Halogen Bonding Provides Heterooctameric Supramolecular Aggregation of Diaryliodonium Thiocyanate

: The crystal structure of the newly synthesized 4-methoxyphenyl(phenyl)iodonium thiocyanate, [PhI(4-C 6 H 4 OMe)](SCN), represents the first example of 16-membered cyclic heterooctamer formed by halogen bonding between the iodonium cation and SCN − . Results of density functional theory (DFT) calculations followed by the topological analysis of the electron density distribution within the framework of the quantum theory of atoms in molecules (QTAIM) method at the ω B97XD / DZP-DKH level of theory reveal that energies of attractive intermolecular noncovalent interactions I ··· S and I ··· N (responsible for the formation of heterooctameric supramolecular clusters {PhI(4-C 6 H 4 OMe)} 4 · {SCN} 4 in the solid state structure of [PhI(4-C 6 H 4 OMe)](SCN)) vary from 0.9 to 8.5 kcal / mol.


Introduction
Halogen bonding (XB) has drawn increased attention in the past decade as a powerful tool for crystal engineering and supramolecular chemistry [1][2][3][4][5], drug design [6][7][8], organic synthesis [9][10][11], and as a route for facile tuning of physicochemical properties [12,13]. The geometry of XB interaction is conventionally studied by single-crystal X-ray diffraction (XRD) and, in accord with the International Union of Pure and Applied Chemistry (IUPAC) requirements [14], XB is confirmed when the R-X···Y contact value is less than the sum of their van der Waals radii and, in addition, ∠(R-X···Y) is close to 180 • ; the theoretical analysis of the electron density topology usually shows a bond path connecting X and Y and a bond critical point between X and Y.

Materials and Instrumentation
All reagents and solvents were obtained from commercial sources and used without further purification from freshly opened containers. Potassium thiocyanate was supplied by Reakhim (Moscow, Russia); methanol and acetone was supplied by Vekton (Saint Petersburg, Russia). [PhI(4-C 6 H 4 OMe)] (CF 3 CO 2 ) was prepared by the previously reported procedure [30]. The melting point was measured on a Stuart SMP30 apparatus (Cole-Parmer, Stone, Staffordshire, UK) in a capillary and is not corrected. High-resolution electrospray ionization (HRESI) mass-spectra were obtained on a Bruker maXis spectrometer (Bruker, Billerica, MA, USA) equipped with an ESI (Electrospray ionization) source. The instrument was operated in positive ion mode using an m/z range 50−1200. The nebulizer gas flow was 1.0 bar and the drying gas flow was 4.0 L/min. The NMR spectra were recorded on a Bruker Avance 400 (Bruker, Billerica, MA, USA) at ambient temperature; the residual solvent signal was used as the internal standard.

Computational Details
The single point calculations based on the experimental X-ray geometry of 1 were carried out at the DFT level of theory using the dispersion-corrected hybrid functional ωB97XD [31] with the help of the Gaussian-09 [32] program package (Gaussian, Inc., Wallingford, CT, USA). The Douglas-Kroll-Hess 2nd order scalar relativistic calculations requested relativistic core Hamiltonian were carried out using the Crystals 2020, 10, 230 3 of 12 DZP-DKH basis sets [33][34][35][36] for all atoms. The topological analysis of the electron density distribution with the help of the atoms in molecules (QTAIM) method developed by Bader [37] has been performed by using the Multiwfn program (version 3.6) (Beijing Kein Research Center for Natural Sciences, Beijing, China) [38]. The Wiberg bond indices were computed by using the Natural Bond Orbital (NBO) partitioning scheme [39]. The Cartesian atomic coordinates for the model heterooctameric cluster {PhI(4-C 6 H 4 OMe)} 4 ·{SCN} 4 are presented in Table S1 (Supporting Information). The Hirshfeld molecular surfaces were generated by CrystalExplorer program (version 17.5) (The University of Western Australia, Perth, Australia) [40,41]. The normalized contact distances, d norm [42], based on Bondi van der Waals radii [43], were mapped into the Hirshfeld surface. In the color scale, negative values of d norm are visualized by the red color indicating contacts shorter than the sum of van der Waals radii. The white areas denote intermolecular distances close to van der Waals contacts with d norm equal to zero. In turn, contacts longer than the sum of van der Waals radii with positive d norm values are colored in blue.

Hirshfeld Surface Analysis for the X-Ray Structure of 1
The Hirshfeld surface (visualization of short interatomic contacts using sums of appropriate vdW radii) represents an area where molecules or atoms come into contact, and its analysis gives the possibility of additional insight into the nature of intermolecular interactions in the crystal state. We carried out the Hirshfeld surface analysis for the X-ray structure of 1 to understand what kind of intermolecular contacts give the largest contributions in the crystal packing. Figure 4 depicts the Hirshfeld surfaces for the [PhI(4-C6H4OMe)] + and SCNions (mapping of the normalized contact distance dnorm was used for the visualization). In these surfaces, the regions of shortest intermolecular contacts are visualized by red circle areas. The main partial contributions of different intermolecular contacts to the Hirshfeld surfaces for the [PhI(4-C6H4OMe)] + and SCNions are given in Table 2. The Hirshfeld surface analysis reveals that the crystal packing is determined primarily by intermolecular contacts involving H atoms. The parameters of morphology proper mean particles shape and appropriate surfaces and provide the basis for the optimal habit for the crystal. These parameters are useful for understanding the rheological attributes of the crystalline materials. The shape index (S) and curvedness (C) topological techniques [41] were employed for Hirshfeld surfaces of [PhI(4-C6H4OMe)] + and SCNions in the crystal structure of 1. The technique S provides the local shape of the 3D surface and define local topography (hollows and bumps in the 3D surface). The technique C represents the total curvature on the 3D surface and its mapping consists of a flat green region separated by dark blue edges. Figure 5 shows the shape index surfaces and curvedness index surfaces plotted over the Hirshfeld surfaces of [PhI(4-C6H4OMe)] + and SCNions in the crystal structure of 1. Taking into account that the Hirshfeld analysis does not allow the determination of energies of all these contacts, we conducted the appropriate DFT calculations.  The thiocyanate-based heterooctameric arrangement has been identified for [Te IV Ph 3 ](SCN) (Figure 3; CSD code: TPTETC10). Its XRD structure displays three annulated cycles [53] and the conformation of {Te IV Ph 3 } 4 ·{SCN} 4 is the same as for {(4-MeC 6 H 4 ) 2 I} 4 ·{Br} 4 in the structure of FASMUH.

Hirshfeld Surface Analysis for the X-Ray Structure of 1
The Hirshfeld surface (visualization of short interatomic contacts using sums of appropriate vdW radii) represents an area where molecules or atoms come into contact, and its analysis gives the possibility of additional insight into the nature of intermolecular interactions in the crystal state. We carried out the Hirshfeld surface analysis for the X-ray structure of 1 to understand what kind of intermolecular contacts give the largest contributions in the crystal packing. Figure 4 depicts the Hirshfeld surfaces for the [PhI(4-C 6 H 4 OMe)] + and SCN − ions (mapping of the normalized contact distance d norm was used for the visualization). In these surfaces, the regions of shortest intermolecular contacts are visualized by red circle areas. The main partial contributions of different intermolecular contacts to the Hirshfeld surfaces for the [PhI(4-C 6 H 4 OMe)] + and SCN − ions are given in Table 2. The Hirshfeld surface analysis reveals that the crystal packing is determined primarily by intermolecular contacts involving H atoms. The parameters of morphology proper mean particles shape and appropriate surfaces and provide the basis for the optimal habit for the crystal. These parameters are useful for understanding the rheological attributes of the crystalline materials. The shape index (S) and curvedness (C) topological techniques [41] were employed for Hirshfeld surfaces of [PhI(4-C 6 H 4 OMe)] + and SCN − ions in the crystal structure of 1. The technique S provides the local shape of the 3D surface and define local topography (hollows and bumps in the 3D surface). The technique C represents the total curvature on the 3D surface and its mapping consists of a flat green region separated by dark blue edges. Figure 5 shows the shape index surfaces and curvedness index surfaces plotted over the Hirshfeld surfaces of [PhI(4-C 6 H 4 OMe)] + and SCN − ions in the crystal structure of 1. Taking into account that the Hirshfeld analysis does not allow the determination of energies of all these contacts, we conducted the appropriate DFT calculations.

Theoretical Study of XB
Inspection of the crystallographic data reveals the presence of intermolecular noncovalent interactions I···S and I···N. These weak contacts are responsible for the supramolecular aggregation to furnish the heterooctameric clusters {PhI(4-C6H4OMe)}4·{SCN}4. To confirm or disprove the hypothesis on the existence of these noncovalent interactions and to quantify their energies from a theoretical viewpoint, we carried out DFT calculations at the ωB97XD/DZP-DKH level of theory and topological analysis of the electron density distribution within the framework of Bader's theory (QTAIM method) [55] for the model system (Tables 3 and S1, Supporting Information). The contour line diagrams of the Laplacian of electron density distribution  2 (r), bond paths, and selected zeroflux surfaces for the intermolecular noncovalent interactions I···S and I···N providing the heterooctameric supramolecular clusters {PhI(4-C6H4OMe)}4·{SCN}4 are shown in Figures 6-9. The

Theoretical Study of XB
Inspection of the crystallographic data reveals the presence of intermolecular noncovalent interactions I···S and I···N. These weak contacts are responsible for the supramolecular aggregation to furnish the heterooctameric clusters {PhI(4-C6H4OMe)}4·{SCN}4. To confirm or disprove the hypothesis on the existence of these noncovalent interactions and to quantify their energies from a theoretical viewpoint, we carried out DFT calculations at the ωB97XD/DZP-DKH level of theory and topological analysis of the electron density distribution within the framework of Bader's theory (QTAIM method) [55] for the model system (Tables 3 and S1, Supporting Information). The contour line diagrams of the Laplacian of electron density distribution  2 (r), bond paths, and selected zeroflux surfaces for the intermolecular noncovalent interactions I···S and I···N providing the heterooctameric supramolecular clusters {PhI(4-C6H4OMe)}4·{SCN}4 are shown in Figures 6-9. The

Theoretical Study of XB
Inspection of the crystallographic data reveals the presence of intermolecular noncovalent interactions I···S and I···N. These weak contacts are responsible for the supramolecular aggregation to furnish the heterooctameric clusters {PhI(4-C 6 H 4 OMe)} 4 ·{SCN} 4 . To confirm or disprove the hypothesis on the existence of these noncovalent interactions and to quantify their energies from a theoretical viewpoint, we carried out DFT calculations at the ωB97XD/DZP-DKH level of theory and topological analysis of the electron density distribution within the framework of Bader's theory (QTAIM method) [55] for the model system (Table 3 and Table S1, Supporting Information). The contour line diagrams of the Laplacian of electron density distribution ∇ 2 ρ(r), bond paths, and selected zero-flux surfaces for the Crystals 2020, 10, 230 7 of 12 intermolecular noncovalent interactions I···S and I···N providing the heterooctameric supramolecular clusters {PhI(4-C 6 H 4 OMe)} 4 ·{SCN} 4 are shown in Figures 6-9. The visualization of these intermolecular contacts using noncovalent interaction (NCI) analysis based on promolecular electron density [56] (high quality grid,~1,728,000 points in total) is shown in Figure 10. Table 3. Values of the density of all electrons-ρ(r), Laplacian of electron density-∇ 2 ρ(r) and appropriate λ 2 eigenvalues (with promolecular approximation), energy density-H b , potential energy density-V(r), and Lagrangian kinetic energy-G(r) (a.u.) at the bond critical points, corresponding to intermolecular noncovalent interactions I···S, H···S and I···N responsible for the formation of heterooctameric supramolecular associates {PhI(4-C 6 H 4 OMe)} 4 ·{SCN} 4 , bond lengths-l (Å), Wiberg bond indices (WI), and estimated energies-E int (kcal/mol) for these contacts.  [43]. a E int = 0.68 (−V(r)) (correlation developed exclusively for noncovalent interactions involving iodine atoms) [48]. b E int = 0.67 G(r) (correlation developed exclusively for noncovalent interactions involving iodine atoms) [48].

Contact
Crystals 2020, 10, x FOR PEER REVIEW 7 of 12 visualization of these intermolecular contacts using noncovalent interaction (NCI) analysis based on promolecular electron density [56] (high quality grid, ~1,728,000 points in total) is shown in Figure  10. Table 3. Values of the density of all electrons-(r), Laplacian of electron density- 2 (r) and appropriate λ2 eigenvalues (with promolecular approximation), energy density-Hb, potential energy density-V(r), and Lagrangian kinetic energy-G(r) (a.u.) at the bond critical points, corresponding to intermolecular noncovalent interactions I···S, H···S and I···N responsible for the formation of heterooctameric supramolecular associates {PhI(4-C6H4OMe)}4·{SCN}4, bond lengths-l (Å ), Wiberg bond indices (WI), and estimated energies-Eint (kcal/mol) for these contacts. * Numeration of atoms in the model structure corresponds to their ordering in Table S1, Supporting Information. ** The shortest van der Waals radii for I, S, N and H atoms are 1.98, 1.80, 1.55 and 1.20 Å , respectively [43]. a Eint = 0.68 (−V(r)) (correlation developed exclusively for noncovalent interactions involving iodine atoms) [48]. b Eint = 0.67 G(r) (correlation developed exclusively for noncovalent interactions involving iodine atoms) [48].  Table S1, Supporting Information.    The quantum theory of atoms in molecules (QTAIM) analysis demonstrates the presence of appropriate bond critical points (BCPs) for intermolecular noncovalent interactions I···S and I···N in the heterooctameric clusters {PhI(4-C6H4OMe)}4·{SCN}4 (the Poincare-Hopf relationship was satisfied during the QTAIM analysis of the model system and all critical points were found). The low magnitude of the electron density (0.004-0.025 a.u.), positive values of the Laplacian of electron density (0.015-0.076 a.u.), and zero or very close to zero positive energy density (0.000-0.001 a.u.) in these BCPs are typical for such weak contacts [57][58][59][60][61]. The estimated energies for these noncovalent   The quantum theory of atoms in molecules (QTAIM) analysis demonstrates the presence of appropriate bond critical points (BCPs) for intermolecular noncovalent interactions I···S and I···N in the heterooctameric clusters {PhI(4-C6H4OMe)}4·{SCN}4 (the Poincare-Hopf relationship was satisfied during the QTAIM analysis of the model system and all critical points were found). The low magnitude of the electron density (0.004-0.025 a.u.), positive values of the Laplacian of electron density (0.015-0.076 a.u.), and zero or very close to zero positive energy density (0.000-0.001 a.u.) in these BCPs are typical for such weak contacts [57][58][59][60][61]. The estimated energies for these noncovalent interactions according to the correlations proposed by Tsirelson et al. [48] are 0.9-1.3 kcal/mol (long I···S contacts), 5.9-6.0 kcal/mol (short I···S contacts), and 8.4-8.5 kcal/mol (I···N contacts). The balance between the Lagrangian kinetic energy G(r) and potential energy density V(r) at the bond critical points reveals the nature of these interactions, if the ratio -G(r)/V(r) > 1 is satisfied, then the nature of appropriate interaction is purely noncovalent, in the case of -G(r)/V(r) < 1 some covalent component takes place [62]; based on this criterion, one can state that a covalent contribution in I···S and I···N interactions is negligible; this correlates with the small values of the Wiberg bond indices for these contacts (0.00-0.07). The Laplacian of electron density in BCPs is typically decomposed into the sum of contributions along the three principal axes of maximal variation, giving the three eigenvalues of the Hessian matrix (λ1, λ2, and λ3), and the sign of λ2 can be utilized to distinguish bonding (attractive, λ2 < 0) weak interactions from nonbonding ones (repulsive, λ2 > 0) [56,63]. Thus, the sign of λ2 in the appropriate BCPs for the I···S and I···N contacts in {PhI(4-C6H4OMe)}4·{SCN}4 reveals that these contacts are of an attractive nature. The quantum theory of atoms in molecules (QTAIM) analysis demonstrates the presence of appropriate bond critical points (BCPs) for intermolecular noncovalent interactions I···S and I···N in the heterooctameric clusters {PhI(4-C 6 H 4 OMe)} 4 ·{SCN} 4 (the Poincare-Hopf relationship was satisfied during the QTAIM analysis of the model system and all critical points were found). The low magnitude of the electron density (0.004-0.025 a.u.), positive values of the Laplacian of electron density (0.015-0.076 a.u.), and zero or very close to zero positive energy density (0.000-0.001 a.u.) in these BCPs are typical for such weak contacts [57][58][59][60][61]. The estimated energies for these noncovalent interactions according to the correlations proposed by Tsirelson et al. [48] are 0.9-1.3 kcal/mol (long I···S contacts), 5.9-6.0 kcal/mol (short I···S contacts), and 8.4-8.5 kcal/mol (I···N contacts). The balance between the Lagrangian kinetic energy G(r) and potential energy density V(r) at the bond critical points reveals the nature of these interactions, if the ratio-G(r)/V(r) > 1 is satisfied, then the nature of appropriate interaction is purely noncovalent, in the case of-G(r)/V(r) < 1 some covalent component takes place [62]; based on this criterion, one can state that a covalent contribution in I···S and I···N interactions is negligible; this correlates with the small values of the Wiberg bond indices for these contacts (0.00-0.07). The Laplacian of electron density in BCPs is typically decomposed into the sum of contributions along the three principal axes of maximal variation, giving the three eigenvalues of the Hessian matrix (λ 1 , λ 2 , and λ 3 ), and the sign of λ 2 can be utilized to distinguish bonding (attractive, λ 2 < 0) weak interactions from nonbonding ones (repulsive, λ 2 > 0) [56,63]. Thus, the sign of λ 2 in the appropriate BCPs for the I···S and I···N contacts in {PhI(4-C 6 H 4 OMe)} 4 ·{SCN} 4 reveals that these contacts are of an attractive nature. Crystals 2020, 10, x FOR PEER REVIEW 9 of 12 Figure 10. Visualization of intermolecular contacts I···S and I···N in {PhI(4-C6H4OMe)}4·{SCN}4 using noncovalent interaction (NCI) analysis based on promolecular electron density (high quality grid, ~1728000 points in total). Numeration of atoms in the model structure corresponds to their ordering in Table S1, Supporting Information.

Conclusions
We found that XBs between the iodonium cations and thiocyanate anions could provide not only the polymeric or heterotetrameric motifs, but also add complexity to the 16-membered heterooctameric clusters {PhI(4-C6H4OMe)}4·{SCN}4. DFT calculations verified three XBs between I and SCN -, namely two conventional contacts with σ-holes of I (C-I···S and C-I···N), and one contact with possible iodine π-hole (C2-I···S). Three relative heterooctameric structures were found by our processing of CCDC. Despite the limited number of the relevant heterooctameric clusters, the similar conformation of two iodonium salt clusters allows the presumption that heterooctamers can be more spread structural motifs.

Conclusions
We found that XBs between the iodonium cations and thiocyanate anions could provide not only the polymeric or heterotetrameric motifs, but also add complexity to the 16-membered heterooctameric clusters {PhI(4-C 6 H 4 OMe)} 4 ·{SCN} 4 . DFT calculations verified three XBs between I and SCN − , namely two conventional contacts with σ-holes of I (C-I···S and C-I···N), and one contact with possible iodine π-hole (C 2 -I···S). Three relative heterooctameric structures were found by our processing of CCDC. Despite the limited number of the relevant heterooctameric clusters, the similar conformation of two iodonium salt clusters allows the presumption that heterooctamers can be more spread structural motifs.