Di-n-butyl[N′-(3-methoxy-2-oxidobenzylidene)-N-phenylcarbamohydrazonothioato]tin(IV): crystal structure, Hirshfeld surface analysis and computational study

The C2NOS donor set about the tin atom in the title compound has a geometry intermediate between trigonal–bipyramidal and square-pyramidal. In the crystal, a helical, supramolecular chain along the b-axis direction features amine-N—H⋯O(methoxy) hydrogen bonding.


Chemical context
Thiosemicarbazones are an important class of compounds that have received wide attention due to their many biological and pharmacological properties, such as anti-bacterial, anti-viral, anti-neoplastic and anti-malarial activities (Kovala-Demerzi et al., 1997;Hu et al., 2006;Khan & Yusuf, 2009). Thiosemicarbazone Schiff bases are similar to their dithiocarbazate counterparts in that complexation with a metal centre is achieved via the nitrogen and sulfur atoms following deprotonation of the S-H and N-H groups Wiecek et al., 2009;Pavan et al., 2010;Parrilha et al., 2011;Singh et al., 2016;Palanimuthu et al., 2017). Tin(IV) compounds of 3-methoxysalicylaldehyde thiosemicarbazone have been evaluated for their in vitro cytotoxicity against a line of human T lymphocyte cells, Jurkat cells (Khandani et al., 2013): in this study, a structure-activity analysis for the dialkyltin(IV) compounds indicated that cytotoxicity increased with the length of the alkyl carbon chain of the tin-bound substituents. Thus, the cytotoxicity was in the order of dibutyl > diphenyl > dimethyl (Khandani et al., 2013). The ability of the 2-acetylpyridine N(4)-cyclohexylthiosemicarbazone Schiff base (LH 2 ) and its distorted pentagonal bipyramidal tin(IV) compound, [Ph 2 Sn(L)(OAc)]ÁEtOH, to inhibit tumour cell growth against HepG2 cells has also been reported (Liu et al., 2017). This study showed the tin(IV) compound to exhibit threefold higher cytotoxic potency compared to the free ligand, i.e. with IC 50 values of 3.32AE0.52 and 10.10AE2.07 mM, respectively, and to be more potent than the reference drug mitoxantone (IC 50 = 5.3AE2.38 mM). Significant activity was also observed in an in vitro cytotoxic assay of tin(IV) compounds of 2-hydroxy-5-methoxybenzaldehyde-N(4)methylthiosemicarbazone (Salam et al., 2016), diphenyltin(IV) compounds of 2-benzoylpyridine N(4)-phenyl thiosemicarbazone and 2-acetylpyrazine N(4)-phenylthiosemicarbazone (Li et al., 2011) in comparison to the standard drugs used. It may be concluded that the coordination of the Schiff base ligand to the tin(IV) centre enhanced cytotoxic activity, where the reported IC 50 values were better than standard drugs.
Further, the enhancement of cytotoxicity in the diphenyltin derivatives has been attributed to the presence of these phenyl groups, which suggested interactions between the tin-bound phenyl groups with intra-cellular biomacromolecules. An independent biological study suggested that the diffusion, lipophilic character and steric effects associated with the ligand could also be factors in determining cytotoxic activity (Salam et al., 2016). The improvement of cytotoxic activity was also suggested to be due to the presence of OH/NH groups, which enabled hydrogen bonding with DNA base pairs (Haque et al., 2015). As part of our on-going studies in the structural elucidation and cytotoxic activity of tin(IV) compounds containing thiosemicarbazones Schiff base (Yusof et al., 2020), herein are described the synthesis of the title dibutyltin(IV) derivative, (I), its single crystal X-ray diffraction analysis and a detailed study of supramolecular association by an analysis of the calculated Hirshfeld surfaces and computational chemistry.

Structural commentary
The molecular structure of (I), Sn(C 15 H 13 N 3 O 2 S)(C 4 H 9 ) 2 ( Fig. 1), comprises a five-coordinate tin centre, being coordinated by a tridentate Schiff base di-anion and two nbutyl groups leading to a C 2 NOS donor set. Selected geometric parameters for (I) are collated in Table 1. While the direct acid analogue for the Schiff base in (I) has yet to be characterized crystallographically, the 4-methoxy analogue is known . Compared to the S1-C1 [1.747 (3) (Spek, 2020), consistent with elongation, shortening and elongation in (I), respectively, confirming the presence of the thiolate-S1 and imine-N1 atoms. The angles subtended at the tin centre, Table 1, indicate a highly distorted coordination geometry. The angle closest to a trans angle is 157.56 (5) , for S1-Sn-O1, with the next two widest angles being N2-  ] and C16-  ]. The distortion from the ideal square-pyramidal and trigonal-bipyramidal geometries is quantified by the value of , with values of 0.0 and 1.0, respectively (Addison et al., 1984) The molecular structure of (I) showing the atom-labelling scheme and displacement ellipsoids at the 70% probability level.  (5) O1-Sn-C20 93.08 (9) S1-Sn-C16 96.03 (8) N2-Sn-C16 126.42 (9) S1-Sn-C20 102.61 (8) N2-Sn-C20 109.11 (10) O1-  82.75 (7) C16-  computes to 0.52, being almost exactly between the two extreme values. The N,O,S mode of coordination of the Schiff base di-anion gives rise to the formation of five-and six-membered chelate rings, the acute chelate angles, Table 1; these are partly responsible for the observed distortions in the coordination environment. The former ring, comprising the Sn, S1, N1, N2 and C1 atoms is almost planar, presenting a r.m.s. deviation of 0.0087 Å : atom N3 lies 0.016 (3) Å out of this plane. By contrast, distortions are evident in the six-membered chelate ring, defined by the Sn, O1, N2, C2-C4 atoms. The simplest description for the conformation is that of an envelope with the tin atom lying 0.519 (3) Å out of the plane defined by the remaining five atoms (r.m.s. deviation = 0.0379 Å ). The dihedral angle between the five-membered chelate ring and the best plane through the five approximately co-planar atoms of the six-membered chelate ring is 13.59 (12) , that between the five-membered and N-bound phenyl ring is 6.92 (12) and that between the peripheral C 6 rings is 19.63 (13) , highlighting the observation the Schiff base di-anion deviates significantly from co-planarity.

Supramolecular features
Conventional hydrogen bonding is noted in the crystal of (I), Table 2. Thus, amine-N-HÁ Á ÁO(methoxy) hydrogen bonds assemble molecules into a helical, supramolecular chain propagating along the b-axis direction, Fig. 2(a). The only other directional interactions based on an analysis of the points of contact between molecules in the crystal (Spek, 2020), are methylene-C-HÁ Á Á(phenyl) interactions. These lead to a supramolecular layer parallel to (101), Fig. 2(b). Layers stack without specific interactions between them, Fig. 2(c).

Analysis of the Hirshfeld surfaces
The Hirshfeld surface analysis for (I) was conducted to ascertain further information on the supramolecular association between molecules in the crystal, in particular in the interlayer region. The calculated Hirshfeld surface was mapped over the normalized contact distance d norm (McKinnon et al., 2004) and electrostatic potential (Spackman et al., 2008), and the associated two-dimensional fingerprint plots were calculated using Crystal Explorer 17 (Turner et al., 2017) following a literature procedure (Tan et al., 2019). The electrostatic potentials were calculated using the STO-3G basis set at the Hartree-Fock level of theory. The only red spots observed on the Hirshfeld surface mapped over d norm , Fig. 3, arose as a result of the conventional amine-N3-H3NÁ Á ÁO2(methoxy) hydrogen bond. This hydrogen bond is also reflected in the Acta Cryst. (2021). E77, 286-293 research communications Table 2 Hydrogen-bond geometry (Å , ).

D-HÁ
Symmetry codes: (i) Àx þ 1 2 ; y þ 1 2 ; Àz þ 1 2 ; (ii) x À 1 2 ; Ày þ 3 2 ; z À 1 2 . Hirshfeld surface mapped over the electrostatic potential, Fig. 4, where the positive electrostatic potential (blue) and negative electrostatic potential (red) regions are evident around the amine-H3N and methoxy-O2 atoms, respectively. Complementing the methylene-C18-H18AÁ Á ÁCg1 contact listed in Table 2, is a longer methylene-C22-H22BÁ Á ÁCg1 contact in the inter-layer region, Table 3. Each interaction is observed as an orange 'hollow' on the Hirshfeld surface mapped over shape-index property, Fig. 5. The overall two-dimensional fingerprint plot for the Hirshfeld surface of (I) is shown with characteristic pseudosymmetric wings in the upper left and lower right sides of the d e and d i diagonal axes, respectively, in Fig. 6(a). The individual HÁ Á ÁH, HÁ Á ÁC/CÁ Á ÁH, HÁ Á ÁO/OÁ Á ÁH, HÁ Á ÁN/NÁ Á ÁH and HÁ Á ÁS/SÁ Á ÁH contacts are illustrated in the delineated fingerprint plots in Fig. 6(b)-(f), respectively. The percentage contributions for the different interatomic contacts to the Hirshfeld surface are included in Fig. 6. The greatest contribution to the overall Hirshfeld surface is from HÁ Á ÁH contacts, i.e. 66.2%. The HÁ Á ÁH contacts appear as a beak-like distribution tipped at d e + d i $2.4 Å in Fig. 6(b), with the short value corresponding to the H6Á Á ÁH22A and H7Á Á ÁH17A contacts, with details listed in Table 3. The HÁ Á ÁC/CÁ Á ÁH contacts contribute 17.8% and appear as two sharp-symmetric wings at d e + d i $2.7 Å , Fig. 6(c). This feature reflects the C-HÁ Á Á contacts as discussed above. Although HÁ Á ÁO/OÁ Á ÁH contacts only contribute 5.2% to the overall Hirshfeld surface, they appear as the shortest contacts at d e + d i $2.1 Å , being 0.6 Å shorter than the sum of their van der Waals radii, Fig. 6 Table 3 A summary of short interatomic contacts (Å ) for (I) a .

Figure 4
A view of the Hirshfeld surface mapped over the calculated electrostatic potential for (I) in the range À0.095 to 0.095 a.u.

Figure 3
A view of the Hirshfeld surface for (I) mapped over d norm in the range À0.40 to +1.61 arbitrary units, highlighting red spots due to N3-H3NÁ Á ÁO2 hydrogen bonds.

Computational chemistry
In the present analysis, the pairwise interaction energies between the molecules in the crystal of (I) were calculated using the wave function at the B3LYP/DGDZVP level of theory. The total interaction energies (E tot ) as well as individual energy components, namely electrostatic (E ele ), polarization (E pol ), dispersion (E dis ) and exchange-repulsion (E rep ) are collated in Table 4. The most significant stabilization energies in the intra-layer region arise from the amine-N3-H3NÁ Á ÁO2(methoxy) hydrogen bond (E tot = À83.4 kJ mol À1 ).

Figure 7
Perspective views of the energy frameworks calculated for (I) showing (a) electrostatic potential force, (b) dispersion force and (c) total energy, each plotted down the b axis. The radii of the cylinders are proportional to the relative magnitudes of the corresponding energies and were adjusted to the same scale factor of 55 with a cut-off value of 5 kJ mol À1 .
i.e. E dis , makes the major contribution to the overall interaction energy in the intra-layer region.
The greatest stabilization energies in the inter-layer region relate to the weak methylene-C22-H22BÁ Á ÁCg1 contact (E tot = À25.7 kJ mol À1 ) with the remaining intermolecular contacts between molecules being stabilizing HÁ Á ÁH contacts. The nature of these contacts leads to the dominance of the E dis component in the molecular packing, Table 4. This observation is also highlighted in the energy framework diagrams of Fig. 7, where the magnitudes of intermolecular energies are represented graphically in the form of cylinders; the wider the cylinder, the greater the energy. The total E ele and E dis components of all pairwise interactions sum to À127.0 and À329.5 kJ mol À1 , respectively.

Database survey
The crystal structure determination of (I) represents the fourth example of a diorganotin derivative containing the same Schiff base ligand, i.e. RR'Sn(L). Each of the literature structures were reported during 2020, i.e. R = R 0 = Me (II) and Ph (III) (Cambridge Structural Database refcodes MUWQED and MUWQAZ, respectively; Yusof et al., 2020) and R = n-Bu and R 0 = CH 2 SiMe 3 (IV; CUJHIB; Xie et al., 2020). It is noted that the R = R 0 = Ph derivative (III) co-crystallized with onehalf mole equivalent of 3-methoxysalicylaldehyde azine (Yusof et al., 2020). Also, two positions were modelled for the tin atom in (IV), with the major component having a site occupancy factor = 0.523 and is designated hereafter as (IVa). Selected geometric parameters for the four structures are collated in Table 5 and an overlay diagram for (I)-(IVa) is shown in Fig. 8. None of the molecules has crystallographic symmetry and all present distorted C 2 NOS coordination geometries. With the exception of (II), the molecules have intermediate coordination geometries with (Addison et al., 1984) ranging from 0.52 in (I) to 0.60 in each of (III) and (IVa). The standout molecule is the dimethyltin derivative (II) which, with = 0.00, is well described as having a squarepyramidal geometry. The S1-Sn-O1 angles span a range greater than 15 , i.e. 145.67 (9) in (II) to 161.81 (7) in (III).
The hydrogen-bonding patterns formed in the crystals of (I)-(IV) are also distinct. Supramolecular helical chains, sustained by amine-HÁ Á ÁO(methoxy) hydrogen bonds are found in each of (I) and (IV). However, in (II), the interactions leading to a helical chain are of the type amine-HÁ Á ÁO(phenoxide). A further distinction is noted in the crystal of (III) in that dimeric aggregates are formed, featuring amine-N-HÁ Á ÁS(thiolate) hydrogen bonding.

Figure 8
An overlay diagram of (I) red image, (II) green, (III) blue and (IVa) pink. The molecules have been overlapped so that the Sn, S1 and N2 atoms of each molecule are coincident.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 6. The carbon-bound H atoms were placed in calculated positions (C-H = 0.95-0.99 Å ) and were included in the refinement in the riding-model approximation, with U iso (H) set to 1.2-1.5U eq (C). The N-bound H atom was located in a difference-Fourier map, but was refined with a N-H = 0.88AE0.01 Å distance restraint, and with U iso (H) set to 1.2U eq (N). The maximum and minimum residual electron density peaks of 1.63 and 0.52 e Å À3 , respectively, were located 0.97 and 0.53 Å from the Sn atom.
Crystal data Chemical formula [Sn(C 4

Di-n-butyl[N′-(3-methoxy-2-oxidobenzylidene)-N-phenylcarbamohydrazonothioato]tin(IV)
Crystal data [Sn(C 4  where P = (F o 2 + 2F c 2 )/3 (Δ/σ) max = 0.001 Δρ max = 1.63 e Å −3 Δρ min = −0.52 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.