Crystal structure and Hirshfeld analysis of trans-bis(5-fluoroindoline-2,3-dione 3-oximato-κ2 O 2,N 3)-trans-bis(pyridine-κN)copper(II)

The crystal structure and the Hirshfeld surface analysis of a 5-fluoroisatin 3-oxime and copper(II) complex are reported. In the crystal, the centrosymmetric complexes are linked by hydrogen bonding into a three-dimensional network. This work is the second report in the literature of a crystal structure with isatin 3-oxime derivatives acting as ligands (for metal complexes).

The reaction in methanol of Cu II acetate monohydrate with 5-fluoroisatin 3-oxime deprotonated with KOH in a 1:2 molar ratio and recrystallization from pyridine yielded the title compound, [Cu(C 8 H 4 FN 2 O 2 ) 2 (C 5 H 5 N) 2 ]. In the centrosymmetric complex, the anionic form of the isatin oxime acts as a 2 N,O donor, building five-membered metallarings. The Cu II cation is sixfold coordinated in a slightly distorted octahedral environment by two trans, equatorial, anionic isatin derivatives and two trans pyridine ligands in axial positions. The complexes are linked by hydrogen bonding into a threedimensional network, which is also stabilized bystacking interactions [centroid-to-centroid distance = 3.7352 (9) Å ] and C-HÁ Á Á contacts. The Hirshfeld surface analysis indicates that the major contributions for the crystal packing are HÁ Á ÁH (31.80%), HÁ Á ÁC (24.30%), HÁ Á ÁO (15.20%) and HÁ Á ÁF (10.80%). This work is the second report in the literature of a crystal structure of a coordination compound with isatin 3-oxime ligands (coordination chemistry).

Chemical context
By the first half of the 19th century, the first reports on the chemistry of the isatin fragment were published independently in Germany and France (Erdmann, 1841a,b;Laurent, 1841). One very nice review concerning the organic synthesis of the isatin derivatives was published 74 years ago (Sumpter, 1944) and the topic remains up-to-date. From the early years, the chemistry of isatin-based molecules emerged from the synthetic approach to a large class of organic compounds with applications in biochemistry and pharmacology. For two recent examples, see: 1-[(2-methylbenzimidazol-1-yl) methyl]-2-oxo-indolin-3-ylidene]amino]thiourea, a derivative with in silico and in vitro inhibition of Chikungunya virus replication (Mishra et al., 2016) and 5-chloroisatin-4-methylthiosemicarbazone, another derivative which appears as an intermediate in the synthesis of an HIV-1 RT inhibitor (Meleddu et al., 2017). The abbreviation HIV-1 RT stands for human immunodeficiency virus type 1 reverse transcriptase. Along the same line of research of the present work, the crystal structure, the Hirshfeld surface analysis and the lock-and-key supramolecular analysis through in silico evaluation with the vascular endothelial growth factor receptor-2 (VEGFR-2) of the isatin derivative ligand of the title complex were recently carried out. The (3Z)-5-fluoro-3-(hydroxyimino)-indolin-2one molecule showed a structure-activity relationship with the selected biological target through hydrogen bonding (Martins et al., 2017). Although the chemistry of isatins is already well reported in several scientific disciplines, crystal structures of complexes with isatin 3-oxime derivatives are surprisingly few in number. Thus, the crystal structure determination of isatinbased molecules has become our major research interest and herein, the synthesis, crystal structure and Hirshfeld surface analysis of a 5-fluoroisatin 3-oxime complex with copper(II) is reported.

Structural commentary
The asymmetric unit of the title coordination compound consists of one Cu II cation, which lies on an inversion center, and two ligands in general positions, the anionic form of 5-fluoroisatin 3-oxime and one pyridine molecule. The Cu II atoms are sixfold coordinated in a slightly distorted octahedral environment by two five-membered chelate 5-fluoroisatin-3oximate ligands, acting as 2 N,O-donors in equatorial positions, and by two pyridine ligands in axial positions (Fig. 1). The isatin 3-oxime derivative is nearly planar with an r.m.s. deviation from the mean plane of the non-H atoms of 0.0145 Å and a maximum deviation of 0.0344 (9) Å for the N2 atom. The dihedral angle between the pyridine ring and the mean plane through the indoline ring system is 73.82 (3) . For the five-membered ring, the r.m.s. from the mean plane through the Cu1/C1/C2/N2/O1 fragment is 0.074 Å and the maximum deviation from that plane is 0.0945 (7) Å for the N2 atom. The N2-Cu1-N3 and O1-Cu1-N3 angles are 88.75 (4) and 89.01 (4) , respectively. Four intramolecular C-HÁ Á ÁO hydrogen bonds are observed for the title compound, forming rings with S(5) graph-set motif. As an interesting feature of the structure, a hydrogen-bonded macrocyclic coordination environment can be assumed based on the S(5) rings (Fig. 2, Table 1).

Supramolecular features and Hirshfeld analysis
In the crystal, the molecules of the centrosymmetric title compound are connected into a three-dimensional hydrogen- The intramolecular C-HÁ Á ÁO hydrogen interactions of the title compound (dashed lines) forming a ring of S(5) graph-set motif. Table 1 Hydrogen-bond geometry (Å , ).

Figure 1
The molecular structure of the title compound, showing the atom labelling and displacement ellipsoids drawn at the 40% probability level.
The molecular units are also connected by C-HÁ Á ÁO interactions into a one-dimensional hydrogen-bonded polymer along the [001] direction ( Fig. 4) and finally, the complexes are linked by N-HÁ Á ÁO interactions into centrosymmetric dimers with graph-set motif R 2 2 (14). Like the dimers of the first structural element, with C-HÁ Á ÁF interactions connecting the molecules, the latter element is also based on dimers as subunits of the polymeric motif, connected through N-HÁ Á ÁO interactions but in this case along the [010] direction (Fig. 5). In addition,stacking interactions [centroid-to-centroid distance: 3.7352 (9) Å ] and C-HÁ Á Á contacts (Table 1) stabilize the crystal structure.
The Hirshfeld surface analysis (Hirshfeld, 1977) of the crystal structure suggests that the contributions of the HÁ Á ÁH, HÁ Á ÁC and HÁ Á ÁO intermolecular interactions to the crystal Acta Cryst.       (Wolff et al., 2012). The d e (y axis) and d i (x axis) values are the closest external and internal distances (values in Å ) from given points on the Hirshfeld surface contacts (Fig. 6). The graphical representation of the Hirshfeld surface for the title compound with transparency and labelled atoms (Fig. 7) indicates, in magenta, the locations of the strongest intermolecular contacts, e.g. the H4, H7, H8, O2 and F1 atoms.  Martins et al., 2011). For that complex, the Na cations shows an octahedral coordination environment builded by the anionic form of the isatin 3-oxime and water molecules (Fig. 8).

Synthesis and crystallization
All the starting materials were commercially available and were used without further purification. The synthesis of the ligand followed the procedure reported previously (Martins et al., 2017). 5-Fluoroisatin 3-oxime was dissolved in methanol (4 mmol, 50 mL) and deprotonated with one pellet of KOH with stirring maintained for 60 min. Simultaneously, a green solution of copper acetate monohydrate in methanol (2 mmol, 50 mL) was prepared under continuous stirring. A darkcoloured mixture of both solutions was maintained with stirring at room temperature for 8 h. A crude dark-red material was obtained by evaporation of the solvent. Purple crystals of the complex, suitable for X-ray analysis, were obtained by recrystallization of the solid from a pyridine/methanol (1:10 v/v) solution.   Computer programs: APEX2 and SAINT (Bruker, 2014), SHELXT2014 (Sheldrick, 2015a), SHELXL2016 (Sheldrick, 2015b), WinGX (Farrugia, 2012), DIAMOND (Brandenburg, 2006), CrystalExplorer (Wolff et al., 2012), publCIF (Westrip, 2010) and enCIFer (Allen et al., 2004).

trans-Bis(5-fluoroindoline-2,3-dione 3-oximato-κ 2 O 2 ,N 3 )-trans-bis(pyridine-κN)copper(II)
Crystal data  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.