Improvement of Anion Transport Systems by Modulation of Chalcogen

Article Cite This: J. Phys. Chem. A XXXX, XXX, XXX−XXX

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Improvement of Anion Transport Systems by Modulation of Chalcogen Interactions: The influence of solvent Published as part of The Journal of Physical Chemistry virtual special issue “Manuel Yáñez and Otilia Mó Festschrift”. Goar Sánchez-Sanz† and Cristina Trujillo*,‡ †

Irish Centre of High-End Computing, Grand Canal Quay, Dublin 2, Ireland School of Chemistry, Trinity Biomedical Sciences, Trinity College Dublin, 152−160 Pearse Street, Dublin 2, Ireland

‡

S Supporting Information *

ABSTRACT: A series of potential anion transporters, dithieno[3,2-b;2′,3′-d]thiophenes (DTT), involving anion− chalcogen interactions have been studied by analyzing the interaction energy, geometry, and charge transfer. It was found that gas phase calculations show very negative interaction energies with short anion−chalcogen distances, but when solvent effects are considered, the interaction energy values decreased drastically concomitantly with an elongation on the interatomic distances. To enhance the chalcogen interaction between the DTT derivatives and the anion, increasing the anion transporter capacity, bisisothioazole moiety was considered; i.e., the σ-hole of the chalcogen atom was modulated by substitution of the adjacent carbon by a nitrogen atom in the S−C axis, increasing the depth of the σ-hole and therefore the interaction between the chalcogen and anion. Finally, different anions were analyzed within the complexes, finding that F− and NO3− would be the best candidates to form complexes and possibly displace other anions such as Cl− or Br−.

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INTRODUCTION Noncovalent interactions, also known weak interactions, are essential elements on the chemistry landscape across the fields.1 Needless to say, they play an important role in materials, biology and even in medicinal chemistry. As mentioned in the literature, hydrogen bonds could be the most important ones, involved in a wide range of scenarios particularly enabling different shapes of proteins (protein folding),2 stabilization of amino acids3 and within protein−protein interactions,4 and other biological roles.5 However, other noncovalent interactions are highlighted in the last years, halogen bonds,6,7 chalcogen bonds,8−14 tetrel bonds,15−18 and pnictogen (also called pnicogen)19−21 bonds. Curiously, chalcogen bonds remain one of the less studied noncovalent interactions. Nevertheless, the importance of chalcogens is undeniable with numerous applications;22 supramolecular chemistry,23 medicinal chemistry,24,25 catalysis,26 synthesis27 and bond activation28 are just a few examples. Chalcogen bonds have been studied within different frameworks using NMR29 and Xray30 techniques, and both by experiment31−34 and from the theoretical perspective.33,35−39 Recently, chalcogen interactions have been highlighted due to their role within anion transporters40,41 and anion recognition.42 Scaffolds or compounds containing sulfur or selenium, such as 2,2′-bithiophene derivatives22,43 and dithieno[3,2-b;2′,3′-d]thiophenes (DTTs) are good candidates to have © XXXX American Chemical Society

anion−chalcogen interactions and therefore to be good anion transporters.40,41,44,45 This capacity of behaving as good anion transporters, or in another words, being good electron acceptors, is due to the existence of a σ-hole, described by Politzer et al.46−48 The term “σ-hole” refers to the electron-deficient outer lobe of a p orbital involved in forming a covalent bond. Several works were devoted to how those interactions through σ-hole can be tuned within kinds of interactions, including halogen, chalcogen, and pnicogen.49−52 Also, the effect on the σ-hole upon substitution on aromatic rings has been previously studied.49,53−55 However, when dealing with noncovalent interactions, the effect of solvation around the molecules involved plays an important role. Previous studies showed that the interaction energy within intramolecular interactions in lactones varies considerably when polar solvents are taken into account and so the different conformation stability.56 Benz et al.41 have reported gas phase calculations on DTTs interacting with different anions. But that raises the question, how would the anion−chalcogen interaction, in DTT-like structures, vary under solvent effects and how, using previous experience in noncovalent interaction, could we modulate, and Received: November 5, 2017 Revised: December 9, 2017 Published: January 10, 2018 A

DOI: 10.1021/acs.jpca.7b10920 J. Phys. Chem. A XXXX, XXX, XXX−XXX

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The Journal of Physical Chemistry A

All complexes with different bridges (Y) present very negative interaction energies (MP2 level), found across the different bridges, ranging from −93.3 to −41.4 kJ·mol−1 in the gas phase (Table 1), which may indicate a strong interaction

eventually enhance, those chalcogen interactions present between DTTs and different anions? (Scheme 1) Scheme 1. Compounds Subject To Study Including (1−6) DTT Derivatives (Left) and Bisisothioazole (1N−6N) Ones (Right) with Different Bridges (Y) Interacting with Different Anions (X−)

Table 1. Interaction Energies (kJ·mol−1) of the Different Bridges Considered in the Gas Phase and PCM Solvent Model at the MP2/6-311++G(d,p) Computational Level comp (Y bridge) 1 2 3 4 5 6

(SO2) (O) (S) (PCH3) (CH2) (NCH3)

gas phase

chloroform

THF

water

−93.3 −60.6 −53.8 −50.7 −45.6 −41.4

−23.7 −14.8 −9.9 −7.9 −9.2 −7.0

−18.5 −13.2 −8.4 −6.6 −8.1 −7.1

−11.5 −12.0 −8.2 −7.0 −8.6 −9.7

between the (Cl−) anion and the scaffold. The more negative interaction energy corresponds to compound 1 (SO2). To mimic the experimental environment, we have also carried out the same calculation of the interaction energy but within different solvents: chloroform, THF, and water (Table 1). When the solvent effect is taken into account, the interaction energies between the anion and the scaffold increases dramatically, becoming more positive (−23.7 to −7.0 kJ· mol−1) in chloroform. Furthermore, the larger the polarity of the solvent considered, the more positive the interaction energies. In the case of PCH3, CH2, and NCH3, interaction energies in THF are slightly larger than in water. However, as is clear from the values of Table 1, the main point to consider is the dramatic effect on the Eint when any solvent model is taken into account. The molecular electrostatic potential (MEP) of each system has been obtained to identify the areas of nucleophilic attack. Actually, it is very clear how the anion will interact with the DDT, but we would like to see whether there is any relationship between the maxima values on the MEP and the interaction energy. As seen in Figure 1, there is a maximum value (VS,max) between both S atoms, coinciding with the areas in which the Cl− is found and associated with the σ-hole on the sulfur atom. As observed in Table S2, the most positive VS,max is found for SO2 bridge (0.0588 au in gas phase). This is a mere corroboration of the previous findings but also, fair linear

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COMPUTATIONAL METHODS The structures of the complexes were optimized at the MP257/ 6-311++G(d,p). Harmonic vibrational frequencies were computed at the same level used for the geometry optimizations to classify the stationary points as local minima. Calculations were performed using the Gaussian 09 program.58 Effects of solvation have been included by means of the SCFRPCM approaches implemented in the Gaussian09 starting from the gas-phase geometries and reoptimizing. The interaction energies within the complexes have been calculated as the difference of the total energy of the complex and the sum of the energies of the isolated monomers. In the case of gas phase calculation, interaction energies have been evaluated and corrected for the inherent basis set superposition error (BSSE) using the Boys−Bernardi59 counterpoise technique over the optimized geometry. The atoms in molecules (AIM) methodology60,61 was used to analyze the electron density of the systems with the AIMAll program.62 The natural bond orbital (NBO) method63 has been employed using the NBO-3 program to analyze chargetransfer interactions between occupied and unoccupied orbitals. The NCI (noncovalent interactions) index, based on the reduced gradient of the electron density, has been calculated to identify attractive and repulsive interactions with the NCI program64 and plotted with the VMD program.65 The molecular electrostatic potentials (MEP) of the isolated monomers have been calculated on the electron density isosurface of 0.001 au. This isosurface has been shown to resemble the van der Waals surface.66 These calculations have been carried out with the facilities of the Gaussian-09 program and the numerical results obtained using the WFA program67 and plotted with Jmol.68

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RESULTS AND DISCUSSION 1. Different Bridges and Solvent Effects. First, we have considered the interaction between chlorine anion and the scaffold with different bridges, SO2, S, O, NCH3, and PCH3 for (1−6) DTT derivatives (Scheme 1). Cartesian coordinates of each compound can be found in Table S1 in the Supporting Information.

Figure 1. Molecular electrostatic potential (MEP) on the 0.001 au electron isosurface for isolated compound 2. The purple dot corresponds to the MEP maxima value (VS,max) associated with the S σ-hole. Color range: −0.015 au (red) to +0.05 (blue). B


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effect of the different basis sets on the structural data and energetics. The results from this experiment have been gathered in Table 3. As observed, gas phase calculations without BSSE do not differ too much from the ones with BSSE correction, ca. 2−3 kJ·mol−1. Once again, as observed for the compounds studied above, when the THF solvent is taken into account, the Eint values become larger, and in compound 3Me are even positive, indicating a nonattractive interaction. MP2 values present a similar view, but with more negative Eint values than in the M06-2X cases and more affected by the BSSE corrections. In terms of intermolecular distances, dS···Cl values for M06-2X are slightly shorter than those found by Benz et al.,41 mainly due to the larger basis set employed. Once more, the solvent has dramatic effects on the Cl−···S distances, particularly for compound 3Me, in which the distance reaches 3.544 Å, more than 0.4 in Å larger than in the gas phase calculations. MP2 calculations provide a similar view of the distance variations. It is well-known that PCM is a very limited model, but it has been used for roughly two decades, providing useful insights in different systems.69,70 To double check the effect of the solvent, the SMD model71 has also been used for 1Me and 3Me complexes at both the MP2 and M06-2X levels in THF solvent. In both cases, the SMD model not only predicts more positive binding energies than the PCM results, but it also captures the drastic changes with respect to the gas phase results, confirming the importance of the solvation effects. We highlight that it is not our intention to discredit other authors’ computational studies but simply point out that solvent effects are important when comparing experiments and theoretical calculations, especially in charged systems.72 Furthermore, in spite of PCM (SMD) limitations, it clearly captures the essence of the solvation effects on the intermolecular interactions in the present systems. Further information on compound 1−6 interactions is provided through atoms in molecules (AIM), which was utilized to carry out an analysis on the electron density on the bond critical points (BCP) between both interacting atoms in two scenarios, gas phase calculations and THF solvent. Molecular graphs of the complexes are depicted in Figure 3. As seen in Table S3, the electron density values at the BCP varies between 0.012 and 0.016 au in gas phase calculations but in THF those values are roughly half of those in the gas phase, indicating a weakening of the interaction in the solvent. However, in both scenarios small values of the electron density at the BCP suggest that those contacts are categorized as weak interactions. Small positive Laplacian values at the BCPs, ∇2ρBCP, indicate that those interactions are within a close shell regimen with no partial covalent character, shown by the small positive total electron energy density, HBCP, values. As occurred with the electron density values, Laplacian values in gas phase complexes are twice the THF values. Furthermore, NBO analysis (Table S4) shows second-order interaction energies, E(2), values corresponding to the donations from the Cl− electron lone pairs into the σ*S−C antibonding orbital ranging from 14.1 to 19.3 kJ·mol−1 for gas phase calculations, whereas in THF those values are reduced drastically (from 3.1 to 6.4 kJ· mol−1), showing again the solvent effects on the intermolecular interactions. 2. Enhancing Chalcogen Interactions. Once the parental systems have been studied and the effect of different solvents on the interatomic distances and Eint evaluated, we are interested about how to modulate the chalcogen interaction. Because the chalcogen interaction takes places through the σ-

correlations between that maximum value and the interaction energies were found (R2 = 0.89) in gas phase and chloroform, which agrees with the idea that electrostatics govern these particular interactions. Correlations between both quantities with more polar solvents such as THF and water are poor, which also shows how the charge transfer due to the electrostatic interaction is affected by the solvent. The interatomic distance between the anion (Cl−) and the chalcogen atoms is evaluated (Table 2); it is also observed that Table 2. Interatomic Cl− ···S Distances (Å) Using Different Bridges Considered in the Gas Phase and PCM Solvent Models at the MP2/6-311++G(d,p) Computational Level comp (Y bridge) 1 2 3 4 5 6

(SO2) (O) (S) (PCH3) (CH2) (NCH3)

gas phase

chloroform

THF

water

3.118 3.172 3.200 3.279 3.210 3.206

3.402 3.402 3.547 3.569 3.550 3.545

3.495 3.535 3.562 3.627 3.552 3.559

3.545 3.569 3.732 3.951 3.658 3.638

the relatively short distances found in the gas phase largely increase when solvents are taken into account, being up to 20% larger with respect to the gas phase calculations for highly polar solvents such as water. For example, for complex 1 the Cl−···S distance in the gas phase is 3.118 Å; when the chloroform solvent is used, that distance increases to 3.405 Å, and even longer with THF (3.495 Å) and water (3.545 Å). This increase of the intermolecular distance is systematically observed across all the bridges (Y) considered. Are those effects worth considering when studying these complexes? Obviously, the answer is yes. As a case of study, Benz et al.41 reported theoretical calculations of similar complexes but in the gas phase. We would like to evaluate what would be the solvent effect implications for the same complexes as those studied by Benz et al.41 and compare gas phase calculations at different levels with PCM and SMD models with the data in the literature. To answer that question, we have carried out a little computational experiment. First of all, we have optimized the geometries of compounds 1 and 5 (from ref 41) (named here as 1Me and 3Me) at M06-2X/6-311++G(d,p) and MP2/6311++G(d,p) levels and both in the gas phase, with and without BSSE correction (to replicate Benz et al.’s calculations), and in THF solvent (to reproduce the experimental conditions) (Figure 2). Also, because calculations in ref 41 were carried out at the M06-2X/6-311G(d,p) level, we can also estimate the

Figure 2. Optimiszed structures for 1Me and 3Me complexes at the MP2/6-311++G(d,p) computational level. C


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Table 3. Interaction Energies (kJ·mol−1) and Interatomic Cl−···S Distances (Å) for Compounds with Methyl Substituents 1Me and 3Me (1 and 5 in ref 41, respectively) in the Gas Phase with and without BSSE Correction and in THF Solvent Modela M06-2X comp (Y bridge)

MP2

GP (GPBSSE)

3Me (S) 1Me (SO2)

−41.7(−39.3)b −82.7(−80.1)c

3Me (S) 1Me (SO2)

3.136 (3.144)d 3.073 (3.083)d

THF Eint −1.3 (2.5)e −12.2(−8.9) dS···Cl 3.544 (3.457)e 3.331 (3.369)e

GP(GPBSSE)

THF

−47.8(−26.4) −86.6(−63.5)

−6.8 (−3.6)e −17.3(−15.0)e

3.203 3.121

3.591 (3.588)e 3.429 (3.448)e

a Both calculations carried out at the M06-2X/6-311++G(d,p) and at the MP2/6-311++G(d,p) computational levels. bEint value = −41.4 kJ·mol−1 at the M06-2X/6-311G(d,p) BSSE -corrected level.41 cEint value = −84.0 kJ·mol−1 at the M06-2X/6-311G(d,p) BSSE-corrected level.41 dTaken from ref 41. eValues using SMD solvent model.

Figure 3. Molecular graphs of the DTT derivatives 1−6 optimized at MP2/6-311++G(d,p) computational level. Green dots correspond to the bond critical points.

hole in the chalcogen atom, it seems rational to modify the depth of that σ-hole to increase the charge transfer between the anion and the chalcogen atom. In other words, we increase the donation from the anion into the σ*S−C antibonding orbital. One possibility to considered would be the substitution of a H atom by one or two vicinal acceptors (such as CN), which would increase the chalcogen interaction.41 However, it is known from previous studies12,73−79 that to directly modulate the σ-hole on a particular atom, whether halogen, pnicogen or chalcogen, substitutions on the axis that contains the σ-hole showed the maximum effects on the depth of the hole; i.e., the addition of heteroatoms into the thiophene rings increases the chalcogen interactions. So, with that in mind we decided to study bisisothioazoles of DTT, replacing the carbon atoms contiguous to the sulfur atom, i.e., S−C, by an electron withdrawing nitrogen atom, S−N, to enhance the chalcogen interaction, as seen in Figure 4. As in the previous section, the effect of the solvent was evaluated and a decrease of the Eint was found with respect to the gas phase calculations (Table S5). However, we have seen that the solvent effects are indeed important, and we have

decided to discuss only those data in the THF solvent model that mimic the experimental conditions in the literature (Table 4).41 The presence of a nitrogen atom in the ring increases (makes more negative) the interaction energy between the scaffold and the Cl− anion. In the case of 1N, Eint is twice as negative as in the parental compound 1, but it is more than 3 times more negative in other cases such as 4N and 6N with respect to the corresponding 4 and 6 compounds. The enhancing of the chalcogen interaction is also corroborated by the shortening of the S···Cl− distances, up to 8.4−11.0% shorter with respect to the parental compounds. In addition, the electron density properties at the BCPs also point to an improving of the chalcogen interactions by an increase of the electron density at the BCP and also Laplacian with respect to each parental compound. HBCP values remain very similar to those found for the parental compounds, which indicates that in spite of the modulated interactions being stronger, both interactions (with and without modulation) do not present any partial covalent character, again in coherence with the electrostatic nature of the interaction. Finally, E(2) values found for the 1N−6N D


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Figure 4. Molecular graphs of the modulated DTT derivatives 1N−6N optimized at the MP2/6-311++G(d,p) computational level. Green dots correspond to the bond critical points.

Table 4. Interaction Energy (kJ·mol−1), S···Cl Distance (Å), Electron Density, Laplacian, and Total Electron Energy Density (au) at the BCP at the MP2/6-311++G(d,p) Level in PCM = THF Solvent Model for the Modulated Systems comp (Z) 1N 2N 3N 4N 5N 6N

(SO2) (O) (S) (PCH3) (CH2) (NCH3)

Eint

dS···Cl

ρBCP

∇2ρBCP

HBCP

−37.7 −31.2 −23.7 −20.9 −23.2 −22.8

3.134 3.238 3.282 3.228 3.263 3.249

0.0151 0.0121 0.0117 0.0127 0.0119 0.0120

0.0465 0.0381 0.0368 0.0397 0.0372 0.0376

0.0012 0.0012 0.0012 0.0012 0.0012 0.0012

Figure 5. Molecular electrostatic potential (MEP) on the 0.001 au electron isosurface for isolated compound 1 and 1N. The purple dot corresponds to the MEP maxima value (VS,max) associated with the S σ-hole. Color range: −0.015 au (red) to +0.05 (blue).

compound are twice as large as those for 1−6 compounds (Table S4), in the THF solvent model. The interaction energies and E(2) charge transfers found are also consistent with the MEP maxima values associated with the σ-hole on the S atom (VS,max), 1N (0.1049 au), 2N (0.0649 au), 3N (0.0691 au), 4N (0.0517 au), 5N (0.0618 au), and 6N (0.0471 au), considerably larger than those found in the parental DTT compounds (Table S2). As an illustrative example, two MEP maps on the 0.001 au electron density isosurface have been plotted for 1 and 1N in Figure 5. It is clear from Figure 5 that in 1N the σ-hole is deeper than in 1N. Also the VS,max values observed for the DTT (1−6) in THF (Table S2) are smaller than those for the bisisothioazole compounds (1N−6N). It is noteworthy that even though the bithioazoles were found inactive as anions transporters,41 the present theoretical study shows that bisisothioazoles present strong binding energies and could efficiently trap anions within the enhanced chalcogen bonds. Hence, this opens a door toward further investigations for a design of different anions transporters. 3. Competition between Different Anions. Finally, the last logical step is to explore the intermolecular interaction between the DTT and bisisothioazole derivatives and different

anions to estimate the interaction strength and the possible competition between them. For such a purpose, we selected the compound showing the strongest interaction, i.e., the more negative Eint, found both in the DTT and in the bisisothioazole derivatives, 1 or 1N, respectively, and four different anions, F−, Cl−, Br−, and NO3− (Figure 4). These anions were chosen following the experimental work of Benz et al.41 Chloride and nitrate are likely the most studied anions in anion transport though a membrane, because the chloride−nitrate exchange assays are typically used to evaluate the efficiency, in other words the potency, of the relevant transporter.45,80,81 Results corresponding to the interaction between those anions and 1 and 1N have been gathered in Table 5, including interaction energies, interatomic distances, and electron density properties at the BCP between both interacting atoms. In the case of halogens anion, interactions with F− present the most negative Eint of the halogen family with 1 (−19.7 kJ· mol−1) and are 3 times larger (−60.7 kJ·mol−1) with 1N. The interaction energy becomes more positive with the size of the halogen anion considered, i.e., F− < Cl− < Br−, both in DTT and in bisisothioazole derivatives. The nitrate anion, NO3−, E


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The Journal of Physical Chemistry A Table 5. Interaction Energy (kJ·mol−1), S···Cl Distance (Å), Electron Density, Laplacian, and Total Electron Energy Density (au) at the BCP and Second-Order Interaction Energies (kJ·mol−1) at the MP2/6-311++G(d,p) Level in PCM = THF Solvent Model for 1 and 1N Interacting with Different Anions Eint

dS···X

F− Cl− Br− NO3−

−19.7 −18.5 −17.8 −27.9

2.619 3.495 3.648 2.866

F− Cl− Br− NO3−

−60.7 −37.7 −34.3 −51.8

2.477 3.134 3.326 2.698

ρBCP

∇2ρBCP

Compound 1 0.0240 0.0775 0.0083 0.0263 0.0078 0.0231 0.0165 0.0524 Compound 1N 0.0304 0.0983 0.0151 0.0465 0.0131 0.0373 0.0217 0.0691

HBCP

E(2)a

−0.0004 0.0011 0.0009 0.0006

21.1 6.4 5.2 7.8

−0.0006 0.0012 0.0009 0.0005

35.6 17.9 15.0 11.6

Figure 6. NCI plots of noncovalent interaction for 1N interacting with F−, Cl−, Br−, and NO3− anions. Blue and green areas correspond to λ2 > 0 (strongly attractive) and λ2 ≈ 0 (weak), respectively, and red areas correspond to λ2 < 0 (repulsive). λ2 is one of the three eigenvalues of the electron density Hessian with λ1 ≤ λ2 ≤ λ3.

E(2) values corresponding to the donation from the lone pair of X− into the σ* S−C(N) antibonding orbital a

presented the most negative interaction of all the anions studied with compound 1 (−27.9 kJ·mol−1). This may imply that due to the nitrate anions binding strongly with 1, they could displace other anions. In the bisisothioazole derivative 1N, NO3− shows the second largest (in absolute value) Eint, more negative than Cl− and Br− anions. This is a bit controversial because some binding studies suggested that chloride is almost always more strongly bound to hydrogen bond donor anion receptors than nitrate due to the higher charge density of Cl−. Competition between anions and anion transporter capacity involves more than simply binding energies, and it is a very complicated process with a wide range of factors including interaction between the transporter and membrane and also involving hydrogen bonds, etc. It is not our intention to reduce that complex process into a unique factor as the interaction between the anion and the transporter, but it is clear that this interaction governs how the anion binds to the transporter and the differences between Eint would indicate, again as a major factor, how easy/hard the anion would be transmembranelly released.44,82 In terms of electron density properties, values of the electron density at the BCP cannot be compared across the anions, because only comparisons between similar types of interacting atoms are possible, but as it was observed in the previous systems, the bisisothioazole complexes presented larger ρBCP and ∇2ρBCP values than in the DTT coherent with the modulated nature of the σ-hole. Also, the NBO analysis showed second-order interaction energies, E(2), greater than in 1N than 1 complexes (Table 5). Finally, to visualize the interaction between anions and 1 and 1N, noncovalent index (NCI) plots have been depicted in Figure 6. In all the cases, a green area corresponding to values of λ2 ≈ 0 (weak attractive) appears between the anions and the chalcogen atoms, indicating the interactions taking place. In the case of F−, two blue areas, λ2 > 0 (strongly attractive), are shown in coincidence with the position of the σ-holes on the sulfur atoms. Those are consistent with the Eint values shown for the fluoride anion complex. Also, nitrate the complex presents small blue areas, weaker than fluoride ones, but stronger than in chloride and bromide cases. NCI plots provide a reliable and qualitative view of the intermolecular interaction at reasonable computational costs.

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CONCLUSIONS The interaction between different DDT derivatives and several anions has been explored and analyzed by means of MP2/6311++G(d,p) calculations and the intermolecular interactions evaluated using AIM and NBO tools. In a first step, we have shown that gas phase calculations should be taken carefully when dealing with charged species, and from the computational point of view, mimicking the experiment should lead to including solvent effects. As observed, solvent effects decrease dramatically the interaction energies in the complexes with the corresponding enlargement of the interatomic distances. Despite the fact that one should be careful using limited models such as PCM or SMD, it is clear that those models can capture the essence of the solvation effects on the intermolecular interactions in the present systems, providing at least a qualitative if not quantitative view of those effects. In a second step, we have modulated the intermolecular chalcogen interaction by increasing the depth of the σ-hole associated with the S atoms. For that, substitution of the carbon atom S−C by N atoms results in a deeper σ-hole and therefore an increase (in absolute value) on the Eint and NBO charge transfers. Four different anions have been taken into account to evaluate the possible displacement between them. As observed, F− and NO3− would be the best candidates to form complexes due to the strongest chalcogen interaction, and in principle, those anions would be more selective than Cl− or Br− anions. As a final remark, the present theoretical models indicate that the inclusion of heteroatoms within the thiophene ring will increase dramatically the performance of the chalcogen bond. Similar compounds, bithioazoles, have been suggested to be poor anion transporters due to their interference with membranes. However, the data presented on bisisothioazoles reveal that they can be used as anion binders, a clear indication that similar approaches can be used to design a new family of DTT derivatives that can act as anion transporters. However, further investigation is needed to explore those new possibilities. F


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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.jpca.7b10920. Cartesian coordinates of all the compounds studied, molecular electrostatic potential maxima values for the different bridges using different solvents, intramolecular S···Cl distances and electron density properties, secondorder perturbation energies E(2) for all the systems studied and interaction energies of the different bridges, and interatomic distances using different bridges considered in gas phase and PCM solvent models for the modulated systems (PDF)

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AUTHOR INFORMATION

Corresponding Author

*Cristina Trujillo. E-mail: [email protected]. ORCID

Goar Sánchez-Sanz: 0000-0002-1390-4004 Cristina Trujillo: 0000-0001-9178-5146 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS Thanks are given to Irish Centre for High-End Computing (ICHEC) and the Trinity Centre for High-Performance Computing (TCHPC) for the provision of computational facilities.

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REFERENCES

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Improvement of Anion Transport Systems by Modulation of Chalcogen

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