A potential anticancer agent: 5-chloro-7-iodo-8-hydroxyquinolinium dichlorido(5-chloro-7-iodoquinolin-8-olato-κ2 N,O)palladium(II) dihydrate

The title PdII coordination compound, (C9H6ClINO)[PdCl2(C9H4ClINO)]·2H2O, was prepared as a potential anticancer agent. Its structure is ionic and consists of a square-planar [PdCl2(CQ)]− complex anion (CQ is 5-chloro-7-iodoquinolin-8-olate), with the PdII atom surrounded by two chloride ligands in a cis configuration and one N,O-bidentate CQ molecule, a protonated anion of CQ as counter-cation and two non-coordinated water molecules. The water molecules are involved in O—H⋯O and N—H⋯O hydrogen bonds, which interconnect the HCQ+ cations into a chain parallel to [010]. Apart from these interactions, the structure is also stabilized by face-to-face π–π interactions [centroid–centroid = 3.546 (3) Å], which occur between the phenolic parts of the complex anions and cations.


Comment
Square-planar complexes of platinum and palladium, as potential chemotherapeutics, are studied worldwide (Bruijnincx &Sadler, 2008 andBielawska et al., 2010). Unfortunately, many of these anticancer drugs exhibit significant side effects and their activity is relatively low (Screnci & McKeage, 1999). One of the approaches to overcome limitations connected with platinum-or palladium-based chemotherapy, new square-planar coordination compounds of these metals with biologically active ligands should be prepared. One of the examples of such ligand is 5-chloro-7-iodo-8-hydroxyquinoline (clioquinol, CQ), as it exhibits wide range of biological activity, including anticancer activity. CQ's favourable effect to human cancer cells is ascribed to its ability to chelate metal ions (Ding et al., 2005). In our efforts to prepare novel square-planar complexes of Pt and Pd with clioquinol of Cat[MCl 2 (CQ)] (M = Pt or Pd; Cat = cation of +1 charge, such as Na + , K + or Cs + ) composition, we prepared crystals of HCQ[PdCl 2 (CQ)].2H 2 O (I) (HCQ = protonated molecule of CQ), which we believe has an increased anticancer activity. Here we present the structure of the title compound.
The molecular structure of the ionic HCQ[PdCl 2 (CQ)].2H 2 O (I) compound consists of discrete [PdCl 2 (CQ)]anion in which the central Pd II atom has a distorted square-planar configuration, protonated molecule of CQ (HCQ + ) as cation, and two non-coordinated water molecules (Fig. 1). Complex anion is formed by Pd II atom which is surrounded by two chlorido ligands in cis-configuration at 2.271 (1) (Pd1-Cl1) and 2.311 (1) Å (Pd1-Cl2) distances, which are close to Pd-Cl distances observed in other square planar Pd II complexes (Cui et al., 2009), and one bidentately coordinated CQ molecule. This is bound to Pd II atom by nitrogen atom of pyridine part and oxygen atom, which is ready to coordinate after deprotonation of the CQ's hydroxyl group in phenolic part; the Pd1-N1 (2.009 (4) Å) and Pd1-O1 (2.035 (3) Å) distances are normal (Yue et al., 2008). Both the coordinated and free protonated CQ molecules are nearly planar, with the largest deviation of atoms from the mean planes through the aromatic rings being 0.05 (1) Å. The geometric parameters within the individual rings resemble those found in similar compounds containing pyridine and phenolic rings (Guney et al., 2011 andKapteijn et al., 1996). The C-X bonds (X = Cl and I; 1.742 (10) and 2.098 (2) Å in average, respectively) are usual for single C sp2 -X bonds (Fazeli et al., 2009 andGniewek et al., 2006).
Besides the ionic forces, the structure is also stabilized by π-π interactions and hydrogen bonds. π-π interactions occur between the phenolic parts of the complex anion and the cation. The distance between centroids of these parts (Cg An -Cg Cat = 3.546 (3) Å) and angle between normal to the plane and vector connecting the two centroids (16.46°) are consistent with the values typical for the face-to-face π-π interactions (Janiak, 2000). Moreover, the distance between Pd1 atom and Cg Cat i of another adjacent cation (i = x, 1 + y, z) of 3.497 Å and the angle between normal to the plane of HCQ + cation and vector   . 3). Distances and angles characterizing these bonds are summarized in Table 2.

Experimental
Ethanolic solution of PdCl 2 prepared from 0.2 cm 3 40% water solution of PdCl 2 in 8 cm 3 of ethanol (0.048 g PdCl 2 ; 0.27 mmol) was cooled down to -15 °C and mixed with a cold (-5 °C) THF solution of CQ (0.17 g CQ dissolved in 15 cm 3 of THF; 0.54 mmol). Resulting solution was stirred at -15 °C for a while and then a cold (3 °C) aqueous solution of CsCl (0.046 g of CsCl dissolved in 2 cm 3 of water; 0.27 mmol) was added. Yellow precipitation of I, which formed immediately after mixing, was filtered off, dried on air and analyzed by IR and elemental analysis. Mother liquor was left for crystallization in refrigerator at -5 °C and after few days we obtained a small amount of orange-red crystals of I. Crystals were filtered off, dried on air and analyzed by IR spectroscopy to prove their identity with the precipitation.

Refinement
H atoms of the CQ moieties were inserted in calculated positions appropriate for the data collection temperature with isotropic displacement parameters riding on that of the parent C and O atoms, U iso (H) = 1.2Ueq(C) and U iso (H) = 1.5Ueq(O).
The hydrogen atom coordinated on the N2 atom in HCQ + was found in the difference electron map and refined freely, water H atoms were found with the program CALC-OH (Nardelli, 1999) and were refined with fixed bond distances and angles.
Hydrogen atoms could be found only for one disordered position (O4A).    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 Rfactors(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.