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

Peter Vranec; Ivan Potočňák

doi:10.1107/S1600536811040803

. 2011 Oct 8;67(Pt 11):m1508–m1509. doi: 10.1107/S1600536811040803

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

Peter Vranec ^a,^*, Ivan Potočňák ^a

PMCID: PMC3246939 PMID: 22219759

Abstract

The title Pd^II 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 Pd^II 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.

Related literature

For background to square-planar complexes of platinum and palladium as potential chemotherapeutics, see: Bielawska et al. (2010 ▶); Bruijnincx & Sadler (2008 ▶); Ding et al. (2005 ▶); Garoufis et al. (2009 ▶). For structures of CQ complexes, see: Di Vaira et al. (2004 ▶) for [Cu(CQ)₂] and [Zn(CQ)₂(H₂O)]·H₂O·THF; Miyashita et al. (2005 ▶) for [ReCl₂(CQ)O(PPh₃)]. The structure of [Pd(8-HQ)₂] (8-HQ = 8-hydroxyquinoline) was previously described by Prout & Wheeler (1966 ▶). For other related structures, see: Cui et al. (2009 ▶); Guney et al. (2011 ▶); Screnci & McKeage (1999 ▶); Yue et al. (2008 ▶); Kapteijn et al. (1996 ▶); Fazeli et al. (2009 ▶); Gniewek et al. (2006 ▶). Structures of complexes containing other halogen-derivatives of 8-HQ may also be found in the Cambridge Structural Database, see: Allen (2002 ▶). For π–π interactions, see: Janiak (2000 ▶).

Experimental

Crystal data

(C₉H₆ClINO)[PdCl₂(C₉H₄ClINO)]·2H₂O
M _r = 824.31
Monoclinic,
a = 34.3212 (10) Å
b = 7.7028 (2) Å
c = 18.4128 (5) Å
β = 104.455 (3)°
V = 4713.7 (2) Å³
Z = 8
Mo Kα radiation
μ = 3.89 mm⁻¹
T = 293 K
0.44 × 0.14 × 0.07 mm

Data collection

Oxford Diffraction Xcalibur Sapphire2 diffractometer
Absorption correction: analytical (CrysAlis RED; Oxford Diffraction, 2007 ▶) T _min = 0.555, T _max = 1.000
24287 measured reflections
4641 independent reflections
3888 reflections with I > 2σ(I)
R _int = 0.049

Refinement

R[F ² > 2σ(F ²)] = 0.032
wR(F ²) = 0.080
S = 1.14
4641 reflections
287 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.61 e Å⁻³
Δρ_min = −0.87 e Å⁻³

Data collection: CrysAlis CCD (Oxford Diffraction, 2007 ▶); cell refinement: CrysAlis RED (Oxford Diffraction, 2007 ▶); data reduction: CrysAlis RED; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶) and CALC-OH (Nardelli, 1999 ▶); molecular graphics: DIAMOND (Brandenburg, 2001 ▶); software used to prepare material for publication: SHELXL97.

Supplementary Material

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536811040803/ff2030sup1.cif

e-67-m1508-sup1.cif^{(19.1KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811040803/ff2030Isup2.hkl

e-67-m1508-Isup2.hkl^{(222.8KB, hkl)}

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Selected geometric parameters (Å, °).

Pd1—N1	2.009 (4)
Pd1—O1	2.035 (3)
Pd1—Cl1	2.2711 (14)
Pd1—Cl2	2.3107 (14)

Open in a new tab

N1—Pd1—O1	82.12 (15)
N1—Pd1—Cl1	94.01 (12)
O1—Pd1—Cl1	175.98 (10)
N1—Pd1—Cl2	175.90 (12)
O1—Pd1—Cl2	94.44 (10)
Cl1—Pd1—Cl2	89.47 (6)

Open in a new tab

Table 2. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O2—H2⋯O3	0.82	2.18	2.782 (7)	131
N2—H2N⋯O4A	0.82 (6)	1.92 (6)	2.737 (10)	174 (6)
N2—H2N⋯O4B	0.82 (6)	1.96 (6)	2.683 (9)	146 (6)
O4A—H1O4⋯O2	0.85	2.00	2.787 (10)	155
C28—H28⋯O3ⁱ	0.93	2.48	3.347 (8)	155

Open in a new tab

Symmetry code: (i) Inline graphic .

Acknowledgments

This work was supported by a grant from the Slovak Grant Agency (VEGA No. 1/0079/08) and by the VVGS (PF 27/2011/CH).

supplementary crystallographic information

Comment

Square-planar complexes of platinum and palladium, as potential chemotherapeutics, are studied worldwide (Bruijnincx & Sadler, 2008 and Bielawska 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[MCl₂(CQ)] (M = Pt or Pd; Cat = cation of +1 charge, such as Na⁺, K⁺ or Cs⁺) composition, we prepared crystals of HCQ[PdCl₂(CQ)].2H₂O (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[PdCl₂(CQ)].2H₂O (I) compound consists of discrete [PdCl₂(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 and Kapteijn 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 and Gniewek 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_Catⁱ 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 connecting Cg_Catⁱ and Pd1 of 171.96° indicate possible η⁶ semi coordination of the phenyl ring of the cation. Thus the coordination number of Pd atom can be considered as 4 + 1 with a tetragonal pyramidal coordination polyhedron. Due to these intermolecular contacts the cations and anions are linked to form a chain parallel with [010] (Fig. 2).

Two uncoordinated water molecules interconnect the HCQ⁺ cations via hydrogen bonds into a chain running along [010] (Fig. 3). Distances and angles characterizing these bonds are summarized in Table 2.

Experimental

Ethanolic solution of PdCl₂ prepared from 0.2 cm³ 40% water solution of PdCl₂ in 8 cm³ of ethanol (0.048 g PdCl₂; 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 cm³ 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 cm³ 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.