- Email: [email protected]
Synthesis and characterization of tri-quinoline based receptors and study interactions with Zn2+ and Cu2+ ions
Accepted Manuscript Synthesis and characterization of tri-quinoline based receptors and study interactions with Zn2+ and Cu2+ ions Prithiviraj Khakhlary, Jubaraj B. Baruah PII: DOI: Reference:
S0020-1693(15)00514-9 http://dx.doi.org/10.1016/j.ica.2015.10.020 ICA 16730
To appear in:
Inorganica Chimica Acta
Received Date: Revised Date: Accepted Date:
14 August 2015 15 September 2015 12 October 2015
Please cite this article as: P. Khakhlary, J.B. Baruah, Synthesis and characterization of tri-quinoline based receptors and study interactions with Zn2+ and Cu2+ ions, Inorganica Chimica Acta (2015), doi: http://dx.doi.org/10.1016/ j.ica.2015.10.020
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Synthesis and characterization of tri-quinoline based receptors and study interactions with Zn2+ and Cu2+ ions Prithiviraj Khakhlary and Jubaraj B. Baruah* Department of Chemistry, Indian Institute of Technology Guwahati, Guwahati 781 039, Assam, India. Phone +91-361-2582311, Fax: +91-361-2690762, http://www.iitg.ernet.in/juba. Abstract: Synthesis, characterization of the two tri-quinoline based receptors and binding with copper and zinc ions are presented. The changes in the fluorescence emissions of such receptors are caused specifically by Zn2+ or Cu2+ ions. But presence of these two ions affects the fluorescence emission intensity of the receptors in an opposite manner. Conventional masking effect on fluorescence emissions caused by copper ions while detecting zinc ions by quinoline based receptors was not observed in one of the receptor. Among the two receptors studied, one receptor shows irreversible but selective detection of Zn2+ and Cu2+ ions over a range of metal ions.
Introduction: There are large numbers of examples of small fluorescent molecules which are used to detect metal ions [1-14]. Metallo-organic frameworks constructed from small molecules are also used in the detection of various metal ions [15-22]. Some analytes show selective fluorescence emission response to two or more metal ions [23-27]. Divalent zinc and copper ions are found together as constituents of some biological systems [28-32]. The Zn2+ ions play vital roles in signal transmission and mammalian reproduction [33-34]. The Cu2+ ions play important roles in physiological processes of organisms [35-37]. Excessive amounts of zinc ions in the human body can cause alzheimer, epilepsy and infantile diarrhea [38], whereas excess copper ions can cause neurodegenerative diseases [39-42]. Thus, fluorescent receptor having ability to specifically cause fluorescence changes by these two ions have general interest, however, the receptors designed for zinc (II) and copper (II) ions fail to detect zinc ions in the presence of copper ions 1
[43-60]. So, it is essential to develop new receptors that would reversibly detect these ions. Fluorescent sulphonamide derivatives of aminoquinolines have potential in imaging zinc ions [61]. Water soluble quinoline derivatives were prepared which have ability to sense zinc ions under biological conditions [62-63]. Fundamental problem with such receptors is that, their fluorescence emissions are affected by series of metal ions other than zinc ions [64]. Such a problem was partly overcome by designing quinoline receptors which operates through internal charge transfer mechanism [65]. Lippard and his coworkers [66] developed very efficient quinoline based sensors for detection of zinc ions. These receptors have two pendant arms bearing 8-aminoquinolines have higher efficiency over similar receptors with quinoline unit at one arm. There exists opportunity to prepare assemblies of multiple numbers of quinoline rings to hold multiple numbers of metal ions as illustrated in Figure 1. The two tri-quinoline based compounds 1 and 2 (Figure 1) would have two flexible arms to hold metal ions and they would have an openly projected 4-quinoline ring. Thus they will be suitable to form metal complexes as illustrated schematically in Figure 1. Compounds 1 and 2 have bis-phenolate ether tethers connecting quinoline amide moieties. Additional 4-quinoline moiety provides a shape like a projectile with two open wings. The choice of these compounds also arises from the facts that the zinc [27, 43-54] and the copper ions [55-60] can change fluorescence emissions of quinoline derivatives with high specificity. Masking of fluorescence emission by copper ions of quinoline derivatives over the zinc ions [67] is not overcome so far in this class of receptors. Bis-8aminoquinoline amide derivatives were shown to lose fluorescence response to zinc ions in the presence of copper ions [68]. There are reports on the steric and electronic effects contributing to stabilize different conformations of amides [69-71]. A substituent atom or group present at an appropriate position of some amide derivatives can change rotational barriers of trans or cis conformers of amides [72]. These factors also contribute to fluorescence emission occurring through twisted intramolecular charge transfer (TICT) mechanism of some amides derivatives [72-74]. On the other hand, compounds 1 and 2 have a portion of the structure which has pincer type of geometry and ligands of such geometrical features easily form copper and zinc complexes [75-79]. We show that compounds 1 and 2 having difference in substituent in their skeleton have distinct selectivity in showing fluorescence changes with divalent copper and zinc
2
ions. Compound 1 irreversibly distinguishes copper and zinc ions, whereas compound 2 does it reversibly. Figure 1 here
Experimental: Physical measurements: UV-Vis spectra data were recorded using Perkin-Elmer Lambda 750 UV-Vis spectrophotometer. The compounds solutions were prepared in methanol.
Fluorescence measurements were
performed on fluoromax-4 spectrofluorometer using 10 mm path length quartz cuvettes with the slit width of 10 nm at room temperature. 1H-NMR spectral data were recorded either on a Varian-AS400 spectrometers or on a Bruker 600MHz NMR spectrometer. Infrared spectra were obtained by using a Perkin-Elmer FT-IR spectrophotometer (4000-400 cm-1). ESI-mass spectra were recorded on a micro mass Q-TOF (Waters) mass spectrometer using a matrix in acetonitrile / formic acid. Energy level calculations were carried out using the hybrid B3LYP functional [80] under the density functional theory framework with the Gaussian03W program package. Thermodynamic parameters of the binding constants of compound 1 were determined on an iTC 200 Microcalorimeter at 20 °C. Absorptions and emissions measurements were performed with solutions of 1 and 2 or metal chloride prepared in methanol. Solution of 1 or 2 (3 mL, 10-5 M) was taken in quartz cuvette and it was titrated with the particular metal chloride solution. Titrations with the solution of each compound with the metal ions were done by recording the UV-visible or the fluorescence emission spectra by adding the desired amount of the solution of the metal ions in aliquot. Synthesis and Characterizations: 2-Bromo-N-(quinolin-8-yl)acetamide [81], 4-quinoline-bis-phenol (1a)21b and 4-quinoline-2,6dimethyl-bis-phenol (2a) [82] were prepared by reported procedures. Synthesis of 4-quinoline-bis-phenol-N-(quinolin-8-yl)acetamide (1):
2-Bromo-N-(quinolin-8-
yl)acetamide (1.06 g, 4 mmol), bis-phenol 1a (0.67 g, 2 mmol) and anhydrous potassium carbonate (1.11 g, 8 mmol) were added to dry acetone (20 mL) under a nitrogen atmosphere and 3
the reaction mixture was stirred at 60°C for 10 h. (Progress of the reaction was monitored at a regular time interval using TLC). After completion of the reaction, solvent was removed under reduced pressure to obtain a pale yellow solid. The solid was washed with a dilute sodium hydroxide solution (5%) followed by water; then extracted with dichloromethane. Subsequent removal of the solvents and purification by column chromatography (silica gel; hexane/ethyl acetate 3:2) gave 1 in 60 % yield. The solid crude product was crystallized from methanol/DMF (4:6) solvent mixture. Melting point: 183 ºC. Elemental anal. Calcd for C44H33N5O4, C, 76.06, H, 4.78; found C, 76.01, H, 4.77. 1H-NMR (600 MHz, DMSO-d6): 10.71(s, 2H), 8.90 (dd, J = 0.8 Hz, 2H), 8.77 (d, J = 3.2 Hz, 1H), 8.67 (d, J = 5.6 Hz, 2H), 8.42 (dd, J = 0.8 Hz, 2H), 8.09 (d, J = 5.6 Hz, 1H), 8.02 (d, J = 6.0 Hz, 1H), 7.71 (m, 3H), 7.65 (d, J=2.8 Hz, 2H), 7.61 (t, J = 5.2 Hz, 2H), 7.50 (t, J = 5.6 Hz, 1H), 7.12 (m, 8H), 6.86 (d, J = 3.2 Hz, 1H), 6.40 (s, 1H) 4.86 (s, 4H). ESI mass: calculated for C44H34N5O4 [m + 1] = 696.2611; found 696.2676. IR (cm-1): 3360 (s), 3339 (s), 2924 (m), 1638 (s), 1598 (m), 1539 (s), 1505 (s), 1425 (m), 1384 (m), 1326 (m), 1237 (s), 1217 (m), 1174 (m), 1055 (m), 826 (m), 786 (m), 754 (m), 603 (m), 513 (w). 4-Quinoline-2,6-dimethyl-bis-phenol-N-(quinolin-8-yl)acetamide (2) was synthesized by a similar procedure as for 1 where 2a was used instead of 1a. The compound 2 was obtained as solid crude product with a yield ~ 40 %. Melting point: 157 ºC. Elemental anal. Calcd for (C48H42N5O4 ).H2O, C, 74.79, H, 5.75; found C, 76.76, H, 5.76.
1
H-NMR (600 MHz, DMSO-
d6): 11.23 (s, 2H), 8.86 (t, J = 3.6 Hz, 3H), 8.83 (d, J =1.2 Hz, 2H), 8.18 (d, J =1.2 Hz, 1H), 8.17 (dd, J =1.2 Hz, 2H), 8.00 (d, J = 8.4 Hz, 1H), 7.70 (t, J = 6.0 Hz, 1H), 7.58 (m, 4H), 7.51 (t, J = 6.0 Hz, 1H), 7.47 (q, J = 4.2 Hz, 2H), 7.26 (s,1H), 6.98 (t, J = 4.2 Hz, 1H), 6.81 (s, 3H), 6.09 (s, 1H), 4.56 (s, 4H) 2.35 (s, 12H). ESI mass: calculated for C48H42N5O4 [m + 1] = 752.8782; found 752.3273. IR (cm-1): 3328 (s), 2922 (s), 2852 (m), 1676 (s), 1591(m), 1536 (s), 1483 (s), 1425 (m), 1384 (m), 1323 (m), 1203 (s), 1145 (s), 1047 (m), 952 (w), 824 (m), 791(m), 748 (m), 663 (w), 595 (w), 555 (w), 506 (w). Results and discussion: The compounds 1 and 2 were synthesised by reacting 2-bromo-N-(quinolin-8-yl)acetamide with the corresponding bis-phenol (1a or 2a) in dry acetone in the presence of anhydrous potassium carbonate (Scheme 1). All the starting materials and the final products were characterised by 1H4
NMR, IR spectroscopy and mass spectrometry. As there are three quinoline moieties present in the compounds 1 and 2, the protons on the quinoline units were assigned from the analysis of the observed coupling patterns of typical 2D-1H-HOMOCOSY spectra of the compound 1 shown in the supporting Figure S1. Scheme 1 here Single crystal X-ray structure of compound 2 revealed that two quinoline rings are almost coplanar and carbonyl groups of amides lie in this plane, but project outward with respect to the nitrogen atoms of quinoline rings. The projection of the carbonyl groups are reflected in the dihedral angles, listed in the caption of Figure 2. Both the compounds 1 and 2 are crystalline solids, but we could not get suitably diffracting crystals to determine the structures with high accuracy but could obtain the information that the compound 1 has also similar structure as that of the structure of the compound 2. Figure 2 here The tri-quinoline derivatives 1 and 2 possess V-shape bis-phenolate ether linkage anchoring flexible methylene groups, such units are flexibile and suitable to adopt different orientations depending on conditions. Generally constraints provided by the substituent present in a flexible receptor enhance selectivity to bind to metal ions [83-84]. Differences in binding ability of metal ions to a receptor influences internal charge transfer which influences the position and the intensity of their fluorescence emissions of the receptor [85]. Since the compounds 1 and 2 have different groups at two aromatic rings, hence their optical properties are expected to differ with coordination environment and electronic factors of different metal ions. Figure 3 here Intensities of the UV absorptions of the 1 present at 252 nm and 360 nm were increased upon the addition of a solution of Zn2+ ions (Figure 3a). The spectral changes took place at a cost of the absorption present at 303 nm. As a result of such changes three isosbestic points at 245 nm, 280 nm and 331 nm had appeared. Similar spectral changes were observed upon the addition of a solution of Cu2+ ions to a solution of 1. A series of ions such as Li+, Na+, K+, Be2+, Mg2+, Ca2+, 5
Ni2+, Co2+, Mn2+, Cd2+ and Hg2+ did not change the absorption spectra of the compound 1. However, the Zn2+ and Cu2+ ions were relatively less effective in changing the UV absorbance spectra of the 2 (figure 3b) as compared to the compound 1. Addition of a solution of Zn2+ ions to a solution of the 2, the absorption peak appearing at 255 nm which is attributed to n→π* transition get increased with a concomitant decrease in the absorption at 226 nm (π→π*) and 286 nm (n→π* transition).
These changes of UV absorbance passed through isosbestic points
appearing at 243 nm, 282 nm and 330 nm. The extinction coefficients of the absorbance at 303 nm of the methanol solution of the compounds 1 and 2 are 8753 cm2 mol-1 and 9671 cm2 mol-1 respectively. From the above titrations and using Benesi and Hildebrand equation association constants and logKa of the compound 1 with Zn2+ and Cu2+ ions were found to be 5.07 and 5.13 respectively. Whereas, from similar experiments with the compound 2, the respective logKa values were found to be 4.84 and 4.91. For both the compounds we obtained comparable binding constants for Zn2+ and Cu2+ ions. Thus, both the metal ions should be able to replace each other. However, Cu2+ ions can replace Zn2+ ions as they have higher tendency of giving stable complex than Zn2+ ions. But due to substituent effect on the compounds 1 and compound 2, the conformational rigidities of these compounds are different hence they may bind in reversible manners to copper and zinc ions. With such anticipation we followed up further studies through fluorescence experiments. Figure 4 here A methanol solution of compound 1 shows a broad fluorescence emission peak at 397 nm on excitation at 310 nm and on similar excitation a methanol solution of the compound 2 showed broad emission peak at 400 nm. Both the emission spectra have a shoulder at 340 nm. This emission peak could be from the quinoline ring, whereas broad and intense emission at 397 nm and 400 nm for the compounds 1 and 2 respectively are originate from the aminoquinoline rings. The positions of emission spectra of the compounds do not change with changes in concentrations, which suggest that there are no interactions between the aminoquinoline groups present in these compounds. These observations are conventional as bis-aminoquinoline derivatives show fluorescence emissions at similar wavelengths [67-68].
6
The intensity of the fluorescence emission peak of the compound 1 present at 397 nm decreases upon addition of Zn2+ ions and a new emission peak at 493 nm appeared. As the concentration of the Zn2+ ions was increased the intensity of this peak was increased to reach a maximum value. Further addition of the Zn2+ ions, this emission peak at 493 nm splits up into two new independent emission peaks appearing at 451nm and 551 nm (Figure 4a). These two broad peaks formed by splitting of an emission peak spreads over range 430-580 nm is a unprecedented observation in quinoline system and resembles white light emission. This occurs at low concentrations of the zinc ions (upon addition of about 0.33 eq of Zn2+ ions) with respect to the compound 1, thus the ligand to metal ion molar ratio is at about 30:1. Based on the observation at a low concentration of zinc ions, effect can be suggested to originate from a sensitization process caused on compound 1 by zinc ions rather than a conventional complex formation. This type of emission phenomenon can be projected as an exceptional observation as Stokes shift 183 nm was observed with emission at 493 nm. When this emission changed to two wavelengths the Stokes shift associated with new peaks were 141 nm and 241 nm. In literature a maximum Stokes shift of 199 nm was observed from an aminoquinoline derivative on interaction with zinc ions due to internal charge transfer (ICT) mechanism [65]. Thus compound 1 is suitable to modulate fluorescence by changing concentrations of zinc ions. Similar fluorescence titrations were carried out with compound 1 by adding Li+, Na+, K+, Be2+, Mg2+, Ca2+, Ni2+, Co2+, Mn2+, Cd2+ and Hg2+ ions. These ions showed insignificant changes in fluorescence emissions of compound 1. We find that addition of a solution of Cu2+ ions to a solution of compound 1 decreases the fluorescence emission of the compound 1 present at 397 nm. In spite of the 96 nm red shift with enhancement of fluorescence on 1 upon addition of Zn2+ ions was observed it loses its fluorescence on addition of Cu2+ ions. It was also observed that once fluorescence of the compound 1 was quenched by Cu2+ ions, the addition of zinc ions to such a solution could not recover the emission. The compound 2 is a more structurally rigid derivative in comparison to the compound 1, as it has two methyl groups attached to each aromatic ring of bis-phenolate groups. Analogous to compound 1, on addition of Zn2+ ions to solution of compound 2 decreases its emission at 400 nm with enhancement of intensity of the emission at 490 nm (Figure 5a). On the other hand this compound also showed decrease in fluorescence emission of the emission at 400 nm upon 7
addition of Cu2+ ions (Figure 5b). However, we found a major difference between the fluorescence emissions of these two compounds on interactions with zinc ions is that at higher concentrations of zinc ions no splitting of fluorescence emission peak was observed in the case of the compound 2. Compound 2 showed single emission peak at 490 nm on addition of Zn2+ ions, and for this emission peak Stokes shift observed was 180 nm. Notable observation is that the quenching of fluorescence on addition solution of Cu2+ ions to a solution of 2 can be recovered by adding a solution of Zn2+ ions; thus each of these metal ions can be detected by fluorescence technique in the presence of each other. Reversibility in the fluorescence emission changes caused by two metal ions on the compound 2 was established by carrying out a series of competitive experiments. To do so, we added equivalent amount of cupric chloride to a solution Figure 5 here of compound 2, this decreased the fluorescence emission at 400 nm to a lowest level. To this solution, a methanol solution of zinc chloride was added in 0.033 mole equivalent in each aliquot. We observed that the fluorescence emission at 490 nm increased as concentrations of zinc ions were increased (Figure 5c). In an another experiment a fluorescence titration was carried out by adding a methanol solution of zinc chloride solution to a solution of
the
compound 2, addition continued till there was no further increase in fluorescence at 490 nm took place (Figure 5d). After reaching this point, a solution of copper chloride was added, which resulted in a decrease in the fluorescence emission at 490 nm and emission continue to shift to show a fluorescence emission peak at 400 nm and after reaching this stage, fluorescence emission at the 400 nm decreases to a minimum on continuation of addition of cupric chloride solution (Figure 5d). To prove competitive effect of these two ions, we have carried out a series of experiments by changing sequence of addition of zinc and copper ions to respective receptor solution and vice-versa. In each experiment metal ions solutions were added until there was no further change in fluorescence emission. Once this stage was reached addition of another solution of metal ion was added. The changes in normalized fluorescence intensities from different control experiments from such fluorescence titration experiments with one metal ion to reach a highest limit of emission intensity followed by another metal ion to reduction of intensity or vice versa 8
are shown in Figure 6. As seen in Figure 6a, addition of the solution of cupric chloride quenched fluorescence emission of the compound 1 at 397 nm; when a zinc chloride solution was added to such a solution, the original fluorescence of the compound 1 could not be recovered, which shown by blue straight line of squares in Figure 6a. However, when a solution of zinc chloride (circles in Figure 6b) was added, the fluorescence emission increased to a particular concentration. But due to splitting of the fluorescence emission beyond this critical concentration as discussed earlier there was an apparent decrease in the fluorescence emission (Figure 6b). Hence to avoid confusion, intensity changes beyond this point are not shown in this figure. When a solution of cupric chloride was added to this solution, the fluorescence got quenched (squares in Figure 6b). These data clearly established the fact that the quenching in the fluorescence emission of compound 1 caused by copper ions could not be retrieved, as the addition of Zn2+ ions did not changed the fluorescence intensity of compound 1 containing Cu2+ ions. On the other hand, similar experiments carried out with compound 2 (Figure 6c and 6d) have revealed that fluorescence quenching at 400 nm caused by the cupric chloride could be retrieved by adding a solution of zinc chloride, and fluorescence enhancement caused by zinc ion could be quenched by cupric chloride. Figure 6 here
We carried out independent isothermal calorimetry titration of compound 1 with zinc chloride and copper chloride. Binding isotherms (supporting Figures S2 and S3) were obtained by integrating raw data which was fitted to a “one-site” model. We found the raio of metal ion binding to ligand as 1.31 : 1 and 1.37 : 1 for zinc and copper ion respectively. Binding constant (K) with zinc ion is 2.67 × 104 M-1and with copper is 3.47 × 104 M-1. The corresponding logKa values are 4.42 and 4.54 respectively. The enthalpy changes in case of zinc and copper ions are 7.843 cal/mol and -9.239 cal/mol and respectives entropy changes are -239 cal/mol/° with zinc (II) ions and -289 cal/mol/° with copper (II) ions These suggest that in each case three ligands are associated with four metal ions. Based on the ratio of metal to ligand obtained from isothermal calorimetry titration, we proposed the structure of the aggregate with divalent copper or zinc as shown in Figure 7, which was generated using GaussView. Figure 7 here 9
1
H-NMR titration of compound 1 with zinc chloride showed emergence of new set of peaks
other than the ones that were observed from parent compound 1. These new signals were similar to signals of parent compound in terms of coupling constants but appeared at different positions. Thus, in solution there is equilibration between the free and the bound compound 1 with zinc (Figure 8) ions. New signals were appeared as a result of the complex formation, which are marked with asterisk in Figure 8. Important point from NMR titration observed is the identification of duplicate set of new signals in addition to the signals of the compound 1. This clearly indicated that only one type of complex was formed by compound 1 with zinc ions in solution. On the other hand, it is seen that the chemical shift positions of the protons of the three quinoline rings were shifted; hence the zinc complex in solution was formed through participation of all the three quinoline rings. Signal at 7.12 ppm is attributed to phenylene protons of the bis-phenolate unit. This assignment is based on a comparison of 1HNMR of compound 1 with compound 2; latter does not show this particular signal as this position is occupied partially by methyl groups. At higher concentrations of the zinc ion the aromatic proton signal appearing at 7.12 ppm splits suggesting that chelation of the 8-aminoquinoline part to zinc ion. On the other hand, it is observed that at low concentrations of the zinc ions NH signal of the compound 1 is not affected, but new signal for NH is observed at higher concentrations of zinc ions, this suggests that further coordination of the initially formed complex with zinc ion affects the amide hydrogen. Some signals of quinoline ring protons appear up-field with respect to parent signals on interaction with zinc ions, which may be attributed to formation of planar geometry by occupying equatorial positions by nitrogen in the chelate, in which ring current may be causing such a shift. However, such up-field shifts observed from protons on quinoline rings coordinating to zinc ions [86] was suggested to arise from restricted bond rotation and/or π-stacking interactions for coordination between the pendant quinoline moieties [87]. We recorded 1H-NMR spectrum of the precipitate obtained from the reaction of zinc chloride with compound 1, it is observed that chemical shifts of the peaks for parent compound are shifted (Figure S4). Figure 8 here To understand fluorescence emissions we have analyzed the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) of the 1 and 2 by DFT calculation 10
using B3LYP basis set. HOMO of 1 spreads over the 8-aminoquinoline amide and phenyl moiety of one arm; however LUMO spreads only on the 8-aminoquinoline amide moiety of another arm. While in 2, HOMO and LUMO are localized on 8-aminoquinoline located at alternate arms of the skeleton (Figure 9). HOMO and LUMO gap of both are comparable; 0.154 eV in 1 and 0.153 eV in 2. Since in the compounds 1 and 2, electrons are localized on 8-quinoline-amide moiety in ground state and excited states, the intervening part has no significant contribution to emission and absorption of these compounds under normal situation. Figure 9 here Increase in the intensity of the fluorescence emissions of compounds 1 and 2 by zinc ions can be explained by formation of a chelated complex initially, which self assembles with additional amount of zinc ions. It was found that the fluorescence change passed through an intitial isoemissive point supporting complexation of these receptor molecules with zinc ions. On the other hand the new emission peak which appeared at higher wavelength immediately addition of definite amount of zinc ions did not show isoemissive point. This suggests that that the second emission peak is related to an exciplex formation. Further evidence to this is obtained from the fact that the control experiment performed on an analogous compound namely 2-phenoxy-N(quinolin-8-yl)acetamide was tested with zinc ions. This compound shows dual fluorescence emission at 406 nm and 474 nm. Intensities of the peak at increased 474 nm on addition of Zn2+ ions without a shift, which can be attributed to interactions of zinc (II) ions with 2-phenoxy-N(quinolin-8-yl)acetamide. Since this compound is comprised of 8-aminoquinoline derivative and has to coordinate through aminoquinoline unit only. Thus through comparison the initial observation on isoemissive points in the case of zinc ions interacting with the compounds 1 and 2 can be safely assigned to coordination through the portion having 8-aminoquinoline backbone. A mixed mechanism involving excited state proton transfer facilitated by zinc ions at low zinc ion concentration and a twisted intramolecular charge transfer mechanism at high concentrations is operative in the case of compound 1. Zinc ions initially participate in excited state proton transfer to show emission at higher wavelength in conventional manner as depicted earlier for analogous compounds [27]; but significant difference in the present case is the dual fluorescence emission at relatively low concentration of zinc ions. As the concentration of zinc ions increase 11
compound 1 forms assembly by coordinating to zinc ions through 4-quinoline moiety to adopt two different orientations across amide units (I and II in figure 10). Such conformations in simple amide containing fluorescent molecules essentially cause dual fluorescence due to twisted intramolecular charge transfer (TICT) process [69-74]. Thus, compound 1 when coordinates to zinc ions shows dual fluorescence. Dual fluorescence generally occurs in flexible structures through twisted internal charge transfer process [88-89]. Besides these the literature suggest that in enolisable fluorescent molecules show dual fluorescence emission peaks due to excited-state intramolecular proton transfer (ESPT) [90-91]; on the other hand by changing functional groups in such molecules show single fluorescence emission and such process is guided by solvent. The shape of the potential surfaces of the ground state and first second electronic state depends on the resonance structure and accordingly the nature of the distributions of intensity of the components of the dual fluorescence peaks[91]. In the present case we guide such an effect by metal ions. On the other hand, addition of Cu2+ ions to a methanol solution of compound 1, reduce the intensity of emission at 397 nm (Figure 4b) and during the process no shift of emission peak was observed. Reduction in intensity of fluorescence of quinoline derivatives routinely occurs [68]; analogously, as a result of electron and energy transfer from excited state of 1 to a low lying empty d-orbital of paramagnetic Cu2+ ions quenching occurs. Various metal ions except Cu2+ ions, such as Li+, Na+, K+, Be2+, Mg2+, Ca2+, Ni2+, Co2+, Mn2+, Cd2+, Hg2+ and with Zn2+ ions, did not interfere in the zinc ions sensing. Effect of the substituent groups, such as the methyl group causing equilibration of conformational isomers of metal complexes were reported earlier [92]. Based on such precedence it is suggested that only excited state proton transfer mechanism operates in the compound 2 due Figure 10 here
steric effect of the methyl groups. This fact is also suggested from the theoretical observations on localization of the HOMO in the compounds. In the case of the compound 2 HOMO are located strictly on 8-aminoquinoline moiety. Thus, the methyl groups present in compound 2, offer relatively higher rigidity to the aggregates formed with metal ions, due to which only the excited state proton transfer (III of Figure 10) takes place to show one emission peak. Accordingly the sensitivity of zinc ions to mask the detection of the copper ions and vice versa decreases in the 12
compound 2. This makes a comparable sensitivity differences caused by these two metal ions. Hence, zinc and copper ions can be detected reversibly by this receptor.
Conclusions: This study has established some novel and unprecedented fluorescence emission properties of aggregates formed by a tri-quinoline based receptors on interactions with zinc ions. Methyl groups present on the aromatic ring of the connecting part of a particular tri-quinoline make distinct impact on fluorescence changes by the zinc ions to make them unique examples to show either single or dual fluorescence at different concentrations of zinc ions. Masking effect of fluorescence emission by copper(II) ions of quinoline derivatives have been overcome in a triquinoline receptor having methyl substituted bisphenolate tether, enabling reversible modulation of the fluorescence intensities by sequential addition of copper(II) and zinc ions and vice versa. Substituent changing the emission properties of the receptors in presence of zinc ions to show dual fluorescence makes new avenues to explore similar system and utilize them as optical materials. Compound 1 showing fluorescence spreading over a wide range of visible spectra intermittent concentration of zinc ions requires definite attention to make new optical materials. Acknowledgement: Authors thank the Ministry of Human Resources and Development (NewDelhi) for departmental research support. Author PK thanks University Grant Commission, New-Delhi for a fellowship. Supporting information: Spectroscopic details of the compounds, fluorescence titrations and Isothermal calorimetric titrations, table for crystallographic parameters of compound 2 are available as supporting information. CIF file of compound 2 is deposited to CCDC and it has CCDC number 1045040. References: 1. X. J. Feng, P. Z. Tian, Z. Xu, S. F. Chen, M. S. Wong, J. Org. Chem. 78 (2013) 11318-11325. 2. M. H. Lee, J. S. Kim, J. L.Sessler, Chem. Soc. Rev. 44 (2015) 4185-4191. 3. J. R. Askim, M. Mahmoudia, K. S. Suslick, Chem. Soc. Rev. 42 (2013) 8649-8682. 4. S. Pal, N. Chatterjee, P. K. Bharadwaj, RSC Adv. 4 (2014) 26585-26620. 5. A. P. de Silva, H. Q. N. Gunaratne, T. Gunnlaugsson, A. J. M. Huxley, C. P. McCoy, J. T. Rademacher, T. E. Rice, Chem. Rev. 97 (1997) 1515-1566. 6. B. Kuswandi, Nuriman, W. Verboom, D. N. Reinhoudt, Sensors 6 (2006) 978-1017. 13
7. B. Valeur, I. Leray, Coord. Chem. Rev. 205 (2000) 3-40. 8. J. S. Kim, D. T. Quang, Chem. Rev. 107 (2007) 3780-3799. 9. R. Martinez-Manez, R. F. Sancenon, Chem. Rev. 103 (2003) 4419-4476. 10.J. F. Callan, A. P. de Silva, D. C. Magri, Tetrahedron 61 (2005) 8551-8588. 11. J. J. R. F. da Silva R. J. P. Williams, in The Biological Chemistry of the Elements, Oxford University Press (1992). 12.A. P. de Silva, H. Q. N. Gunaratne, T. Gunnlaugsson, A. J. M. Huxley, C. P. McCoy, J. T. Rademacher, T. E. Rice, Chem Rev. 97 (1997) 1515-1566. 13. L. Prodi, F. Bolletta, M. Montalti, N. Zaccheroni, Coord. Chem. Rev. 205 (2000) 59-83. 14. Optical Sensors and Switches edited by V. Ramamurthy, K. S. Schanze, CRC Press (2001). 15. L. E. Kreno, K. Leong, O. K. Farha, M. Allendorf, R. P. Van Duyne, J. T. Hupp, Chem. Rev. 112 (2012) 1105-1125. 16. S. Dang, E. Ma, Z. -M. Sun, H. Zhang, J. Mater. Chem. 22 (2012) 16920-16926. 17. X. Zhao, X. Bu, T. Wu, S. -T. Zheng, L. Wang, P. Feng, Nature Commun. 4 (2013) 2344. 18. Y. Gao, X. Zhang, W. Sun, Z. Liu, Dalton Trans. 44 (2015) 1845-1849. 19. L. E. Kreno, K. Leong, O. K. Farha, M. Allendorf, R. P. Van Duyne, J. T. Hupp, Chem. Rev. 112 (2012) 1105-1125. 20. S. Dang, E. Ma, Z. -M. Sun, H. Zhang, J. Mater. Chem. 22 (2012) 16920-16926. 21. K. K. Kartha, S. S. Babu, S. Srinivasan, A. Ajayaghosh, J. Am. Chem. Soc., 134 (2012) 4834-4841. 22. J. R. Long, O. M., Yaghi, Chem. Soc. Rev., 38, 2009, 1213-1214. 23. H. Komatsu, D. Citterio, Y. Fujiwara, K. Minamihashi, Y. Araki, M. Hagiwara, K. Suzuki, Org. Lett. 7 (2005) 2857-2859. 24. M. Schmittel, H. W. Lin, Angew. Chem. Int. Ed. 46 (2007) 893-896. 25. N. Singh, R. C. Mulrooney, N. Kaur, J. F. Callan, Chem. Commun. (2008) 4900-4902. 26. H. J. Jung, N. Singh, D. Y. Lee, D. O. Jang, Tetrahedron Lett. 51 (2010) 3962-3965. 27. J. -F. Zhu, H. Yuan, W. -H. Chan, A. W. M. Lee, Org. Biomol. Chem. 2010, 8, 3957-3964. 28. S. Y. Assaf, S. -H. Chung, Nature 308 (1984) 734-36. 29. J. M. Berg, Y. Shi, Science 271 (1996) 1081-1085. 30. G. Sivaraman, T. Anand, D. Chellappa, Anal. Methods 6 (2014) 2343-2348. 14
31. M. C. Aragoni, M. Arca, A. Bencini, A. J. Blake, C. Caltagirone, G. De Filippo, F. A. Devillanova, A. Garau, T. Gelbrich, M. B. Hursthouse, F. Isaia, V. Lippolis, M. Mameli, P. Mariani, B. Valtancoli, C. Wilson, Inorg. Chem. 46 (2007) 4548-1559. 32. C. R. Goldsmith, S. J. Lippard, Inorg. Chem. 45 (2006) 6474-6478. 33. E. Maryon, S. Molloy, A. Zimnicka, J. Kaplan, Biometals 20 (2007) 355-364. 34. M. L. Turski, D. J. Thiele, J. Biol. Chem. 284 (2009) 717-721. 35. J. D. Capro, T. Oury, C. Rabouille, J. W. Slot, L. -Y. Chang, Proc. Nat. Acad. Sci. USA 89 (1992) 10405-10409. 36. J. A. Tainer, E. D. Getzoff, J. S. Richardson, D. C. Richardson, Nature, 306 (1983) 284287. 37. G. Rotilio, L. Calabrese, F. Bossa, D. Barra, A. F. Agro, B. Mondovi, Biochem. 11 (1972) 2182-2187. 38. C. F. Walker, R. E. Black, Annu. Rev. Nutr. 24 (2004) 255-275. 39. G. Multhaup, A. Schlicksupp, L. Hesse, D. Beher, T. Ruppert, C. L. Masters, K. Beyreuther, Science 271 (1996) 1406-1409. 40. R. S. C. Mail, C. Howells, E. D. Eaton, L. Shabala, K. Zovo, P. Palumaa, R. Sillard, A. Woodhouse, W. R. Bennett, S. Ray, J. C. Vickers, A. K. West, Plosone 5 (2010) e12030. 41. I. Zawisza, M. Rozga, W. Bal, Coord. Chem. Rev. 256 (2012) 2297-2307. 42. J. E. Spretsma, Med. Hypothese 52 (1999) 529-538. 43. L. Xue, H. -H. Wang, X. -J. Wang, H. Jiang, Inorg. Chem. 47 (2008) 4310-4318. 44. L. Xue, C. Liu, H. Jiang, Chem. Commun. (2009) 1061-1063. 45.C. C.; Woodroofe, S. J. Lippard, J. Am. Chem. Soc. 125 (2003) 11458-11459. 46. E. M. W. M. van Dongen, L. M. Dekkers, K. Spijker, E. W. Meijer, L. W. W. J. Klomp, M. Merk, J. Am. Chem. Soc. 128 (2006) 10754-10762. 47. G. K. Walkup, S. C. Burdette, S. J. Lippard, R. Y. Tsien, J. Am. Chem. Soc. 122 (2000) 5644-5645. 48. Y. Shiraishi, C. Ichimura, T. Hirai, Tetrahedron Lett. 48 (2007) 7769-7773. 49. D. A. Pearce, N. Jotterand, I. S. Carrico, B. Imperiali, J. Am. Chem. Soc. 123 (2000) 51605161. 50. X. M. Meng, M. Z. Zhu, L. Liu, Q. X. Guo, Tetrahedron Lett. 47 (2006) 1559-1562. 15
51. S. Mizukami, S. Okada, S. Kimura, Inorg. Chem. 48 (2009) 7630-7638. 52. K. Komatsu, Y. Urano, H. Kojima, T. Nagano, J. Am. Chem. Soc. 129 (2007) 13447-13454. 53. M. M. Henary, Y. Wu, C. J. Fahrni, Chem. Eur. J. 10 (2004) 3015-3025. 54. T. Hirano, K. Kikuchi, Y. Urano, T. Nagano, J. Am. Chem. Soc. 124 (2002) 6555-6562. 55. X. H. Wang, J. Cao, C. F. Chen, Chinese J. Chem. 28 (2010) 1777-1779. 56. T. Moriuchi-Kawakami, J. Sato, Y. Shibutani, Anal. Sci. 25 (2009) 449-452. 57. G. -K. Li, Z. -X. Xu, C. -F. Chen, Z. -T. Huang, Chem. Commun. (2008) 1774-1776. 58. V. Dujols, F. Ford, A. W. Czarnik, J. Am. Chem. Soc. 119 (1997) 7386-7387. 59. E. Ballesteros, D. Moreno, T. Gomez, T. Rodriguez, J. Rojo, M. Garcia-Valverde, T. Torroba, Org. Lett. 11 (2009) 1269-1272. 60. A. C. Burdette, S. J. Lippard, Proc. Nat. Acad. Sci. USA, 2003, 100, 3605-3610. 61. C. J. Frederickson, E. J. Kasarskis, D. Ringo, R. E. Frederickson, J. Neurosci. Meth. 20 (1987) 91-103. 62. P. D. Zalewski, I. J. Forbes, R. Borlinghaus, W. H. Betts, S. F. Lincoln, A. D. Ward, Chem. Bio. 1 (1994) 153-161. 63. P. D. Zalewski, S. H. Millard, I. J. Forbes, O. Kapaniris, A. Slavotinek, W. H. Betts, A. D. Ward, S. F. Lincoln, I. Mahadevan, J. Histochem. Cytochem. 42 (1994) 877-884. 64. L. Xue, H. -H. Wang, X. -J. Wang, H. Jiang, Inorg. Chem. 47 (2008) 4310-4318 65. L. Xue, C. Liu, H. Jiang, Chem. Commun. (2009) 1061-1063. 66. E. M. Nolan, J. Jaworski, K. -I. Okamoto, Y. Hayashi, M. Sheng, S. J. Lippard, J. Am. Chem. Soc. 127 (2005) 16812-16823. 67. X. Y. Zhou, B. R. Yu, Y. L. Guo, X. L. Tang, H. H. Zhang, W. S. Liu, Inorg. Chem. 49 (2010) 4002-4007. 68. J. Jiang, H. Jiang, X. Tang, L. Yang, W. Dou, W. Liu, R. Fang, W. Liu, Dalton Trans. 2011, 40, 6367-6370. 69. H. Kagechika, T. Himi, E. Kawachi, K. Shudo, J. Med. Chem. 32 (1989) 2292-2296. 70. Y. Toriumi, A. Kasuya, A. Itai, J. Org. Chem. 55 (1990) 259-263. 71. A. Itai, Y. Toriumi, N. Tomioka, H. Kagechika, I. K. Azumaya, Tetrahedron Lett. 30 (1989) 6177-6180.
16
72. I. Azumaya, H. Kagechika, Y. Fujiwara, M. Itoh, K. Yamaguchi, K. Shudo, J. Am. Chem. Soc. 113 (1991) 2833-2838. 73. J. Kim, T. Morozumi, N. Kurumatani, H. Nakamura, Tetrahedron Lett. 49 (2008) 19841987. 74. J. Kim, T. Morozumi, H. Nakamura, Tetrahedron 64 (2008) 10735-10740. 75. G. Ambrosi, M. Formica, V. Fusi, L. Giorgi , A. Guerri, M. Micheloni, P. Paoli, R. Pontellini, P. Rossi, Inorg. Chem. 46 (2007) 4737-4748. 76. A. Anichini, L. Fabbrizzi, P. Paoletti, R. M. Clay, J. Chem. Soc., Dalton Trans., (1978) 577-583. 77. P. Dapporto, M. Formica, V. Fusi, L. Giorgi, M. Micheloni, P. Paoli, R. Pontellini, P. Rossi, Inorg. Chem. 40 (2001) 6186-6192. 78. G. Ambrosi, M. Formica, V. Fusi, L. Giorgi, A. Guerri, M. Micheloni, P. Paoli, R. Pontellini, P. Rossi, Inorg Chem. 46 (2007) 309-320. 79. G. Ambrosi, M. Formica, V. Fusi, L. Giorgi, A. Guerri, S. Lucarini, M. Micheloni, P. Paoli, P. Rossi, G. Zappia, Inorg. Chem. 44 (2005) 3249-3260. 80. A. D. Becke, J. Chem. Phys. 98 (1993) 5648-5652. 81. A. Karmakar, R. J. Sarma, J. B. Baruah, CrystEngComm 9 (2007) 379-389. 82. S. De, J. B. Baruah, Der Pharma Chemica 5 (2013) 145-149 83. J. S. Kim, D. T. Quang, Chem. Rev. 107 (2007)3780-3799. 84. S. Patra, D. Maity, R. Gunupuru, P. Agnihotri, P. Paul, J. Chem. Sci. 2012, 124, 1287-1299. 85. Y. Chen, C. Zhu, Yang, Z.; Li, J.; Jiao, Y.; He, W.; Chen, J.; Guo, Z. Chem. Commun. 48 (2012) 5094-5096. 86. P. -S. Yao, Z. Liu, J. -Z. Ge, Y. Chen, Q. -Y. Cao, Dalton Trans., 44 (2015) 7470-7476. 87. Q. -Y. Cao, Z. -C. Wang, M. Li, J. -H. Liu, Tetrahedron Lett. 54 (2013) 3933-3936. 88. Z. Grabowski, K. Rotkiewicz, W. Rettig, Chem. Rev. 103 (2003) 3899-4031. 89. J. K. Nath, J. B. Baruah, J. Fluorosc. 24 (2014) 649-655. 90. C. J. Fahrni, M. M. Henary, D. G. VanDerveer, J. Phys. Chem. A 106 (2002) 7655-7663. 91. S. -I. Nagaoka, J. Kusunoki, T. Fujibuchi, S. Hatakenaka, K. Mukaia, U. Nagashima, J. Photochem. Photobiol. A: Chem. 122 (1999) 151-159. 92. M. S. Jeletic, C. E. Lower, I. Ghiviriga, A. S. Veige, Organometallics 30 (2011) 6034-6043. 17
Figures, Schemes and Tables
(a) N R
R
H
O
O
N
O
H N
R
N H
R
N
O R = H (1) or -CH3 (2)
(b)
Figure 1: (a) Design principle of assemblies of tri-quinoline receptor for binding metal ions and (b) compounds 1-2. N
N
H
R
R
HO
+
OH R
H
R
K2CO3
N HN
O
Dry acetone
O O
O R
NH
Br
R
R
N
R
O HN N
When R = H (1a) or -CH3 (2a) When R = H (1) or -CH3 (2)
Scheme 1: Synthesis of 1-2. 18
Figure 2: Structure of the compound 2 (ORTEP of with 35% thermal ellipsoids) showing the relevant dihedral angles: C12-O4-C11-C10 = 150.08°, O4-C11-C10-N2 = -1.45°, C31-O2-C30C29 = 171.17°, O2-C30-C29-N5 = 0.35°.
(a)
(b)
Figure 3: Changes in the absorption spectra of (a) the compound 1 and (b) the compound 2, upon addition of a solution of Zn2+ ions (in each case 0.033 equivalent from a solution of methanol in aliquots).
19
(a)
(b)
Figure 4: The changes in the emission spectra of the compound 1 (10-5 M in methanol, 3 mL) upon excitation at 310 nm upon addition of the solutions of (a) Zinc chloride and (b) Cupric chloride solution (in each case 0.033 equivalent from a solution of methanol in aliquot).
(a)
20
(b)
(c)
(d)
Figure 5: Changes in the emission spectra of the 2 (10-5 M in methanol, 3 mL, and excitation at 310 nm) upon addition of (a) zinc chloride and (b) cupric chloride (in each case 0.033 equivalent of methanol solution in aliquot). (c) Changes in the fluorescence of a solution of 2 (10-5 M in methanol) containing 1 equivalent cupric chloride (red lines), followed by the addition of a solution of zinc chloride in 0.033 equivalent in aliquot (black lines). (d) Changes in the fluorescence of a solution of 2 on addition of zinc chloride 0.033 equivalent (six times, black lines) followed by addition of cupric chloride in 0.033 equivalent aliquots (red lines).
21
(a)
(c)
(b)
(d)
Figure 6: Competitive fluorescence titrations showing the changes in the fluorescence emission at 493 nm of a solution of 1 upon addition of solution of (a) cupric chloride (squares) followed by solution of zinc chloride (filled circles). (b) Zinc chloride (filled circles) followed by addition of cupric chloride (squares). Similar titration with solution of compound 2 at 490 nm (c) Zinc chloride (filled circles) followed by solution of cupric chloride (squares). (d) Cupric chloride (filled circles) followed by addition of zinc chloride (squares); (in each case ligand 10-5 M in 3 mL in methanol).
22
Figure 7: Proposed ball and stick model of aggregate of 1 with Zn2+ ions generated through GaussView.
23
Figure 8: 1H-NMR (600MHz, DMSO-d6) spectra (aromatic region) of the (i) 1; and 1 in the presence of (ii) 0.5 equivalent, (iii) 1.0 equivalent and (iv) excess amounts of zinc chloride dissolved in DMSO-d6. Peaks marked by # are from compound 1; whereas peaks marked as * are from compound 1 bound to zinc ions. Inset is the expansion in the NH protons appearing in offset region.
24
(a)
(b)
Figure 9: The HOMO and LUMO in the compound (a) 1 and (b) 2 (Calculated are gas phase energies are not scaled).
Figure 10: I and II are orientations of keto forms for TICT; III is the planar enol form for ESPT.
25
Graphical abstract: Synthesis and characterization of tri-quinoline based receptors and study interactions with Zn2+ and Cu2+ ions
Reversible switching of fluorescence intensities of a tri-quinoline receptor by copper and zinc ions was observed. P. Khakhlary and J. B. Baruah
26
Graphical synopsis: Synthesis and characterization of tri-quinoline based receptors and study interactions with Zn2+ and Cu2+ ions
Two fluorescent receptors having three quinoline anchored flexible tether are synthesized and characterized. In solution these receptors from assemblies zinc or copper ions. Such assemblies are comprised of three receptor molecules with four metal ions which are established by microcalorimetric study. Reversible switching of fluorescence intensities of a tri-quinoline receptor by sequential addition copper and zinc ions was observed. P. Khakhlary and J. B. Baruah
27
Highlights: Two tri-quinoline containing ligands connected through spacers having bisphenol-ether and amide groups are synthesized and characterized. Both the ligands selectively interact with Zn2+ and Cu2+ ions to cause fluorescence changes. Reversibility of the fluorescence changes caused by sequential addition of the Zn2+ and Cu2+ ions are evaluated. Methyl substituent on the spacer bisphenol-ether has a role to cause reversible effect.
28
S0020-1693(15)00514-9 http://dx.doi.org/10.1016/j.ica.2015.10.020 ICA 16730
To appear in:
Inorganica Chimica Acta
Received Date: Revised Date: Accepted Date:
14 August 2015 15 September 2015 12 October 2015
Please cite this article as: P. Khakhlary, J.B. Baruah, Synthesis and characterization of tri-quinoline based receptors and study interactions with Zn2+ and Cu2+ ions, Inorganica Chimica Acta (2015), doi: http://dx.doi.org/10.1016/ j.ica.2015.10.020
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Synthesis and characterization of tri-quinoline based receptors and study interactions with Zn2+ and Cu2+ ions Prithiviraj Khakhlary and Jubaraj B. Baruah* Department of Chemistry, Indian Institute of Technology Guwahati, Guwahati 781 039, Assam, India. Phone +91-361-2582311, Fax: +91-361-2690762, http://www.iitg.ernet.in/juba. Abstract: Synthesis, characterization of the two tri-quinoline based receptors and binding with copper and zinc ions are presented. The changes in the fluorescence emissions of such receptors are caused specifically by Zn2+ or Cu2+ ions. But presence of these two ions affects the fluorescence emission intensity of the receptors in an opposite manner. Conventional masking effect on fluorescence emissions caused by copper ions while detecting zinc ions by quinoline based receptors was not observed in one of the receptor. Among the two receptors studied, one receptor shows irreversible but selective detection of Zn2+ and Cu2+ ions over a range of metal ions.
Introduction: There are large numbers of examples of small fluorescent molecules which are used to detect metal ions [1-14]. Metallo-organic frameworks constructed from small molecules are also used in the detection of various metal ions [15-22]. Some analytes show selective fluorescence emission response to two or more metal ions [23-27]. Divalent zinc and copper ions are found together as constituents of some biological systems [28-32]. The Zn2+ ions play vital roles in signal transmission and mammalian reproduction [33-34]. The Cu2+ ions play important roles in physiological processes of organisms [35-37]. Excessive amounts of zinc ions in the human body can cause alzheimer, epilepsy and infantile diarrhea [38], whereas excess copper ions can cause neurodegenerative diseases [39-42]. Thus, fluorescent receptor having ability to specifically cause fluorescence changes by these two ions have general interest, however, the receptors designed for zinc (II) and copper (II) ions fail to detect zinc ions in the presence of copper ions 1
[43-60]. So, it is essential to develop new receptors that would reversibly detect these ions. Fluorescent sulphonamide derivatives of aminoquinolines have potential in imaging zinc ions [61]. Water soluble quinoline derivatives were prepared which have ability to sense zinc ions under biological conditions [62-63]. Fundamental problem with such receptors is that, their fluorescence emissions are affected by series of metal ions other than zinc ions [64]. Such a problem was partly overcome by designing quinoline receptors which operates through internal charge transfer mechanism [65]. Lippard and his coworkers [66] developed very efficient quinoline based sensors for detection of zinc ions. These receptors have two pendant arms bearing 8-aminoquinolines have higher efficiency over similar receptors with quinoline unit at one arm. There exists opportunity to prepare assemblies of multiple numbers of quinoline rings to hold multiple numbers of metal ions as illustrated in Figure 1. The two tri-quinoline based compounds 1 and 2 (Figure 1) would have two flexible arms to hold metal ions and they would have an openly projected 4-quinoline ring. Thus they will be suitable to form metal complexes as illustrated schematically in Figure 1. Compounds 1 and 2 have bis-phenolate ether tethers connecting quinoline amide moieties. Additional 4-quinoline moiety provides a shape like a projectile with two open wings. The choice of these compounds also arises from the facts that the zinc [27, 43-54] and the copper ions [55-60] can change fluorescence emissions of quinoline derivatives with high specificity. Masking of fluorescence emission by copper ions of quinoline derivatives over the zinc ions [67] is not overcome so far in this class of receptors. Bis-8aminoquinoline amide derivatives were shown to lose fluorescence response to zinc ions in the presence of copper ions [68]. There are reports on the steric and electronic effects contributing to stabilize different conformations of amides [69-71]. A substituent atom or group present at an appropriate position of some amide derivatives can change rotational barriers of trans or cis conformers of amides [72]. These factors also contribute to fluorescence emission occurring through twisted intramolecular charge transfer (TICT) mechanism of some amides derivatives [72-74]. On the other hand, compounds 1 and 2 have a portion of the structure which has pincer type of geometry and ligands of such geometrical features easily form copper and zinc complexes [75-79]. We show that compounds 1 and 2 having difference in substituent in their skeleton have distinct selectivity in showing fluorescence changes with divalent copper and zinc
2
ions. Compound 1 irreversibly distinguishes copper and zinc ions, whereas compound 2 does it reversibly. Figure 1 here
Experimental: Physical measurements: UV-Vis spectra data were recorded using Perkin-Elmer Lambda 750 UV-Vis spectrophotometer. The compounds solutions were prepared in methanol.
Fluorescence measurements were
performed on fluoromax-4 spectrofluorometer using 10 mm path length quartz cuvettes with the slit width of 10 nm at room temperature. 1H-NMR spectral data were recorded either on a Varian-AS400 spectrometers or on a Bruker 600MHz NMR spectrometer. Infrared spectra were obtained by using a Perkin-Elmer FT-IR spectrophotometer (4000-400 cm-1). ESI-mass spectra were recorded on a micro mass Q-TOF (Waters) mass spectrometer using a matrix in acetonitrile / formic acid. Energy level calculations were carried out using the hybrid B3LYP functional [80] under the density functional theory framework with the Gaussian03W program package. Thermodynamic parameters of the binding constants of compound 1 were determined on an iTC 200 Microcalorimeter at 20 °C. Absorptions and emissions measurements were performed with solutions of 1 and 2 or metal chloride prepared in methanol. Solution of 1 or 2 (3 mL, 10-5 M) was taken in quartz cuvette and it was titrated with the particular metal chloride solution. Titrations with the solution of each compound with the metal ions were done by recording the UV-visible or the fluorescence emission spectra by adding the desired amount of the solution of the metal ions in aliquot. Synthesis and Characterizations: 2-Bromo-N-(quinolin-8-yl)acetamide [81], 4-quinoline-bis-phenol (1a)21b and 4-quinoline-2,6dimethyl-bis-phenol (2a) [82] were prepared by reported procedures. Synthesis of 4-quinoline-bis-phenol-N-(quinolin-8-yl)acetamide (1):
2-Bromo-N-(quinolin-8-
yl)acetamide (1.06 g, 4 mmol), bis-phenol 1a (0.67 g, 2 mmol) and anhydrous potassium carbonate (1.11 g, 8 mmol) were added to dry acetone (20 mL) under a nitrogen atmosphere and 3
the reaction mixture was stirred at 60°C for 10 h. (Progress of the reaction was monitored at a regular time interval using TLC). After completion of the reaction, solvent was removed under reduced pressure to obtain a pale yellow solid. The solid was washed with a dilute sodium hydroxide solution (5%) followed by water; then extracted with dichloromethane. Subsequent removal of the solvents and purification by column chromatography (silica gel; hexane/ethyl acetate 3:2) gave 1 in 60 % yield. The solid crude product was crystallized from methanol/DMF (4:6) solvent mixture. Melting point: 183 ºC. Elemental anal. Calcd for C44H33N5O4, C, 76.06, H, 4.78; found C, 76.01, H, 4.77. 1H-NMR (600 MHz, DMSO-d6): 10.71(s, 2H), 8.90 (dd, J = 0.8 Hz, 2H), 8.77 (d, J = 3.2 Hz, 1H), 8.67 (d, J = 5.6 Hz, 2H), 8.42 (dd, J = 0.8 Hz, 2H), 8.09 (d, J = 5.6 Hz, 1H), 8.02 (d, J = 6.0 Hz, 1H), 7.71 (m, 3H), 7.65 (d, J=2.8 Hz, 2H), 7.61 (t, J = 5.2 Hz, 2H), 7.50 (t, J = 5.6 Hz, 1H), 7.12 (m, 8H), 6.86 (d, J = 3.2 Hz, 1H), 6.40 (s, 1H) 4.86 (s, 4H). ESI mass: calculated for C44H34N5O4 [m + 1] = 696.2611; found 696.2676. IR (cm-1): 3360 (s), 3339 (s), 2924 (m), 1638 (s), 1598 (m), 1539 (s), 1505 (s), 1425 (m), 1384 (m), 1326 (m), 1237 (s), 1217 (m), 1174 (m), 1055 (m), 826 (m), 786 (m), 754 (m), 603 (m), 513 (w). 4-Quinoline-2,6-dimethyl-bis-phenol-N-(quinolin-8-yl)acetamide (2) was synthesized by a similar procedure as for 1 where 2a was used instead of 1a. The compound 2 was obtained as solid crude product with a yield ~ 40 %. Melting point: 157 ºC. Elemental anal. Calcd for (C48H42N5O4 ).H2O, C, 74.79, H, 5.75; found C, 76.76, H, 5.76.
1
H-NMR (600 MHz, DMSO-
d6): 11.23 (s, 2H), 8.86 (t, J = 3.6 Hz, 3H), 8.83 (d, J =1.2 Hz, 2H), 8.18 (d, J =1.2 Hz, 1H), 8.17 (dd, J =1.2 Hz, 2H), 8.00 (d, J = 8.4 Hz, 1H), 7.70 (t, J = 6.0 Hz, 1H), 7.58 (m, 4H), 7.51 (t, J = 6.0 Hz, 1H), 7.47 (q, J = 4.2 Hz, 2H), 7.26 (s,1H), 6.98 (t, J = 4.2 Hz, 1H), 6.81 (s, 3H), 6.09 (s, 1H), 4.56 (s, 4H) 2.35 (s, 12H). ESI mass: calculated for C48H42N5O4 [m + 1] = 752.8782; found 752.3273. IR (cm-1): 3328 (s), 2922 (s), 2852 (m), 1676 (s), 1591(m), 1536 (s), 1483 (s), 1425 (m), 1384 (m), 1323 (m), 1203 (s), 1145 (s), 1047 (m), 952 (w), 824 (m), 791(m), 748 (m), 663 (w), 595 (w), 555 (w), 506 (w). Results and discussion: The compounds 1 and 2 were synthesised by reacting 2-bromo-N-(quinolin-8-yl)acetamide with the corresponding bis-phenol (1a or 2a) in dry acetone in the presence of anhydrous potassium carbonate (Scheme 1). All the starting materials and the final products were characterised by 1H4
NMR, IR spectroscopy and mass spectrometry. As there are three quinoline moieties present in the compounds 1 and 2, the protons on the quinoline units were assigned from the analysis of the observed coupling patterns of typical 2D-1H-HOMOCOSY spectra of the compound 1 shown in the supporting Figure S1. Scheme 1 here Single crystal X-ray structure of compound 2 revealed that two quinoline rings are almost coplanar and carbonyl groups of amides lie in this plane, but project outward with respect to the nitrogen atoms of quinoline rings. The projection of the carbonyl groups are reflected in the dihedral angles, listed in the caption of Figure 2. Both the compounds 1 and 2 are crystalline solids, but we could not get suitably diffracting crystals to determine the structures with high accuracy but could obtain the information that the compound 1 has also similar structure as that of the structure of the compound 2. Figure 2 here The tri-quinoline derivatives 1 and 2 possess V-shape bis-phenolate ether linkage anchoring flexible methylene groups, such units are flexibile and suitable to adopt different orientations depending on conditions. Generally constraints provided by the substituent present in a flexible receptor enhance selectivity to bind to metal ions [83-84]. Differences in binding ability of metal ions to a receptor influences internal charge transfer which influences the position and the intensity of their fluorescence emissions of the receptor [85]. Since the compounds 1 and 2 have different groups at two aromatic rings, hence their optical properties are expected to differ with coordination environment and electronic factors of different metal ions. Figure 3 here Intensities of the UV absorptions of the 1 present at 252 nm and 360 nm were increased upon the addition of a solution of Zn2+ ions (Figure 3a). The spectral changes took place at a cost of the absorption present at 303 nm. As a result of such changes three isosbestic points at 245 nm, 280 nm and 331 nm had appeared. Similar spectral changes were observed upon the addition of a solution of Cu2+ ions to a solution of 1. A series of ions such as Li+, Na+, K+, Be2+, Mg2+, Ca2+, 5
Ni2+, Co2+, Mn2+, Cd2+ and Hg2+ did not change the absorption spectra of the compound 1. However, the Zn2+ and Cu2+ ions were relatively less effective in changing the UV absorbance spectra of the 2 (figure 3b) as compared to the compound 1. Addition of a solution of Zn2+ ions to a solution of the 2, the absorption peak appearing at 255 nm which is attributed to n→π* transition get increased with a concomitant decrease in the absorption at 226 nm (π→π*) and 286 nm (n→π* transition).
These changes of UV absorbance passed through isosbestic points
appearing at 243 nm, 282 nm and 330 nm. The extinction coefficients of the absorbance at 303 nm of the methanol solution of the compounds 1 and 2 are 8753 cm2 mol-1 and 9671 cm2 mol-1 respectively. From the above titrations and using Benesi and Hildebrand equation association constants and logKa of the compound 1 with Zn2+ and Cu2+ ions were found to be 5.07 and 5.13 respectively. Whereas, from similar experiments with the compound 2, the respective logKa values were found to be 4.84 and 4.91. For both the compounds we obtained comparable binding constants for Zn2+ and Cu2+ ions. Thus, both the metal ions should be able to replace each other. However, Cu2+ ions can replace Zn2+ ions as they have higher tendency of giving stable complex than Zn2+ ions. But due to substituent effect on the compounds 1 and compound 2, the conformational rigidities of these compounds are different hence they may bind in reversible manners to copper and zinc ions. With such anticipation we followed up further studies through fluorescence experiments. Figure 4 here A methanol solution of compound 1 shows a broad fluorescence emission peak at 397 nm on excitation at 310 nm and on similar excitation a methanol solution of the compound 2 showed broad emission peak at 400 nm. Both the emission spectra have a shoulder at 340 nm. This emission peak could be from the quinoline ring, whereas broad and intense emission at 397 nm and 400 nm for the compounds 1 and 2 respectively are originate from the aminoquinoline rings. The positions of emission spectra of the compounds do not change with changes in concentrations, which suggest that there are no interactions between the aminoquinoline groups present in these compounds. These observations are conventional as bis-aminoquinoline derivatives show fluorescence emissions at similar wavelengths [67-68].
6
The intensity of the fluorescence emission peak of the compound 1 present at 397 nm decreases upon addition of Zn2+ ions and a new emission peak at 493 nm appeared. As the concentration of the Zn2+ ions was increased the intensity of this peak was increased to reach a maximum value. Further addition of the Zn2+ ions, this emission peak at 493 nm splits up into two new independent emission peaks appearing at 451nm and 551 nm (Figure 4a). These two broad peaks formed by splitting of an emission peak spreads over range 430-580 nm is a unprecedented observation in quinoline system and resembles white light emission. This occurs at low concentrations of the zinc ions (upon addition of about 0.33 eq of Zn2+ ions) with respect to the compound 1, thus the ligand to metal ion molar ratio is at about 30:1. Based on the observation at a low concentration of zinc ions, effect can be suggested to originate from a sensitization process caused on compound 1 by zinc ions rather than a conventional complex formation. This type of emission phenomenon can be projected as an exceptional observation as Stokes shift 183 nm was observed with emission at 493 nm. When this emission changed to two wavelengths the Stokes shift associated with new peaks were 141 nm and 241 nm. In literature a maximum Stokes shift of 199 nm was observed from an aminoquinoline derivative on interaction with zinc ions due to internal charge transfer (ICT) mechanism [65]. Thus compound 1 is suitable to modulate fluorescence by changing concentrations of zinc ions. Similar fluorescence titrations were carried out with compound 1 by adding Li+, Na+, K+, Be2+, Mg2+, Ca2+, Ni2+, Co2+, Mn2+, Cd2+ and Hg2+ ions. These ions showed insignificant changes in fluorescence emissions of compound 1. We find that addition of a solution of Cu2+ ions to a solution of compound 1 decreases the fluorescence emission of the compound 1 present at 397 nm. In spite of the 96 nm red shift with enhancement of fluorescence on 1 upon addition of Zn2+ ions was observed it loses its fluorescence on addition of Cu2+ ions. It was also observed that once fluorescence of the compound 1 was quenched by Cu2+ ions, the addition of zinc ions to such a solution could not recover the emission. The compound 2 is a more structurally rigid derivative in comparison to the compound 1, as it has two methyl groups attached to each aromatic ring of bis-phenolate groups. Analogous to compound 1, on addition of Zn2+ ions to solution of compound 2 decreases its emission at 400 nm with enhancement of intensity of the emission at 490 nm (Figure 5a). On the other hand this compound also showed decrease in fluorescence emission of the emission at 400 nm upon 7
addition of Cu2+ ions (Figure 5b). However, we found a major difference between the fluorescence emissions of these two compounds on interactions with zinc ions is that at higher concentrations of zinc ions no splitting of fluorescence emission peak was observed in the case of the compound 2. Compound 2 showed single emission peak at 490 nm on addition of Zn2+ ions, and for this emission peak Stokes shift observed was 180 nm. Notable observation is that the quenching of fluorescence on addition solution of Cu2+ ions to a solution of 2 can be recovered by adding a solution of Zn2+ ions; thus each of these metal ions can be detected by fluorescence technique in the presence of each other. Reversibility in the fluorescence emission changes caused by two metal ions on the compound 2 was established by carrying out a series of competitive experiments. To do so, we added equivalent amount of cupric chloride to a solution Figure 5 here of compound 2, this decreased the fluorescence emission at 400 nm to a lowest level. To this solution, a methanol solution of zinc chloride was added in 0.033 mole equivalent in each aliquot. We observed that the fluorescence emission at 490 nm increased as concentrations of zinc ions were increased (Figure 5c). In an another experiment a fluorescence titration was carried out by adding a methanol solution of zinc chloride solution to a solution of
the
compound 2, addition continued till there was no further increase in fluorescence at 490 nm took place (Figure 5d). After reaching this point, a solution of copper chloride was added, which resulted in a decrease in the fluorescence emission at 490 nm and emission continue to shift to show a fluorescence emission peak at 400 nm and after reaching this stage, fluorescence emission at the 400 nm decreases to a minimum on continuation of addition of cupric chloride solution (Figure 5d). To prove competitive effect of these two ions, we have carried out a series of experiments by changing sequence of addition of zinc and copper ions to respective receptor solution and vice-versa. In each experiment metal ions solutions were added until there was no further change in fluorescence emission. Once this stage was reached addition of another solution of metal ion was added. The changes in normalized fluorescence intensities from different control experiments from such fluorescence titration experiments with one metal ion to reach a highest limit of emission intensity followed by another metal ion to reduction of intensity or vice versa 8
are shown in Figure 6. As seen in Figure 6a, addition of the solution of cupric chloride quenched fluorescence emission of the compound 1 at 397 nm; when a zinc chloride solution was added to such a solution, the original fluorescence of the compound 1 could not be recovered, which shown by blue straight line of squares in Figure 6a. However, when a solution of zinc chloride (circles in Figure 6b) was added, the fluorescence emission increased to a particular concentration. But due to splitting of the fluorescence emission beyond this critical concentration as discussed earlier there was an apparent decrease in the fluorescence emission (Figure 6b). Hence to avoid confusion, intensity changes beyond this point are not shown in this figure. When a solution of cupric chloride was added to this solution, the fluorescence got quenched (squares in Figure 6b). These data clearly established the fact that the quenching in the fluorescence emission of compound 1 caused by copper ions could not be retrieved, as the addition of Zn2+ ions did not changed the fluorescence intensity of compound 1 containing Cu2+ ions. On the other hand, similar experiments carried out with compound 2 (Figure 6c and 6d) have revealed that fluorescence quenching at 400 nm caused by the cupric chloride could be retrieved by adding a solution of zinc chloride, and fluorescence enhancement caused by zinc ion could be quenched by cupric chloride. Figure 6 here
We carried out independent isothermal calorimetry titration of compound 1 with zinc chloride and copper chloride. Binding isotherms (supporting Figures S2 and S3) were obtained by integrating raw data which was fitted to a “one-site” model. We found the raio of metal ion binding to ligand as 1.31 : 1 and 1.37 : 1 for zinc and copper ion respectively. Binding constant (K) with zinc ion is 2.67 × 104 M-1and with copper is 3.47 × 104 M-1. The corresponding logKa values are 4.42 and 4.54 respectively. The enthalpy changes in case of zinc and copper ions are 7.843 cal/mol and -9.239 cal/mol and respectives entropy changes are -239 cal/mol/° with zinc (II) ions and -289 cal/mol/° with copper (II) ions These suggest that in each case three ligands are associated with four metal ions. Based on the ratio of metal to ligand obtained from isothermal calorimetry titration, we proposed the structure of the aggregate with divalent copper or zinc as shown in Figure 7, which was generated using GaussView. Figure 7 here 9
1
H-NMR titration of compound 1 with zinc chloride showed emergence of new set of peaks
other than the ones that were observed from parent compound 1. These new signals were similar to signals of parent compound in terms of coupling constants but appeared at different positions. Thus, in solution there is equilibration between the free and the bound compound 1 with zinc (Figure 8) ions. New signals were appeared as a result of the complex formation, which are marked with asterisk in Figure 8. Important point from NMR titration observed is the identification of duplicate set of new signals in addition to the signals of the compound 1. This clearly indicated that only one type of complex was formed by compound 1 with zinc ions in solution. On the other hand, it is seen that the chemical shift positions of the protons of the three quinoline rings were shifted; hence the zinc complex in solution was formed through participation of all the three quinoline rings. Signal at 7.12 ppm is attributed to phenylene protons of the bis-phenolate unit. This assignment is based on a comparison of 1HNMR of compound 1 with compound 2; latter does not show this particular signal as this position is occupied partially by methyl groups. At higher concentrations of the zinc ion the aromatic proton signal appearing at 7.12 ppm splits suggesting that chelation of the 8-aminoquinoline part to zinc ion. On the other hand, it is observed that at low concentrations of the zinc ions NH signal of the compound 1 is not affected, but new signal for NH is observed at higher concentrations of zinc ions, this suggests that further coordination of the initially formed complex with zinc ion affects the amide hydrogen. Some signals of quinoline ring protons appear up-field with respect to parent signals on interaction with zinc ions, which may be attributed to formation of planar geometry by occupying equatorial positions by nitrogen in the chelate, in which ring current may be causing such a shift. However, such up-field shifts observed from protons on quinoline rings coordinating to zinc ions [86] was suggested to arise from restricted bond rotation and/or π-stacking interactions for coordination between the pendant quinoline moieties [87]. We recorded 1H-NMR spectrum of the precipitate obtained from the reaction of zinc chloride with compound 1, it is observed that chemical shifts of the peaks for parent compound are shifted (Figure S4). Figure 8 here To understand fluorescence emissions we have analyzed the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) of the 1 and 2 by DFT calculation 10
using B3LYP basis set. HOMO of 1 spreads over the 8-aminoquinoline amide and phenyl moiety of one arm; however LUMO spreads only on the 8-aminoquinoline amide moiety of another arm. While in 2, HOMO and LUMO are localized on 8-aminoquinoline located at alternate arms of the skeleton (Figure 9). HOMO and LUMO gap of both are comparable; 0.154 eV in 1 and 0.153 eV in 2. Since in the compounds 1 and 2, electrons are localized on 8-quinoline-amide moiety in ground state and excited states, the intervening part has no significant contribution to emission and absorption of these compounds under normal situation. Figure 9 here Increase in the intensity of the fluorescence emissions of compounds 1 and 2 by zinc ions can be explained by formation of a chelated complex initially, which self assembles with additional amount of zinc ions. It was found that the fluorescence change passed through an intitial isoemissive point supporting complexation of these receptor molecules with zinc ions. On the other hand the new emission peak which appeared at higher wavelength immediately addition of definite amount of zinc ions did not show isoemissive point. This suggests that that the second emission peak is related to an exciplex formation. Further evidence to this is obtained from the fact that the control experiment performed on an analogous compound namely 2-phenoxy-N(quinolin-8-yl)acetamide was tested with zinc ions. This compound shows dual fluorescence emission at 406 nm and 474 nm. Intensities of the peak at increased 474 nm on addition of Zn2+ ions without a shift, which can be attributed to interactions of zinc (II) ions with 2-phenoxy-N(quinolin-8-yl)acetamide. Since this compound is comprised of 8-aminoquinoline derivative and has to coordinate through aminoquinoline unit only. Thus through comparison the initial observation on isoemissive points in the case of zinc ions interacting with the compounds 1 and 2 can be safely assigned to coordination through the portion having 8-aminoquinoline backbone. A mixed mechanism involving excited state proton transfer facilitated by zinc ions at low zinc ion concentration and a twisted intramolecular charge transfer mechanism at high concentrations is operative in the case of compound 1. Zinc ions initially participate in excited state proton transfer to show emission at higher wavelength in conventional manner as depicted earlier for analogous compounds [27]; but significant difference in the present case is the dual fluorescence emission at relatively low concentration of zinc ions. As the concentration of zinc ions increase 11
compound 1 forms assembly by coordinating to zinc ions through 4-quinoline moiety to adopt two different orientations across amide units (I and II in figure 10). Such conformations in simple amide containing fluorescent molecules essentially cause dual fluorescence due to twisted intramolecular charge transfer (TICT) process [69-74]. Thus, compound 1 when coordinates to zinc ions shows dual fluorescence. Dual fluorescence generally occurs in flexible structures through twisted internal charge transfer process [88-89]. Besides these the literature suggest that in enolisable fluorescent molecules show dual fluorescence emission peaks due to excited-state intramolecular proton transfer (ESPT) [90-91]; on the other hand by changing functional groups in such molecules show single fluorescence emission and such process is guided by solvent. The shape of the potential surfaces of the ground state and first second electronic state depends on the resonance structure and accordingly the nature of the distributions of intensity of the components of the dual fluorescence peaks[91]. In the present case we guide such an effect by metal ions. On the other hand, addition of Cu2+ ions to a methanol solution of compound 1, reduce the intensity of emission at 397 nm (Figure 4b) and during the process no shift of emission peak was observed. Reduction in intensity of fluorescence of quinoline derivatives routinely occurs [68]; analogously, as a result of electron and energy transfer from excited state of 1 to a low lying empty d-orbital of paramagnetic Cu2+ ions quenching occurs. Various metal ions except Cu2+ ions, such as Li+, Na+, K+, Be2+, Mg2+, Ca2+, Ni2+, Co2+, Mn2+, Cd2+, Hg2+ and with Zn2+ ions, did not interfere in the zinc ions sensing. Effect of the substituent groups, such as the methyl group causing equilibration of conformational isomers of metal complexes were reported earlier [92]. Based on such precedence it is suggested that only excited state proton transfer mechanism operates in the compound 2 due Figure 10 here
steric effect of the methyl groups. This fact is also suggested from the theoretical observations on localization of the HOMO in the compounds. In the case of the compound 2 HOMO are located strictly on 8-aminoquinoline moiety. Thus, the methyl groups present in compound 2, offer relatively higher rigidity to the aggregates formed with metal ions, due to which only the excited state proton transfer (III of Figure 10) takes place to show one emission peak. Accordingly the sensitivity of zinc ions to mask the detection of the copper ions and vice versa decreases in the 12
compound 2. This makes a comparable sensitivity differences caused by these two metal ions. Hence, zinc and copper ions can be detected reversibly by this receptor.
Conclusions: This study has established some novel and unprecedented fluorescence emission properties of aggregates formed by a tri-quinoline based receptors on interactions with zinc ions. Methyl groups present on the aromatic ring of the connecting part of a particular tri-quinoline make distinct impact on fluorescence changes by the zinc ions to make them unique examples to show either single or dual fluorescence at different concentrations of zinc ions. Masking effect of fluorescence emission by copper(II) ions of quinoline derivatives have been overcome in a triquinoline receptor having methyl substituted bisphenolate tether, enabling reversible modulation of the fluorescence intensities by sequential addition of copper(II) and zinc ions and vice versa. Substituent changing the emission properties of the receptors in presence of zinc ions to show dual fluorescence makes new avenues to explore similar system and utilize them as optical materials. Compound 1 showing fluorescence spreading over a wide range of visible spectra intermittent concentration of zinc ions requires definite attention to make new optical materials. Acknowledgement: Authors thank the Ministry of Human Resources and Development (NewDelhi) for departmental research support. Author PK thanks University Grant Commission, New-Delhi for a fellowship. Supporting information: Spectroscopic details of the compounds, fluorescence titrations and Isothermal calorimetric titrations, table for crystallographic parameters of compound 2 are available as supporting information. CIF file of compound 2 is deposited to CCDC and it has CCDC number 1045040. References: 1. X. J. Feng, P. Z. Tian, Z. Xu, S. F. Chen, M. S. Wong, J. Org. Chem. 78 (2013) 11318-11325. 2. M. H. Lee, J. S. Kim, J. L.Sessler, Chem. Soc. Rev. 44 (2015) 4185-4191. 3. J. R. Askim, M. Mahmoudia, K. S. Suslick, Chem. Soc. Rev. 42 (2013) 8649-8682. 4. S. Pal, N. Chatterjee, P. K. Bharadwaj, RSC Adv. 4 (2014) 26585-26620. 5. A. P. de Silva, H. Q. N. Gunaratne, T. Gunnlaugsson, A. J. M. Huxley, C. P. McCoy, J. T. Rademacher, T. E. Rice, Chem. Rev. 97 (1997) 1515-1566. 6. B. Kuswandi, Nuriman, W. Verboom, D. N. Reinhoudt, Sensors 6 (2006) 978-1017. 13
7. B. Valeur, I. Leray, Coord. Chem. Rev. 205 (2000) 3-40. 8. J. S. Kim, D. T. Quang, Chem. Rev. 107 (2007) 3780-3799. 9. R. Martinez-Manez, R. F. Sancenon, Chem. Rev. 103 (2003) 4419-4476. 10.J. F. Callan, A. P. de Silva, D. C. Magri, Tetrahedron 61 (2005) 8551-8588. 11. J. J. R. F. da Silva R. J. P. Williams, in The Biological Chemistry of the Elements, Oxford University Press (1992). 12.A. P. de Silva, H. Q. N. Gunaratne, T. Gunnlaugsson, A. J. M. Huxley, C. P. McCoy, J. T. Rademacher, T. E. Rice, Chem Rev. 97 (1997) 1515-1566. 13. L. Prodi, F. Bolletta, M. Montalti, N. Zaccheroni, Coord. Chem. Rev. 205 (2000) 59-83. 14. Optical Sensors and Switches edited by V. Ramamurthy, K. S. Schanze, CRC Press (2001). 15. L. E. Kreno, K. Leong, O. K. Farha, M. Allendorf, R. P. Van Duyne, J. T. Hupp, Chem. Rev. 112 (2012) 1105-1125. 16. S. Dang, E. Ma, Z. -M. Sun, H. Zhang, J. Mater. Chem. 22 (2012) 16920-16926. 17. X. Zhao, X. Bu, T. Wu, S. -T. Zheng, L. Wang, P. Feng, Nature Commun. 4 (2013) 2344. 18. Y. Gao, X. Zhang, W. Sun, Z. Liu, Dalton Trans. 44 (2015) 1845-1849. 19. L. E. Kreno, K. Leong, O. K. Farha, M. Allendorf, R. P. Van Duyne, J. T. Hupp, Chem. Rev. 112 (2012) 1105-1125. 20. S. Dang, E. Ma, Z. -M. Sun, H. Zhang, J. Mater. Chem. 22 (2012) 16920-16926. 21. K. K. Kartha, S. S. Babu, S. Srinivasan, A. Ajayaghosh, J. Am. Chem. Soc., 134 (2012) 4834-4841. 22. J. R. Long, O. M., Yaghi, Chem. Soc. Rev., 38, 2009, 1213-1214. 23. H. Komatsu, D. Citterio, Y. Fujiwara, K. Minamihashi, Y. Araki, M. Hagiwara, K. Suzuki, Org. Lett. 7 (2005) 2857-2859. 24. M. Schmittel, H. W. Lin, Angew. Chem. Int. Ed. 46 (2007) 893-896. 25. N. Singh, R. C. Mulrooney, N. Kaur, J. F. Callan, Chem. Commun. (2008) 4900-4902. 26. H. J. Jung, N. Singh, D. Y. Lee, D. O. Jang, Tetrahedron Lett. 51 (2010) 3962-3965. 27. J. -F. Zhu, H. Yuan, W. -H. Chan, A. W. M. Lee, Org. Biomol. Chem. 2010, 8, 3957-3964. 28. S. Y. Assaf, S. -H. Chung, Nature 308 (1984) 734-36. 29. J. M. Berg, Y. Shi, Science 271 (1996) 1081-1085. 30. G. Sivaraman, T. Anand, D. Chellappa, Anal. Methods 6 (2014) 2343-2348. 14
31. M. C. Aragoni, M. Arca, A. Bencini, A. J. Blake, C. Caltagirone, G. De Filippo, F. A. Devillanova, A. Garau, T. Gelbrich, M. B. Hursthouse, F. Isaia, V. Lippolis, M. Mameli, P. Mariani, B. Valtancoli, C. Wilson, Inorg. Chem. 46 (2007) 4548-1559. 32. C. R. Goldsmith, S. J. Lippard, Inorg. Chem. 45 (2006) 6474-6478. 33. E. Maryon, S. Molloy, A. Zimnicka, J. Kaplan, Biometals 20 (2007) 355-364. 34. M. L. Turski, D. J. Thiele, J. Biol. Chem. 284 (2009) 717-721. 35. J. D. Capro, T. Oury, C. Rabouille, J. W. Slot, L. -Y. Chang, Proc. Nat. Acad. Sci. USA 89 (1992) 10405-10409. 36. J. A. Tainer, E. D. Getzoff, J. S. Richardson, D. C. Richardson, Nature, 306 (1983) 284287. 37. G. Rotilio, L. Calabrese, F. Bossa, D. Barra, A. F. Agro, B. Mondovi, Biochem. 11 (1972) 2182-2187. 38. C. F. Walker, R. E. Black, Annu. Rev. Nutr. 24 (2004) 255-275. 39. G. Multhaup, A. Schlicksupp, L. Hesse, D. Beher, T. Ruppert, C. L. Masters, K. Beyreuther, Science 271 (1996) 1406-1409. 40. R. S. C. Mail, C. Howells, E. D. Eaton, L. Shabala, K. Zovo, P. Palumaa, R. Sillard, A. Woodhouse, W. R. Bennett, S. Ray, J. C. Vickers, A. K. West, Plosone 5 (2010) e12030. 41. I. Zawisza, M. Rozga, W. Bal, Coord. Chem. Rev. 256 (2012) 2297-2307. 42. J. E. Spretsma, Med. Hypothese 52 (1999) 529-538. 43. L. Xue, H. -H. Wang, X. -J. Wang, H. Jiang, Inorg. Chem. 47 (2008) 4310-4318. 44. L. Xue, C. Liu, H. Jiang, Chem. Commun. (2009) 1061-1063. 45.C. C.; Woodroofe, S. J. Lippard, J. Am. Chem. Soc. 125 (2003) 11458-11459. 46. E. M. W. M. van Dongen, L. M. Dekkers, K. Spijker, E. W. Meijer, L. W. W. J. Klomp, M. Merk, J. Am. Chem. Soc. 128 (2006) 10754-10762. 47. G. K. Walkup, S. C. Burdette, S. J. Lippard, R. Y. Tsien, J. Am. Chem. Soc. 122 (2000) 5644-5645. 48. Y. Shiraishi, C. Ichimura, T. Hirai, Tetrahedron Lett. 48 (2007) 7769-7773. 49. D. A. Pearce, N. Jotterand, I. S. Carrico, B. Imperiali, J. Am. Chem. Soc. 123 (2000) 51605161. 50. X. M. Meng, M. Z. Zhu, L. Liu, Q. X. Guo, Tetrahedron Lett. 47 (2006) 1559-1562. 15
51. S. Mizukami, S. Okada, S. Kimura, Inorg. Chem. 48 (2009) 7630-7638. 52. K. Komatsu, Y. Urano, H. Kojima, T. Nagano, J. Am. Chem. Soc. 129 (2007) 13447-13454. 53. M. M. Henary, Y. Wu, C. J. Fahrni, Chem. Eur. J. 10 (2004) 3015-3025. 54. T. Hirano, K. Kikuchi, Y. Urano, T. Nagano, J. Am. Chem. Soc. 124 (2002) 6555-6562. 55. X. H. Wang, J. Cao, C. F. Chen, Chinese J. Chem. 28 (2010) 1777-1779. 56. T. Moriuchi-Kawakami, J. Sato, Y. Shibutani, Anal. Sci. 25 (2009) 449-452. 57. G. -K. Li, Z. -X. Xu, C. -F. Chen, Z. -T. Huang, Chem. Commun. (2008) 1774-1776. 58. V. Dujols, F. Ford, A. W. Czarnik, J. Am. Chem. Soc. 119 (1997) 7386-7387. 59. E. Ballesteros, D. Moreno, T. Gomez, T. Rodriguez, J. Rojo, M. Garcia-Valverde, T. Torroba, Org. Lett. 11 (2009) 1269-1272. 60. A. C. Burdette, S. J. Lippard, Proc. Nat. Acad. Sci. USA, 2003, 100, 3605-3610. 61. C. J. Frederickson, E. J. Kasarskis, D. Ringo, R. E. Frederickson, J. Neurosci. Meth. 20 (1987) 91-103. 62. P. D. Zalewski, I. J. Forbes, R. Borlinghaus, W. H. Betts, S. F. Lincoln, A. D. Ward, Chem. Bio. 1 (1994) 153-161. 63. P. D. Zalewski, S. H. Millard, I. J. Forbes, O. Kapaniris, A. Slavotinek, W. H. Betts, A. D. Ward, S. F. Lincoln, I. Mahadevan, J. Histochem. Cytochem. 42 (1994) 877-884. 64. L. Xue, H. -H. Wang, X. -J. Wang, H. Jiang, Inorg. Chem. 47 (2008) 4310-4318 65. L. Xue, C. Liu, H. Jiang, Chem. Commun. (2009) 1061-1063. 66. E. M. Nolan, J. Jaworski, K. -I. Okamoto, Y. Hayashi, M. Sheng, S. J. Lippard, J. Am. Chem. Soc. 127 (2005) 16812-16823. 67. X. Y. Zhou, B. R. Yu, Y. L. Guo, X. L. Tang, H. H. Zhang, W. S. Liu, Inorg. Chem. 49 (2010) 4002-4007. 68. J. Jiang, H. Jiang, X. Tang, L. Yang, W. Dou, W. Liu, R. Fang, W. Liu, Dalton Trans. 2011, 40, 6367-6370. 69. H. Kagechika, T. Himi, E. Kawachi, K. Shudo, J. Med. Chem. 32 (1989) 2292-2296. 70. Y. Toriumi, A. Kasuya, A. Itai, J. Org. Chem. 55 (1990) 259-263. 71. A. Itai, Y. Toriumi, N. Tomioka, H. Kagechika, I. K. Azumaya, Tetrahedron Lett. 30 (1989) 6177-6180.
16
72. I. Azumaya, H. Kagechika, Y. Fujiwara, M. Itoh, K. Yamaguchi, K. Shudo, J. Am. Chem. Soc. 113 (1991) 2833-2838. 73. J. Kim, T. Morozumi, N. Kurumatani, H. Nakamura, Tetrahedron Lett. 49 (2008) 19841987. 74. J. Kim, T. Morozumi, H. Nakamura, Tetrahedron 64 (2008) 10735-10740. 75. G. Ambrosi, M. Formica, V. Fusi, L. Giorgi , A. Guerri, M. Micheloni, P. Paoli, R. Pontellini, P. Rossi, Inorg. Chem. 46 (2007) 4737-4748. 76. A. Anichini, L. Fabbrizzi, P. Paoletti, R. M. Clay, J. Chem. Soc., Dalton Trans., (1978) 577-583. 77. P. Dapporto, M. Formica, V. Fusi, L. Giorgi, M. Micheloni, P. Paoli, R. Pontellini, P. Rossi, Inorg. Chem. 40 (2001) 6186-6192. 78. G. Ambrosi, M. Formica, V. Fusi, L. Giorgi, A. Guerri, M. Micheloni, P. Paoli, R. Pontellini, P. Rossi, Inorg Chem. 46 (2007) 309-320. 79. G. Ambrosi, M. Formica, V. Fusi, L. Giorgi, A. Guerri, S. Lucarini, M. Micheloni, P. Paoli, P. Rossi, G. Zappia, Inorg. Chem. 44 (2005) 3249-3260. 80. A. D. Becke, J. Chem. Phys. 98 (1993) 5648-5652. 81. A. Karmakar, R. J. Sarma, J. B. Baruah, CrystEngComm 9 (2007) 379-389. 82. S. De, J. B. Baruah, Der Pharma Chemica 5 (2013) 145-149 83. J. S. Kim, D. T. Quang, Chem. Rev. 107 (2007)3780-3799. 84. S. Patra, D. Maity, R. Gunupuru, P. Agnihotri, P. Paul, J. Chem. Sci. 2012, 124, 1287-1299. 85. Y. Chen, C. Zhu, Yang, Z.; Li, J.; Jiao, Y.; He, W.; Chen, J.; Guo, Z. Chem. Commun. 48 (2012) 5094-5096. 86. P. -S. Yao, Z. Liu, J. -Z. Ge, Y. Chen, Q. -Y. Cao, Dalton Trans., 44 (2015) 7470-7476. 87. Q. -Y. Cao, Z. -C. Wang, M. Li, J. -H. Liu, Tetrahedron Lett. 54 (2013) 3933-3936. 88. Z. Grabowski, K. Rotkiewicz, W. Rettig, Chem. Rev. 103 (2003) 3899-4031. 89. J. K. Nath, J. B. Baruah, J. Fluorosc. 24 (2014) 649-655. 90. C. J. Fahrni, M. M. Henary, D. G. VanDerveer, J. Phys. Chem. A 106 (2002) 7655-7663. 91. S. -I. Nagaoka, J. Kusunoki, T. Fujibuchi, S. Hatakenaka, K. Mukaia, U. Nagashima, J. Photochem. Photobiol. A: Chem. 122 (1999) 151-159. 92. M. S. Jeletic, C. E. Lower, I. Ghiviriga, A. S. Veige, Organometallics 30 (2011) 6034-6043. 17
Figures, Schemes and Tables
(a) N R
R
H
O
O
N
O
H N
R
N H
R
N
O R = H (1) or -CH3 (2)
(b)
Figure 1: (a) Design principle of assemblies of tri-quinoline receptor for binding metal ions and (b) compounds 1-2. N
N
H
R
R
HO
+
OH R
H
R
K2CO3
N HN
O
Dry acetone
O O
O R
NH
Br
R
R
N
R
O HN N
When R = H (1a) or -CH3 (2a) When R = H (1) or -CH3 (2)
Scheme 1: Synthesis of 1-2. 18
Figure 2: Structure of the compound 2 (ORTEP of with 35% thermal ellipsoids) showing the relevant dihedral angles: C12-O4-C11-C10 = 150.08°, O4-C11-C10-N2 = -1.45°, C31-O2-C30C29 = 171.17°, O2-C30-C29-N5 = 0.35°.
(a)
(b)
Figure 3: Changes in the absorption spectra of (a) the compound 1 and (b) the compound 2, upon addition of a solution of Zn2+ ions (in each case 0.033 equivalent from a solution of methanol in aliquots).
19
(a)
(b)
Figure 4: The changes in the emission spectra of the compound 1 (10-5 M in methanol, 3 mL) upon excitation at 310 nm upon addition of the solutions of (a) Zinc chloride and (b) Cupric chloride solution (in each case 0.033 equivalent from a solution of methanol in aliquot).
(a)
20
(b)
(c)
(d)
Figure 5: Changes in the emission spectra of the 2 (10-5 M in methanol, 3 mL, and excitation at 310 nm) upon addition of (a) zinc chloride and (b) cupric chloride (in each case 0.033 equivalent of methanol solution in aliquot). (c) Changes in the fluorescence of a solution of 2 (10-5 M in methanol) containing 1 equivalent cupric chloride (red lines), followed by the addition of a solution of zinc chloride in 0.033 equivalent in aliquot (black lines). (d) Changes in the fluorescence of a solution of 2 on addition of zinc chloride 0.033 equivalent (six times, black lines) followed by addition of cupric chloride in 0.033 equivalent aliquots (red lines).
21
(a)
(c)
(b)
(d)
Figure 6: Competitive fluorescence titrations showing the changes in the fluorescence emission at 493 nm of a solution of 1 upon addition of solution of (a) cupric chloride (squares) followed by solution of zinc chloride (filled circles). (b) Zinc chloride (filled circles) followed by addition of cupric chloride (squares). Similar titration with solution of compound 2 at 490 nm (c) Zinc chloride (filled circles) followed by solution of cupric chloride (squares). (d) Cupric chloride (filled circles) followed by addition of zinc chloride (squares); (in each case ligand 10-5 M in 3 mL in methanol).
22
Figure 7: Proposed ball and stick model of aggregate of 1 with Zn2+ ions generated through GaussView.
23
Figure 8: 1H-NMR (600MHz, DMSO-d6) spectra (aromatic region) of the (i) 1; and 1 in the presence of (ii) 0.5 equivalent, (iii) 1.0 equivalent and (iv) excess amounts of zinc chloride dissolved in DMSO-d6. Peaks marked by # are from compound 1; whereas peaks marked as * are from compound 1 bound to zinc ions. Inset is the expansion in the NH protons appearing in offset region.
24
(a)
(b)
Figure 9: The HOMO and LUMO in the compound (a) 1 and (b) 2 (Calculated are gas phase energies are not scaled).
Figure 10: I and II are orientations of keto forms for TICT; III is the planar enol form for ESPT.
25
Graphical abstract: Synthesis and characterization of tri-quinoline based receptors and study interactions with Zn2+ and Cu2+ ions
Reversible switching of fluorescence intensities of a tri-quinoline receptor by copper and zinc ions was observed. P. Khakhlary and J. B. Baruah
26
Graphical synopsis: Synthesis and characterization of tri-quinoline based receptors and study interactions with Zn2+ and Cu2+ ions
Two fluorescent receptors having three quinoline anchored flexible tether are synthesized and characterized. In solution these receptors from assemblies zinc or copper ions. Such assemblies are comprised of three receptor molecules with four metal ions which are established by microcalorimetric study. Reversible switching of fluorescence intensities of a tri-quinoline receptor by sequential addition copper and zinc ions was observed. P. Khakhlary and J. B. Baruah
27
Highlights: Two tri-quinoline containing ligands connected through spacers having bisphenol-ether and amide groups are synthesized and characterized. Both the ligands selectively interact with Zn2+ and Cu2+ ions to cause fluorescence changes. Reversibility of the fluorescence changes caused by sequential addition of the Zn2+ and Cu2+ ions are evaluated. Methyl substituent on the spacer bisphenol-ether has a role to cause reversible effect.
28