Halogen, chalcogen, and hydrogen bonding in organoiodine cocrystals of heterocyclic thiones: imidazolidine-2-thione, 2-mercaptobenzimidazole, 2-mercapto-5-methylbenzimidazole, 2-mercaptobenzoxazole, and 2-mercaptobenzothiazole

A series of 18 cocrystals were obtained through the combination of the heterocyclic molecules imidazolidine-2-thione, 2-mercaptobenzimidazole, 2-mercapto-5-methylbenzimidazole, 2-mercaptobenzoxazole, and 2-mercaptobenzothiazole with the common halogen-bond donors 1,2-, 1,3-, and 1,4-diiodotetrafluorobenzene, 1,3,5-trifluorotriiodobenzene, and tetraiodoethylene. A rich series of hydrogen-, halogen-, and chalcogen-bonding interactions were observed.


Introduction
Halogen and chalcogen bonding, defined by IUPAC as 'a net attractive interaction between an electrophilic region associated with . . . ' a halogen or chalcogen atom, respectively, ' . . . in a molecular entity and a nucleophilic region in another, or the same, molecular entity (Desiraju et al., 2013;Aakeroy et al., 2019),' has drawn increasing attention in recent years (Parisini et al., 2011;Zhou et al., 2010;Ajani et al., 2015;Arman et al., 2008;Aakeroy et al., 2015;Metrangolo & Resnati, 2012;Cavallo et al., 2016;Metrangolo et al., 2005;Legon, 1998). Similar to hydrogen bonding, halogen bonding is strong, selective, and directional. Organic iodines are among the most commonly utilized halogen-bond donors (Corradi et al., 2000), largely due to their greater polarizability. When paired with halogen-bond acceptor molecules with a diversity of heteroatoms, the combined effects of halogen, chalcogen, and hydrogen bonding can be revealed. Imidazoles, thiazoles, and oxazoles are ideal systems to study in this regard.
Benzimidazole, and its derivatives, have been investigated for a diverse range of biological applications, including in the treatment of tuberculosis (Foks et al., 2006), as antimicrobial agents (Alasmary et al., 2015), and also as analgesic and antiinflammatory compounds (Achar et al., 2010;Fletcher et al., 2006). These mercaptobenzimidazoles, thiazoles, and oxazoles have also seen significant utilization as ligands in transitionmetal complexes. Providing some insight into the role of heteroatoms in differing positions, of the 31 crystal structures containing 2-mercaptobenzothiazole (MBZTH) and a transition metal currently deposited with the Cambridge Structural Database (CSD; Groom et al., 2016), all demonstrate metal coordination through the thione S atom and not the thiazole S atom. They range from simple species, such as (2-mercaptobenzothiazole)bis(triphenylphosphine)silver(I) iodide (Banti et al., 2014), to more complex copper and ruthenium complexes (Zhou et al., 2013a;Zafar et al., 2019). Similarly, the mercaptobenzimidazole (or benzimidazolethione) derivatives present an interesting field of study for their potential intermolecular interactions in halogen-bonding systems (Fig. 1). In these systems, hydrogen, halogen, and chalcogen bonding are all viable intermolecular interactions, and structural studies of the cocrystals can be useful in determining which interactions are preferred as the organoiodine and the heterocyclic systems are varied.

Materials and instrumentation
For single-crystal X-ray analysis, crystals were mounted on low background cryogenic loops using paratone oil. Data were collected using Mo K radiation ( = 0.71073 Å ) on a Bruker D8 Venture diffractometer with an Incoatec Ims microfocus source and a Photon 2 detector.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 1. H atoms on C atoms were calculated in idealized positions riding on their parent atoms, with C-H = 0.98 Å and U iso (H) = 1.5U eq (C) for methyl H atoms, and C-H = 0.95 Å and U iso (H) = 1.2U eq (C) for other H atoms. H atoms on heteroatoms were located in difference Fourier maps and refined isotropically, utilizing appropriate restraints [N-H = 0.86 (2) Å ] where necessary to maintain chemically reasonable geometries. The H atoms of the water molecule in 2(MMBZIM)Á(1,4-F 4 DIB)Á2(H 2 O) were modeled in a disordered arrangement due to symmetry considerations.

Figure 2
Cocrystalline structures containing IT. Hydrogen and halogen bonding are indicated by black dotted lines. Displacement ellipsoids are drawn at the 50% probability level. H atoms, except those bound to N atoms, have been omitted for clarity.
hydrogen bonding (Table 4). Instead, C-IÁ Á ÁS halogen bonding occurs between alternating molecules of IT and 1,3,5-F 3 I 3 B to form chains propagating in the c direction. The third I atom of 1,3,5-F 3 I 3 B, which does not participate in significant interactions with sulfur, instead serves to link chains in the ac plane via C-IÁ Á ÁI halogen bonding.

Figure 3
Cocrystal structures containing MBZIM. Hydrogen and halogen bonding are indicated by black dotted lines. Displacement ellipsoids are drawn at the 50% probability level. H atoms, except those bound to N atoms, have been omitted for clarity. Table 5 Hydrogen-bond geometry (Å , ) for 4(MBZIM)Á3(1,3-F 4 DIB). 1,4-F 4 DIB act as pendants along these ribbons, linked via C-IÁ Á ÁS halogen bonding. With four I atoms available, tetraiodoethylene (TIE) often enables structural motifs that are different from the typical aromatic halogen-bond donors. The cocrystal (MBZIM)Á (TIE) was refined in the orthorhombic space group Pnma, with one molecule each of MBZIM and TIE in the asymmetric unit. As in the previous examples, molecules of MBZIM form infinite ribbons through thiourea hydrogen bonding (Table 7). Three of the four I atoms of TIE function as C-IÁ Á ÁS halogenbond donor atoms to link these ribbons, creating a threedimensional framework through the combination of hydrogen and halogen bonding. The fourth I atom participates in a C-IÁ Á Á interaction [IÁ Á Á = 3.351 (3) Å ] to reinforce the framework.

Cocrystals of 2-mercapto-5-methylbenzimidazole (MMBZIM)
Adding a methyl group to MBZIM, resulting in 2-mercapto-5-methylbenzimidazole (MMBZIM), induces significant changes to the overall hydrogen-and halogen-bonding motifs. The structural literature of this substrate is limited, having only been characterized by single-crystal X-ray diffraction when acting as a ligand for transition metals coordinating through its S atom (Lin et al., 2017;Ozturk et al., 2009;Mitra et al., 2012). The first halogen-bonded cocrystal of MMBZIM in this study, (MMBZIM)Á(1,2-F 4 DIB), was refined in the triclinic space group P1, with one molecule each of MMBZIM and 1,2-F 4 DIB in the asymmetric unit (Fig. 4). A discrete hydrogen-bonded dimer of two MMBZIM molecules is observed, in contrast to the infinite ribbons in (MBZIM)Á(1,2-F 4 DIB) and most of the cocrystals in the present study (Table 8). Two molecules of 1,2-F 4 DIB per MMBZIM molecule link the dimers via C-IÁ Á ÁS halogen bonds, leading to the formation of chains along the c axis.
with 1,4-F 4 DIB were unsuccessful, suggesting the packing arrangement formed strictly by halogen bonding contains small but meaningful voids that must be occupied by the water molecule. Discrete hydrogen-bonded dimers are again observed by hydrogen bonding of the thioamides (Table 9). Differing from (MMBZIM)Á(1,2-F 4 DIB), with two halogen bonds to each S atom, 2(MMBZIM)Á(1,4-F4DIB)Á2(H 2 O) utilizes one C-IÁ Á ÁS halogen bond and one O-HÁ Á ÁS hydrogen bond at each S atom. It is the halogen bonding that contributes to the formation of infinite chains by linking the discrete dimers. The water molecule also acts as an N-HÁ Á ÁO hydrogen-bond acceptor from the N atom that does not participate in thioamide hydrogen bonding and so is an intermediate linker facilitating the formation of an expanded thioamide ribbon motif. Finally, the combination of 1,3,5-F 3 I 3 B and MMBZIM resulted in the cocrystal (MMBZIM)Á(1,3,5-F 3 I 3 B), refined in the monoclinic space group P2 1 /c with one unique molecule of each component in the asymmetric unit. The overall packing motif in this structure is strikingly similar to that in (MMBZIM)Á(1,2-F 4 DIB). Two molecules of MMBZIM form dimeric pairs through hydrogen bonding of the thioamides (Table 10). The remaining N-H hydrogens are involved in weak N-HÁ Á ÁI hydrogen bonds [HÁ Á ÁI = 3.02 (8) Å ]. A pair of C-IÁ Á ÁS halogen bonds occurs at each S atom, contributing to chains propagating in the a direction. The third I atom is oriented as a potential acceptor for a C-FÁ Á ÁI interaction, though the interaction distance is very near the sum of the van der Waals radii and it is unclear if there is a significant attraction to this interaction. Given the similar motifs of (MMBZIM)Á(1,3,5-F 3 I 3 B) to (MMBZIM)Á(1,2-F 4 DIB), it may be that the C-FÁ Á ÁI contact is merely coincident within the motif formed by the N-HÁ Á ÁS and C-IÁ Á ÁS interactions.
interactions. In 2(MBZOX)Á(1,4-F 4 DIB), which was refined in the monoclinic space group C2/c, with one molecule of MBZOX and one-half of a molecule of 1,4-F 4 DIB, the packing motif is more reminiscent of its MMBZIM analogue. Thioamide hydrogen-bonding dimers are linked into chains through C-IÁ Á ÁS halogen bonding (Table 13). The final example in the MBZOX series, (MBZOX)Á(1,3,5-F 3 I 3 B), was refined in the monoclinic space group P2 1 /c, with one molecule each of MBZOX and 1,3,5-F 3 I 3 B in the asymmetric unit. Much of the packing is similar to (MBZOX)Á(1,3-F 4 DIB), with thioamide hydrogen-bonding dimers stacking in the b direction (Table 14). Neighboring stacks are linked along the a axis by both C-IÁ Á ÁS halogen bonding and a C SÁ Á ÁI chalcogen bond to again form a two-dimensional substructure. In this instance though, the third I atom of 1,3,5-F 3 I 3 B acts as a C-IÁ Á ÁI halogen-bond donor, further consolidating the packing in the c direction to form a three-dimensional framework. In all cases of these MBZOX cocrystals, hydrogen-and halogenbonding preference is given toward the thione S atom as the acceptor rather than the O atom of the heterocycle.

Cocrystals of 2-mercaptobenzothiazole (MBZTH)
As with MBZOX, 2-mercaptobenzothiazole lacks the thiourea functionality to allow for the formation of infinite ribbons through hydrogen bonding; however, the additional S atom can potentially act in either halogen-or chalcogenbonding interactions (Fig. 6). Just as with MBZOX, the prior structural literature is dominated by examples of MBZTH acting as a ligand in transition-metal complexes (Aslanidis et al., 2002;Zhou et al., 2013b;Hadjikakou & Kubicki, 2000) or reactions with dihalides (Daga et al., 2002;  Cocrystalline structures containing MBZOX. Hydrogen and halogen bonding are indicated by black dotted lines. Displacement ellipsoids are drawn at the 50% probability level. H atoms, except those bound to N atoms, have been omitted for clarity.
2015a,b). The first and most complex of the MBZTH structures obtained, 3(MBZTH)Á4(1,2-F 4 DIB), crystallized in the triclinic space group P1, with three molecules of MBZTH and four molecules of 1,2-F 4 DIB in the asymmetric unit. Thioamide dimers stack along the a axis (Table 15), with one molecule of 1,2-F 4 DIB within alternating layers. The remaining molecules of 1,2-F 4 DIB are oriented approximately perpendicular to the thioamide dimers, linking layers of the stack through a series of C-IÁ Á ÁS halogen bonds. The intrastack molecule of 1,2-F 4 DIB is also linked to a molecule of 1,2-F 4 DIB on the edge of the stack through a C-IÁ Á ÁI halogen bond. This complex series of interactions ultimately forms a three-dimensional framework. The packing motif of (MBZTH)Á(1,3-F 4 DIB), refined in the triclinic space group P1, with one molecule each of MBZTH and 1,3-F 4 DIB within the asymmetric unit, is similar to that of (MMBZIM)Á(1,2-F 4 DIB) and (MMBZIM)Á(1,3,5-F 3 I 3 B). Thioamide hydrogen-bonding dimers (Table 16)   Cocrystalline structures containing MBZTH. Hydrogen and halogen bonding are indicated by black dotted lines. Displacement ellipsoids are drawn at the 50% probability level. H atoms, except those bound to N atoms, have been omitted for clarity. space group P2 1 , the asymmetric unit of (MBZTH)Á2(1,3-F 4 DIB) contains two unique molecules of MBZTH and four molecules of 1,3-F 4 DIB. In this case, the thioamide hydrogenbonding dimers (Table 17) are linked by molecules of 1,3-F 4 DIB via C-IÁ Á ÁS halogen bonding to form chains. These interactions occur to the thione and thiazole S atoms, with the interaction to the thione S atom occurring at a distance approximately 0.35 Å shorter than to the thiazole S atom. The remaining two molecules of 1,3-F 4 DIB are located as pendants along the chain, linked by C-IÁ Á ÁI halogen bonding.
The packing motif of 2(MBZTH)Á(1,4-F 4 DIB), refined in the monoclinic space group P2 1 /n, with one complete molecule of MBZTH and one-half of a molecule of 1,4-F 4 DIB in the asymmetric unit, is similar to that of 2(MBZOX)Á(1,4-F 4 DIB). Thioamide hydrogen-bonding dimers (Table 18) are linked into chains via C-IÁ Á ÁS halogen bonding to the thione S atom. As the final example with an aromatic halogen-bond donor, (MBZTH)Á(1,3,5-F 3 I 3 B) was obtained in the monoclinic space group P2 1 /c, with one unique molecule each of both MBZTH and 1,3,5-F 3 I 3 B in the asymmetric unit. The primary packing motif is similar to that of (MBZTH)Á2(1,3-F 4 DIB), with the thioamide hydrogen-bonding dimers (Table 19) linked into chains by C-IÁ Á ÁS halogen bonds to both the thione and thiazole S atoms. The third I atom serves to link neighboring chains through a weak C-IÁ Á ÁS-C interaction to a thiazole S atom; however, the geometry of this interaction [C-IÁ Á ÁS = 149.3 (1) and 142.48 (13) ] is indicative of a dispersive Type I interaction and not a true halogen or chalcogen bond. Finally, (MBZTH)Á(TIE) crystallized in the triclinic space group P1 with one unique molecule of MBZTH and two unique half molecules of TIE in the asymmetric unit. Thioamide hydro-gen-bonding dimers (Table 20) are linked into chains by C-IÁ Á ÁS halogen bonding to the thione S atom. These chains are linked in the ab plane by additional C-IÁ Á ÁS halogen bonding to the thione S atom. The second unique TIE molecule serves to consolidate the packing in the c direction via C-IÁ Á ÁI halogen bonding, forming a three-dimensional framework.

Conclusion
A rich structural chemistry of cocrystals was observed between organoiodine molecules and heterocyclic thiones in the present study of 18 crystal structures. The structures are primarily directed by the co-operative effects of hydrogenand halogen-bonding interactions. Certain features of the long-range structures were controlled through the selection of the heterocyclic thione, where the formation of primarily hydrogen-bonded ribbons in benzimidazoles could be truncated to hydrogen-bonded dimers in benzoxazoles and benzothiazoles. The hydrogen-bonded units were then aggregated into longer-range one-or two-dimensional motifs through C-IÁ Á ÁS halogen bonding. Additional C-IÁ Á ÁI halogen bonding, either through the stoichiometric excess of organoiodine or through the use of more iodine-rich organoiodine substrates (tetraiodoethylene, for example) extended some structures into three-dimensional frameworks. The R XB value for the majority of the halogen-bonding interactions lies within a typical range from 0.85 to 1.0. The interactions to a thione S atom generally occurred at shorter distances than the thiane S atom, as expected due to the hybridization state. The linearity parameter, , ranges from 0.02 to 0.83. This wide range is supported by the distribution of electron density on S or I acceptor atoms. Occasional C SÁ Á ÁI chalcogen bonding was observed. Halogen-bond preference toward the thione S atom over the heterocyclic O or S atom was observed in both the benzoxazoles and benzothiazoles. However, there were at least some occasional occurrences of C-IÁ Á ÁS to the thiazole S atom.   Symmetry codes: (i) Àx À 1; Ày þ 1; Àz þ 1; (ii) Àx; Ày þ 1; Àz þ 1; (iii) Àx þ 3 2 , y þ 1 2 ; Àz þ 1 2 .

Special details
Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

1H-1,3-Benzodiazole-2-thiol-1,2,4,5-tetrafluoro-3,6-diiodobenzene (1/1) (MBZIM_14F4DIB)
Crystal data C 6 F 4 I 2 ·C 7 H 6 N 2 S M r = 552.06 Monoclinic, P2 1 /c a = 5.5641 (2)  Special details Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters
Hydrogen-bond geometry (Å, º) Special details Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å 2 )
x y z U iso */U eq I1 0.64136 (2) 0.39079 (5) 0.46092 (2) 0.01937 (7) 180.0 (3) C7-O1-C1-S1 179.5 (2) C1-O1-C7-C2 Special details Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes. Special details Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes. Refinement. Refined as a 2-component twin.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å 2 )
x y z U iso */U eq I1 0.09620 (3) 0.50667 (2) 0.18841 (2) 0.01843 (6)  where P = (F o 2 + 2F c 2 )/3 (Δ/σ) max = 0.003 Δρ max = 0.67 e Å −3 Δρ min = −0.73 e Å −3 Special details Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.