Crystal structure of bis-p-anizidinegossypol with an unknown solvate

In the solid-state, bis-p-anizidinegossypol exists in the enamine or quinoid form. The naphthyl moieties are close to perpendicular [dihedral angle = 72.08 (5)°]. In the crystal, molecules are linked by O—H⋯O hydrogen bonds, generating layers which surround channels occupied by disordered guest molecules.


Gossypol
[2,2 0 -bis(8-formyl-1,6,7-trihydroxy-5-isopropyl-3methylnaphthalene)] is a yellow pigment of cotton seeds (Adams et al., 1960). This compound was first isolated over 110 years ago (Marchlewski, 1899). Its study was initially important because the compound is associated with anti-nutritive or even toxic effects when cottonseed is overfed to animals. Many attempts have been made to either remove it from cottonseed or reduce its toxicity (Kenar, 2006). However, the compound also has a wide range of biological action, including anti-HIV (Jian Yang et al., 2014), anticancer (Zhan et al., 2009) and antifertility (Coutinho, 2002) effects. This interest has led to the synthesis and isolation of various gossypol derivatives, including many diamine-based gossypol Schiff bases. Gossypol and its Schiff base formed with aniline have been previously reported to form inclusion compounds with many small organic compounds (Beketov et al., 1994;Gdaniec et al., 1996;Talipov et al., 2004). Some gossypol polymorphs (referred to as the P3 polymorph; Ibragimov et al., 1994), dianhydrogossypol (Talipov et al., 2009) and gossypol tetramethyl ether (Honkeldieva et al., 2015) form open-channel structures with channels of 5-8 Å width. In this report, we demonstrate that the Schiff base of gossypol with p-anizidine also forms an open-channel structure when the compound is crystallized from solutions in dichloromethane. ISSN 2056-9890

Structural commentary
Gossypol can exist in one of the following tautomeric forms: aldehyde, quinoid and lactol (Adams et al., 1960). In most solvents it is found in the aldehyde form; however, there are some reports that gossypol also exists in a pure lactol form (Reyes et al., 1986) or as a dynamic equilibrium mixture of aldehyde and lactol forms in some highly polar solvents (Kamaev et al., 1979). In the structure described here, the title compound is in the enamine or quinoid form. The highest symmetry which the title compound molecule can possess is C 2 (twofold axis perpendicular to the C2-C12 bond). However, bis-p-anizidinegossypol crystallizes in a triclinic (P1) space group and the symmetry of the molecule is not retained in the crystal. An ORTEP diagram of the molecule and the atom numbering in the structure are given in Fig. 1.

Supramolecular features
The packing of the title molecules in the crystal is shown in Fig. 2. Bis-p-anizidinegossypol molecules are incorporated into centrosymmetric dimers typical for gossypol and dianilinogossypol crystal structures by means of a pair of inversionrelated hydrogen bonds O5-H5Á Á ÁO3 [graph set R 2 2 (20)]. By further centrosymmetric O8-H8Á Á ÁO7 hydrogen bonds [graph set R 2 2 (10)], molecules are associated into columns running in the [111] direction, as also seen for the dianilinegossypol clathrate with ethylacetate (Beketov et al., 1994). A layer parallel to (011)  Molecular structure of the title compound showing 50% probability displacement ellipsoids. Table 1 Hydrogen-bond geometry (Å , ).  (3) 158 (3) O2Á Á ÁC7(À1 À x, 1 À y, 1 À z) contact [3.254 (4) Å ] and a very weak aromaticstacking interaction with a CgÁ Á ÁCg(À1 À x, 1 À y, 1 À z) distance of 4.182 (2) Å where Cg is the centroid of the C31-C36 ring. The packing of these layers in the crystal structure gives rise to wide ragged channels in the [011] direction. The stabilization of the crystal structure is supported by hydrophobic interactions between adjacent layers. The channels in the structure are 5-7 Å wide and the void volume of each cell is 655 Å 3 , corresponding to 26.6% of the cell volume. Disordered solvated molecules, probably solvent and water molecules, occupy these voids of the crystal; their contribution to the scattering was removed with the SQUEEZE routine (Spek, 2015) of PLATON (Spek, 2009).

Synthesis and crystallization
Gossypol was obtained from the Experimental Plant of the Institute of Bioorganic Chemistry, Uzbekistan Academy of Sciences where it is produced from by-products of the cottonseed oil industry. To prepare the Schiff base complex, gossypol was mixed with p-anizidine in a 1:2 molar ratio in dichloromethane. This reaction solution was allowed to stand in the dark for some days, during which crystalline precipitates have been formed within the solution. The precipitate was recovered by filtration. Yield: 64%. After numerous attempts, a suitable crystal was selected from the precipitate and used for the diffraction study without additional recrystallization.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2. The H atom of the hydroxy substituent was located in an electron density map and its coordinates were freely refined with U iso = 1.5U eq (O A portion of the crystal packing viewed approximately along the a axis.   (2009), Empirical absorption correction using spherical harmonics, implemented in SCALE3 ABSPACK scaling algorithm. Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes. Refinement. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > σ(F 2 ) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.