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Interplay of Hydrophobic and Electrostatic Interactions in Modulation of Protonation-Deprotonation Equilibria of Two Positional Isomers in Their Complexes with Cucurbiturils Vijaykant Khorwal, Uma Nudurupati, Sohidul Islam Mondal, and Anindya Datta J. Phys. Chem. C, Just Accepted Manuscript • DOI: 10.1021/acs.jpcc.6b13006 • Publication Date (Web): 09 Feb 2017 Downloaded from http://pubs.acs.org on February 18, 2017

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The Journal of Physical Chemistry

Interplay of Hydrophobic and Electrostatic Interactions in Modulation of Protonation-Deprotonation Equilibria of Two Positional Isomers in Their Complexes with Cucurbiturils

Vijaykant Khorwal,* Uma Nudurupati, Sohidul Islam Mondal and Anindya Datta Department of Chemistry Indian Institute of Technology Bombay, Powai Mumbai, India 400 076 Phone: +91 22 2576 7149, Fax: +91 22 2570 3480 Email: [email protected]

1

ACS Paragon Plus Environment


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Abstract Elucidation of host-guest chemistry of 2-(4'-Pyridyl)benzimidazole (4PBI) and 2-(2'Pyridyl)benzimidazole (2PBI) with cucurbiturils in aqueous solution is rather challenging. The guest molecules are capable of binding in three different states of protonation: cation C, tautomer T, and normal N. Charge distribution on the species governs the formation of the inclusion complexes. Binding modes of the guest molecules with cucurbiturils have been investigated by proton NMR spectroscopy. 4PBI binds with its benzimidazole ring pointing inward, while the binding mode is opposite for 2PBI. This difference is governed by the position of substitution of the pyridyl ring. Energetics of complexation has been studied by quantum chemical calculations for 4PBI-CB as 2PBI-CB type complexes, for each form (C, T, and N) of both the molecules. Release of high energy water from cucurbituril cavity is the main driving force for complexation. Excited state proton transfer (ESPT) in 2PBI and 4PBI are affected strongly upon complexation, as is manifested in steady state and time resolved fluorescence experiments.

2


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1. Introduction Interaction between guest molecules and supramolecular hosts has been an active area of research over the last few decades, due to its potential in chemical sensing, design of formulations for drug delivery and removal of pollutants.1 In this context, cucurbit[n]urils (CB) have generated considerable interest due to the potential application of their inclusion complexes in chemical separation, exchange reactions, catalysis, sensing, drug delivery and preparation of novel molecular devices like rotaxanes, catenanes etc.2-7. CBs are pumpkin-shaped rigid macrocyclic compounds, made up of a number of glycoluril units (=C4H2N4O2=) linked by methylene bridges (Scheme 1).8-11 Size of the hydrophobic cavity and diameter of the portal depend on the number of glycoluril units, which is 5, 6, 7 and 8 for CB5, CB6, CB7 and CB8, respectively (Table S1).12-15 Rims of these macrocycles are polar, by virtue of partially negative charge on the O atoms of the C=O groups of the ureido moieties. This is what enables cucurbiturils to form strong complexes with positively charged species, by ion-dipole interaction. Hydrophobic effect is an additional factor, for organic cations.16,17 CBs contain encapsulated “high energy water”, which is devoid of hydrogen-bonded networks. Release of these high energy water molecules, upon incorporation of a guest molecule, provides a strong enthalpic driving force to the association. Recently, Biedermann and coworkers have computationally and experimentally quantified the effects of the release of such high-energy water molecules from the inner cavity of CBn macrocycles.18-22 Compatibility in size of the cavity and the cation is an important factor that governs the strength of complexation and renders selectivity in cation sensing by cucurbiturils.19 The

present

study

focuses

on

inclusion

complexes

of

CBs

with

2-(2′-

pyridyl)benzimidazole (2PBI) and 2-(4′-pyridyl)benzimidazole, which undergo excited state proton transfer (ESPT). Such molecules have potential application as materials for light emitting diodes and lasers, photostabilizers of polymers and development of fluorescent probes and sensors, molecular switches and logic gates.23-27 Mechanism of ESIPT in 2PBI and 4PBI in homogeneous solutions has been studied in great detail (Scheme S1, S2, S3).28-31 2PBI can exist in four different forms in the ground state: neutral N, monocation C, protonated at benzimidazole nitrogen atom, dication D, where both nitrogen atoms are protonated and the anion A. 4PBI, on the other hand, can also occur as the tautomer T, protonated at pyridyl nitrogen atom. This form 3



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is not present in the ground state of 2PBI at any pH, but is formed from the excited state of the cation, C*, by ESPT (Scheme S1, S2, Table S2(a), S2(b)).30 In 4PBI, N*T* ESPT is observed. This process is affected by the microenvironment of micelles and cyclodextrins. Direct excitation of ground state tautomer can also lead to the formation of T*.32-33

CB5

CB6

CB7

CB8

O C N

H H C N

HC C H N

N C O

C H H n

Scheme 1. X-ray crystal structure of CB5, CB6, CB7, CB8 and glycoluril unit of Cucurbit[n]uril. The co-ordinates have been taken from PDB-RCSB site for Cucurbiturils. Different forms of 4PBI (Upper) and 2PBI (Lower)

4PBI is preferentially protonated at the pyridyl nitrogen atom in ground state at pH < 7. In sodium dodecyl sulfate (SDS) micelle, protonation of the benzimidazole nitrogen occurs only in the excited state. Such an effect is not observed in cationic cetyltrimethylammonium bromide (CTAB) and neutral Triton X-100 (TX-100). Thus, excited state protonation of 2PBI is selective to

negatively

charged

interfaces 33

microheterogeneous media.

between

aqueous

and

apolar

compartments

in

This is reminiscent of earlier studies, in which ESPT in 2PBI has 4


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been found to be promoted in restricted microenvironments with a negatively charged interface between aqueous and apolar compartments. This has been rationalized in the light of a lower local pH of such interfaces (Scheme S3).34-38 In its inclusion complexes with cyclodextrins (CD), orientation of 4PBI molecule is such that it can form hydrogen bonds with primary/secondary – OH groups of the macrocycle. Hence, by virtue of its small pKa* value, the pyridyl nitrogen of 4PBI can abstract protons from the hydroxyl groups inside the CD cavity. In 2PBI, however, cyclodextrins hinder ESPT in all conditions.39 With this background, the field is set for the study of modulation of protonation deprotonation equilibria of 2PBI and 4PBI by ion-dipole and/or hydrogen bonding interactions offered by the polar rims of cucurbiturils.40-43 These molecules provide an opportunity to examine the role of positional isomerism on the modulation of these equilibria, as the levels of exposure to water of nitrogen atoms present in the molecules are different. The mode of binding would also be affected by positional isomerism, as has been observed with cyclodextrins.32 These are the issues that have been dealt with in the present article.

2. Experimental Section 2.1. Experiments and methods 4PBI from Alfa Aesar and 2PBI from Sigma have been purified by repeated recrystallization from ethanol/water mixture and from cyclohexane, respectively. Cucurbit[5]uril (CB5) and Cucurbit[6]uril (CB6) from Sigma have been used as received. Cucurbit[7]uril (CB7) and, cucurbit[8]uril (CB8), obtained as a gift from Prof. Dr. Werner M. Nau, Jacobs University, Bremen, Germany have been used as received. Double distilled water is used to prepare the solutions. HClO4 and NaOH are used to adjust the pH of the solution, which is measured on a pH meter of model S2K712 from ISFETCOM, Japan. Absorption and fluorescence spectra have been recorded on JASCO V530 and Varian Cary Eclipse spectrophotometer/spectrofluorimeter respectively. Fluorescence quantum yields (φf) have been determined relative to that of quinine sulfate in 0.55 M H2SO4. Fluorescence decays have been recorded on a time correlated single photon counting (TCSPC) system from IBH with excitation by a pulsed light emitting diode (NanoLED, λex = 295 nm). The emission polarizer has been kept at a magic angle polarization of 54.7° with respect to the polarization of 5



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the excitation light. Decays have been fitted to multiexponential functions by an iterative reconvolution method using IBH DAS v6.0 software. The fitting function is of the following form

where I(t) and I(0) are intensities at time t and 0, after excitation pulse of light. ai and τi are the amplitude and lifetime of the ith component, respectively. All experiments are carried out at 25°C.

2.2. Proton NMR Spectroscopy Proton NMR spectra of 4PBI have been recorded on Bruker Avance III 400 MHz spectrometer in absence and presence of 1:1 equivalent cucurbit[n]uril in D2O at room temperature.

2.3. Computational Study Structures

of

Cucurbit[n]uril,

2-(2′pyridyl)benzimidazole

(2PBI)

and

2-(4′-

pyridyl)benzimidazole (4PBI) monomers and the host-guest complexes have been optimized at M06-2X levels of theory using 6-31+G* basis set. Frequency calculations have been carried out for the optimized structures at the same (M06-2X) level of theory and stabilization energies were corrected for the zero point vibrational energy (ZPVE). The M06-2X functional has been recommended for the study of nonbonding interactions as well as main-group thermochemistry and kinetics.44 All calculations have been performed using GAUSSIAN-09 suite of programs.45

3. Results and Discussion 3.1. 1H NMR Spectra The 1H NMR spectra of 4PBI in absence and presence of cucurbituril in D2O have been shown in figure 1. NMR experiments of 2PBI have not been performed due to inadequate solubility in D2O. 4PBI contains four different sets of equivalent protons that are responsible for four types of proton NMR signals. Two belong to the pyridyl moiety: H6′/H2′, H5′/H3′, δ = 8.6 ppm, 7.85 ppm, respectively. Two more belong to the benzimidazole moiety, H7/H4, H6/H5, δ = 6


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7.65 ppm, 7.35 ppm, respectively. Complexation leads to shielding of benzimidazole protons and deshielding of pyridyl protons (Table 1, Figure 1), indicating that the benzimidazole ring is buried in to the hydrophobic cavity of cucurbituril while the pyridyl ring resides outside, near the carbonyl groups at the rim of the macrocycle.9 In contrast to these observations, no significant shielding/deshielding is observed for 4PBI in CB5 (Table 1), indicating the possibility of formation of exclusion complex between 4PBI and CB5, which has the smallest cavity size. Proton NMR shifts of 4PBI, with CB6, CB7 and CB8, indicate the formation of inclusion complexes in these cases. In CB6/7/8, benzimidazole protons are partly shielded while pyridyl protons are deshielded in 4PBI (Table 1, Figure 1), implying a similar orientation of the molecule as in the case of 2PBI in CB5. Significant upfield shifts of benzimidazole protons indicate deep cavity binding. Complexation of 4PBI with CB6/7/8 is governed by hydrophobic interaction, inner portal ion-dipole interaction between the benzimidazole N atom and carbonyl oxygen of the CBs and outer portal ion-dipole interaction between the N atom on the excluded pyridyl ring of 4PBI and the portal of the macrocycle. The last factor leads to a further incorporation of the benzimidazole ring deeply in the cavity of cucurbituril.46, 47

Table 1. Chemical shifts (ppm) of protons of 4PBI in absence and presence of cucurbit[n]uril Proton

4PBI

CB5

∆δ#

CB6

∆δ#

CB7

∆δ#

CB8

∆δ#

H6′/H2′

8.58

8.57

-0.01

8.96

+0.38

8.58

0.00

8.86

+0.28

H5′/H3′

7.86

7.86

+0.00

8.37 8.53

+0.51 +0.67

8.07

+0.21

8.40

+0.54

H7/H4

7.62

7.59

-0.03

7.82 7.55

+0.20 -0.07

7.11

-0.51

7.23

-0.39

H6/H5

7.33

7.29

-0.04

7.26 7.10

-0.07 -0.23

6.88

-0.45

7.05

-0.28

∆δ# = (4PBI_CB)-4PBI

In CB6, the cavity shields the protons of the encapsulated benzimidazole ring. H6/H5 protons show upfield shifts. H7/H4 proton resonance is split into two upfield and downfield signals, as is the signal of pyridyl protons H5′/H3′. This indicates that the benzimidazole ring 7



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cannot penetrate all the way into the smaller cavity of CB6. Fast interchange between the included and excluded guest molecules (Table 4, Figure 4), leads to the observed splitting.48 H6′/H2′ lines do not exhibit splitting, as the protons reside outside the cavity and are exposed to water. In CB7, the shifts are same, but no splitting is observed. H6′/H2′ do not show appreciable shifts. In CB8, benzimidazole protons are shielded and pyridyl protons are deshielded, which confirms the mode of complexation.

H3 C3 H1

O1

H3

C2

C5'

N3 H2

N 5'

C4 C4'

N3' C2' C3'

H3

O 1'

N5

H1

H2

C5

H1

H7

H1

H6 C8

H1

H3

H5

H6'

N C2

C9

H5'

C4'

N1'

N3

H4

H3'

H2'

Figure 1. 1H NMR spectra (D2O) of 4PBI alone and 1:1 equivalent of CB5, CB6, CB7 and CB8

3.2. Steady state electronic spectra Absorption spectra of 4PBI and 2PBI consist of a single band at 310 nm at pH 9, assigned to the N form. In 4PBI, an additional tautomer band occurs at 350 nm at pH 4 (Figure 2, Figure S1, S2). This band is not observed for 2PBI at any pH (Figure 3, Figure S9, S10). The 310 nm 8


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band at pH 4 is ascribed to C rather than N.30, 36 Fluorescence emission spectra of 4PBI (λex = 310 nm) exhibit two bands at 380 nm (C*/T*) and 490 nm (T*) at both values of pH. Intensity of the two bands is almost the same at pH = 4, but T* emission is more prominent than N* emission at pH = 9. On the other hand, emission spectra (λex = 310 nm) for 2PBI at pH = 9, comprises a single band at 380 nm (N*/C*). At pH= 4, a new band at 460 nm appears due to formation of T*. In 4PBI, T absorption band at 350 nm becomes stronger at the cost of the N band at 310 nm in complexes with CB5 at both pH values. No prominent increase in C absorption at 290 nm is observed, indicating that CB5 selectively promotes the formation of T over C. Lack of a significant spectral shift (Figure 2, Figure S1, S2) suggests the possibility of formation of an exclusion, rather than an inclusion complex between 4PBI and CB5 at pH = 4.49 This may be rationalized by the small cavity size of CB5 (Scheme 1, Table S1) and is in agreement with proton NMR data. Moreover, the increase in φf with CB5 at pH = 4 is miniscule, in contrast to the case of CB6 and CB7 (Figure S3), further supporting the contention of formation of exclusion complex of 4PBI with CB5. At pH = 9, the N*/C* band at 380 nm becomes prominent with increase in CB5 concentration (Figure S4). At the same pH, ESPT from N* to T* and T to T* contributes to the increase in intensity of the 490 nm band (T*).33 This is a result of the increased basicity of the molecule in its excited state, aided by ion-dipole interaction with the oxygen atoms at the rim of CB5. A combination of these two factors leads to proton abstraction from nitrogen atom of protonated form (C*/T*) of 4PBI by the more electronegative oxygen atom of ureido carbonyl group of cucurbituril. Hence, the neutral form of dye is formed in its exclusion complex with CB5. Thus, it appears that at pH = 9, 4PBI loses a proton in the excited state in its complex with CB5 leading to the formation of N*-CB5 type exclusion complex. This argument finds support in the increase in of 380 nm emission intensity along with the 490 nm band. The significant increase in the intensity at 490 nm is a result of direct excitation of ground state tautomer (Figure S2 and S4). These dramatic changes in the spectra are not observed at pH = 4, possibly because the formation of the neutral N* form is not favored in the exclusion complex at this pH. (Figure S1 and S3). Interestingly, such an excited state deprotonation is not observed for 2PBI, indicating that the intramolecular hydrogen bond between benzimidazolium hydrogen and pyridyl nitrogen in 2PBI is too strong to be disrupted

38

(Scheme S3), even in the

excited state, by the ion-dipole interactions with the rim of CB5. This is in stark contrast to the 9



excited state deprotonation of another fluorophore, (2,2′-Bipyridyl)-3-3′-diol in nafion.50 In that case, the driving force was ion-ion interaction, which is much stronger than the ion-dipole interactions that we have in the present case. There is no possibility of the formation of a tautomer form of 2PBI in the ground state, as T is nonexistent in 2PBI. In summary, 4PBI undergoes protonation in the ground state and deprotonation in the excited state, in its exclusion complex formed with CB5, as the pyridyl nitrogen is isolated. Moreover, the more exposed pyridyl nitrogen is selectively protonated to form T. On the other hand, there is no such modulation of protonation-deprotonation equilibria for 2PBI, as the pyridyl nitrogen is hydrogen bonded to the benzimidazolium cation.38 250 325 400 475 550 625 700

CB6

2 CB5

1

Aqueous

0

CB8

5

4PBI, pH=9

4

CB7

3

CB6

2 CB5

1

Aqueous

0 250 325 400 475 550 625 700

λ/nm

2.

Normalized

absorption

4

CB7

3

CB6

2 CB5

1

aqueous

0

5

CB8

2PBI, pH=9

4

CB7

3

CB6

2 CB5

1

aqueous

Fluorescence Intensity (arb. unit)

3

CB8

2PBI, pH=4

Absorbance (arb. unit)

CB7

5

Fluorescence Intensity (arb. unit)

4PBI, pH=4

4

Figure

250 325 400 475 550 625 700

CB8

5

Absorbance (arb. unit)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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0 250 325 400 475 550 625 700

and Figure

3.

Normalized

absorption

and

fluorescence spectra of aqueous solution of fluorescence spectra of aqueous solution of 4PBI in absence and presence of CB5, CB6, 2PBI in absence and presence of CB5, CB6, CB7 and CB8 at pH = 4 and pH = 9

CB7 and CB8 at pH = 4 and pH = 9 10


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CB6 and CB7 affect the ground state protonation-deprotonation equilibrium of 4PBI in an exactly opposite manner. They do not promote the T absorption band at pH = 9, while it gets suppressed at pH = 4. The predominant N/C band undergoes a blue shift, indicating incorporation in the macromolecular cavity. 2PBI gets incorporated within the cavities as well, as is indicated by the emergence of vibronic structure in its absorption band (Figure S9, S10), usually observed for fluorophore in nonpolar media.51-53 Fluorescence spectra are altered remarkably with these two hosts. For both the molecules, at both the pH values, T* emission is suppressed and N*/C* emission is promoted (Figure 2, 3, S3. S4, S11, S12). Fluorescence maxima at highest concentrations of CB6 and CB7 occur at 380 nm and 375 nm for 4PBI and 2PBI, respectively (Figure 2, 3). For 4PBI, the ratio of N*/C* to T* fluorescence peak intensities increases with progressive addition of CB6 as well as CB7 (Figure S3, S4), while φf decreases, indicating N* to be the predominant species in the complexes of 4PBI with CB6 and CB7. N* has a φf of 0.002, compared to values of 0.12 for T* and 0.06 for C* in water.30 Of course, φf of N* is expected to be greater in nonpolar media. CB6 and CB7 bring about an increase in φf of the N* form of 2PBI, with a blue shift of 5 nm. At pH = 4, this is accompanied by a suppression of T* emission (Figure S11, 12). Thus, both fluorophores appear to form inclusion complexes with CB6 and CB7, in which they are sequestered from the external medium. No matter what the pH is, the neutral N form is stabilized. From the steady state spectra, CB6 and CB7 appear to behave similar to cyclodextrins32, where the incorporation and subsequent sequestration is driven by hydrophobic interactions. The role of hydrogen bonding with the rim of the macrocycle is not evident so far. The ratio of peak absorbance of N/C and T forms of 4PBI increases with progressive increase in the concentration of CB8 at pH = 4 (Figure 2, S1). At first glance, this appears to indicate sequestration, analogous to the situation in CB6 and CB7. Surprisingly, at pH = 9, a prominent tautomer emission band develops upon addition of CB8 (Figure S2). At pH = 4, however, fluorescence intensity decreases and the T* band gradually wanes, with the emergence of a band at 411 nm (Figure S3, S4). The red shift of almost 40 nm, with respect to the spectra in CB6 and CB7, indicate that the situation in CB8 is more complicated. This issue has been discussed later. At pH = 9, the red shift is even more prominent. Decrease of fluorescence intensity of both bands reveal that the N* to T * transition is hindered at pH = 4. There is no 11



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tautomer in the ground state, so the possibility of direct excitation is also ruled out. At pH = 9, ESPT is hindered as expected, The 380 nm band becomes stronger upon gradual addition of CB8. Emergence and the broadening of this band indicates that the stoichiometry of the complex with CB8 is different from that in with CB6 and CB7. 2:1 complexes are likely to have formed here, due to the larger cavity diameter of CB8. For 2PBI, absorption maxima are not affected significantly upon addition of CB8 (Figure 3, S9, S10). At pH = 4, total fluorescence intensity decreases and then increases, along with the peak ratios, with progressive addition of CB8 (Figure S11). At pH = 9, similar behavior is observed for the 380 nm band, with one difference: over all fluorescence intensity increases, with a distinct emergence of T* emission (Figure S12). This is different from the observation with CB6 and CB7 and indicates the formation of 2:1 type complexes, similar to the case of 4PBI. Binding in such a complex is less tight than in those with CB6 and CB7, due to the large cavity size of CB8. So ESPT is not hindered, unlike in the complexes with the two smaller macrocycles. At pH = 4, the molecule is in C form and it is this form that participates in the inclusion complex. At pH = 9, 2PBI in its complexed form gets protonated to form C, which undergoes ESPT to give rise to T*. This process can be hindered at high CB8 concentration. Thus, the complexation of 2PBI with CB8 is significantly different from that of 4PBI and may be rationalized in the light of the close proximity of the two nitrogen atoms, which can lead to the formation of a bridged structure involving a water molecule (Scheme S3). This is possible even in the hydrophobic cavity of CB8, which does contain some water molecules due to its large size. 18, 19

Although, the water present in the hydrophobic cavity is considerably differ from bulk water

and unable to form a water network inside the cavity. In case of CB6 and CB7, water is usually removed from the cavity during formation of the inclusion complex, due to the good match between the size of the cavity and that of the guest molecule. The difference between the inclusion complexes of 4PBI and 2PBI with CB8 may also be rationalized in the light of stoichiometry. A deviation in the linearity in the Benesi–Hildebrand plots at high concentration of host (Figure S17) indicates the formation of complexes involving one guest (4PBI or 2PBI) and two host (CB8) molecules. The linear section at lower concentrations of CB8 has been fitted to a straight line, in order to analyze the binding constant for the 1:1 complexes. In order to

12


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determine the binding constants of the 1:2 complexes with the CB8, the plot of φf against the host concentration ([CD]), has been fitted to the equation

Where ,

and

are the fluorescence quantum yields of the free fluorophore, 1:1 complex and

1:2 complex, respectively. Values of

and

from Benesi–Hildebrand analysis of the initial

part are used as constants in the equation. Binding constants and φf are then calculated by iterative non-linear least squares regression (Table 2, Figure S17). 2PBI is found to bind stronger than 4PBI with CB8. The reason behind this high binding constant can be understand by the steric effect of benzimidazole part, which is quite high compared with that of the pyridyl part.

Table 2. Benesi–Hildebrand plots for the determination the binding constants of 4PBI and 2PBI with the supramolecular host CB8. Binding constants are calculated from the ratios of intercepts and slopes. The two linear plots in the different concentration ranges in CB8 denote two kinds of stoichiometries: 1:1 at low concentration and 1:2 at higher one of CB8 at pH = 4 and pH = 9

System

Binding Constant pH 9 K1/(µM)-1

pH 4 K2/(µM)-1

K1/(µM)-1

K2/(µM)-1

CB8-4PBI

0.372

149.25

--

--

CB8-2PBI

0.987

178.21

0.142

139.64

3.3. Time resolved fluorescence Fluorescence decays of aqueous 4PBI in absence and presence of CBs at pH = 4 and 9, have been recorded at two different emission wavelengths (λem): 380 nm (N*/C* emission) and 490 nm (T* emission) with excitation at 295 nm (λex). The observation in absence of cucurbiturils is as follows: The decay at 380 nm is biexponential at pH = 4. τ = 0.35 nm (N*) and 13



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5.80 (C*) with amplitudes of 0.82 and 0.18, respectively. At λem = 490 nm, τ = 4.76 ns is assigned to the tautomer form of the dye formed by ESPT. At pH = 9, τ = 0.15 ns (N*) and 4.30 ns (T*) at λem = 380 nm and 490 nm, respectively. The fluorescence decays do not change appreciably upon addition of CB5 (Figure 4, S5, S6, S7, S8), which is in line with the weak interaction as discussed already.

Table 3. Fluorescence decay parameter of 4PBI at pH = 4, at λem = 380 nm and λem = 490 nm in absence and the presence of the Cucurbit[n]uril in aqueous medium, λex = 295 nm. Cucurbit[n]uril Concentration (µM)

λem/nm 380

Aqueous solution of 4PBI 490 CB5

250

380 490

CB6

100

CB7

100

380 490 380 490

CB8

52

380 490

Emitting species

τ/ns Amplitude

N C T

0.35 5.86 4.76

0.82 0.18 ---

N C T

0.37 5.63 4.86

0.60 0.40 ---

(4PBI-CB6) (4PBI-CB6) N (4PBI-CB7) T (4PBI-CB7)

1.64 1.67 0.32 0.55 5.17 0.60

----0.84 0.16 0.09 0.91

(4PBI-CB8) T (4PBI-CB8)

3.13 5.35 1.89

--0.27 0.73

Biexponential decay at pH = 9, with lifetimes and amplitudes almost similar to those at pH = 4, suggests the formation of the same kind of exclusion complex with CB5 at both of pH values. At pH = 4, addition of CB6 causes the decays at the two emission wavelengths to become single exponential and superimposable, with lifetime of ca. 1.65 ns (Table 3, Figure 4, S5, S7), which supports the contention of occurrence of a single emissive species, proposed from the steady state results. This species is ascribed to the inclusion complex, with a significantly longer lifetime of N* form, due to incorporation inside the hydrophobic cavity of CB6.

14


Page 15 of 31

pH = 4 3

IRF 4PBI CB5 CB6 CB7 CB8

λem = 380 nm

10

2

10

1

10

0

10


λem = 490 nm

3

10

2

10

1

10

Counts

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


0

10


pH = 9

3

10

λem = 380 nm

2

10

1

10

0

10


3

10

λem = 490 nm 2

10

1

10

0

10

5

10

15

20

25

30

35

40

45

50

Time/ns Figure 4. Fluorescence decay of 4PBI in aqueous solution at highest concentration of Cucurbit[n]uril at λem = 380 nm and 490 nm at pH = 4 and pH = 9, λex = 295 nm.

15



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Page 16 of 31

Table 4. Fluorescence decay parameter of 4PBI at pH = 9, at λem = 380 nm and λem = 490 nm in absence and the presence of the Cucurbit[n]uril in aqueous medium, λex = 295 nm. Cucurbit[n]uril Concentration (µM)

λem/nm

Emitting species

Aqueous solution of 4PBI

380 490

N T

0.15 4.30

----

CB5

380

N C T

0.40 5.41 4.60

0.70 0.30 ---

500

490

τ/ns Amplitude

CB6

150

380 490


1.64 4.21 1.40

--0.54 0.46

CB7

150

380

N (4PBI-CB7) T (4PBI-CB7)

0.32 0.69 4.57 0.57

0.84 0.16 0.05 0.95


3.03 4.79 1.79

--0.40 0.60

490 CB8

150

380 490

Lifetime at 380 nm is also ca. 1.64 ns at pH = 9 at 100 µM concentration of CB6 (Table 4, Figure 4, S6). In this case, the decays become slower with progressive addition of the host. Since the only species emitting at this pH is N*, the contention of increase in the lifetime of N* upon incorporation in the hydrophobic cavity gains credence. At λem = 490 nm, the 1.4 ns component has an amplitude of 0.46, with a second component of 4.21 ns, corresponding to T* (Figure S8). Thus, at pH = 9, CB6 does not completely suppress the N* → T* transition due to the high proportion of normal form present at this pH. Still, the process takes place inside the cavity, in agreement with the inference drawn from the steady state data. However, the intensity of 490 nm band is not completely suppressed. The decays of complexes with CB7 are biexponential at both emission wavelengths and at both pH values, with predominant subnanosecond lifetimes. Hence, we infer that the predominant emitting species is N*, no matter what the pH value is (Table 3, 4, Figure 4, S5, S6, S7, S8). The significantly smaller lifetime, compared to those observed in CB6, indicates that the fluorophore experiences a more water-like environment in CB7, compared to CB6. This is likely to be interplay of the loose binding of the guest molecule to the 16


Page 17 of 31

comparatively larger CB7 cavity, as well as interaction of the fluorophore with encapsulated water molecules. τ = 5.17 ns and 4.57 ns is also in line support with the hypothesis of loose binding with CB7, and the incorporation of the dye at different region of the host, whereas ESPT can take place in hydrophobic cavity at both pH.

pH = 4

Counts

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


10

3

10

2

10

1

10

3

10

2

10

1

10

3

10

2

10

1

10

3

10

2

10

1


λ em = 380 nm


λ em = 460 nm

pH = 9


λ em = 380 nm


λ em = 460 nm

5

10

15

20

25

30

Time/ns

Figure 5. Fluorescence decays of 2PBI in aqueous solution at highest concentration of Cucurbit[n]uril at λem = 380 nm and 460 nm at pH = 4 and pH = 9, λex = 295 nm.

In contrast, the decay of 2PBI in aqueous solution at λem = 380 nm is single exponential with τ = 0.90 ns (C*). The decay at λem = 460 nm is associated with a rise time of 0.91 ns (C*) and τ = 1.67 ns (T*), at pH = 4 (Table 5, Figure 5). The decay at pH = 9, at both emission 17



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Page 18 of 31

wavelengths, are biexponential. Here, N*, with τ =50 ps (Table 6, Figure 5), also contributes. Upon addition of CB5, the lifetime does not change appreciably expect that at λem = 380 nm at pH = 9, the decay becomes single exponential (τ = 0.88 ns) and almost superimposable with that at pH = 4. Hence, the exclusion complex with CB5 is the same at the two pH values. For complexes with CB6, the decays at λem = 380 nm and 460 nm are single exponential (Figure S14), indicating that ESPT is not operative in these complexes. The difference in behavior of 2PBI and 4PBI is due to the difference in position of the pyridyl nitrogen atom. In case of CB7, the decay at λem = 380 nm is biexponential (0.26-0.37 ns and∼2.65 ns). The longer component is due to the inclusion complex and the shorter one is due to uncomplexed N form of 2PBI (Table 6, 7, Figure S15). The single exponential decay at λem = 460 nm with τ = 3.41 ns is assigned to the inclusion complex at pH= 4. The biexponential decay at pH =9 with τ = 2.38 ns and 4.24 ns is due to the incorporation of the dye at different region of the CB7.

Table 5. Fluorescence decay parameter of 2PBI at pH = 4, at λem = 380 nm and λem = 460 nm in absence and the presence of the Cucurbit[n]uril in aqueous medium, λex = 295 nm. Cucurbit[n]uril Concentration (µM) Aqueous solution of 2PBI

λem/nm 380 460

species

τ/ns

Amplitude

C C T

0.90 0.91 1.67

-2.90 3.90

CB5

400

380 460

C C T

0.86 0.83 1.71

-2.86 3.86

CB6

30

380 460

(2PBI-CB6) (2PBI-CB6)

1.24 1.25

-

CB7

40

380

C (2PBI-CB7) (2PBI-CB7)

0.26 2.67 3.41

0.58 0.42 -

C (2PBI-CB8) C (2PBI-CB8)

0.66 1.60 0.77 3.71

0.63 0.37 -1.56 2.56

460 CB8

200

380 460

18


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Table 6. Fluorescence decay parameter of 2PBI at pH = 9, at λem = 380 nm and λem = 460 nm in absence and the presence of the Cucurbit[n]uril in aqueous medium, λex = 295 nm Cucurbit[n]uril Concentration (µM)

λem/nm 380

Aqueous solution of 2PBI 460

species N C N T

τ/ns 0.05 0.89 0.05 1.76

Amplitude 0.94 0.06 0.92 0.08

CB5

200

380 460

C N T

0.88 0.09 1.68

-3.07 4.07

CB6

26

380 460

(2PBI-CB6) (2PBI-CB6)

1.26 1.27

-

CB7

100

380

C (2PBI-CB7) (2PBI-CB7) (2PBI-CB7)

0.37 2.64 2.38 4.24

0.53 0.47 0.60 0.40

C (2PBI-CB8) C (2PBI-CB8)

0.75 1.65 0.81 3.57

0.65 0.35 -0.65 1.65

460 CB8

150

380 460

4PBI exhibits a single exponential decay at 380 nm for both pH values, in its complex with CB8. A biexponential decay at 490 nm observed at both pH is indicative of a different Stoichiometry than in the complexes with CB6 and CB7. Biexponential decays are obtained for 2PBI/ CB8 as well, at λem = 380 nm. τ = 0.66-0.75 ns and 1.60-1.65 ns are assigned to N* and inclusion complex, respectively at both pH (Figure S16). The decay at 460 nm is also biexponential with a rise time of 0.77 ns, due to the free cation, which can undergo ESPT in the large cavity of CB8. The decay time of 3.57-3.71 ns is due to the inclusion complex with the tautomer form of 2PBI. This is in line with water mediated ESPT in CB8 cavities, as discussed earlier (Table 5, 6, Figure 4, S16). The reason behind the difference in the behavior of the two positional isomers is likely to lie in the difference in the modes of binding/insertion of these molecules to the hydrophobic cavity of cucurbiturils as discussed in the section on proton NMR. The mode of insertion of dye inside the hydrophobic cavity is explored using quantum chemical calculations (vide infra). 19



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Page 20 of 31

3.4. Quantum chemical calculation Density Functional Theory (DFT) calculations have been performed with three different forms of 4PBI and 2PBI (N, C, T) and CB5, CB6, CB7 and CB8, in an attempt to identify the modes of encapsulation. Prior to the host-guest complexation study, it is very informative to investigate the properties of the different forms of 4PBI and 2PBI. It has been found that the all three forms (C, N, T) are planar. This facilitates binding through both heterocyclic rings (pyridyl and benzimidazole). Binding energies (Tables 7, 8) are calculated from the following equation CB+PBI → CB-PBI Energy minimized structures for CB6, CB7 and CB8 are shown in figure 6. The large size of the system (>160 atoms) has come in th way of considering solvent effects. Irrespective of the cavity size of the host, the C form is largely favoured as compared to the T form, with the benzimidazole side for 4PBI. The binding of 4PBI with CB5 is not favourable due to the mismatch of the cavity size of this macrocycle. Calculated energy values for the cation form of the dye approaching CB6, CB7 and CB8 with the benzimidazole side are -233.82, -253.46 and 236.74 kcal mol-1, respectively (Figure 6, Table 7 and Table S11). This mode has been identified in the 1H NMR experiments on 4PBI (Figure 1, Table 1). Binding of 2PBI with host is found to be more favourable when the approach is with the pyridyl part. Consequently, ESPT is hindered effectively in complexes with CB6 and CB7, but not with CB8. So, in its inclusion complex with CB8, the molecule can undergo ESPT. The calculated energy value for inclusion complex with CB6, CB7 and CB8 are -264.45, -276.24 and -265.66 kcalmol-1 with the cationic form of the dye (Figure 6, Table 8 and Table S20). The stronger affinity for CB7 compared to CB6 obviates the hypothesis of loose binding of guest in CB7 can be ruled out. The modes of binding of the two positional isomers with cucurbiturils are affected by the position of the nitrogen atom in the molecules. It has been observed that the benzimidazole part is inserted in to the hydrophobic cavity and the pyridyl part is lying outside the bulk in 4PBI. The tautomer form is already present in the ground state in case of 4PBI and the basicity of the pyridyl nitrogen increases in the excited state, thus the ground and excited state is more populated by the tautomer. This positively charged tautomer attracts towards the host molecules due to ion-dipole interaction and makes a strong binding with ureido carbonyl group. Thus the

20


Page 21 of 31

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positively charged pyridyl part of 4PBI already binds to the surface of the cucurbituril and than the benzimidazole ring approaches towards the cavity and form a inclusion complex.

Table 7. Binding energies of the complexes of cucurbiturils with different forms of 4PBI. Binding Energy (kcal mol-1) Species

CB6

CB7

CB8

Pyridyl

Benzimidazole

Pyridyl

Benzimidazole

Pyridyl

Benzimidazole

Neutral

+4.4

-24.9

-43.4

-44.6

-53.5

-43.8

Cation

-212.3

-233.8

-242.3

-253.5

-220.6

-236.7

Tautomer

-166.7

-160.5

-213.4

-194.4

-212.6

-212.6

Table 8. Binding energies of the complexes of cucurbiturils with different forms of 2PBI. Binding Energy (kcal mol-1) Species

CB6

CB7

CB8

Pyridyl

Benzimidazole

Pyridyl

Benzimidazole

Pyridyl

Benzimidazole

Neutral

-29.53

-27.66

-53.94

-50.80

+279.50

-43.83

Cation

-264.45

-244.27

-276.24

-267.20

-265.66

-256.44

Tautomer

-170.79

-189.62

-181.40

-222.19

-182.20

-214.52

This mode of insertion is completely different in 2PBI, for which the benzimidazole part is outside and the pyridyl part is inside the hydrophobic cavity. This can be explained by considering the protonation of 2PBI at the benzimidazole nitrogen and generation of the cation in the ground state. It may be noted here that the tautomer is formed in the excited state by the C* to T* transition. Then the protonated species approaches to the host molecules by ion-dipole interaction and the pyridyl part is accommodated inside the hydrophobic cavity. Once the molecule approaches to the cavity the removal of high energy water is played the crucial role to accommodate the guest molecule inside the hydrophobic cavity. Formation of inclusion complex of cucurbituril with 4PBI and 2PBI is more favourable in CB6 and CB7 with three forms of the dye with varying degree of complexation. This phenomenon is governed by the hydrophobic

21



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Page 22 of 31

interaction inside the cavity, ion-dipole interaction and the exclusion of high energy water from the cavity.

Figure 6. Geometry optimized structure of Cation form of 2PBI-CB inclusion complexes (Upper) and 4PBI-CB inclusion complexes (Lower). 22


Page 23 of 31

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4. Conclusion Photophysics of two positional isomers, 4PBI and 2PBI, has been studied inside the hydrophobic cavity of cucurbiturils by steady state and time resolved fluorescence spectroscopy. Dynamics of ESPT in these molecules depends on the pH, size of the macrocycle and mode of binding of these two positional isomers with cucurbiturils. DFT calculation and proton NMR experiments reveal that the benzimidazole part is inserted in to the hydrophobic cavity and the pyridyl part is outside in case of 4PBI. The situation is exactly the opposite in case of 2PBI. Formation of inclusion complex is favoured by ion-dipole interaction and hydrophobic interaction of the cavity. Removal of high energy water from the cavity, marked by hindrance to ESPT, plays an important role in stabilization of the complexes. Inclusion complex of 4PBI and 2PBI is more favourable with CB6 and CB7. The three forms of the dye bind with varying degrees of complexation. Inclusion complexes with CB5 and CB8 are not stable, due to incompatibility of the size of the host and the guest. Quantum chemical calculations reveal that the energy of the formation of the inclusion complex with 4PBI is more in case of CB6, CB7 and CB8 with the cation form of the dye in which the dye is accommodated in the cavity from the benzimidazole side. This is the good agreement with the 1H NMR experiments. On the other hand, an opposite orientation yields the stable structure for 2PBI.

Acknowledgement VK thanks CSIR, New Delhi, for Senior Research Fellowship and Dr. Pratap Vishnoi for help in 1H NMR experiments. We thank Prof. Werner M. Nau and Mr. Indrajit Ghosh for kind gift of CB7 and CB8.

Supporting Information Absorption, emission spectra and lifetime data of 4PBI and 2PBI in aqueous solution without and with varying concentration cucurbiturils (CB5/6/7/8) at pH=4, pH=9. Binding energy of different forms (C, N, T) of 4PBI and 2PBI with (CB5/6/7/8) calculated using GAUSSIAN-09 suite of programs. This material is available free of charge via the Internet at http://pubs.acs.org.

23



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Page 24 of 31

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