trans-Bis(3-acetyl­pyridine-κN)diiodoplatinum(II)

In the square-planar title complex, [PtI₂(C₇H₇NO)₂], the Pt atom lies on a crystallographic inversion center, coinciding with an anti arrangement of the 3-acetyl­pyridine ligands. The dihedral angles between the pyridine rings and the Pt coordination plane are 67.5 (2)°, while those between the pyridine rings and the acetyl planes are 20.8 (5)°. The ¹⁹⁵Pt NMR resonance of the title complex (CD₂Cl₂) was observed at −3224 p.p.m. The major structural parameters are compared with those from previously reported related structures.

S1. Comment

The anticancer drug cisplatin, cis-Pt(NH₃)₂Cl₂, and a few other platinum agents are widely used in the clinical treatment of testicular, ovarian, bladder, head and neck tumors (Farrell, 1989; O'Dwyer et al., 1999). Structure–activity rules that emerged from early studies include the assessment that trans complexes are therapeutically inactive, as opposed to cis complexes – a rule based mainly on the lack of activity for transplatin. Some exceptions from this paradigm were found in 1989, including trans-Pt(pyridine)₂Cl₂ (Farrell et al., 1989), which is even active towards leukemia L1210 cisplatin-resistant cell lines (Van Beusichem & Farrell, 1992). A review of the cytotoxicity of trans-platinum complexes has been published recently (Natile & Coluccia, 2001).

Platinum–pyridine derivative compounds not only gained interest because of this rule-breaking finding, but also due to the recently reported anticancer complex cis-PtCl₂(NH₃)(2-picoline) (AMD473) (Chen et al., 1998; Holford et al., 1998). This compound, active both via oral administration and injection, is currently in phase II clinical trials. Other than AMD473 itself and its trans-isomer (McGowan et al., 2005), recent studies involving platinum complexes containing pyridine derivatives (Ypy) include Pt(ESDT)(Ypy)(NH₃)Cl (Marzano et al., 2002, 2004; Giovagnini et al., 2005), in which the ethylsarcosinedithiocarbamate ligand (ESDT) is used to reduce nephrotoxic effects, Pt(OAc)₂(Ypy)₂ and Pt(OAc)₂(Ypy)(NH₃) (Ma et al., 2005; Quiroga et al., 2006), in which the acetate ligands were used in order to obtain water-soluble complexes, and trans-PtCl₂(4-pic)L (Najajreh et al., 2005), where L is a nonplanar heterocyclic amine ligand. The cytotoxicity of this last compound is improved compared to transplatin (Khazanov et al., 2002; Najajreh et al., 2003), but the non-activity of trans-Pt(NH₃)Cl₂(hmpy), trans-Pt(hmpy)₂Cl₂ and [Pt(hmpy)₃Cl]Cl (hmpy is 3- or 4-hydroxymethylpyridine) precludes any generalization.

A few years ago, we undertook a systematic and detailed study of complexes of the type cis- and trans-Pt(Ypy)₂X₂ (X is Cl^-, I^- or NO₃^-) (Tessier & Rochon, 1999, 2001) and their hydrolysis products (Rochon & Tessier, 2002) by various techniques, including multinuclear NMR and X-ray crystallography. The pyridine derivatives included pyridine, the three picoline isomers, 2,4-lutidine and 3,5-lutidine. This series was used to study the steric and ligand basicity effects on the nature of the Pt—Ypy bond, as well as the number of hydrolyzed species in neutral media. As expected, the steric effects preclude formation of hydroxy-bridged oligomers (Rochon & Tessier, 2002). We also observed a relation of the NMR chemical shifts with the pK_a of the protonated ligands, indicating that the σ(Ypy→Pt) bond is more important than the π(Pt←Ypy) back-donation. We established the relative position of the ligands in the trans-influence series. In the course of the study, we obtained the title compound, (I), during an attempt to synthesize its cis-isomer. Compound (I) is the first example of an acetylpyridine–platinum complex to be structurally characterized.

Complex (I) is the trans-isomer. cis→trans isomerization in Pt(Ypy)₂X₂ complexes is not uncommon (Kong & Rochon, 1978; Tessier & Rochon, 1999). The Pt atom lies on a crystallographic inversion center, resulting in an anti arrangement of the 3-acetylpyridine ligands. Table 1 lists the geometric parameters. The Pt—N and Pt—I bond distances are identical to those obtained for other trans-Pt(Ypy)₂I₂ complexes (Table 2). The bond angles and the coplanarity of the atoms indicate a square-planar geometry around the Pt center. The O atom in the acetyl group does not participate in any hydrogen bonding or long-range contact. The dihedral angle between the pyridine ring and the Pt coordination plane is 67.5 (2)°.

Table 2 lists the dihedral angles for previously reported trans-Pt(Ypy)₂I₂ complexes, while a more complete list for all square-planar complexes containing the trans-Pt(Ypy)₂ moiety, as listed in the Cambridge Structural Database, (CSD, Version 5.27; Allen, 2002), is provided in the supplementary material (Table S1). The value obtained for compound (I) lies between the values obtained for the 3-methylpyridine (63.5°; KARVAA; Tessier & Rochon, 1999) and (3-pyridyl)methane-sulfonamide (69.1°; ACAZOU; Dodoff et al., 2004) complexes (Table 2). Various factors, such as steric hindrance, the other ligands and intermolecular interactions, could influence the orientation of the pyridine rings. As a general rule, ortho-substituted pyridine derivatives are almost perpendicular to the Pt coordination plane [for example, trans-Pt(2-Mepy)₂I₂ in Table 2]. The other ligands also seem to influence the dihedral angles. The order is as follows (from greater to smaller): I > Cl ~NH₃ ~ C≡ C > NO₃. The values obtained for the nitrate complexes are noticeably smaller (39–40°; Tessier & Rochon, 2001).

The acetate moiety of (I) is not coplanar with the pyridine ring, as indicated by the dihedral angle of 20.8 (2)° (or see torsion angles in Table 1). This phenomenon is not uncommon for other platinum structures found in the CSD that contain at least one RC(O)-pyridine derivative (Table 3). The first five structures in Table 3 are monosubstituted on the pyridine derivative, the four following are disubstituted and the rest are tetrasubstituted. No general rule can be found, except that values seem to be smaller for monosubstituted complexes. The hydrogen-bonding pattern certainly plays an important role, as it occurs to some extent in all complexes in Table 3, with the exception of trans-Pt(4-(COOEt)py)₂Cl₂, where the ethoxycarbonyl moiety is almost coplanar with the pyridine ring (1.2°; Camalli et al., 1980). No hydrogen-bonding pattern is observed in (I).

The ¹⁹⁵Pt NMR resonance of compound (I) was observed at -3224 p.p.m. This observation is in the expected range for trans-Pt(Ypy)₂I₂ complexes (-3122 to -3264 p.p.m.; Tessier & Rochon, 1999). The reaction of compound (I) with silver nitrate in acetone (Souchard et al., 1990; Tessier & Rochon, 2001) results in the formation of the trans-Pt(3-Acpy)₂(NO₃)₂ species, as indicated by the ¹⁹⁵Pt NMR signal (CDCl₃) observed at -1474 p.p.m. The expected values for trans-Pt(Ypy)₂(NO₃)₂ are from -1402 to -1481 p.p.m. (Tessier & Rochon, 2001).

S2. Experimental

Compound (I) was prepared by the published procedure for cis-Pt(amine)₂I₂ complexes (Souchard et al., 1990) using 3-acetylpyridine as a ligand [yield 75%; m.p. (decomposition) 523–528 K]. Yellow crystals suitable for X-ray crystallography were obtained by recrystallization from dichloromethane.

S3. Refinement

The structure was solved by direct methods with SHELXS97 (Sheldrick, 1997) and refined against all data by full-matrix least-squares techniques on F² using SHELXL97 (Sheldrick, 1997). All non-H atoms were refined anisotropically. H atoms were placed in idealized positions on C atoms, with C—H = 0.93 and 0.96 Å for aromatic and methyl H atoms, respectively. PLATON (Spek, 2003) was used to check missing symmetry or voids in the structure. None was found.

Computing details

Data collection: XSCANS (Siemens, 1995); cell refinement: XSCANS; data reduction: XSCANS; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL (Bruker, 2003); software used to prepare material for publication: SHELXTL.

Figures

Fig. 1. A diagram of compound (I) with the atom-labeling scheme. Displacement ellipsoids are drawn at the 50% probability level.

trans-Bis(3-acetylpyridine-κN)diiodoplatinum(II)

Crystal data

[PtI2(C7H7NO)2]	F(000) = 624
Mr = 691.16	Dx = 2.652 Mg m^−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 22 reflections
a = 4.632 (1) Å	θ = 2.2–13.6°
b = 16.456 (5) Å	µ = 11.68 mm^−1
c = 11.483 (3) Å	T = 292 K
β = 98.57 (3)°	Platelet, yellow
V = 865.5 (4) Å^3	0.31 × 0.10 × 0.04 mm
Z = 2

Data collection

Siemens P4 diffractometer	1494 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.028
Graphite monochromator	θmax = 27.5°, θmin = 2.2°
2θ/ω scans	h = −6→0
Absorption correction: integration (XPREP; Bruker, 2003)	k = −21→0
Tmin = 0.313, Tmax = 0.631	l = −14→14
2206 measured reflections	3 standard reflections every 97 reflections
1970 independent reflections	intensity decay: none

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.035	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.078	H-atom parameters constrained
S = 1.00	w = 1/[σ^2(Fo^2) + (0.0276P)^2] where P = (Fo^2 + 2Fc^2)/3
1970 reflections	(Δ/σ)max < 0.001
98 parameters	Δρmax = 0.87 e Å^−3
0 restraints	Δρmin = −0.78 e Å^−3

Special details

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 F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
Pt1	0.0000	0.0000	0.0000	0.03634 (12)
I1	0.33217 (12)	0.04824 (3)	0.19118 (4)	0.04814 (15)
N1	0.0164 (14)	−0.1154 (4)	0.0620 (5)	0.0384 (13)
O1	0.4735 (16)	−0.2958 (4)	−0.0833 (6)	0.0726 (19)
C2	0.1508 (16)	−0.1749 (4)	0.0096 (6)	0.0383 (16)
H2	0.2463	−0.1614	−0.0534	0.046*
C3	0.1527 (15)	−0.2547 (4)	0.0453 (6)	0.0351 (15)
C4	0.0141 (17)	−0.2749 (5)	0.1416 (6)	0.0424 (17)
H4	0.0108	−0.3283	0.1682	0.051*
C5	−0.1182 (18)	−0.2130 (5)	0.1962 (7)	0.0491 (19)
H5	−0.2077	−0.2244	0.2616	0.059*
C6	−0.1179 (17)	−0.1358 (5)	0.1545 (6)	0.0439 (17)
H6	−0.2135	−0.0955	0.1909	0.053*
C7	0.2979 (18)	−0.3172 (5)	−0.0218 (6)	0.0457 (18)
C8	0.213 (2)	−0.4039 (5)	−0.0139 (8)	0.065 (2)
H8A	0.3677	−0.4380	−0.0325	0.098*
H8B	0.0389	−0.4142	−0.0686	0.098*
H8C	0.1769	−0.4155	0.0646	0.098*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
Pt1	0.0495 (2)	0.02541 (17)	0.03624 (19)	0.0038 (2)	0.01324 (15)	0.00082 (17)
I1	0.0585 (3)	0.0408 (3)	0.0453 (3)	0.0025 (3)	0.0083 (2)	−0.0036 (2)
N1	0.047 (3)	0.032 (3)	0.037 (3)	0.003 (3)	0.008 (3)	0.003 (2)
O1	0.079 (5)	0.063 (4)	0.083 (4)	0.001 (4)	0.037 (4)	−0.016 (4)
C2	0.041 (4)	0.032 (4)	0.042 (4)	−0.005 (3)	0.007 (3)	−0.007 (3)
C3	0.040 (4)	0.032 (3)	0.035 (3)	0.003 (3)	0.009 (3)	0.000 (3)
C4	0.049 (4)	0.036 (4)	0.044 (4)	−0.006 (4)	0.011 (3)	0.005 (3)
C5	0.059 (5)	0.049 (5)	0.044 (4)	0.000 (4)	0.021 (4)	0.007 (4)
C6	0.050 (4)	0.044 (4)	0.040 (4)	0.008 (4)	0.014 (3)	0.001 (3)
C7	0.061 (5)	0.038 (4)	0.041 (4)	0.004 (4)	0.015 (4)	0.001 (3)
C8	0.095 (7)	0.037 (4)	0.065 (5)	0.009 (5)	0.016 (5)	0.001 (4)

Geometric parameters (Å, º)

Pt1—N1	2.026 (6)	C4—C5	1.386 (11)
Pt1—I1	2.6097 (10)	C4—H4	0.9300
N1—C2	1.349 (9)	C5—C6	1.358 (11)
N1—C6	1.351 (9)	C5—H5	0.9300
O1—C7	1.206 (9)	C6—H6	0.9300
C2—C3	1.375 (10)	C7—C8	1.486 (11)
C2—H2	0.9300	C8—H8A	0.9600
C3—C4	1.400 (9)	C8—H8B	0.9600
C3—C7	1.503 (10)	C8—H8C	0.9600
N1—Pt1—I1	90.19 (17)	C6—C5—H5	119.8
N1—Pt1—I1^i	89.81 (17)	C4—C5—H5	119.8
C2—N1—C6	117.9 (6)	N1—C6—C5	122.3 (7)
C2—N1—Pt1	121.3 (5)	N1—C6—H6	118.9
C6—N1—Pt1	120.7 (5)	C5—C6—H6	118.9
N1—C2—C3	122.9 (6)	O1—C7—C8	121.6 (8)
N1—C2—H2	118.5	O1—C7—C3	119.5 (7)
C3—C2—H2	118.5	C8—C7—C3	118.8 (7)
C2—C3—C4	118.6 (7)	C7—C8—H8A	109.5
C2—C3—C7	119.0 (6)	C7—C8—H8B	109.5
C4—C3—C7	122.4 (7)	H8A—C8—H8B	109.5
C5—C4—C3	117.9 (7)	C7—C8—H8C	109.5
C5—C4—H4	121.0	H8A—C8—H8C	109.5
C3—C4—H4	121.0	H8B—C8—H8C	109.5
C6—C5—C4	120.3 (7)
I1—Pt1—N1—C2	−113.5 (5)	C7—C3—C4—C5	−178.8 (7)
I1^i—Pt1—N1—C2	66.5 (5)	C3—C4—C5—C6	1.6 (12)
I1—Pt1—N1—C6	69.2 (6)	C2—N1—C6—C5	0.8 (11)
I1^i—Pt1—N1—C6	−110.8 (6)	Pt1—N1—C6—C5	178.1 (6)
C6—N1—C2—C3	0.9 (11)	C4—C5—C6—N1	−2.1 (13)
Pt1—N1—C2—C3	−176.4 (5)	C2—C3—C7—O1	19.7 (11)
N1—C2—C3—C4	−1.3 (11)	C4—C3—C7—O1	−161.5 (8)
N1—C2—C3—C7	177.5 (7)	C2—C3—C7—C8	−158.1 (8)
C2—C3—C4—C5	0.0 (11)	C4—C3—C7—C8	20.6 (11)

Symmetry code: (i) −x, −y, −z.