Recognition of anions using urea and thiourea substituted calixarenes: A density functional theory study of non-covalent interactions

Accepted Manuscript Recognition of Anions using urea and thiourea substituted calixarenes: A DFT assessment of Non-Covalent Interactions Mohd. Athar, Mohsin Y. Lone, Prakash C. Jha PII: DOI: Reference:

S0301-0104(17)30812-1 https://doi.org/10.1016/j.chemphys.2017.12.002 CHEMPH 9883

To appear in:

Chemical Physics

Received Date: Accepted Date:

26 September 2017 4 December 2017

Please cite this article as: Mohd. Athar, M.Y. Lone, P.C. Jha, Recognition of Anions using urea and thiourea substituted calixarenes: A DFT assessment of Non-Covalent Interactions, Chemical Physics (2017), doi: https:// doi.org/10.1016/j.chemphys.2017.12.002

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.

Recognition of Anions using urea and thiourea substituted calixarenes: A DFT assessment of Non-Covalent Interactions 1

1

*2

Mohd. Athar , Mohsin Y. Lone & Prakash C. Jha 1

School of Chemical Sciences, Central University of Gujarat, Gandhinagar 382030, Gujarat, India

2

Centre for Applied Chemistry, Central University of Gujarat, Gandhinagar 382030, Gujarat, India

Mohd.Athar [email protected] +917405498220 Mohsin Y. Lone [email protected] +919033526257 Prakash Chandra Jha [email protected] +918866823510 *Corresponding author: Dr. Prakash C. Jha, Centre for Applied Chemistry, Central University of Gujarat, Gandhinagar-382030 Gujarat, INDIA Email:[email protected] Telephone number: +91 8866823510

1

Graphical Abstract

-

Receptor 1, 2 and 3 containing urea/thiourea substitutions were modelled with spherical halides (F , Cl , Br ) and linear anions (CN , N3 ,SCN ) to obtain binding energies, non-covalent and NBO related interactions.

Recognition of Anions using urea and thiourea substituted calixarenes: A DFT assessment of Non-Covalent Interactions 1

1

*2

Mohd. Athar , Mohsin Y. Lone & Prakash C. Jha 1

School of Chemical Sciences, Central University of Gujarat, Gandhinagar 382030, Gujarat, India

2

Centre for Applied Chemistry, Central University of Gujarat, Gandhinagar 382030, Gujarat, India *Corresponding Author: E-mail: [email protected]

ABSTRACT: Designing of new calixarene receptors for the selective binding of anions is an age-old concept; even though expected outcomes from field are at premature stage. Therefore, quantum chemical calculations were performed for providing structural basis of anion binding with urea and -

-

-

thiourea substituted calixarenes (1,2, and 3). In particular, spherical halides (F , Cl , Br ) and linear -

-

-

anions (CN , N3 , SCN ) were modelled for calculating binding energies with receptor 1, 2 and 3 followed by their marked IR vibrations; taking the available experimental information into account. We found that the thiourea substitutions have better capability to stabilize the anions. However, the structural behaviour of macrocyclic motifs were responsible for displaying the anion binding potentials. Further, second order “charge transfer” interactions of n‐σ*NH and n‐σ*OH type along the H‐bond axis played critical role in developing hydrogen bonds. In addition, thermodynamic properties, noncovalent interactions (NCI), chemical-reactivity descriptors and NCI index were discussed.

Keywords: DFT; anion binding; calixarenes; non-covalent; urea-thiourea.

3

INTRODUCTION Non Covalent-bonding interactions (NCI) facilitate the diverse routes for the entrapment of analytes 1-2

(metals, ions) and play vital a role in living and non-living systems . This strategy has been successfully exploited to design receptors virtually for any guest by proper bonding control3-4. Such interactions can 5

be classical non-covalent ranging from H-bonding to cation-π , π-π stacking

6

7

or anion- π . However, the

8

9-10

dimension of NCI is also extended to aromatic moieties , weak C-H hydrogen bonds 11-14

between halogen atoms and Lewis bases

15

16

or interactions 17

. In particular, halogen , pnictogen or chalcogen are most

widely used Lewis base centres forming the σ- hole bonds 18-19. Moreover, loss of electronic charge at the covalent bonds resulted in the generation of positive electrostatic potential which thereby, act as Lewis acid 20-21

centre

.

Among supramolecules, the calix[n]arenes were found to be easily-tailored anion binding agents due to adoption of range of conformations and capability of being functionalized at both upper and lower rim. Such receptors with amide and thioamide (or urea and thiourea) have the capability to act as strong H-bond donor22-23 with analyte molecule containing H-bond acceptor. Ungaro and co-workers explicated the importance of urea functionalities in mimicking the natural receptors and highlighted their role in designing 24

uncharged (neutral) receptors . Monte Carlo simulations also deciphered that 1,3-difunctionalised bis(urea)calix[4]arenes (with long flexible butyl spacers) can selectively bind to fluoride ions in the cleft formed by NH bonds

25

. Studies also suggested that the selectivity and binding capability of an anionic

receptor depends upon the number of binding site and the distance separating the two sites within the 26

binding unit . Based on these findings, Liu et al., synthesized neutral anion receptors by tailoring binding site that demonstrate the selectivity against dicarboxylate anions

26

. Later, it was pointed out that the

increased acidity of NH protons in urea (pKa=26.9) and thioarea (pKa=21.0) were responsible for the 27

enhanced complexation ability of such receptors . Among the anion binding of calixarene framework, most of the theoretical and experimental studies are focussed on calixpyrrole23, 28-30, however little attention has been devoted to calixarenes. Nowadays, Density Functional Theory (DFT) is considered as an important approach to unveil most of the 31

structual details related to conformational alteration

or their complexes with anions

32

, cations33 and

34-36

with neutral guests

. Moreover, the available spectroscopic techniques have provided only insufficient

and indirect information of binding events. Therefore, for understanding selective anion binding, effects of chemical functionalities and resulting non-covalent interactions of calixarenes, a DFT method with proper experimental comparison was used. The calix based urea/thiourea receptors were chosen from the Qureshi et al.,

27

37

-

-

-

-

-

& H. Machuca et al., reports whereas spherical (F , Cl , Br ) and linear (CN , N3 ,

SCN-) anions were used as the modeled systems. In continuation with our earlier studies on calix related supramolecular architectures

31, 34, 38-42

, the present work is an attempt to support

advancement in the allied field.

4

Figure 1. Modelled Anion Receptors used in the study

COMPUTATIONAL SECTION All the optimized geometries and vibrational frequencies were computed with Gaussian 09W program 43

suite . The structural coordinates of the compound 1 and 2 used in the study were extracted from the 44

Cambridge Crystal Structure Database (CSD) with entries 1003765 and 1003767 respectively . Gas phase geometry optimization of the structures was performed at the B97D/6-31G*. Motivated from the previous results27, 37, 45, the input geometries of 18 anionic-complexes for six anions were optimized without any symmetry constrains. Further, the frequencies calculations were also performed at the same level to assure the structures were at the global minima and have no imaginary frequency. Thermodynamic parameters were also calculated from the normal mode vibrational frequencies utilizing the principle of statistical mechanics. Thereafter, the single point calculations were carried out at B97D/6-31+G*, for computing the interaction energies. The energies were corrected for the basis set superposition error (BSSE) using Boys–Bernardi counterpoise technique46-47. The binding energies (  ) of anions in various complexes was obtained using the following formula: Eq. 3

(∆ =    − (   +  )

Moreover, realizing the fact the number of atoms were large and the calculations are time-consuming, we performed the geometry optimization of representeive complexes (1--F-,1--Cl-, 1--N3-, 3--F-, 3--

-

SCN , 3---CN ) with diffuse function (B97D/6-31+G*) to evaluate and validate the level of theory. Using frequency calculations, thermochemical analysis was performed with thermal corrections to obtain approximate free energies as reported by Gaussian G09. The procedure considers zero-point effects, entropy as well as thermal corrections to enthalpy at 298 K and 1 atm. with unscaled frequencies. 48

The population analysis was performed by the natural bond orbital (NBO) method , using NBO 3.1 version of Gaussian 09 package at the same level of level of theory. Further, the solvent effects were also modelled by utilizing the Conductor-like Polarizable Continuum Model (CPCM) with the dielectric 49

50

constant of chloroform (ε = 4.71) . Non-covalent interactions were monitored by NCIplot , using scalar fields, electron density and the reduced density gradients. Among several reactivity descriptors defined by DFT, energy of highest occupied molecular orbital (EHOMO), global hardness(η), chemical potential (µ) and electrophilicity(ω) were considered for analyzing the reactivity of the title systems in the present study. By definition, global hardness is the 51-52

second derivatives of energy with respect to the number of electrons

5

and can be derived from

finite difference approximation and Koopmans’ theorem as η=(ELUMO-E HOMO)/2 2

52

whereas µ and ω

53

can be expressed as µ=(ELUMO+EHOMO)/2 and ω = µ /2η respectively . RESULTS AND DISCUSSION For comprehending role of chemical functionalities in anion binding events, we have chosen the representative receptors based on the following criterion: (a) It should be synthetically feasible and reported in the literature; (b) It should have chemically tuneable H-bond donors, and (c) comprise urea or thiourea substituents. Relying on these paradigms, we have selected three receptors for the anion-receptor modelling (Figure 1). Conceivably, the rendered modeling was performed to address 54

the importance of NH’s in stabilising the anion in the cavities, as pointed by earlier studies . Structure Optimisation In recent times, dispersion corrected DFT methods with adequate level of accuracy have evolved as an alternate methods that include extensive electron correlation. Several studies have outlined the suitability of B97D functional for estimating strength of hydrogen bonding interaction. Moreover, selection of this functional was also made due to its adequacy to handle dispersion interactions of π electron clouds as well as weak non-bonding interactions55-56. The gas phase optimized structure (B97D/6-31G*) of the receptors (hosts) 1, 2 and 3 are illustrated in Figure 2. For validating the level of theory employed, the optimised coordinates of receptor 2 were compared with the available crystallized structure27. We observed RMSD of 0.332 Å that suggested towards the appropriateness of the calculations. Results have shown that the urea motif in host 1 adopts an unusual cis-trans 27

conformation engaged in different intermolecular interactions . One β-NH out of two urea group forms symmetric hydrogen bonds of 2.35 Å with respective phenolic oxygen atoms. This conformational observation of 1 is similar to one of the crystallized structure of napthyl substituted 27

calixarene, with CSD entry 1003766 . Reasonably, it seems evident that bulkier nature of m-tol groups brings the structure to cis-trans conformation and m-tol groups involves π-π (or CH-π) interactions with the calixarene aromatic rings. However, the receptor 2 adopts trans-trans conformation with urea α-tape hydrogen bonding of 2.12 and 2.25 Å, where carbonyl oxygen atoms acts an acceptor for NH---O=C hydrogen bond

57-58

,

25

analogous to the geometry calculated for R=Ph using Monte carlo simulations .This arrangement further led to the dominance of π-π interactions of appended phenyl groups and as a result forms a cavity. Also, calix phenolic oxygens don’t associate with urea groups, instead 2 exhibits intramolecular hydrogen bonding interactions involving the calixarene hydroxyl groups (2.98, 2.95, 1.88 and 1.76 Å) (Figure 2, Figure S3). In general, all three receptors were reported to have adequate cavity containing acidic hydrogens; readily available to stabilize anions via forming electronic interactions. As shown in Figure 2, the shape of positively charged cavity is compatible for linear and spherical anions. Based on the results, we speculated that other polyatomic pyramidal, tetrahedeal and octaherdeal anions cannot bind selectively with these receptors.

6

Previous studies reveal that anions stabilize at the lower rim (near to amide linker)

45

. Owing to it,

anion-receptors complexes (with different anions) were modeled by positioning the anions close to electron deficient blue cavity/regions (amide/thioamide related substituents); as depicted from the molecular electrostatic potential surface (Figure 3).

1

2 Figure 2. Molecular Electrostatic potential Surface

3

27

Based on these observations that they fit to a 1:1 stoichiometry model , structures of 1:1 anionreceptor complex were generated and optimized at B97D/6-31G*. Calculated respective hessian (matrix of analytically determined second derivative of energy) for all the optimized structures of anionic complexes were found real, suggesting that they are at their global minima on the potential energy surface (PES) (Table S1). The important geometrical parameters of optimized geometries of three receptors can be found in supporting information. It was observed that all anions in general interact with hydrogen’s attached to more electronegative atoms. In this respect, acidic hydrogen’s attached to oxygen (OHa, OHb), nitrogen (N1Ha, N1Hb, N2Ha and N2Hb) and carbon (C1Ha, C1Hb, C2Ha and C2Hb) as illustrated from the graphical illustrations in Figure 2, were reported to influenced during the anion binding with the receptor. Allocated binding cavity of receptor was surrounded with such donor hydrogen’s that led the anionic-complex stability via forming electrostatic and other noncovalent interactions. There upon, halides interact with two N–H donor groups with bent N–H⋯X −

−

−

angles, where X = F , Cl and Br . Moreover, location and variation of different spherical and linear anions can be easily perceived by the non-bonding distances as tabulated in Table 1 and characteristic IR vibrations (Table S1, Figure S5). The Fluoride anion penetrates largely into the 59

cavity due to its smaller size and greater net negative charge . Consequently, the non-bonding -

-

-

-

-

-

-

distance of F and other anions varies in the order of F
7

towards greater electrophilicty of the centre and its implication in generating H-bond. The receptor 1 prominently interacts with F- via NH groups with a bond length of 1.54 Å that increases to 2.62 Å in -

case of Br (Figure S3). However, the symmetrical azide anion approaches more close to the binding domain through N1Ha and N1Hb with bond distance 1.92 and 1.93 Å respectively. Notably, anions with receptor 1 were unable to reach close to the OH groups due to steric crowding. It is important to highlight that on complex formation, intramolecular hydrogen bonding of urea is replaced by a number …

-

of NH Anion hydrogen bonds, in agreement with earlier studies

60-61

. Moreover, it is likely that lower

…

rim OH H hydrogen bonding interaction becomes apparently weaker on complexation with the anionic guest. Smaller fluoride ion approaches much closer to the cavity and interacts much more 59

strongly with the amide/thioamide protons . Conspicuously, it was noted that the interatomic distances between the complexed bromide ion and the amide/thioamide protons are larger than those of the corresponding chloride ions; even though, the binding energy was marginally preferred for Br-

over Cl in receptors 1 and 2. Nonetheless, the cavity formed by the amide motifs was more −

62

complementary-fit for the size of F than other anions . The receptor 2 is the urea counterpart of modelled receptors was interacted though its extended cavity. Due to the asymmetric exposition of the lower rim substituents (Fig. 2), the anions were able to reach closer to one of the OH group with 1.5-1.8 Å (Table 1).

1

3

2

Figure 3. Gaseous phase optimised structures of the modelled receptors at B97D/6-31G* level of approximation

Table 1. Calculated bond length of anions from the interacting atoms (in Å) C1Ha C2Ha C1Hb C2Hb N1Ha N1Hb N2Ha N2Hb 1--F 2.387 2.387 1.547 1.547 1--Cl 2.701 2.701 2.492 2.494 1--Br 2.759 2.759 2.629 2.63 1--N3 2.558 2.571 1.924 1.938 1--CN 2.467 2.468 2.039 2.055 1--SCN 2.529 2.529 2.058 2.054 2--F 4.448 4.225 2.229 1.798 1.64 1.804 2--Cl 6.108 5.159 4.066 2.485 2.722 2.877 2--Br 4.798 4.835 2.738 2.603 2.323 2.31

8

OHa 3.39 4.369 4.497 3.283 3.717 3.396 1.531 3.623 2.352

Ohb 3.391 4.369 4.911 3.281 3.722 3.394 4.413 6.576 5.018

2--N33.84 4.056 1.942 2.489 2.773 3.196 1.849 4.351 2--CN 4.552 4.448 2.44 2.485 2.04 2.877 1.819 4.634 2--SCN 5.032 3.948 2.943 2.189 2.136 3.082 1.899 5.271 3--F 4.603 2.218 2.154 3.541 2.8 5.064 1.041 5.161 3--Cl 4.11 2.681 2.84 5.691 2.125 4.887 2.07 4.648 3--Br 4.006 2.914 2.896 4.743 2.209 5.512 2.157 4.577 3--N3 3.619 3.025 2.585 5.706 1.796 4.667 1.687 4.295 3--CN 4.429 2.87 2.962 4.594 2.841 5.272 1.1 5.436 3--SCN 2.52 5.325 3.027 5.813 3.25 5.137 1.8 4.539 *For linear anions (CN , SCN , N3 ), the bond distance is measured from the largely nucleophilic nitrogen atoms. -

In case of 2--Cl , host interacts with β NH’s (2.72 & 2.87) and involved largely through one of the phenolic oxygen. The computed binding supports observed chemical shift change in NH and OH 27

resonances i.e., downfield (∆?? ??=1.72ppm) and upfield (∆?? ??=-0.27ppm) . We hereby reported that the ?? ?? …

lower rim OH O intramolecular hydrogen bonding interactions retained in the complex. Similarly, such observation was also observed in receptor 3. However, the binding site was shifted to one side and form a cavity contributed by the calix rings with exposed substituted adjacent rings. The halide ions sit asymmetrically in receptor 2 and 3, while it locates between the two exposed thiourea groups in receptor 1. The bulkier nature of benzoxazole ring engender highly asymmetric geometry of 3 and thereby reorients the amide groups for making it inadequate to react with anions. In particular, the anions evade out from the cavity of receptor 3. Moreover, in contrast to receptor 3, all urea/thiourea protons participate in hydrogen bonding with anions (Figure 1) in 1 and 2. In particular, the anions prefer to lie between the plane of two amide groups in receptor 3, and they primarily orient towards the plane of one of benzoxazole ring. However, in receptor 2 m-MeSC6H4 rings sandwiched one over facing their amide protons towards the anion. There was a clear polarity change (dipole moment) observed on solvation with chloroform, as -

-

depicted from Table S4. In general, hosts (1, 2, and 3) complexes with SCN and CN were more polar due to possibility of charge shifting across the π-bond. Receptor 2 and 3 were more polar in gas phase with dipole moment of 9.25 D and 8.39 D respectively; whereas the values slightly increases in chloroform i.e., 9.32 D (2) and 10.50 D (3). The results were further suggested that the complexes were more polar in gas phase for host 1-anion complexes, however this trend was deviated in host 2 and 3. This may be due to relatively larger polarity of host 2 and 3. Consequently, 2-Cl-, 3-F-, 3-Cl were more polar on solvation. Free Energy of Binding: Binding Feasibility It is of significant interest to examine the thermochemistry of the anion complexation with the calixarene receptor for quantifying the binding feasibility. The values of complexation enthalpy and free energy at 298 K obtained from the DFT computation are listed in Table 2. Considering the lack of experimental analysis on given anion binding of these receptors, it is difficult to directly compare the energetics involving charged species

63

. In such instance, the calculated energies provide an estimate

of the receptor-anion binding potentials. Binding enthalpy (∆Hbind) and free energy of complexation (∆Gbind) are calculated using the supramolecular model and particularly the following equations-

9

 =    − (   +  ) Eq. 1  =    − (   +  ) Eq. 2

Table 2. Calculated thermochemistry values of Enthalpy and free energy change of the reaction in gaseous phase,  !"# + %&'"& →  !"# − %&'"& 1 2 3 Compone Free Free Free nt of the Enthalpy Enthalpy Enthalpy Energy Energy Energy complex (∆H298) (∆H298) (∆H298) (∆G298) (∆G298) (∆G298) F -113.73789 -104.14892 -142.94655 -131.05776 -123.79309 -113.49693 Cl -43.51963 -34.96794 -60.44480 -50.66068 -48.60810 -39.42576 Br-51.68980 -43.52340 -70.66567 -60.29483 -60.38833 -49.86500 CN -49.51548 -40.32875 -68.87790 -58.56165 -53.68026 -44.27892 N3 -46.24302 -34.94096 -60.30989 -48.70913 -51.09806 -41.17400 SCN-36.38485 -24.58455 -49.75080 -37.48488 -39.06620 -27.87144 *Energies are represented in kcal/mol. Term Enthalpy and Free Energy includes sum of electronic and thermal enthalpies/free energies respectively at 298.15K. Table 2 reports free energy and enthalpy change of corresponding interaction of receptor 1, 2 and 3 with a series of anions. The calculated energy changes and the free energy changes demonstrate the feasibility of anion binding in thermal aspect. In general, change in the energy on complex formation is the measure of binding energy, which is related to the stability of corresponding complex. In other words, larger the magnitude of energy, stronger the binding capability and therefore more stable will be the complex. The results indicate that for all complex formatxion, the reaction is endergonic and -

-

-

-

-

-

their calculated free energies decreases in the order F >Br >CN >N3 >Cl >SCN . Moreover, observed reaction thermodynamics clearly indicated the role of substituents and receptor chemistry in anion binding.

Relative Energy of Binding: Interaction Energies In order to quantitatively estimate the preference of thiourea derivative over to less acidic urea analog for anion binding, we compared the binding and complexation potentials of thiourea receptor (1) and its urea analog (1a), as represented in Table 3 (strutures are given in Figure S1). Table 3. Comparison of BSSE corrected binding energies (∆ ) of thiourea (1) and urea (1a) substituted receptor at B97D/6-31+G* 1 (thiourea 1a (urea System derivative) derivative) (kcal/mol) (kcal/mol) F -57.4818 -49.489 Cl-43.1005 -29.4929 Br-39.3055 -25.1004 ..

The calculated results suggest that the NH S hydrogen bond in 1a (2.673 Å) is longer than that of …

o

o

NH O bonds (2.403 Å) in 1 whereas the dihederal angle of NHSO group (161.77 , 10.27 ) in 1 is o

o

59

larger than NHCO group (154.96 , 13.13 ) in 1a, analogous to Jose et al. . Upon substitution of urea

10

with thiourea, we find that the binding energy (∆ ) increases upto 15 kcal/mol for the halides. Further, attributed to the larger degree of charge transfer from nitrogen to sulphur in thioamide than 64

nitrogen to oxygen in amides, the N-H bonds are better donors in the former case . Although the NH protons of thiourea (1) are more acidic than urea (2), the anion complexation ability of 1 is expected to be stronger than 265. However, in contrary to it, host 2 depicted significantly larger anion binding ability. This behaviour can be understood by the fact that 1 comprise m-tol groups attached with thiourea motifs that were incapable to create positive potential surface due to its charecteristic 3D-geometry. Importantly, weakening of intramolecular thiourea hydrogen bonding potentially reduces number of H-bond donors thus lacks the stabilizing interactions. The design of selective hosts for anions requires careful assignment of geometry, anion basicity and nature of the solvent medium. Among them, complementarity between the receptor and anion imperatively determines the selectivities. For this reason, binding energies were calculated in order to comprehend role of possible types of noncovalent interaction viz. electrostatic interactions, hydrogen 66

bonding, hydrophobicity and combinations of these interactions . For the quantitative estimation of complexation abilities, the binding energies were corrected for basis set superposition errors (BSSE)67 and Zero-Point energies (ZPE). Among the three receptors, the anion binding ability of 2 was found to be highest in gas phase followed by 1 and 3. It is imperative to mention that these energies are overestimated as they excludes the solvent and entropic effects. Even though, the trend is useful for 68

the sake of comparison purposes . Furthermore, for rendering deeper insight, solvation effects were also estimated (chloroform) with self-consistent reaction field (SCRF) conductor-like polarizable continuum model (CPCM) model

69

at B97D/6-31G* level; as depicted in Table S2. We observed a -

-

-

noticeable reduction in energetic for CN , N3 and SCN (i.e., 60%) for receptor 1 and 3; however for receptor 2, little higher reduction was observed (~67%) on solvation. Typically, ~40% and ~72% -

-

reduction in enthalpy change was observed for F and Cl respective anion binding with receptors attributed to solvation-desolvation effects. Table 4. Interaction energies of three series of the complexes computed at B97D/6-31+G* level of theory. Total binding energies (∆ET), the binding energies corrected by BSSE (∆EBSSE), the binding energies that corrected by BSSE and ZPE (∆ ). 1

2

3

System

∆ET

∆EBSSE

∆

∆ET

∆EBSSE

∆

∆ET

∆EBSSE

∆

F-

-60.958

-57.482

-57.644

-89.544

-85.512

-83.963

-63.856

-66.106

-62.540

Cl-

-36.290

-35.808

-35.635

-54.183

-53.530

-53.356

-41.234

-41.355

-40.515

Br-

-47.702

-32.673

-32.504

-67.323

-48.417

-47.750

-19.599

-38.756

-18.825

N3-

-38.235

-36.078

-34.898

-52.316

-49.899

-48.905

-39.062

-40.495

-38.523

SCN-

-32.682

-31.209

-29.862

-47.169

-45.576

-44.475

-32.825

-34.402

-33.161

CN-

-36.268

20.689

21.440

-54.406

-52.681

-51.896

-36.085

-36.376

-34.607

*Energies are represented in kcal/mol, **BSSE are the basis set superposition error corrected energies (in kcal/mol). ∆ZPE, ∆ET, are the differences in the zero-point energy and total energy between the product(s) and reactant(s) respectively As evident from Table 4, fluoride and chloride anions binds with 2 through a binding energy of -

-

83.963 kcal/mol and -53.35 kcal/mol respectively. The order of the binding of anions with 1 was F
-

-

-

-

-

-


11

-

(~3 kcal/mol). Larger binding energies in case of F can be attributed to the change in the bond length of phenyl hydroxyl and urea hydrogen bonds (Table 1). Upon substitution of (1,3-benzoxazol-2-ylsulfanyl)urea (3) by m-MeSC6H4 (2), binding energies increases ~20 kcal/mol. These results were in good agreement with the decrease in hydrogen …

-

bonding distance of N-H Anions illustrated in Table 1. For Fluoride ion, there was 30kcal/mol increases in binding energies over to Cl-. Specifically, CN- displays larger binding potentials with 2. -

Moreover, lower ability of SCN to bind with 2 (-44.47 kcal/mol) can be apprehended to its larger size and electronic distribution (Figure 1) that makes it unfavourable to bind tightly with the receptor. Similar to receptor 2, the receptor 3 also orients its side arms towards one side and forms a cavity through two rings of benzoxazole and one calixarene ring. For this reason, the binding energies of receptor 3 are stronger than 1. Clearly, this observation led us to argue that conformational orientations play a great role in determining the fate of predominant type of complexation behaviour31. -

-

-

-

The large difference in binding energy between F and Cl /N3 /Br may result in preferential binding for -

-

-

59, 70

F over Cl /Br in all cases as noted earlier

. Presence of only one NH donor (amide) in receptor 3

led to the reduction in the number of donor to form the electrostatic interactions with anion, which results in lower binding energies. The computed trend for gas-phase selectivity of halides and other anions was in good agreement with available experimentally determined patterns; however, we have noticed few exceptions in the predicted trend for these anions. Possible reason for the behaviour is the exclusion of explicit solvent 71-73

that can affect the qunatitative binding preferences

. It is also possible that the ab-initio

calculations did not fully explore the potential energy surface, considering both enthalpic and entropic factors74. Moreover, enhanced flexibility of basic macrocyclic skeletons can also alter the selectivity 75-76

trends for some of these anions

. The results were qualitatively in agreement with the observed 59

association constant for receptors 1 and 2 with fluoride ion . We assesses the suitability of the basis set employed for geometry optimisation (B97D/6-31G*). The represented structures were re-optimised at B97D/6-31+G* level and the binding energies were compared (Table S5) to evaluate the effect of one diffuse function (B97D/6-31+G*). It was interesting to note that no changes in the trend and only insignificant deviations in the ∆EBSSE were observed. Gas phase reactivity descriptors Interpreting chemical reactivity of a chemical structure by density functional theory (DFT) based descriptors have become a back-of-an-envelop tool for computational chemists. Among such reactivity descriptors, HOMO energy (EHOMO), global hardness (η) and chemical potential (µ) possess pertinent potential to explain the chemical reactivity pattern. Accordingly, we have computed the reactivity parameters of the systems in gas phase, as depicted in Table 5. Measurement of EHOMO of the complex is an estimate of electron donating ability. Sharp drop in the HOMO energies accentuates the realization that the reactivity of receptors 1, 2 and 3 drops sharply on forming complex with anions. Certainly, this advocates towards greater stability of complex than bare receptors. Larger values of 1 (EHOMO=0.033) suggests that this receptors is more prone to donate electrons and less tendency to act as an electrophilic centre for anions. However, HOMO energiesof3

12

and 2 were more negative which predicts that it is low lying and weaken from the viewpoint of electron donation. Similarly, more negative values of chemical potential (µ) signifies more stability of systems. Global hardness (half of HOMO-LUMO gap) also quantifies the stability with changing environment 77-78

according to the principle of maximum hardness -

-

-

. As evident from Table5, the values of η

-

-

-

increases on anion binding in the order F >Cl >CN >Br =SCN >N3 . Nevertheless, for receptor 2 and 3, it was maximum with SCN- and N3-. Likewise, the similar trend was complemented by the principle of minimum electrophilicity (MEP) which assign that chemical stability is inversely related to 79

electrophilicity . Table5. Gas phase reactivity parameters (in kcal/mol) global chemical Electrophilicity Systems EHOMO hardness potential (ω) (η) (µ) 1* 0.03394 14.12524 11.11947 4.376654 1-F -44.0763 36.25122 -7.82504 0.844541 1-Cl -45.0301 34.93659 -10.0935 1.458049 1-Br-39.9912 32.32615 -7.66503 0.908748 1-CN -42.4259 33.7757 -8.65022 1.107694 1-SCN -41.767 32.67128 -9.09575 1.266138 1-N3 -29.4365 27.34059 -2.09588 0.080333 2* -4.03489 6.654738 2.619852 0.515695 2-F -48.9646 36.70931 -12.2553 2.045686 2-Cl -43.317 31.1935 -12.1235 2.355921 2-Br-51.8637 37.34309 -14.5206 2.823105 2-CN -51.8637 37.09522 -14.7684 2.939822 2-SCN -52.2088 36.30142 -15.9074 3.485322 2-N3 -51.9327 37.50311 -14.4296 2.775941 3* -3.34463 6.752002 3.407377 0.859761 3-F -38.5479 24.225 -14.3229 4.23417 3-Cl-52.8489 28.42304 -24.4258 10.49536 3-Br -51.1922 28.51089 -22.6813 9.021863 3-CN -39.1064 21.84674 -17.2596 6.817846 3-SCN -56.1935 32.69324 -23.5002 8.4461 3-N3 -50.8785 32.12535 -18.7531 5.473552 *1, 2 and 3 represents for only hosts (unbounded state) Reactivity descriptors computed for the anion binding in solvation (chloroform) is depicted in Table S3. On solvation, binding of receptor 1 with F- anion produces larger value of η (39.87) that indicate -

its resistance for transferring charge. This behaviour was much more pronounced in 1--F over others in order N3->Cl ->SCN-=Br-. Moreover, more negative values of µ in case of 1--SCN- (-56.805 kcal/mol) -

-

-

and 1—Cl (55.86 kcal/mol) indicates large global stability than 1--CN and 1--F . It argues that 1 show -

-

more escaping tendency of electrons with CN and F anions. The hosts 1 and 2 are more stable compared to 3 as the global reactivity descriptors (η, µ and ω) were drastically changes in 1 and 2. In particular, it was noted that in gas phase the hardness of 1 (14.12 kcal/mol), 2 (6.65 kcal/mol) and 3 (6.75 kcal/mol) that changes to 1 (13.02), 2 (39.69) and 3 (36.36) (in kcal/mol) on solvation. Further, it is important to mention that global hardness for receptor 3 (36.36 kcal/mol) decreases on complex formation with anions which suggest that the receptor display resistance for charge transfer

13

processes. Consequently, the complex formation with receptor 3 was not favourable on solvation. Likewise, only 1-2 kcal/mol change in the η and µ values was reported for receptor 2 complexes with anions. Overall, we reported that the anion binding of receptor 1 was favoured whereas receptor 3 was disfavoured on solvation; however, receptor 2 remains unaffected.

Non-Covalent Interaction (NCI) Plots For mapping the real space regions to account for dominating non-covalent interactions, NCI method was used which relies on scalar fields, electron density and the reduced density gradients50. Figure 3 provides the qualitative information of molecular interacting regions with green-blue color schemes. This illustration allow the assessment of host-guest complementarity and the extent of weak noncovalent interactions

20-21, 68

. As observed from the table 4, receptor 2 presents most favourable

interaction energies greater than 20-25 kcal/mol compare to 1 and 3 for the same anion. These … -

results clearly indicate that generated symmetric non-covalent cloud is contributed by NH X (where X is anion) and the C-H…X- hydrogen bond is central to stabilising interactions (see Figure 3 for an illustration).

Specifically, lower binding energy of halides other than F- is due to the fact that …

-

directionality of the hydrogen bond for them is not adequate as they display higher N-H X distance. Moreover, among pseudohalides (CN-, SCN-, and N3-), azide presents much more affinity than thiocyanide and cyanide to contribute anion hydrogen-bonded interactions (Figure S4). Such interactions involve O−H, N−H and C−H donor contributes markedly in generating the cloud of NCI interactions around anion. NCI plots of all anions in complex with receptor 1, 2 and 3 are given in Figure S4 of supplementary information. Second-order interaction energies, energy gaps and charge transfer NBO analysis was performed to examine the coordination and second-order interactions between the filled orbital of one subsystem and vacant orbital of another subsystem80. Such charge transfer interactions are measure of the intermolecular delocalization or hyper-conjugation (partial covalent bond with σ* antibonding orbitals) and play a prominent role in governing ∆)*+,- values of complex. The charge transfer second-order interaction energies Eij with respect to the hydrogen atoms and anionic atom were computed using E.q. 1. )(.) = ∆)+/ = 0+

1(+,/). 3/ 43+

E.q. 1

Here, (i) and (j) indicates the donor and acceptor NBO occupancy that associates with delocalization (2e-stabilization) i → j. whereas F(i,j) is the off-diagonal NBO Fock matrix element and εi/εj are diagonal elements.

14

2--F 1--F

-

-

3--F-

1--F2--F 3--F Figure 4. Illustration of the binding cavity and non-covalent interaction (NCI) plots of representative structures of receptor 1, 2 and 3 in complexed with Fluoride anion. (Distance from the anion is depicted in Å).

15

The calculated stabilization energies are a measure of the intensity of charge transfer interaction between Lewis-type NBOs (donor) and non-Lewis NBOs (acceptor). Thereupon, larger energies would indicate the higher charge transfer and relatively stronger interaction. Table 6 depicts the perturbation energies of two most significant donor-acceptor interactions present in each complex and their corresponding atomic numbers depicted in Figure S2. Fluoride in complex with 1 have the NBO charge of -0.69 and the second order most stabilization -

donor acceptor interaction was contributed by lone pair of F (donor) to thiourea σ* NH (acceptor) (22.02 and 22.06 kcal/mol). However, smaller stabilization energies (3-6kcal/mol) were reported with -

-

-

Cl , Br and SCN that were only marginally different from each other with a factor of ~2kcal/mol. -

Nitrogen atom oriented towards receptor 1 cavity in 1--N3 complex possess NBO charge of -0.5631 and the most stabilization of the complex was contributed from thiourea σ* NH acceptor orbitals (8.40 -

-

and 4.55 kcal/mol). In this context, it is worthwhile to state that Cl (-0.855) and Br (-0.828) have -

-

larger NBO charge than F (-0.696). This observation led us to conclude that in comparison to F and Cl -, Br-anions were not significantly involve in forming second order donor (i)-acceptor (j) interaction -

-

and hence NBO charges on such anions were retained. However, in 1--N3 and 1--CN complex observed larger stabilisation energies than expected can be possibly due to natural orbital interaction of filled nitrogen to its antibonding, nN155→ σ*N7-H77 . ...

In contrast to receptor 1, σ* of phenyl O H participate in two mostly significant second order -

stabilizing interactions in anionic complexes of receptor 2. As expected, F shows the highest stabilization energies among the anions that interacts through σ*OH acceptor (33.34kcal/mol) and σ*NH -

acceptor (21.66Kcal/mol). Among halides, Cl own the highest natural atomic charge (-0.826) followed -

-

..

..

by Br (-0.757) and F (-0.682). Moreover, stabilization interactions with σ* orbital of N H and O H acceptors Table 6. Donor–acceptor NBO interactions for the stable structures E(2) Energy NBO Ej–Ei System Donor(i)-Acceptor(j) (kcal/ [a] Gap(eV) Charge (a.u.) mol) NF155→ σ*N7-H77 22.02 0.58 -0.6967 1…F3.144 nF155→ σ*N8-H78 22.06 0.58 NCl155 → σ*N7-H77 3.49 0.63 … -0.8550 1 Cl 3.030 nCl155→ σ*N8-H78 3.51 0.63 nBr155→ σ*N7-H77 3.44 0.61 … -0.8284 1 Br 2.804 nBr155→ σ*N8-H78 3.46 0.61 nN155→ σ*N7-H77 9.11 0.49 … -0.5631 1 N3 2.371 nN155→ σ*N8-H78 8.40 0.84 -0.6255 (N) nN155→ σ*N7-H77 4.55 0.82 … 1 SCN 2.833 -0.3003 (S) nN155→ σ*N8-H78 4.66 0.82 2.929

-0.8081 (N) -0.0454 (C)

… -

3.183

-0.6827

…

2.705

-0.8269

…

-

1 CN 2 F

2 Cl

-

nN155→ σ*N7-H77

6.44

0.80

nN155→ σ*N8-H78 nF157→ σ*O5-H152 nF157→ σ*N12-H153 nCl157→ σ*N9-H148 nCl157→ σ*N10-H150

5.83 33.34 21.66 13.90 8.48

0.80 0.67 0.66 0.63 0.63

16

2…Br…

-

2 N3 …

-

2 SCN 2…CN-

3.239

-0.7579

3.253

-0.5033

0.69

21.71 20.36

0.72 0.81

33.34 21.66 25.98 22.71 30.07 25.35 24.30 12.80 16.46 5.82

0.67 0.66 0.56 0.66 0.56 0.59 0.83 0.87 0.80 0.64

3.217

-0.7315 (N) -0.0420 (C)

…

-

2.465

…

-

2.473

3 N3

…

-

2.786

3…SCN-

2.835

3 Br

5.21

nN158→ σ*N10-H150 nN158→ σ*O5-H152

-0.6481 (N) -0.2642 (S) σ N157-C159 → σ*N12-H153

2.101

3 Cl

12.72 12.20 12.23 11.23 16.05

3.148

… -

3 F

nBr157→ σ*N10-H150 nBr157→ σ*N12-H153 nN159→ σ*O5-H152 nN159→ σ*N9-H148 nN157→ σ*O5-H152

nF157→ σ*O5-H152 nF157→ σ*N12-H153 nCl157→ σ*O2-H155 -0.7804 nCl157→ σ*N5-H57 n N157 → σ*O2-H155 -0.7405 nN159→ σ*N5-H57 nN157→ σ*O2-H155 -0.5938 nN159→ σ*N5-H57 -0.6064 (N) nN157→ σ*O2-H155 -0.3066 (S) σ N157-C158 → σ*NO2-H155 -0.6827

0.58 0.58 0.50 0.55 0.81

nN158→ σ*O2-C12 5.80 0.04 nN158→ σ*N5-H57 5.31 0.03 **Entries are included of two most stabilizing second order interactions. Anions were considered as Donor and σ*of receptor 1, 2 and 3 are treated as acceptors, however Nitrogen was considered in SCN- and CN- anions. [a] Ej–Ei indicate Energy difference between donor and acceptor i and j NBO orbitals. …

-

3 CN

1.895

-0.7237 (N)

-

-

-

-

-

-

in different anionic complexes were in the order of F >CN >SCN >Cl >Br >N3 . Nature of such interactions clearly indicates the role of hydrogen bonding interactions in stabilizing the anions and the resultant orbital ∆ of the complex. Similarly, the receptor 3 exhibits dominant interaction between non-bonding filled orbital of anion (donor) and σ* orbitals of NH and OH bond (acceptors). Interactions involving OH acceptors were more prominent in such complexes in 3-F- (33.34kcal/mol), -

-

-

-

1-Cl (25.98 kcal/mol), 1-Br (30.07 kcal/mol), 1-N3 (24.30 kcal/mol), 1-SCN (16.46 kcal/mol). In all these complexes, NH acceptors lack ability for forming such stabilization due to its preformed optimized geometry and orbital orientation. The orbital energies (in eV), ELUMO and EHOMO, and frontier molecular orbital energy gap, ∆EHOMO−LUMO of all receptors and their complexes with halide ions shows that larger energy complexes formed with more electronegative anions. It can also be related with the themal stability of the complexes. CONCLUSIONS In this study, equilibrium geometries, vibrational spectroscopy, thermodynamic properties and BSSE corrected binding energies ( ∆)*+,- ) of anionic complexes with receptor 1, 2 and 3 have been calculated. The analysis of electrostatic potential maps gives an idea about the location of binding sites surrounded by the lower rim urea/thiourea substituted calixarenes, in complement with experimental studies. The results of ab-initio calculations showed the shifting of the amide/thioamide acidic hydrogen’s attached to oxygen (OHa, OHb), nitrogen (N1Ha, N1Hb, N2Ha and N2Hb) and carbon (C1Ha, C1Hb, C2Ha and C2Hb) (Table 1) which evidently suggest towards the association of intramolecular hydrogen bonding. The calculation confirmed that fluoride generates the strongest complex with the urea/thiourea receptors among all the modelled anions. Consequently, there seems no compelling reason to argue that these receptor systems can be used in sensing applications, anion

17

transport as well as purifications. Subsequently, we also developed interrelations between energetic, geometrical, and topological parameters signifying the persuasive role of both favourably oriented urea motifs (2) which exceeded even the weight of unfavourably oriented thiourea motifs (1). We believe that the study is quite useful to comprehend the fact that not only the reactive groups are essential for anion recognition, but the construction and composition of the binding subunit is crucial for consolidating complexation events. Moreover, for the preferential binding, the pattern of the charge density may not always be the sole deciding factor for the maximum stability of complex. Rather, optimal geometric arrangement of the NH donor and other weak bondings are the crucial paradigms that need to be considered in achieving selectivities. Distinctly, obtained results can support the designing of the receptors in association with the available approaches

[54]

.

ASSOCIATED CONTENT Supporting Information: The supporting information is attached with this manuscript. Corresponding Author Prakash C. Jha [email protected] Acknowledgements This work was supported by Department of Science & Technology (DST), New Delhi under INSPIREJRF grant awarded to Mohd. Athar.Prakash C. Jha would also like to thank UGC for start-up grants. The authors also acknowledge Central University of Gujarat-Gandhinagar (CUG) for providing basic infrastructure and facilities. The authors declare no competing financial interest. REFERENCES 1. Wang, D.-X.; Wang, M.-X., Anion− π interactions: generality, binding strength, and structure. Journal of the American Chemical Society 2013, 135 (2), 892-897. 2. Estarellas, C.; Frontera, A.; Quiñonero, D.; Deyà, P. M., Relevant anion–π interactions in biological systems: The case of urate oxidase. Angewandte Chemie International Edition 2011, 50 (2), 415-418. 3. Oshovsky, G. V.; Reinhoudt, D. N.; Verboom, W., Supramolecular chemistry in water. Angewandte Chemie International Edition 2007, 46 (14), 2366-2393. 4. Zayed, J. M.; Nouvel, N.; Rauwald, U.; Scherman, O. A., Chemical complexity—supramolecular self-assembly of synthetic and biological building blocks in water. Chemical Society Reviews 2010, 39 (8), 2806-2816. 5. Ma, J. C.; Dougherty, D. A., The cation− π interaction. Chemical reviews 1997, 97 (5), 1303-1324. 6. Schneider, H. J., Binding mechanisms in supramolecular complexes. Angewandte Chemie International Edition 2009, 48 (22), 3924-3977. 7. Frontera, A.; Gamez, P.; Mascal, M.; Mooibroek, T. J.; Reedijk, J., Putting anion–π interactions into perspective. Angewandte Chemie International Edition 2011, 50 (41), 9564-9583. 8. Meyer, E. A.; Castellano, R. K.; Diederich, F., Interactions with aromatic rings in chemical and biological recognition. Angewandte Chemie International Edition 2003, 42 (11), 1210-1250. 9. Desiraju, G.; Steiner, T., The Weak Hydrogen BondOxford University Press. New York 1999. 10. Steiner, T., The hydrogen bond in the solid state. Angewandte Chemie International Edition 2002, 41 (1), 48-76. 11. Legon, A. C., The halogen bond: an interim perspective. Physical Chemistry Chemical Physics 2010, 12 (28), 7736-7747. 12. Scholfield, M. R.; Zanden, C. M. V.; Carter, M.; Ho, P. S., Halogen bonding (X‐bonding): A biological perspective. Protein Science 2013, 22 (2), 139-152. 13. Erdelyi, M., Halogen bonding in solution. Chemical Society Reviews 2012, 41 (9), 3547-3557. 14. Parisini, E.; Metrangolo, P.; Pilati, T.; Resnati, G.; Terraneo, G., Halogen bonding in halocarbon–protein complexes: a structural survey. Chemical Society Reviews 2011, 40 (5), 2267-2278. 15. Metrangolo, P.; Resnati, G., Halogen bonding: a paradigm in supramolecular chemistry. Chemistry-a European Journal 2001, 7 (12), 2511-2519.

18

16. Sundberg, M. R.; Uggla, R.; Viñas, C.; Teixidor, F.; Paavola, S.; Kivekäs, R., Nature of intramolecular interactions in hypercoordinate C-substituted 1, 2-dicarba-closo-dodecaboranes with short P⋯ P distances. Inorganic Chemistry Communications 2007, 10 (6), 713-716. 17. Sanz, P.; Yáñez, M.; Mó, O., The Role of Chalcogen–Chalcogen Interactions in the Intrinsic Basicity and Acidity of β‐Chalcogenovinyl (thio) aldehydes HC ( X) CH CH CYH (X= O, S; Y= Se, Te). Chemistry-A European Journal 2002, 8 (17), 3999-4007. 18. Cavallo, G.; Metrangolo, P.; Pilati, T.; Resnati, G.; Sansotera, M.; Terraneo, G., Halogen bonding: a general route in anion recognition and coordination. Chemical Society Reviews 2010, 39 (10), 3772-3783. 19. McDowell, S. A., Sigma-hole cooperativity in anionic [FX⋯ CH 3⋯ YF]−(X, Y= Cl, Br) complexes. Chemical Physics Letters 2014, 598, 1-4. 20. Politzer, P.; Murray, J. S.; Clark, T., Halogen bonding and other σ-hole interactions: a perspective. Physical Chemistry Chemical Physics 2013, 15 (27), 11178-11189. 21. Clark, T., σ‐Holes. Wiley Interdisciplinary Reviews: Computational Molecular Science 2013, 3 (1), 13-20. 22. Scheerder, J.; Fochi, M.; Engbersen, J. F.; Reinhoudt, D. N., Urea-derivatized p-tert-butylcalix [4] arenes: neutral ligands for selective anion complexation. The Journal of Organic Chemistry 1994, 59 (25), 7815-7820. 23. Zhang, Y.-M.; Ren, H.-X.; Zhou, Y.-Q.; Luo, R.; Xu, W.-X.; Wei, T.-B., Studies on the anion recognition properties of synthesized receptors III: A novel thiourea-based receptor constructed by benzo-15-crown-5 for sensing anions in a strong polar solvent. Turkish Journal of Chemistry 2007, 31 (3), 327-334. 24. Casnati, A.; Pirondini, L.; Pelizzi, N.; Ungaro, R., New Tetrafunctionalized Cone Calix [4] arenes as Neutral Hosts for Anion Recognition. Supramolecular Chemistry 2000, 12 (1), 53-65. 25. McDonald, N. A.; Duffy, E. M.; Jorgensen, W. L., Monte Carlo investigations of selective anion complexation by a bis (phenylurea) p-tert-butylcalix [4] arene. Journal of the American Chemical Society 1998, 120 (20), 5104-5111. 26. Liu, S.-Y.; He, Y.-B.; Wu, J.-L.; Wei, L.-H.; Qin, H.-J.; Meng, L.-Z.; Hu, L., Calix [4] arenes containing thiourea and amide moieties: neutral receptors towards α, ω-dicarboxylate anions. Organic & biomolecular chemistry 2004, 2 (11), 1582-1586. 27. Qureshi, N.; Yufit, D. S.; Steed, K. M.; Howard, J. A.; Steed, J. W., Hydrogen bonding effects in anion binding calixarenes. CrystEngComm 2014, 16 (36), 8413-8420. 28. Wu, Y.-D.; Wang, D.-F.; Sessler, J. L., Conformational features and anion-binding properties of calix [4] pyrrole: a theoretical study. The Journal of organic chemistry 2001, 66 (11), 3739-3746. 29. Sessler, J. L.; Gross, D. E.; Cho, W.-S.; Lynch, V. M.; Schmidtchen, F. P.; Bates, G. W.; Light, M. E.; Gale, P. A., Calix [4] pyrrole as a chloride anion receptor: solvent and countercation effects. Journal of the American Chemical Society 2006, 128 (37), 12281-12288. 30. Pichierri, F., Effect of fluorine substitution in calix [4] pyrrole: A DFT study. Journal of Molecular Structure: THEOCHEM 2008, 870 (1), 36-42. 31. Athar, M.; Lone, M. Y.; Jha, P. C., Investigation of structure and conformational equilibrium of Oxacalix [4] arene: A density functional theory approach. Journal of Molecular Liquids 2017, 237, 473-483. 32. Yadav, U. N.; Pant, P.; Sharma, D.; Sahoo, S. K.; Shankarling, G. S., Quinoline-based chemosensor for fluoride and acetate: a combined experimental and DFT study. Sensors and Actuators B: Chemical 2014, 197, 73-80. 33. Murphy, P.; Dalgarno, S. J.; Paterson, M. J., Transition Metal Complexes of Calix [4] arene: Theoretical Investigations into Small Guest Binding within the Host Cavity. The Journal of Physical Chemistry A 2016, 120 (5), 824-839. 34. Mehta, V.; Athar, M.; Jha, P.; Kongor, A.; Panchal, M.; Jain, V., A turn-off fluorescence sensor for insensitive munition using anthraquinone-appended oxacalix [4] arene and its computational studies. New Journal of Chemistry 2017, 41, 51255132. 35. Karaush, N. N.; Baryshnikov, G. V.; Minaeva, V. A.; Ågren, H.; Minaev, B. F., Recent progress in quantum chemistry of hetero [8] circulenes. Molecular Physics 2017, 1-13. 36. Lula, I.; Denadai, Â. L.; Resende, J. M.; de Sousa, F. B.; de Lima, G. F.; Pilo-Veloso, D.; Heine, T.; Duarte, H. A.; Santos, R. A.; Sinisterra, R. D., Study of angiotensin-(1–7) vasoactive peptide and its β-cyclodextrin inclusion complexes: complete sequence-specific NMR assignments and structural studies. Peptides 2007, 28 (11), 2199-2210. 37. Gómez-Machuca, H.; Quiroga-Campano, C.; Jullian, C.; Fuente, J.; Pessoa-Mahana, H.; Escobar, C. A.; Dobado, J. A.; Saitz, C., Study by fluorescence of calix [4] arenes bearing heterocycles with anions: highly selective detection of iodide. Journal of Inclusion Phenomena and Macrocyclic Chemistry 2014, 3 (80), 369-375. 38. Panchal, M.; Athar, M.; Jha, P.; Kongor, A.; Mehta, V.; Bhatt, K.; Jain, V., Turn-off fluorescence probe for the selective determination of pendimethalin using a mechanistic docking model of novel oxacalix [4] arene. RSC Advances 2016, 6 (58), 53573-53577. 39. Mehta, V.; Athar, M.; Jha, P.; Panchal, M.; Modi, K.; Jain, V., Efficiently functionalized oxacalix [4] arenes: Synthesis, characterization and exploration of their biological profile as novel HDAC inhibitors. Bioorganic & medicinal chemistry letters 2016, 26 (3), 1005-1010. 40. Panchal, M.; Athar, M.; Jha, P.; Kongor, A.; Mehta, V.; Jain, V., Quinoline appended oxacalixarene as turn-off fluorescent probe for the selective and sensitive determination of Cu 2+ ions: A combined experimental and DFT study. Journal of Luminescence 2017. 41. Athar, M.; Lone, M. Y.; Jha, P. C., Theoretical assessment of calix[n]arene as drug carriers for second generation tyrosine kinase inhibitors. Journal of Molecular Liquids 2017, 247 (Supplem ent C), 448-455. 42. Panchal, M. K.; Kongor, A.; Athar, M.; Mehta, V. A.; Jha, P. C.; Jain, V. K., Sensing of Ce(III) using di-naphthoylated oxacalix[4]arene via realistic simulations and experimental studies. New Journal of Chemistry 2017. 43. M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, G. Scalmani, V. Barone, B. Mennucci, G. A. Petersson, H. Nakatsuji, M. Caricato, X. Li, H. P. Hratchian, A. F. Izmaylov, J. Bloino, G. Zheng, J. L. Sonnenberg, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, T. Vreven, J. A. Montgomery, J. E. Peralta, F. Ogliaro, M. Bearpark, J. J. Heyd, E. Brothers, K. N. Kudin, V. N. Staroverov, R. Kobayashi, J. Normand, K. Raghavachari, A. Rendell, J. C. Burant, S. S. Iyengar, J. Tomasi, M. Cossi, N. Rega, J. M. Millam, M. Klene, J. E. Knox, J. B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W. Ochterski, R. L. Martin, K. Morokuma, V. G. Zakrzewski, G. A. Voth, P. Salvador, J. J. Dannenberg, S. Dapprich, A. D. Daniels, Farkas, J. B. Foresman, J. V. Ortiz, J. Cioslowski and D. J. Fox, Gaussian 09, Revision B.01, Wallingford CT, 2009. 44. Allen, F. H., The Cambridge Structural Database: a quarter of a million crystal structures and rising. Acta Crystallographica Section B: Structural Science 2002, 58 (3), 380-388.

19

45. Nehra, A.; Bandaru, S.; Yarramala, D. S.; Rao, C. P., Differential Recognition of Anions with Selectivity towards F− by a Calix [6] arene–Thiourea Conjugate Investigated by Spectroscopy, Microscopy, and Computational Modeling by DFT. Chemistry-A European Journal 2016, 22 (26), 8903-8914. 46. Boys, S. F.; Bernardi, F. d., The calculation of small molecular interactions by the differences of separate total energies. Some procedures with reduced errors. Molecular Physics 1970, 19 (4), 553-566. 47. Boys, S.; Bernardi, F., The calculation of small molecular interactions by the differences of separate total energies. Some procedures with reduced errors. Molecular Physics 2002, 100 (1), 65-73. 48. Glendening, E.; Reed, A.; Carpenter, J.; Weinhold, F., NBO Version 3.1, TCI. University of Wisconsin, Madison 1998, 65. 49. Barone, V.; Cossi, M., Quantum calculation of molecular energies and energy gradients in solution by a conductor solvent model. The Journal of Physical Chemistry A 1998, 102 (11), 1995-2001. 50. Contreras-García, J.; Johnson, E. R.; Keinan, S.; Chaudret, R.; Piquemal, J.-P.; Beratan, D. N.; Yang, W., NCIPLOT: a program for plotting noncovalent interaction regions. Journal of chemical theory and computation 2011, 7 (3), 625-632. 51. Parr, R. G.; Pearson, R. G., Absolute hardness: companion parameter to absolute electronegativity. Journal of the American Chemical Society 1983, 105 (26), 7512-7516. 52. Parr, R. G.; Donnelly, R. A.; Levy, M.; Palke, W. E., Electronegativity: the density functional viewpoint. The Journal of Chemical Physics 1978, 68 (8), 3801-3807. 53. Deka, B. C.; Bhattacharyya, P. K., DFT study on host-guest interaction in chitosan–amino acid complexes. Computational and Theoretical Chemistry 2017, 1110, 40-49. 54. Sessler, J. L.; Camiolo, S.; Gale, P. A., Pyrrolic and polypyrrolic anion binding agents. Coordination chemistry reviews 2003, 240 (1), 17-55. 55. Galindo-Murillo, R.; Olmedo-Romero, A.; Cruz-Flores, E.; Petrar, P.; Kunsagi-Mate, S.; Barroso-Flores, J., Calix [n] arene-based drug carriers: a DFT study of their electronic interactions with a chemotherapeutic agent used against leukemia. Computational and Theoretical Chemistry 2014, 1035, 84-91. 56. Grimme, S.; Ehrlich, S.; Goerigk, L., Effect of the damping function in dispersion corrected density functional theory. Journal of computational chemistry 2011, 32 (7), 1456-1465. 57. Qureshi, N.; Yufit, D. S.; Steed, K. M.; Howard, J. A.; Steed, J. W., Anion hydrogen bonding from a ‘revealed’urea ligand. CrystEngComm 2016, 18 (28), 5333-5337. 58. Etter, M. C., Encoding and decoding hydrogen-bond patterns of organic compounds. Accounts of Chemical Research 1990, 23 (4), 120-126. 59. Jose, D. A.; Kumar, D. K.; Ganguly, B.; Das, A., Efficient and simple colorimetric fluoride ion sensor based on receptors having urea and thiourea binding sites. Organic letters 2004, 6 (20), 3445-3448. 60. Prins, L. J.; Reinhoudt, D. N.; Timmerman, P., Noncovalent synthesis using hydrogen bonding. Angewandte Chemie International Edition 2001, 40 (13), 2382-2426. 61. Mogck, O.; Böhmer, V.; Vogt, W., Hydrogen bonded hom o-and heterodimers of tetra urea derivatives of calix [4] arenes. Tetrahedron 1996, 52 (25), 8489-8496. 62. Yamato, T.; Zhang, F., Synthesis, conformations and inclusion properties of hexahom otrioxacalix [3] arene triamide derivatives having hydrogen-bonding groups. Journal of inclusion phenomena and macrocyclic chemistry 2001, 39 (1), 55-64. 63. Blas, J. R.; Márquez, M.; Sessler, J. L.; Luque, F. J.; Orozco, M., Theoretical study of anion binding to calix [4] pyrrole: the effects of solvent, fluorine substitution, cosolute, and water traces. Journal of the American Chemical Society 2002, 124 (43), 12796-12805. 64. Wiberg, K. B.; Rush, D. J., Solvent effects on the thioamide rotational barrier: An experimental and theoretical study. Journal of the American Chemical Society 2001, 123 (9), 2038-2046. 65. Gómez, D. E.; Fabbrizzi, L.; Licchelli, M.; Monzani, E., Urea vs. thiourea in anion recognition. Organic & biomolecular chemistry 2005, 3 (8), 1495-1500. 66. Beer, P. D.; Gale, P. A., Anion recognition and sensing: the state of the art and future perspectives. Angewandte Chemie International Edition 2001, 40 (3), 486-516. 67. Valadbeigi, Y.; Farrokhpour, H.; Tabrizchi, M., Theoretical study on the mechanism and kinetics of atmospheric reactions NH 2 OH+ OOH and NH 2 CH 3+ OOH. Physics Letters A 2014, 378 (10), 777-784. 68. Bauzá, A.; Ramis, R.; Frontera, A., Computational study of anion recognition based on tetrel and hydrogen bonding interaction by calix [4] pyrrole derivatives. Computational and Theoretical Chemistry 2014, 1038, 67-70. 69. Cossi, M.; Rega, N.; Scalmani, G.; Barone, V., Energies, structures, and electronic properties of molecules in solution with the C‐PCM solvation model. Journal of computational chemistry 2003, 24 (6), 669-681. 70. Jose, D. A.; Singh, A.; Das, A.; Ganguly, B., A density functional study towards the preferential binding of anions to urea and thiourea. Tetrahedron letters 2007, 48 (21), 3695-3698. 71. Merrill, G.; Webb, S., Anion− Water Clusters A-(H2O) 1-6, A= OH, F, SH, Cl, and Br. An Effective Fragment Potential Test Case. The Journal of Physical Chemistry A 2003, 107 (39), 7852-7860. 72. Jose, D. A.; Kumar, D. K.; Ganguly, B.; Das, A., Urea and thiourea based efficient colorimetric sensors for oxyanions. Tetrahedron letters 2005, 46 (32), 5343-5346. 73. Hay, B. P.; Gutowski, M.; Dixon, D. A.; Garza, J.; Vargas, R.; Moyer, B. A., Structural criteria for the rational design of selective ligands: convergent hydrogen bonding sites for the nitrate anion. Journal of the American Chemical Society 2004, 126 (25), 7925-7934. 74. McMahon, T.; Ohanessian, G., An experimental and ab initio study of the nature of the binding in gas-phase complexes of sodium ions. CHEMISTRY-WEINHEIM-EUROPEAN JOURNAL- 2000, 6 (16), 2931-2941. 75. Brooks, S. J.; Gale, P. A.; Light, M. E., Anion-binding modes in a macrocyclic amidourea. Chemical Communications 2006, (41), 4344-4346. 76. Beer, P. D.; Davis, J. J.; Drillsma-Milgrom, D. A.; Szemes, F., Anion recognition and redox sensing amplification by selfassembled monolayers of 1, 1′-bis (alkyl-N-amido) ferrocene. Chemical Communications 2002, (16), 1716-1717. 77. Parr, R. G.; Chattaraj, P. K., Principle of maximum hardness. Journal of the American Chemical Society 1991, 113 (5), 1854-1855. 78. Chattaraj, P. K., Chemical reactivity theory: a density functional view. CRC press: 2009. 79. Chattaraj, P. K.; Roy, D. R., Update 1 of: electrophilicity index. Chemical reviews 2007, 107 (9), PR46-PR74. 80. Rajesh, P.; Kandan, P.; Sathish, S.; Manikandan, A.; Gunasekaran, S.; Gnanasambandan, T.; Abiramig, S. B., Vibrational spectroscopic, UV–Vis, molecular structure and NBO analysis of Rabeprazole. Journal of Molecular Structure 2017, 1137, 277-291.

20