677. Elemental analysis for C60H75N7O9 (experimental/ calculated): C = 69.84/69.41, H = 7.39/7.28, and N = 9.38/ 9.44. All the characterization spectra of L are given in Figure S19. Absorption and Fluorescence Titration of L with Metal Ions. All the absorption and fluorescence titrations were carried out using metal ions (viz., Na+, K+, Mg2+, Ca2+, Al3+, Cr3+, Mn2+, Fe2+, Fe3+, Co2+, Ni2+, Cu2+, and Zn2+) in methanol in a 1 cm quartz cell with 50 μL of calix[4]arene conjugate (L) (6 × 10−4 M) prepared in CHCl3. The total volume was made up to 3 mL in each measurement in order to 7731
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ACS Omega the other atoms were treated with 6-31G(d,p). The complexation energies (CEs) are computed using the supermolecule approach. All the complexes optimized were confirmed to be at the minima by carrying out the vibrational frequency analysis. Cell Culture, MTT Assay, and Imaging Studies. The MCF7 cells were cultured in Dulbecco’s modified Eagle’s medium (DMEM) with 10% fetal bovine serum (FBS) and 1% antibiotic and antimycotic (penicillin and streptomycin). Cells were maintained in an incubator at 37 °C and 5% CO2 conditions. For imaging studies, cells were seeded in 60 mm culture dishes (2 million cells per dish) with DMEM media and allowed to grow for 24 h. In order to evaluate the in vitro cytotoxicity of L, the MTT assay was performed. The MCF7 breast cancer cell lines were seeded in a 96-well plate with ∼15,000 cells per well in Dulbecco’s modified Eagle’s medium (DMEM) with 10% FBS. The cells were allowed to grow for 24 h at 37 °C in a 5% CO2 atmosphere and treated with various concentrations of L (0, 10, 20, 30, 50, 80 μM) and incubated for another 24 h. Each well was treated with 0.5 mg/mL MTT reagent and incubated for 4 h. The medium was removed, and 200 μL of DMSO was added into each well to dissolve the crystals formed. The absorbance at λmax = 570 nm was measured using the plate reader. For cell imaging studies, each dish was incubated with L (50 μM) for 60 min. After incubation with L, the cells were treated with 250 μM Al3+ and incubated for another 60 min. At this stage, the cells were thoroughly washed with 1× phosphatebuffered saline (PBS) to remove any excess L or metal ion. The cells were imaged using an inverted fluorescence microscope (Nikon Eclipse Ti Series).
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ACKNOWLEDGMENTS
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REFERENCES
C.P.R. acknowledges financial support from the DST/SERB (EMR/2014/000985) and J. C. Bose National Fellowship (SB/S2/JCB-066/2015) and IIT Bombay for Institute Chair Professorship. S.K.D. acknowledges CSIR for the award of Senior Research Fellowship (09/087(0796)/2014-EMR-I). A.U. acknowledges UGC for the award of Senior Research Fellowship (Ref. No. 21/12/2014(II) EU-V; Serial No. 2121410051). S.P. acknowledges INSPIRE-DST for Ph.D. fellowship (IF150417). We acknowledge the services provided by the central facilities of IIT Bombay, viz., SEM, AFM, TEM, and TCSPC.
(1) Zheng, W.; Li, H.; Chen, W.; Ji, J.; Jiang, X. Recyclable Colorimetric Detection of Trivalent Cations in Aqueous Media Using Zwitterionic Gold Nanoparticles. Anal. Chem. 2016, 88, 4140−4146. (2) Wu, Z.; Liang, D.; Tang, X. Visualizing Hydrogen Sulfide in Mitochondria and Lysosome of Living Cells and in Tumors of Living Mice with Positively Charged Fluorescent Chemosensors. Anal. Chem. 2016, 88, 9213−9218. (3) Liu, T.; Liu, S. Responsive Polymers-Based Dual Fluorescent Chemosensors for Zn2+ Ions and Temperatures Working in Purely Aqueous Media. Anal. Chem. 2011, 83, 2775−2785. (4) Kwon, J. Y.; Jang, Y. J.; Lee, Y. J.; Kim, K. M.; Seo, M. S.; Nam, W.; Yoon, J. A Highly Selective Fluorescent Chemosensor for Pb2+. J. Am. Chem. Soc. 2005, 127, 10107−10111. (5) Wang, M.; Liu, X.; Lu, H.; Wang, H.; Qin, Z. Highly Selective and Reversible Chemosensor for Pd2+ Detected by Fluorescence, Colorimetry, and Test Paper. ACS Appl. Mater. Interfaces 2015, 7, 1284−1289. (6) Bera, K.; Das, A. K.; Nag, M.; Basak, S. Development of a Rhodamine−Rhodanine-Based Fluorescent Mercury Sensor and Its Use to Monitor Real-Time Uptake and Distribution of Inorganic Mercury in Live Zebrafish Larvae. Anal. Chem. 2014, 86, 2740−2746. (7) Uttam, B.; Kandi, R.; Hussain, M. A.; Rao, C. P. Fluorescent Lower Rim 1,3-Dibenzooxadiazole Conjugate of Calix[4]arene in Selective Sensing of Fluoride in Solution and in Biological Cells Using Confocal Microscopy. J. Org. Chem. 2018, 83, 11850−11859. (8) Samanta, K.; Rao, C. P. A Bifunctional Thioether Linked Coumarin Appended Calix[4]arene Acquires Selectivity Toward Cu2+ Sensing on Going from Solution to SAM on Gold. ACS Appl. Mater. Interfaces 2016, 8, 3135−3142. (9) Nehra, A.; Yarramala, D. S.; Bandaru, S.; Rao, C. P. Cyclohexyldiimine capped lower rim 1,3-di-derivatized calix[4]arene conjugate as sensor for Al3+ by spectroscopy, microscopy, titration calorimetry and DFT computations. Supramol. Chem. 2018, 30, 619−626. (10) Mummidivarapu, V. V. S.; Hinge, V. K.; Tabbasum, K.; Gonnade, R. G.; Rao, C. P. Triazole-Linked Anthracenyl-Appended Calix[4]arene Conjugate As Receptor for Co(II): Synthesis, Spectroscopy, Microscopy, and Computational Studies. J. Org. Chem. 2013, 78, 3570−3576. (11) Pathak, R. K.; Dessingou, J.; Hinge, V. K.; Thawari, A. G.; Basu, S. K.; Rao, C. P. Quinoline Driven Fluorescence Turn On 1,3-Biscalix[4]arene Conjugate-Based Receptor to Discriminate Fe3+ from Fe2+. Anal. Chem. 2013, 85, 3707−3714. (12) Uttam, B.; Hussain, M. A.; Joshi, S.; Rao, C. P. Physicochemical and Ion-Sensing Properties of Benzofurazan-Appended Calix[4]arene in Solution and on Gold Nanoparticles: Spectroscopy, Microscopy, and DFT Computations in Support of the Species of Recognition. ACS Omega 2018, 3, 16989−16999. (13) Bhatt, M.; Maity, D.; Hingu, V.; Suresh, E.; Ganguly, B.; Paul, P. Functionalized calix[4]arene as a colorimetric dual sensor for Cu(II) and cysteine in aqueous media: experimental and computational study. New J. Chem. 2017, 41, 12541−12553. (14) Chawla, H. M.; Gupta, T. Novel bis-calix[4]arene based molecular probe for ferric iron through colorimetric, ratiometric, and
ASSOCIATED CONTENT
S Supporting Information *
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsomega.9b00582. Characterization data of P2, P3, and L, construction of the model structure for L, initial optimized geometry of the metal complex, absorption spectra of L with different metal ions, Job plots of L with Cr3+, Fe3+, and Al3+, fluorescence titration spectra of L with different metal ions, binding constant determination, plot for the determination of quantum yield, determination of the limit of detection, 1H NMR titration of L with Fe3+ and Cr3+ , optimized structures of L with M3+ ions, parameters computed for optimized L and its metal complexes, pictorial representation of the HOMO and LUMO of L, EDAX and elemental mapping of {L + Fe3+} and {L + Al3+} complexes, fluorescence titration of {L + M3+} with H2PO4−, and histogram of the fluorescence intensity of L in the presence of M3+ and H2PO−4 (PDF)
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AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected]. Phone: 91 22 2576 7162. Fax: 91 22 2572 3480. ORCID
Chebrolu Pulla Rao: 0000-0002-1004-0028 Notes
The authors declare no competing financial interest. 7732
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detection in aqueous medium and its biological application. Chem. Commun. 2014, 50, 12258−12261. (33) Simon, T.; Shellaiah, M.; Srinivasadesikan, V; Lin, C. C.; Ko, F. H.; Sun, K. W.; Lin, M. C. A simple pyrene based AIEE active schiff base probe for selective naked eye and fluoresence off−on detection of trivalent cations with live cell application. Sens. Actuators, B 2016, 231, 18−29. (34) Barba-Bon, A.; Costero, A. M; Gil, S; Parra, M.; Soto, J.; Martínez-Máñez, R.; Sancenón, F A new selective fluorogenic probe for trivalent cations. Chem. Commun. 2012, 48, 3000−3002. (35) Shellaiah, M.; Simon, T.; Srinivasadesikan, V.; Lin, C. M.; Sun, K. W.; Ko, F. H.; Lin, M. C; Lin, H. C. Novel pyrene containing monomeric and dimeric supramolecular AIEE active nano-probes utilized in selective “off−on” trivalent metal and highly acidic pH sensing with live cell applications. J. Mater. Chem. C 2016, 4, 2056− 2071. (36) Dey, S.; Sarkar, S.; Maity, D.; Roy, P. Rhodamine based chemosensor for trivalent cations: Synthesis, spectral properties, secondary complex as sensor for arsenate and molecular logic gates. Sens. Actuators, B 2017, 246, 518−534. (37) Chereddy, N. R.; Nagaraju, P.; Raju, M. V. N.; Krishnaswamy, V. R.; Korrapati, P. S.; Bangal, P. R.; Rao, V. J A novel FRET ‘off−on’ fluorescent probe for the selective detection of Fe3+, Al3+ and Cr3+ ions: Its ultrafast energy transfer kinetics and application in live cell imaging. Biosens. Bioelectron. 2015, 68, 749−756. (38) Singh, A.; Singh, R.; Shellaiah, M.; Prakash, E. C.; Chang, H.C.; Raghunath, P.; Lin, M.-C.; Lin, H.-C. A new pyrene-based aggregation induced ratiometric emission probe for selective detections of trivalent metal ions and its living cell application. Sens. Actuators, B 2015, 207, 338−345. (39) Joseph, R.; Ramanujam, B.; Acharya, A.; Khutia, A.; Rao, C. P. Experimental and computational studies of selective recognition of hg2+ by amide linked lower rim 1,3-dibenzimidazole derivative of calix[4]arene: species characterization in solution and that in the isolated complex, including the delineation of the nanostructures. J. Org. Chem. 2008, 73, 5745−5758. (40) Bond, A. D.; Creaven, B. S.; Donlon, D. F.; Gernon, T. L.; McGinley, J.; Toftlund, H. Metal complexation of calix[4]azacrown derivatives evidence for communication between upper and lower functionalised rims. Eur. J. Inorg. Chem. 2007, 749−756. (41) Frisch, M. J.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H. P.; Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenberg, J. L.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, J. A., Jr.; Peralta, J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin, K. N.; Staroverov, V. N.; Kobayashi, R.; Norm, J.; Raghavachari, K.; Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega, N.; Millam, J. M.; Klene, M.; Knox, J. E.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Martin, R. L.; Morokuma, K.; Zakrzewski, V. G.; Voth, G.A.; Salvador, P.; Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas, Ö .; Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J. Gaussian 09, Gaussian, Inc., Wallingford CT. 2009. (42) Reed, A. E.; Curtiss, L. A.; Weinhold, F. Chem. Rev. 1988, 88, 899. (43) Glendening, E. D.; Landis, C. R.; Weinhold, F. Wiley Interdiscip. Rev.: Comput. Mol. Sci. 2012, 2, 1. (44) Bandela, A.; Chinta, J. P.; Rao, C. P. Role of the conformational changes brought in the arms of the 1,3-di-capped conjugate of calix[4]arene (L) in turning on the fluorescence of L by Hg2+. Dalton Trans. 2011, 40, 11367−11370.
fluorescence enhancement response. Tetrahedron Lett. 2015, 56, 793− 796. (15) Dhir, A.; Bhalla, V.; Kumar, M. Ratiometric Sensing of Hg2+ Based on the Calix[4]arene of Partial Cone Conformation Possessing a Dansyl Moiety. Org. Lett. 2008, 10, 4891−4894. (16) Park, S. Y.; Yoon, J. H.; Hong, C. S.; Souane, R.; Kim, J. S.; Matthews, S. E.; Vicens, J. A Pyrenyl-Appended Triazole-Based Calix[4]arene as a Fluorescent Sensor for Cd2+ and Zn2+. J. Org. Chem. 2008, 73, 8212−8218. (17) Lee, Y. H.; Lee, M. H.; Zhang, J. F.; Kim, J. S. Pyrene ExcimerBased Calix[4]arene FRET Chemosensor for Mercury(II). J. Org. Chem. 2010, 75, 7159−7165. (18) Maya, R. J.; Krishna, A.; Sirajunnisa, P.; Suresh, C. H.; Varma, R. L. Lower Rim-Modified Calix[4]arene−Bentonite Hybrid System as a Green, Reversible, and Selective Colorimetric Sensor for Hg2+ Recognition. ACS Sustainable Chem. Eng. 2017, 5, 6969−6977. (19) Han, H.; Zhang, G.; Li, K.; Liao, W. A Tb-calixarene coordination chain for luminescent sensing of Fe3+, Cr2O72− and 2,4-DNT. Polyhedron 2019, 163, 84−90. (20) Kaur, H.; Singh, N.; Kaur, N.; Jang, D. O. Nano-aggregate-Fe3+ complex based on benzimidazole-modified calix[4]arene for amplified fluorescence detection of ADP in aqueous media. Sens. Actuators, B 2019, 284, 193−201. (21) Wang, H. W.; Feng, Y. Q.; Chen, C.; Xue, J. Q. Two novel fluorescent calix[4]arene derivatives with benzoazole units in 1,3alternate conformation for selective recognition to Fe3+ and Cr3+. Chin. Chem. Lett. 2009, 20, 1271−1274. (22) Ruan, Y. B.; Depauw, A.; Leray, I. Aggregation-induced emission enhancement upon Al3+ complexation with a tetrasulfonated calix[4]bisazacrown fluorescent molecular sensor. Org. Biomol. Chem. 2014, 12, 4335−4341. (23) Liu, J. M.; Zheng, Q. Y.; Yang, J. L.; Chen, C. F.; Huang, Z. T. A new fluorescent chemosensor for Fe3+ and Cu2+ based on calix[4]arene. Tetrahedron Lett. 2002, 43, 9209−9212. (24) Zhan, J.; Wen, L.; Miao, F.; Tian, D.; Zhu, X.; Li, H. Synthesis of a pyridyl-appended calix[4]arene and its application to the modification of silver nanoparticles as an Fe3+colorimetric sensor. New J. Chem. 2012, 36, 656−661. (25) Sutariya, P. G.; Soni, H.; Gandhi, S. A.; Pandya, A. Novel luminescent paper based calix[4]arene chelation enhanced fluorescence- photoinduced electron transfer probe for Mn2+, Cr3+ and F‑. J. Lumin. 2019, 208, 6−17. (26) Alam, R.; Bhowmick, R.; Islam, A. S. M.; Katarkar, A.; Chaudhuri, K.; Ali, M. A Rhodamine based fluorescent trivalent sensor (Fe3+, Al3+, Cr3+) with potential applications for live cell imaging and combinational logic circuits and memory devices. New J. Chem. 2017, 41, 8359−8369. (27) Goswami, S.; Aich, K.; Das, S.; Das, A. K.; Sarkar, D.; Panja, S.; Mondal, T. K.; Mukhopadhyay, S. A red fluorescence ‘off−on’ molecular switch for selective detection of Al3+, Fe3+ and Cr3+: Experimental and theoretical studies along with living cell imaging. Chem. Commun. 2013, 49, 10739−10741. (28) Marín-Hernández, C.; Santos-Figueroa, L. E.; Moragues, M. E.; Raposo, M. M. M.; Batista, R. M. F.; Costa, S. P. G.; Pardo, T.; Martínez-Máñez, R.; Sancenón, F. Imidazoanthraquinone derivatives for the chromofluorogenic sensing of basic anions and trivalent metal cations. J. Org. Chem. 2014, 79, 10752−10761. (29) Zhan, Z.; Liang, X.; Zhang, X.; Jia, Y.; Hu, M. A water-stable europium-MOF as a multifunctional luminescent sensor for some trivalent metal ions (Fe3+, Cr3+, Al3+), PO43− ions, and nitroaromatic explosives. Dalton Trans. 2019, 48, 1786−1794. (30) Goswami, S.; Aich, K.; Das, A. K.; Manna, A.; Das, S. A naphthalimide−quinoline based probe for selective, fluorescence ratiometric sensing of trivalent ions. RSC Adv. 2013, 3, 2412−2416. (31) Venkateswarulu, M.; Mukherjee, T.; Mukherjee, S.; Koner, R. R. Turn-on trivalent cation selective chemodosimetric probe to image native cellular iron pools. Dalton Trans. 2014, 43, 5269−5273. (32) Wang, J.; Li, Y.; Patel, N. G.; Zhang, G.; Zhou, D.; Pang, Y. A single molecular probe for multi-analyte (Cr3+, Al3+ and Fe3+) 7733
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