A 1:2 co-crystal of 2,2′-thiodibenzoic acid and triphenylphosphane oxide: crystal structure, Hirshfeld surface analysis and computational study

The asymmetric unit of the title co-crystal comprises two twisted molecules of 2,2′-thiodibenzoic acid and four molecules of triphenylphosphane oxide. The three-dimensional molecular packing is stabilized by hydroxy-O—H⋯O(oxide) hydrogen bonds and TPPO-C—H⋯O(oxide, carbonyl) and TDBA-C—H⋯(oxide, carbonyl) interactions.


Chemical context
2-Thiosalicylic acid, also known as 2-mercaptobenzoic acid, being an analogue to salicylic acid, has many applications. In medicine, is dianion is found in the salt Na[EtHg(SC 6 H 4 CO 2 )], which displays anti-fungal and anti-septic activities (Bigham & Copes, 2005). Other uses include as anti-corrosion agents (Chien et al., 2012), as reactive agents or modifiers for nanoparticles and electrochemical sensing (Cang et al., 2017;Sikarwar et al., 2014), as catalysts for organic syntheses (Yang et al., 2018;Selig & Miller, 2011) as well as being the precursor for some anti-viral and anti-microbial agents (Saha et al., 2017). The compound readily coordinates a wide variety of metals, in both neutral and anionic form, due to the presence of both hard (oxygen) and soft (sulfur) donor atoms and exhibits different modes of coordination. Very recent reviews of the coordination chemistry of 2-thiosalicylic acid (Wehr-Candler & Henderson, 2016) and the isomeric 3-and 4-species (Tiekink & Henderson, 2017) are available. However, a restriction in the chemistry of this molecule is found as it can undergo various pH-dependent transformations, i.e. it remains intact in acidic condition but may be oxidized to form 2,2 0dithiodibenzoic acid at neutral pH. For example and relevant to the present contribution, are studies of co-crystal formation between 2-thiosalicylic acid and bipyridyl-type molecules (Broker & Tiekink, 2007) whereby 2-thiosalicylic acid was oxidized to 2,2 0 -dithiodibenzoic acid during co-crystallization. During attempts to react 2-thiosalicylic acid with copper(I) chloride in the presence of two equivalents of triphenylphosphane, motivated by the desire to prepare analogues of phosphanecopper(I) dithiocarbamate derivatives which exhibit promising anti-bacterial activity (Jamaludin et al., 2016), the title co-crystal was isolated, i.e. the 1:2 co-crystal of 2,2 0 -thiodibenzoic acid and triphenylphosphane oxide (I). Unexpectedly, both organic reagents were found to have oxidized in the presence of copper(I) chloride in acetonitrile solution under neutral conditions. While the actual mechanism remains unclear, a very recent study describes related synthetic outcomes (Gorobet et al., 2018). Herein, the crystal and molecular structures, the analysis of the calculated Hirshfeld surface and calculation of the interaction energies through a computational approach for (I) are described.
Each TDBA molecule comprises two benzoic acid residues connected in the 2-positions by a sulfur bridge. The confirmation of the presence of carboxylic acid groups is readily seen in the disparity in the C-O(hydroxy) and C O(carbonyl) bond lengths with the minimum difference seen for the C100 O11 and C100-O12 bonds of 1.3126 (15) and 1.2075 (16) Å , respectively. As expected, the thiophenyl residues are almost planar with the maximum r.m.s. deviation of 0.053 Å being found for the S1,C80-C85 atoms. The thiophenyl rings are deviated from the perfect perpendicular bisector with dihedral angles of 74.40 (5) and 72.58 (5) for the S1-and S2-molecules, respectively. Finally, the O6-, O8-, O10and O12-carboxylic acid groups are tilted from the phenyl rings they are connected to by 60.43 (8), 24.24 (7), 19.87 (6) and 45.78 (7) , respectively. That there are no major conformational differences between the molecules is evidenced from the overlay diagram of Fig. 3 (r.m.s. deviation = 0.118 Å ).

Figure 1
The molecular structures of the two independent molecules of 2,2 0thiodibenzoic acid in the asymmetric unit of (I), showing the atomlabelling scheme and displacement ellipsoids at the 70% probability level.

Figure 2
The molecular structures of the four independent molecules of triphenylphosphane oxide in the asymmetric unit of (I), showing the atom-labelling scheme and displacement ellipsoids at the 70% probability level.
In terms of distinguishing between molecules based on intermolecular contacts, the carbonyl-O5 atom of DTBA accepts C-HÁ Á ÁO interactions from phenyl rings derived from TPPO and DTBA, whereas the carbonyl-O11 atom accepts contacts from TPPO only. The DPPO-O4 atom is distinct from the O1-O3 atoms based on the number of interactions it forms. In common with the O4 atom, O3 accepts a C-HÁ Á ÁO interaction from TPPO, whereas each of the O1 and O2 participates in DTBA-C-HÁ Á ÁO contacts. A view of the unit-cell contents shown in projection down the a axis. The molecules are colour-coded as for Fig. 4.

Hirshfeld surface analysis
The independent 2,2 0 -thiodibenzoic acid (TDBA) and triphenylphosphane oxide (TPPO) molecules of (I) were subjected to Hirshfeld surface analysis following a literature precedent on a multi-component crystal (Jotani et al., 2018) to further understand the nature of the intermolecular interactions in the crystal. As shown in Fig. 6(a)-(f), the pair of TDBA-S1 and -S2 molecules, shown with the respective pairs of hydrogen bonded TPPO molecules, as well as the TPPO-P1-P4 molecules exhibit some similarities especially on the prominent close contacts as represented by the intense red regions on the corresponding d norm surface mappings, which are mainly dominated by hydroxy-O-HÁ Á ÁO(oxide) interactions. Upon close inspection on the surface mapping, minor differences are observed between the pair of TDBA molecules. Specifically, a diminutive red spot is observed near one of the terminal carboxylic groups of the S1-molecule arising from a TPPO-phenyl-C-HÁ Á ÁO(carbonyl) interaction but, no such contact is apparent for the S2-molecule. As for the two pairs of TPPO molecules, the significant difference between the TPPO-P1 and -P4 molecules, linked to S1-DTBA, and the TPPO-P2 and P3 molecules, linked to the S2-TDBA, is the presence of additional red spots on the surface mapping of the phenyl rings for P1-and P2-molecules in contrast to their P3and P4-containing counterparts. This difference may be attributed to the complementary phenyl-C-HÁ Á Á(phenyl) interactions between centrosymmetrically-related molecules, as illustrated in Fig. 7 and tabulated in Table 2. Here, the interacting H10 and H28 atoms are directed towards two carbon atoms of a symmetry-related ring so that the interactions are best described as being semi-localized as opposed to delocalized, which corresponds to the situation where the interacting hydrogen atom is equally separated from all six carbon atoms of the ring (Schollmeyer et al., 2008).
Quantitative evaluation of the Hirshfeld surfaces by the combination of the d i and d e (i is internal and e is external to the surface) contact distances in intervals of 0.01 Å gives the overall two-dimensional fingerprint plots for the entire asymmetric unit of (I), Fig. 8(a), and each of the individual TDBA, Fig. 9(a), and TPPO, Fig. 10(a), molecules. Further, these can be delineated into specific contacts (McKinnon et al., 2007) and Figs. 9-10(b)-(d) give fingerprint plots delineated into HÁ Á ÁH, OÁ Á ÁH/HÁ Á ÁO and CÁ Á ÁH/HÁ Á ÁC contacts. The relative contributions of these contacts to the surfaces is given in Table 3.
The overall fingerprint plot for (I), Fig. 8a, is quite different for the individual components, Figs. 9-10a, as the former is a sum of all the individual surface contacts, which differ for the individual molecules. As expected, the same is true for the corresponding decomposed fingerprint plots. The major contribution to the overall surface of (I), i.e. 49.4%, comes from HÁ Á ÁH contacts. The OÁ Á ÁH/HÁ Á ÁO contacts (d e + d i $ 2.34 Å ) make a significant contribution at 13.7%, while the CÁ Á ÁH/HÁ Á ÁC interactions (d e + d i $ 2.66 Å ), at 30.1%, play a more prominent role.

Figure 6
Views of the Hirshfeld surfaces mapped over d norm for components of (I) for the: (a) S1-DTBA molecule hydrogen bonded (  identical claw-like fingerprint profile but arranged in the exact reverse order, i.e. Fig. 9(a) cf. Fig. 10 The OÁ Á ÁH hydrogen bonds constitute the strongest among all interactions present in the co-crystal and lead to formation of asymmetric, forceps-like profiles in the corresponding decomposed fingerprint plots, Figs. 9-10(c). These feature two tips -one at relatively short d e + d i $1.6 Å that can be attributed to the hydroxy-HÁ Á ÁO(oxide) hydrogen bonds for the S1-and S2-TDBA molecules, Fig. 10(c), or oxide-OÁ Á ÁH(hydroxy) hydrogen bonds for P1-P4-TPPO. The other tip has a relatively long d e + d i value of $2.4 Å and arises as a result of hydroxy-OÁ Á ÁH(phenyl) contacts for S1-and S2-TDBA or phenyl-HÁ Á ÁO(hydroxy) for P1-P4-TPPO. The OÁ Á ÁH/HÁ Á ÁO contacts constitute the second most dominant interactions for the TDBA molecules and third most for the TPPO molecules, Table 3.
Similar to the HÁ Á ÁH contacts, the CÁ Á ÁH/HÁ Á ÁC interactions contribute weakly to the molecular packing of the cocrystal as evidenced from the d e + d i distance range of 2.7-2.8 Å , i.e. close to the sum of van der Waals radii of 2.9 Å , despite the contacts constituting the third most dominant interaction in the TDBA molecules (ca 22%) and being the second most dominant for the TPPO molecules (ca 32%). An exception to the trend is found for the P1-and P2-TPPO molecules, which display relatively short contact distances at ca 2.6 Å owing to the formation of C-HÁ Á Á interactions as discussed above.
1768 Tan  (a) The full two-dimensional fingerprint plot for the two independent TDBA molecules in (I) and (b)-(d) those delineated into HÁ Á ÁH, OÁ Á ÁH/HÁ Á ÁO and CÁ Á ÁH/HÁ Á ÁC contacts, respectively. Table 3 Percentage contributions of interatomic contacts to the Hirshfeld surface for (I) and for the the individual TDBA and DPPO molecules.   In summary the Hirshfeld surface analysis on (I), with six individual constituents, was able to distinguish between these in terms of different intermolecular interactions, akin to the recently reported analysis of a structure with four independent cation/anion pairs (Jotani et al., 2018).

Computational study
The co-crystal was subjected to intermolecular interaction energy calculations using CE-B3LYP/6-31G(d,p) available in Crystal Explorer (version 17; Turner et al., 2017), with the crystal geometry being used as the input but, with hydrogenatom positions normalized to the standard neutron diffraction values. By default, a cluster of molecules (defined as density matrices) would need to be generated by applying crystallographic symmetry operations with respect to a selected central molecule (density matrix) within the radius of 3.8 Å for interaction energy calculation (Turner et al., 2014). However, as the co-crystal contains multiple independent molecules in the asymmetric unit, a cluster of molecules was first generated surrounding the S1-molecule of TDBA for the calculation and then the procedure was repeated for the cluster of molecules surrounding the S2-molecule. The total intermolecular energy is the sum of energies of four main components comprising electrostatic, polarization, dispersion and exchange-repulsion with a scale factors of 1.057, 0.740, 0.871 and 0.618, respectively (Mackenzie et al., 2017).
Selected results obtained from the interaction energy calculations involving the DTBA molecules as reference molecules are tabulated in Table 4 and the environment about the S1-molecule of TDBA is shown in Fig. 11. As expected, O-HÁ Á ÁO hydrogen bonding interactions give the greatest energies among the close contacts present in the crystal. The total intermolecular energy (E tot ) of the hydroxy-O-HÁ Á ÁO(oxide) hydrogen bonds is consistent across the series and lies in the range À50.7 to À53.3 kJ mol À1 . The other close contacts which exerts a relatively strong influence in the energy frameworks of the co-crystal are DTBA-phenyl-C-HÁ Á ÁO(oxide) interactions, with the E tot amounting of ca À40 kJ mol À1 ,

Database survey
The only other structure of 2,2 0 -thiodibenzoic acid in the literature is that of the pure compound (Dai et al., 2005). While this presents essentially the same features as for the two independent molecules in (I), the dihedral angle between the thiophenyl rings is up to 4 smaller at 68.0 (2) , and the tilts of the carboxylic acid groups are less pronounced at 6.9 (5) and 29.8 (5) . A survey of the Cambridge Structural Database (Groom et al., 2016), revealed 110 molecules of (non-coordinated) triphenylphosphane oxide. A plot of the retrieved P O bond lengths is shown in Fig. 12. The mean value found for the P O bond length is 1.494 Å with a standard deviation of 0.008 Å , with the minimum and maximum bond lengths being 1.478 (3) and 1.530 (7) Å , found in the multi-component structures of NUCHIC (Okawa et al., 1997) and DUYXUQ (Arens et al., 1986), respectively. In the latter structure, charge-assisted hydrogen bonds are formed between Ph 3 P O and Ph 3 P O (+) H. The observed P O bond lengths in (I), i.e. in the range 1.4975 (8) to 1.5018 (8) Å are at the lower end of the range of such bonds.

Synthesis and crystallization
All chemical precursors were of reagent grade and used as received without purification. Thiosalicylic acid (Merck; 0.154 g, 0.001 mol) and triphenylphosphane (Merck; 0.262 g, 0.002 mol) were dissolved in acetonitrile (40 ml) and the mixture subsequently added into an acetonitrile solution (25 ml) of copper(I) iodide (Merck; 0.19 g, 0.001 mol). The reaction mixture was stirred for 1 h at room temperature before the white product was filtered, washed with cold ethanol and dried in vacuo. The filtrate was left at room temperature, yielding colourless prisms after 1 week; Yield

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 5. The carbon-bound H atoms were placed in calculated positions (C-H = 0.93 Å ) and were included in the refinement in the riding-model approximation, with U iso (H) set to 1.2U eq (C). The oxygen-bound H atoms were located from difference Fourier maps and refined without constraint. Owing to poor agreement, three reflections, i.e. ( 1 5 9), (3 15 3) and (5 7 9)

Figure 11
The interaction energy framework about the S1-molecule of DTBA (indicated by an asterisk) viewed along the b-axis direction.

Funding information
The support of Sunway University for studies in co-crystals, through Grant No. INT-FST-RCCM-2016-01, is gratefully acknowledged.  CrysAlis PRO (Rigaku OD, 2018); program(s) used to solve structure: SHELXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL (Sheldrick, 2015b); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012), OLEX2 (Dolomanov et al., 2009) and Mercury (Macrae et al., 2006); software used to prepare material for publication: publCIF (Westrip, 2010). 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.