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Home > Substitution Effect on Near Infrared Absorbance Based Selective Fluoride Sensing of Indole Functionalized Thiourea Molecules
Substitution Effect on Near Infrared Absorbance Based Selective Fluoride Sensing of Indole Functionalized Thiourea Molecules
Bijit Chowdhury, Sanghamitra Sinha, and Pradyut Ghosh
Introduction
Chemical sensing of fluoride is of high importance due to its applications in industry, food, toxicity and the major role played by it in a wide range of biological and environmental processes.[1,2] Several research groups are actively working on the area of designing fluoride sensors based on different mecha- nisms.[3–10] Literature reports are well enriched with colorimetric detection of fluoride utilizing urea, thiourea amides, sulfon- amides, pyrroles, indoles etc. units having acidic hydrogen at- oms.[7–11] On the other hand, a chemosensor with a near-infra- red (NIR) optical response which could avoid interference from endogenous chromophores are useful in biological systems and hence emerge high demand in practical purposes. Our group has shown a characteristic NIR signal based sensing of fluoride along with the change in color using indole functionalized urea/ thiourea receptors.[7e,10d] These reports ascertain that, ind- ole conjugated urea/ thiourea units are the key to achieve the NIR signature. Thus, to design a class of sensors which can be useful for sensing of fluoride in broad NIR window, the indole conjugated urea/ thiourea platform could be the choice, where the indole unit can be functionalized with the substituents and would have an effect on the NIR signature by virtue of position, conjugation, steric and inductive/ mesomeric effects. We envis- age that the planarity of the system and electronic effect of the functional groups in the indole moiety might play an important role on the NIR signatures. Thus 2 and 5 positions of the indole moiety could be cosidered to functionalize with suitable sub- stituents having different steric and electronic effects for tuning the NIR sensing behaviour by fluoride. Here we report six such simple indole conjugated thiourea systems eg. S1–S6 which show fluoride sensing within a broad NIR window i.e. from 825 nm to 1160 nm, depending on the nature and position of the substituent in the indole moiety. To the best of our knowledge, this is the first ever report of such a huge red-shifted (≈ 800 nm) NIR signal at ≈ 1160 nm in the presence of fluoride.
Results and Discussion
Synthesis and Characterization: All the ligands S1-S6 are syn- thesized from the corresponding indole-3-carboxaldehyde de- rivatives via Schiff base condensation reaction with thiocarbo- hydrazide in ethanol/water (2:1; v/v) mixture under reflux for 24 h and followed by the collection of precipitates by filtration (Scheme 1). All the ligands S1-S6 are fully characterized by NMR, ESI-MS, elemental analysis (Figure S1-S17, Supporting In- formation) and single-crystal X-ray structural analysis wherever possible.
Colorimetric detection of Anions: Firstly, colorimetric changes of sensors S1-S6 are investigated in the presence of different anions e.g. F–, Cl–, Br–, I–, NO –, HCO –, AcO–, BzO–HSO –, H PO –, HP O 3– etc. Among them, only F–, BzO–, AcO–, less acidic and as a result the interaction with anion is expected to be less. However, 5-methoxy substitution does not alter the UV/Vis-NIR absorption spectra of the deprotonated species obstituted deprotonated species where the extra conjugative dou- ble bond is absent. Binding affinities of sensors S1-S6 with F–, AcO–, BzO–, H2PO – and HP O 3– are determined using UV–vistained from the unsubstituted indole conjugated thiourea de- rivative (S1). Methoxy substitution in the 5-position have nega- tive inductive effect (-I) and positive mesomeric effect (+R) and as a whole it turns out to add no extra effect compared to the unsubstituted indole conjugated thiourea derivative (S1). Thus 5-MeO substituted derivative (S5) show similar color change and UV/Vis-NIR spectral pattern as that of S1. Substitution of -NO2 group at the 5-position of indole unit in the case of S4, where is -NO2 can exert both -I as well as -R effects and this eventually increases the acidity of the -NH proton of the thio- urea unit. Thus this sensor S4 is expected to interact better with anions. However, the NIR peak position is blue shifted com- pared to that of unsubstituted one (S1). This may be due to the cross conjugation of the deprotonated species with the competitive nitro group which in turn affects its conjugation in the entire structure as the case normally obtained for other sensors S1-S3, S5 and S6. As the normal conjugation is affected by the cross conjugation with the nitro group the sensor S4 shows weak absorbance in the NIR region. In case of S6, ab- sorption peak of the deprotonated species formed in the pres- ence of F– appears at around 1160 nm (Figure 2f) along with dark greenish yellow coloration and visible peaks at 412, 597 and 670 nm. This can be justified from the fact that in case of sensor S6, the presence of extra conjugation in the structural framework of the sensor increases to some extent compared to that of unsubstituted one which allows more stabilization of the deprotonated species via delocalization of the negative charge throughout the entire structure compared to that of the unsubstituted deprotonated species where the extra conjugative dou- ble bond is absent. Binding affinities of sensors S1-S6 with F–, AcO–, BzO–, H2PO – and HP O 3– are determined using UV–vistitration experiments. From UV/Vis titration of S1-S6 with F–, it is clear that upon gradual addition of F–, the absorption peak for the sensors S1-S6 at ≈ 350 nm decreases with concomitant appearance of a new absorption peak at ≈ 400–435 nm with one clear isosbestic point. All the titrations reach saturation limit at ≈ 4 equiv. F– concentration for all these sensors (Fig- ure 3). As the concentration of fluoride increases (>4 equiv.), the absorbance of S1-S6 at ≈ 400–435 nm gradually decrease, with the concomitant appearance of NIR peak ≈ 942, 956, 825, 948, 890 and 1160 nm, respectively. This process continues till the addition of 12 equiv. F– and no more changes in absorb- ance takes place upon further addition of F–.
The apparent binding affinities towards fluoride are calcu- lated for sensors S1-S6 from the UV/Vis titration data using non-linear fitting equation, considering a 1:1 binding pattern (Figure 4). The calculated association constants with F– for sen- sors S1-S5 are enlisted in Table S1, Supporting Information. Here it has to be mentioned that, the deprotonation equilib- rium which takes place at higher fluoride concentration, has not been taken into account for calculation of association constants. Only the equilibrium for the adduct formation between ligand and fluoride has been considered.
To ensure the photostability of the sensors, which is a com- mon issue for thiourea based systems, the photophysical prop- erty and colorimetric sensing phenomenon for each ligand is done repeatedly which gives the same response. The colors of the solutions after fluoride addition also remain intact for sev- eral days.
We have also performed the UV/Vis titration of the sensors S1-S6 with AcO–, BzO–, H2PO – and HP O 3– under the same experimental condition (Figure S19-S30, Supporting Information). The corresponding spectral pattern matches with that ob- tained with 0–4 equiv. addition of F–. However, further addition of these three anions (2–10 equiv.) fails to develop any NIR signature in the corresponding absorption spectra. These UV/Vis titration experiments lead us to conclude that initially anions (F–, AcO–, BzO–, H2PO – and HP O 3–) are bound to the thiourea and indole -NH units via hydrogen bonding interac- tion. Existence of one isosbestic points for all the sensors indi- cates the presence of two species in equilibrium; one of them is free sensor and the other is hydrogen bonded anion adduct of the sensor. However, the highly basic anion F– further depro- tonate the thiourea and indole-NH protons resulting extensive delocalization of the corresponding deprotonated species throughout the receptor framework and leads to the generation of the NIR absorption characteristics where peak position varies with varying functional groups because of their different posi- tional, conjugational, size and inductive effects.
Single Crystal X-ray Structural Study: We were able to iso- late the single-crystal X-ray structures of S2, S4 and S5 via slow evaporation of its DMF/Ethanol mixture. The crystal structure is presented in Figure 5. From the crystal structures, it is clearly seen that the receptors adapt syn-anti conformation around thiourea group which reduces the steric interaction between the side chains resulting almost planar geometry. For S2, the phenyl group at the 2-position of the indole moiety is exactly bisecting the molecular plane and is situated at a perpendicular orientation with respect to the molecular plane. Therefore, sub- stitution of the indole group at the 2-position by phenyl unit does affect the planarity of the molecule. Again, for S4 and S5 X-ray structures indicate planarity of the indole unit and its conjugated 5-NO2 or 5-OMe groups, respectively. Thus, the spectroscopic changes of the said two sensors only differs from the electronic effect of the substituted group. Though we have not got single-crystal X-ray structure of other receptors, we ex- pect similar structural pattern for the other receptors. Single crystal X-ray structures of phosphate adducts of ligand S1 and S5 are isolated by ether diffusion of DMF/ methanol (3:1) solu- tion. Interestingly, these crystal structure shows that the phos- phate anion is present as dimer through the hydrogen bonding interaction between two phosphate unit (Figure 6). Importantly, the indole –NH and thiourea –NH functionalities provide strong hydrogen bonding interactions towards the oxygen atoms of the phosphates for their recognition (Tables S2-S4 and Figures S31-S32, Supporting Information). However, the conformation around the thiourea group remains almost unchanged, i.e. syn- anti even after anion binding. This might be due to the use of same solvent i.e. DMF for crystallization of the ligands as well as their anion adducts, which may nullify the effect of solvent on conformational change of thiourea during crystallization.[12a] Moreover, as evidenced from the single-crystal X-ray structures, the dihydrogen phosphate anion binds with the receptors not via two thiourea NH groups, which, in general leads to confor- mational changes at that center. Rather, it forms non-covalent bonds with imidazole NH group keeping the conformation around thiourea center intact. From UV/Vis experiment it is clear that the anions AcO–, BzO–, HP O 3– and H PO – render similar shift in the free sensor spectra and as the single crystal struc- ture demonstrates hydrogen bonded phosphate adduct of the sensors it can be said that AcO–, BzO–, HP O 3 and H PO, all these anions interacts with the sensors S1-S6 through hydrogen bonding interactions.
Mechanistic Investigation by 1H-NMR experiment: 1H NMR titration studies are carried out to find out the mechanism of the anion binding with the sensors. Upon gradual addition of tetrabutylammoniumfluoride to the [D6]DMSO solution of the receptors, broadening of indole and thiourea -NH protons take place after the addition of 1 equivalent of F–. This may be due to binding as evident from single crystal structural studies.
However, the appearance of broad HF – signals at δ =16.1 ppm (Figure S33-S34, Supporting Information) upon addi- tion of higher equiv. of F– suggests deprotonation of the indole and/or thiourea -NH protons. The negative charge of the depro- tonated moiety is delocalized over the molecule due to the overall conjugation and this, in turn, could be responsible for the NIR signal along with a visible color change in the presence of fluoride.
Conclusions
In summary, we have synthesized a new series of indole func- tionalized thiourea derivatives having substituents of varying electronic and steric effect. All the sensor molecules show NIR fluoride sensing behaviour and are useful to differentiate fluor- ide from other closely related basic anions e.g. acetate, benzo- ate, dihydrogen phosphate and hydrogen pyrophosphate by colorimetric as well as optical studies. Deprotonation of indole- NH in the presence of F– leads to the generation of NIR signa- ture in the range ≈ 825–1160 nm depending upon the substitu- tion and conjugation in the indole unit. Interestingly, the syn- thesized indole conjugated thiourea derivative with one extra alkene unit in the receptor framework shows NIR signal at 1160 nm and to the best of our knowledge this is the first ever report on such a huge red shift (≈ 800 nm) in the absorption spectra of a receptor molecule in the presence of fluoride. This series of sensors can be useful for the sensing of fluoride in a broad NIR window i.e. in the range ≈ 825–1160 nm. The conjugation on the indole substituent can further be increased to get re- sponse close to IR region.
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