научная статья по теме CRYSTAL STRUCTURE AND ANTI-CANCER ACTIVITY OF A NOVEL MIXED-LIGAND COMPLEX: [PD(РHEN)(РHE)]CL A H2O Химия

КООРДИНАЦИОННАЯ ХИМИЯ, 2007, том 33, № 2, с. 125-128

УДК 541.49

CRYSTAL STRUCTURE AND ANTI-CANCER ACTIVITY OF A NOVEL MIXED-LIGAND COMPLEX: [Pd(Phen)(Phe)]Cl • H2O

© 2007 E. J. Gao*, Q. T. Liu**, L. Y. Duan***

*Shenyang Institute of Chemical Technology, Shenyang, 110142 P. R. China **School of Chemical Science and Engineering, Liaoning University, Shenyang, 110036 P. R. China ***School of Pharmaceutical Engineering, Shenyang Pharmaceutical university, Shenyang, 110016 P. R. China

Received December 1, 2005

A mixed-ligand complex [Pd(Phen)(Phe)]Cl • H2O (Phen - o-phenantroline, Phe - L-phenylalanine) is synthesized and structurally characterized by elemental analyses and single-crystal X-ray diffraction. Diffraction data: C21H19ClN3O3Pd, monoclinic, P21/n, a = 9.478(4), b = 22.395(9), c = 9.528 (4) А, в = 104.358(11)°, V =

= 1959.3(14) А3, Z = 4. The Pd atom has planar-square coordination geometry and is surrounded by the Phen and Phe ligand to form a monovalent complex cation, Cl- is filled in the crystal lattice asa counterion. The Cl atom connects the complex cation through an electrostatic interaction and has a very weak hydrogen bond with a water molecule. Hydrogen bonding interactions and n-n stacking interactions stabilize the crystal lattice. The anticancer activity of the complex increases with the increasing concentration of the complex, which shows that the complex has strong anticancer activity.

Organic-inorganic hybrid materials based on palladium and different organic moieties (such as amino acid, amino-compound derivatives, and carbene) have attracted considerable attention in recent years owing to their potential applications in catalysis and biochemical activity [1, 2]. Since the anticancer activities of the platinum coordination complex have been extensive reported taking cis-diaminedichloroplatinum(n) (cis-DDP) as a representation [3] researchers are focused on the palladium complexes owing to their similar coordination geometry. Some novel structures of palladium organic-inorganic hybrid materials have been reported including mononuclear complex [4], binuclear complex [5-7], trinuclear complex [8-9], and 3-D coordination polymers [10]. In general, the central Pd atom adopts planar square coordination environment [11]. In the biochemistry activity aspects, there are some different advantages comparing with the platinum complex [12-13]. Some complexes of palladium even have excellent inhibiting ability to HIV [14]. More recently, a series of palladium complexes have been synthesized, research on inhibiting ability to AGZY-83a and interaction mechanism with DNA have been reported by our groups [1517]. L-phenylalanine (Phe) is an avirulent amino acid and has physiological affinity to DNA molecule. We adopt Phe and o-phenantroline (Phen) as mixed-ligand to expect superbiochemical activity. Herein, we report the novel crystal structure and anticancer activity of a mixed-ligand complex [Pd(Phen)(Phe)] Cl ■ H2O (I).

EXPERIMENTAL

Chemical reagents and methods. PdCl2, KCl, KOH, o-phenanthroline purchased were of reagent

grade and used without further purification. L-Phenyla-lanine was biochemical reagent. Elemental analyses (C, H, N) were performed on a Perkin-Elmer 2400 CHN Elemental analyzer. Pd was determined on a Leaman inductively coupled plasma (ICP) spectrometer. The IR spectrum was recorded in a range of 400-4000 cm-1 on a Nicolet IR-470 spectrophotometer using KBr pellets.

Synthesis of [Pd(Phen)(Phe)] Cl • H2O (I).

K2[PdCl4] crystal was obtained by PdCl2 reacted with KCl. K2[PdCl4] (0.5 mmol) and Phe were dissolved in water (20 ml), respectively. Phen (0.5 mmol) was dissolved in ethanol (20 ml). A brown precipitate appeared when mixing above-mentioned three types of solution with stirring. A KOH solution (0.5 mol/l) was added to adjust pH until the turbid solution became clear. Then the clear solution was heated to 60°C for evaporation with vigorous stirring. About 30 ml of the clear solution was kept at room temperature (about 20°C), and brown single crystals were collected two weeks later. (Yield: 29%, based on Pd.)

For C21H19ClN3O3Pd (I)

anal. calcd, %: C, 50.1; H, 3.8; N, 8.4; Pd, 21.1. Found, %: C, 50.3; H, 3.7; N, 8.2; Pd, 20.9.

X-ray crystallography. The crystal structure of compound I was determined by single-crystal X-ray diffraction. The suitable single crystal was mounted in a glass fiber capillary. Data were collected on a Bruker Smart 100 CCD X-ray single crystal diffractometer with Mo^a radiation (X = 0.71073 À) at 293(2) K in the ro-scan mode. The structure was solved by the direct method using the SHELXS-97 and SHELXL-97 programs [18, 19] and re-

Table 1. Summary of crystallgraphic data for compound I

Parameter Value

Formula weight 503.25

Crystal system, space group Monoclinic, P21/n

Unitcell dimensions:

a, A 9.478(4)

b, A 22.395(9)

c, A 9.528(4)

P, deg 104.358(11)

V, A3 1959.3(14)

Z 4

Crystal size, mm 0.452 x 0.325 x 0.287

8 range for data collection, deg 3.50 < 9 < 26.45

Limiting indices -4 < h < 11

-24 < k < 27

-11 < l < 11

Reflections collected/unique, 9797/3992 (fiiBt = 0.0238)

T > 2a(I)

Completeness, % 99.0

Parameters 262

Goodness-of-fit on F2 1.102

Final R indices (I > 2 a(I)) R1 = 0.0303, wR2 = 0.0631

R indices (all data) R1 = 0.0410, wR2 = 0.0668

Table 2. Selected bond lengths (A) and bond angels (deg)

Bond d, Â Bond d, Â

Pd(1)-O(1) 1.986(2) Pd(1)-N(2) 2.018(2)

Pd(1)-N(3) 2.018(2) Pd(1)-N(1) 2.021(2)

C(1)-O(2) 1.220(4) C(1)-O(1) 1.289(4)

Angle œ, deg Angle œ, deg

O(1)Pd(1)N(2) 176.65(9) O(1)Pd(1)N(3) 95.16(9)

N(2)Pd(1)N(3) 81.58(10) O(1)Pd(1)N(1) 83.17(9)

N(2)Pd(1)N(1) 100.11(10) N(3)Pd(1)N(1) 177.69(10)

O(2)C(1)O(1) 123.2(3) O(2)C(1)C(2) 120.4(3)

fined by the full-matrix least-squares method on F2. All the non-hydrogen atoms were refined anisotropically. The hydrogen atoms were located from different Fourier maps. The crystal data and structure refinement are summarized in Table 1, and selected bond lengths and angles are provided in Table 2. Supplementary material (no. CCDC 263418) can be obtained by contacting the the Cambridge Crystallographic Data Center (12 Union Road, Cambridge CB2 1EZ, UK).

RESULTS AND DISCUSSION

The crystal structure of complex I. Single-crystal X-ray diffraction analyses revealed that compound I contains one crystallographically independent palladium atom (Fig. 1). The Pd(1) atom is tetracoordinated by one nitrogen atom, one oxygen atom from the Phe ligand, and two nitrogen atoms from Phen ligand. Thus Pd(1) has planar square coordination geometry. A usual, the carboxy group of the Phe ligand adopts unidentate coordination mode. The Pd-O bond length is 1.986 A, and the Pd-N distances are in a range of 2.018-2.021 A. The NPdN(O) bond angles are in a range of 81.58°-100.11° and 177.65°-176.65°. The Pd atom is surrounded by the Phen and Phe ligands to form a monovalent complex cation, Cl- is filled in the crystal lattice as a counterion. The Cl- anion connects the complex cation through an electrostatic interaction and has a very weak hydrogen bond with the water molecule (Cl(1)-H(3C) 2.37 A).

In the parking arrangement, the complex cations contact with each other to form 1-D chain with phen n-n stacking interactions shown in Fig. 2. The narrowest in-terplanar distance of the Phen unit is about 3.4 A. Since the aromatic rings of Phen (N(2), C(10)-C(21), N(3)) and Phe (C(4)-C(9)) approach to vertical, and the dihedral angle is 89.7°, the Phe ligand is absent in the n-n stacking. Furthermore, there are three types of hydrogen bonding arising from Cl(l), NH, and O of the Phe ligand and water molecule (Cl(1)-H(3C) 2.37, O(1)-H(3D) 2.33, O(2)-H(1A) 2.54 A). Hydrogen bonding interactions and n-n stacking interactions stabilize the crystal lattice.

IR spectroscopy. In the IR spectrum of compound I, the strong and broad vibration in a range of 14311658 cm-1 are assigned as characteristic peaks of Phen vibration. The 5(C-O) vibration of Phe in the plane occurs in sharp peaks at 1311 cm-1. The bands at 3500 cm-1 are attributed to the crystal water vibration.

Anticancer activity of complex I. A series of research on the inhibition ability to AGZY-83a and interaction mechanism with DNA have been reported by our groups. The method and experiment conditions refer to our literature [15-17]. The tumor-inhibition rate of the compound to the lung cancer cell AGZY-83a in the different concentrations are: 8.0 (6.3), 16.0 (9.9), 32.0 (20.3), 64.0 (36.6), 128.0 ^g/ml (76.1%), respectively. There is a linear rela-

KOOP,n,HHAU,HOHHAü XHMHü tom 33 < 2 2007

CRYSTAL STRUCTURE AND ANTI-CANCER ACTIVITY

127

C(5) C(6) C(7)

Fig. 1. Asymmetric unit of [Pd(Phen)(Phe)]Cl ■ H2O showing Pd(II) planar square coordination geometry.

Fig. 2. View of the 1-D chain constructed by the complex cation with Phen n-n stacking interactions. КООРДИНАЦИОННАЯ ХИМИЯ том 33 < 2 2007

ci, |g/ml

Fig. 3. Relation between the concentration of the complex I (cj) and tumor-inhibition rate.

tion between the concentration and tumor-inhibition rate, and the IC50 of the complex calculated by least-squares method is 88.4 |g/ml (Fig. 3). With the increasing concentration of the complex, the actican-cer activity of the complex also increases, showing that this complex has strong anticancer activity.

In summary, the study about anticancer activity of the palladium complex is a brand-new field and can enrich the category of inorganic medicine. We successfully synthesized a mixed-ligand complex [Pd(Phen)(Phe)]Cl ■ ■ H2O, which has good anticancer activity.

REFERENCES

1. Broring, M., Brandt, C.D., and Stillwag, S., Chem. Commun., 2003, p. 2344.

2. Cornell, C.N. and Sigman, M.S., J. Am. Chem. Soc., 2005, vol. 127, no. 9, p. 2796.

3. Tang, W.X., Guan, Y.T., Shao, R.Q., et al., Kexue Tong-bao, 1982, vol. 27, p. 116.

4. Broring, M. and Brandt, C.D., Chem. Commun., 2003, p. 2156.

5. Yu, S.Y., Fujita, M., and Yamaguchi, K., Dalton Trans., 2001, p

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