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Synthesis and characterization of platinum(II) and (IV) complexes containing hexamethyleneimine ligand: crystal structure of [PtII(hexamethyleneimine)2(cyclobutanedicarboxylato)]·H2O
Polyhedron 21 (2002) 2659 /2665 www.elsevier.com/locate/poly
Synthesis and characterization of platinum(II) and (IV) complexes containing hexamethyleneimine ligand: crystal structure of [PtII(hexamethyleneimine)2(cyclobutanedicarboxylato)] × H2O /
Mohammad S. Ali a, John H. Thurston b, Kenton H. Whitmire b, Abdul R. Khokhar a, a
Department of Experimental Therapeutics, M.D. Anderson Cancer Center, The University of Texas, Box 353, 1515 Holcombe Boulevard, Houston, TX 77030, USA b Department of Chemistry, MS-60, Rice University, 6100 Main Street, Houston, TX 77005, USA Received 16 March 2002; accepted 15 September 2002
Abstract A series of new platinum(II) and platinum(IV) complexes of the type [PtII(HMI)2X] (where HMI /hexamethyleneimine, X/ dichloro, sulfato, 1,1-cyclobutanedicarboxylato [CBDCA], oxalato, methylmalonato, or tatronato) and [PtIV(HMI)2Y2Cl2] (where Y /hydroxo, acetato, or chloro) were synthesized and characterized by infrared (IR) spectroscopy, 13C and 195Pt nuclear magnetic resonance (NMR) spectroscopy and elemental analysis. Among the complexes synthesized, [PtII(hexamethyleneimine)2(1,1cyclobutanedicarboxylato)] ×/H2O was examined by single-crystal X-ray diffraction. The slightly distorted square planar coordination environment of the platinum metal includes the amino group of the hexamethyleneimine (HMI) molecule and the oxygen atoms of the carboxylato ligand. The cyclobutanedicarboxylic acid (CBDCA) molecule adopts six-member chelating rings with platinum. Hydrogen bonding plays an important part in holding the crystal lattice together. # 2002 Elsevier Science Ltd. All rights reserved. Keywords: Platinum; Hexamethyleneimine; 1,1-Cyclobutanedicarboxylato; Synthesis; Crystal structure
1. Introduction In chemotherapy, a major obstacle to extend treatment with platinum anticancer drugs is the development of acquired and intrinsic tumor resistance [1,2]. Possible mechanisms of cisplatin resistance have been studied in a wide variety of murine and human cell lines and have recently been reviewed [3,4]. Platinum anticancer agents with different carrier amino ligands (such as 1,2diaminocyclohexane, 1,4-diaminocyclohexane, homopiperazine) and leaving non-amino ligands (such as choloro, mono and dicarboxylato, and hydroxo) have been developed in an attempt to overcome this problem. Platinum(II) and (IV) complexes containing 1,2-diaminocyclohexane carrier ligands (such as ormaplatin (tetrachlolro-trans -dl -1,2-diamminocyclohexane-plati-
Corresponding author. Tel.: /1-713-792-2837; fax: /1-713-7451176 E-mail address: [email protected] (A.R. Khokhar).
num(IV)), oxaliplatin (trans -l -1,2-diamminocyclohexane-oxalatoplatinum(II)), and liposomal-entrapped ci sbis(neodecanoato)(trans -1(R ),2(R )-diamminocyclohexane)platinum(II) (L-NDDP) and cyclohexylamine carrier ligands (such as JM216 (bis(acetato)amminedicholoro(cyclohexanamine)platinum(IV)) are often effective in overcoming cell resistance to platinum complexes containing cis -diammine carrier ligands (such as cisplatin (cis -diamminedicholorplatinum(II)) and carboplatin (diammine-1,1-cyclobutanedicarboxylatoplatinum(II)) [5 /11]. Once inside the cell, the compounds lose the nonamine ligands, bind to cellular DNA, and form several stable Pt /DNA adducts. The majority of these adducts are represented by intrastrand cross-links between adjacent guanosines [12]. Both nuclear magnetic resonance (NMR) and crystallographic structural studies have revealed that when a platinum complex such as cisplatin or JM216 binds to adjacent guanine residues on duplex DNA, it distorts the double helix by causing a
0277-5387/02/$ - see front matter # 2002 Elsevier Science Ltd. All rights reserved. PII: S 0 2 7 7 - 5 3 8 7 ( 0 2 ) 0 1 2 6 3 - 9
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bend toward the major groove and a widening and flattening of the minor groove. Studies showing significant differences in the effectiveness of EN /Pt (EN / 1,2-ethylenediamine) and DACH/Pt (DACH/1,2-diaminocyclohexane) adducts in inhibiting transformation efficiency in a repair-deficient strain of Escherichia coli suggest that some carrier ligand effects on resistant cell lines arise from differences in the ability of certain Pt / DNA adducts to inhibit other processes like replication or transcription [5,6,12 /14]. These structural distortions and differences in carrier ligand effects in turn likely affect the ability of the platinum drugs to block DNA replication and transcription [15,16]. A series of compounds with 1,2-DACH, 1,4-DACH and homopiperazine as carrier ligands have been synthesized in our laboratory [17,18]. Here at the M.D. Anderson Cancer Center, DACH /acetate / Pt(IV) complexes have been identified as circumventing cisplatin resistance [19]. This led us to design and synthesize platinum complexes of a monodentate seven-member hexamethyleneimine (HMI) ligand as a stable amine with different leaving groups. We wish to report here the synthesis, and characterization of new platinum complexes and the crystal structure of [PtII(hexamethyleneimmine)2(cyclobutanedicarboxylato)] ×/H2O complex.
2. Experimental 2.1. Chemicals K2PtCl4 and silver sulfate were purchased from Johnson Matthey, Seabrook, NH. HMI, 1,1-cyclobutanedicarboxylic acid (CBDCA), sodium oxalate, malonic acid disodium salt, and acetic anhydride were purchased from Aldrich Chemical Co., Milwaukee, WI. Silver nitrate and HCl were obtained from Fisher Scientific Co., Houston, TX. All chemicals obtained from commercial sources were used as supplied. 2.2. Physical measurements Elemental analyses of the complexes were performed by Robertson Laboratory Inc., Madison, NJ. Infrared (IR) spectra in the range of 600 /4000 cm 1 and far-IR spectra in the range of 150 /600 cm 1 were recorded in KBr and polyethylene pellets, respectively, on a Perkin/ Elmer 2000 spectrophotometer. 13C and 195Pt NMR spectra in methanol were recorded using a Bruker Advance 300 spectrometer. 13C spectra were recorded with a 5 mm tunable probe at 75.13 MHz, 195Pt spectra were recorded at 43.055 MHz, and the shifts were measured relative to an external standard of 2.2 M Na2PtCl6 in D2O at 0.00 ppm.
2.3. Synthesis 2.3.1. Preparation of [Pt(HMI)2Cl2] (complex 1) K2PtCl4 (20.00 g, 48.19 mmol) was dissolved in 300 ml of deionized water and filtered. A solution of KI (63.99 g, 385.54 mol) in 150 ml of water was added to it, and the reaction mixture was stirred for 10 min. Next, HMI (9.55 g, 96.38 mmol) was added dropwise to the mixture while stirring to obtain a yellow precipitate of [Pt(HMI)2I2] (1a). The stirring was continued for a further 30 min, and the precipitate was then collected by filtration. This compound was stirred in 100 ml of dimethylformamide, filtered, washed with water, ethanol, and acetone, and dried under vacuum (yield, 95%). [Pt(HMI)2I2] (13.00 g, 20.08 mmol) was suspended in an aqueous solution of silver nitrate (6.87 g, 40.16 mmol) in 400 ml of water. The reaction mixture was stirred for 24 h at room temperature (r.t.) in the dark. The AgI precipitate was filtered off, and a solution of 1:1 concentrated HCl was added to the filtrate with constant stirring until a yellow precipitate of 1 formed. It was filtered washed with water and acetone and dried under vacuum. Complex 1 was used as a precursor for Pt(IV) complexes 7 /9 (see below). 2.3.2. [PtII(HMI)2(OSO3)H2O] (complex 2) To a suspension of 1a (3.1 g, 4.79 mmol) in 250 ml of water Ag2SO4 (1.49, 4.79 mmol) was added. The reaction mixture was then stirred in the dark at r.t. for 24 h. The dark yellow precipitate was filtered off, and the filtrate was evaporated to dryness under reduced pressure at 35 8C. A pale yellow solid was obtained. The product was recrystallized from water, to yield a white compound. Complex 2 was used as a precursor for Pt(II) complexes 3/6 (see below). 2.3.3. [PtII(HMI)2(CBDCA)] ×/H2O (complex 3) Complex 2 (0.40 g, 0.84 mmol) was dissolved in 50 ml of water and then added to 50 ml of sodium salt of CBDCA (0.067 g, 1.68 mmol) prepared in situ. The reaction mixture was stirred for 24 h, filtered, and evaporated to 10 ml under reduced pressure. It was cooled at 0 8C for 24 h in a refrigerator. A white precipitate of 3 was obtained. The final product was filtered, washed with cold water, and dried in vacuum. Recrystallization of 3 was achieved by dissolving 0.025 g of the compound in 100 ml of methanol, after which the volume of the solution was reduced to 50 ml and filtered. The filtrate was allowed to evaporate slowly at r.t. Within 2 weeks, colorless needle-shaped crystals were separated from the solution and used for singlecrystal X-ray diffraction. Complexes 4 /6 were prepared by the same procedure as described for the complex 3.
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2.3.4. [Pt1V(HMI)2trans -(OH)2Cl2] (complex 7) To a suspension of 1 (2.00 g, 4.30 mmol) in 200 ml of water was added 30 ml of 30% H2O2. The reaction mixture was then stirred for 3 h at 70 8C and thereafter continuously stirred for 24 h at r.t. It was filtered and evaporated to dryness and precipitated with acetone. A pale yellow precipitate of 7 formed and was filtered, washed with acetone, and dried in vacuo. 2.3.5. [Pt1V(HMI)2trans -(acetato)2Cl2] (complex 8) Complex 7 (1.00 g, 2.00 mmol) was suspended in 25 ml of acetic anhydride and stirred at r.t. for 24 h. Methanol (25 ml) was added to the reaction mixture and stirred. A clear solution formed, which was filtered and evaporated to dryness. The crude product was dissolved in acetone, supplemented with activated carbon, and filtered. The resulting solution was then evaporated to dryness. A pale yellow compound was obtained and dried in vacuo. 2.3.6. [Pt1V(HMI)2Cl4] (complex 9) Complex 7 (1.00 g, 2.20 mmol) was suspended in 20 ml of water supplemented with 15 ml of concentrated HCl. A clear solution was obtained. The stirring was continued for 4 days at r.t. to obtain a yellow crystalline compound. This was filtered and washed with water. The solid was recrystallized from acetone and dried in vacuo. 2.4. Single-crystal X-ray crystallographic study The experimental details of the X-ray data collection, the structure solution, and refinement of the title compound are compiled in Table 1. A single-crystal of [PtII(HMI)2(CBDCA)] ×/H2O was coated with a thin layer of epoxy cement and mounted on the goniometer of a Bruker SMART 1K diffractometer equipped with a CCD area detector. The data was corrected for Lorentz and polarization effects. An empirical absorption correction was applied using the program SADABS [20]. No appreciable decay of the crystal was detected during data collection. The structure was solved using direct methods with the SHELXTL software package [20]. Scattering factors were taken from the literature [21]. Heavy atoms were located initially to set the correct phases for the model. All other atoms were located by successive Fourier maps and were refined using the full-matrix least-squares method on F2. Two complete molecules were found to occupy the asymmetric unit of the crystal lattice. Attempts to transform the crystallographic data to a space group that possessed higher symmetry and would presumably only contain a single molecule in the asymmetric unit, did not result in successful solution of the data. The choice of the space group Pc was confirmed through symmetry software in the PLATON
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Table 1 Crystal data and structure refinement for [PtII(HMI)2(CBDCA)]× H2O Empirical formula Formula weight Temperature (K) ˚) Wavelength (A Crystal system Space group Unit cell dimensions ˚) a (A ˚) b (A ˚) c (A b (8) ˚ 3) V (A Z Dcalc (Mg m 3) Absorption coefficient F (000) (mm 1) Crystal size (mm) u Range for data collection (8) Limiting indices
C18H32N2O4Pt× H2O 552.54 293(2) 0.71073 monoclinic Pc
13.144(3) 11.285(2) 14.483(3) 98.42(3) 2125.3(7) 4 1.724 6.630 1084 0.30 0.27 0.25 1.57 /23.29 14 5 h 5 14, 125 k 5 9, 16 5 l 5 16 Reflections collected 8948 Independent reflections 5697 [Rint 0.0305] Completeness to u 23.298, 99.4% Absorption correction empirical Max/min transmission 1.000000, 0.603765 Refinement method full-matrix least-squares on F2 Data/restraints/parameters 5697/53/438 Goodness-of-fit on F2 1.040 Final R indices [I 2s (I )] R1 0.0348, wR2 0.0916 R indices (all data) R1 0.0367, wR2 0.0927 Absolute structure parameter 0.017(13) Largest difference peak and hole 1.480 and 1.411 ˚ 3) (e A
crystallographic package [22]. Hydrogen atoms were placed in calculated positions and allowed to ride on the adjacent atom. Toward the end of the refinement it was discovered that one of the amine ligands on each platinum atom was disordered over two positions. The disorder was modeled and the structure was refined accordingly. Carbon /carbon bonds in the disordered ligands were constrained to the same distances. Disordered atoms were allowed to refine isotropically. All other non-hydrogen atoms were refined anisotropically. Refinement of positional and anisotropic parameters led to convergence.
3. Results and discussion 3.1. Synthesis of platinum complexes The steps involved in the synthesis of platinum(II) and platinum(IV) complexes are shown in Schemes 1 and 2. Compound 1 was prepared according to the method described by Dhara [23], which was adopted because it is rapid and easy and provides a much higher yield than when K2PtCl4 is treated directly with HMI.
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Scheme 1. Where HMI/hexamethyleneimine; X/1,1-cyclobutyldicarboxylato (CBDCA), methylmalonato, oxalato, or tartronato; Y/ chloro or acetato.
Scheme 2. Where HMI/hexamethyleneimine; X/1,1-cyclobutyldicarboxylato (CBDCA), methylmalonato, oxalato, or tartronato; Y/ chloro or acetato.
Complexes 1 and 2 were used as precursors for both [PtII(HMI)2X]- and [PtIV(HMI)2trans -(Y)2Cl2]-type complexes. In Scheme 1, K2PtCl4 mixed with an excess of KI produced K2PtI4 in solution. K2PtI4 was then treated with 2 equiv. of HMI to precipitate [PtII(HMI)2I2]. The reaction of [PtII(HMI)2I2] with AgNO3 led to the formation of [PtII(HMI)2(H2O)2](NO3)2 in solution, which was further converted to [PtII(HMI)2Cl2] by treating it with a concentrated 1:1 HCl solution. The reaction of [PtII(HMI)2Cl2] with Ag2SO4 formed [PtII(HMI)2(OSO3)H2O]. The reaction of [PtII(HMI)2(OSO3)H2O] with 1 equiv. of corresponding sodium salt of dicarboxylic acids in methanol produced [PtII(HMI)2X] type complexes (complexes 3 /6). In Scheme 2, Pt(II) complexes of the type [PtII(HMI)2X] were oxidized with 30% H2O2 to form corresponding axial dihydroxyplatinum(IV) complex 7 [PtIV(HMI)2trans -(OH)2Cl2]. By substitution of the hydroxo group with acetate using acetic anhydride, complex 8 [PtIV(HMI)2trans -(acetato)2Cl2] was produced. Hydroxide was substituted with chloride by reacting trans -hydroxy complex with conc. HCl to form complex 9 [PtIV(HMI)2Cl4]. 3.2. Characterization of platinum complexes The complexes were characterized by elemental analysis and IR, 13C NMR, and 195Pt NMR spectroscopy. The composition of each complex as determined by elemental analysis showed good agreement between the
theoretical and actual values. The analytical results are summarized in Table 2. The results of characterization by IR, 13C NMR, and 195Pt NMR are shown in Table 3. These values are close to the values reported for similar types of platinum complexes [18,24 /27]. The IR spectra of the complexes in general showed a broad absorption between 3204 and 3009 cm 1, which was due to the nNH stretching vibrations of coordinated HMI. The carboxyl groups in complexes 3 /6 displayed a band in the range of 1580/1610 cm 1 corresponding to the nas(COO ) band. The ns(COO ) band appeared in the range of 1360 /1390 cm 1. Two intense bands at 620 and 1130 cm 1 in complex 2 indicated the presence of an SO4 group in the complex. The Pt /N, Pt /Cl, and Pt /O stretching frequencies showed peaks in the range of 520/525, 325 /360, and 420/430 cm1, respectively. The proton-decoupled 13C NMR spectra showed a signal in the range of 180 /190 ppm for magnetically equivalent carbonyl carbons in complexes 3 /7. The values of the free acids and platinum complexes are shown in the Table 3. Complexation shifts (DC / d [complex]/d[ligand]) fell between 1.8 and 2.5 ppm. The 195Pt NMR data shown in Table 3 further confirmed the structures of these platinum complexes. [PtII(HMI)2Cl2] showed a signal at /2210 ppm, which is characteristic of the square planar platinum(II) complex in which the two adjacent corners are occupied by two nitrogen and the other two positions by two chlorides. Two peaks were observed at /1623 and /1666 ppm in the spectrum of complex 2. Complexes 3 /7 showed signals in the range of /1802 through /1821 ppm. Such chemical shifts are characteristic of square planar platinum(II) complexes having two nitrogens and two oxygen atoms as donor ligands. As oxidation of platinum(II) to platinum(IV) leads to a large shift, complex 7 showed a singlet at 1069 ppm and complex 8 a singlet at 1150 ppm. These values are close to those of the related platinum(IV) complexes having two nitrogen atoms, two oxygen atoms, and two chloride ions as donor ligands. In these complexes (7 and 8), the chloride ions occupied the equatorial positions. Complex 9 showed a signal at /150 ppm, consistent with the values of platinum(IV) complexes having two nitrogen atoms and four chloride ions as donor ligands. Figs. 1 and 2 show the general structure of the complexes.
3.3. Crystal structure Fig. 3 shows a view of the crystal structure of [PtII(HMI)2(CBDCA)] ×/H2O. Selected bond lengths and bond angles are given in Table 4. In this molecule, the coordination environment around the platinum atom is a slightly distorted square plane, with the angles ranging from 88.0(4)8 to 92.9(4)8. The distortion is caused by limitation in the bite distances of the chelating ligand.
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Table 2 Elemental analysis of platinum complexes Complex
Complex name
Observed (calculated) C
II
[Pt (HMI)2Cl2] [PtII(HMI)2(OSO3)H2O] [PtII(HMI)2(CBDCA)]× H2O [Pt(HMI)2(methylmalonato)] [PtII(HMI)2(oxalato)] [PtII(HMI)2(tartronato)] [PtII(HMI)2(trans -(OH)2Cl2] [PtII(HMI)2trans- (acetato)2)Cl2] [PtIV(HMI)2Cl4]
1 2 3 4 5 6 7 8 9
31.62 27.50 39.04 36.27 34.45 35.04 28.64 32.54 26.76
Yield (%)
H (32.77) (28.04) (39.05) (36.42) (34.92) (35.22) (28.91) (32.(98) (26.91)
5.70 5.47 5.99 5.58 5.30 5.47 5.70 5.51 4.98
N (5.46) (5.52) (6.14) (6.07) (5.40) (5.47) (5.62) (5.49) (4.85)
6.00 5.41 5.05 5.44 5.64 5.31 5.35 4.72 4.83
Cl (5.88) (5.52) (5.06) (5.31) (5.82) (5.47) (5.62) (4.81) (5.23)
14.88 (14.91)
61.53 90.90 64.22 52.00 46.00 53.84 48.00 36.45 87.00
14.00(14.25) 21.32 (21.19) 26.90 (26.54)
HMI, hexamethlyeneimine.
Table 3 IR, 13C NMR, and Complex
195
3182 3165 3076 3170 3189 3180 3168 3180 3145 a b c d
a 13
IR (cm 1) n (N H)
1 2 3 4 5 6 7 8 9
Pt NMR spectroscopic data for platinum complexes
195
C (C O)
na(C O)
ns(C O)
1610 1644 1637 1655
1367 1374 1371 1380
1649
1382
n (Pt N)
n (Pt O)
525 518 560 578 553 536 565 545 530
448 465 466 445 440 471 457
n (Pt Cl)
Ligand
Pt
Complex
DC
327
332 341 320, 334
177.3 175.8 176.4 172.7
180.8 179.7 181.4 177.0
3.5 3.8 5.0 4.3
178.2
181.6
3.4
2267b 1666, 1623c 1802c 1821c 1872c 1890c 1069c 1245d 150d
See Figs. 1 and 2 for structures. Recorded in N ,N -dimethylformamide. Recorded in methanol. Recorded in acetone; DC d [complex]d [ligand].
The platinum coordination environment contains two adjacent corners occupied by the two nitrogen atoms of
Fig. 1. Structure of [PtII(HMI)2X]; HMI/hexamethyleneimine; X/ dichloro in complex 1; sulfato in complex 2; CBDCA, methylmalonato, oxalato, or tatronato in complexes 3 /6, respectively.
Fig. 2. Structure of [PtII(HMI)2(CBDCA)]×/H2O; X/chloro in complexes 7 /9; Y/OH in complex 7, acetato in complex 8, and chloro in complex 9.
the HMI ligand, whereas the remaining two cis positions are coordinated with two of the oxygen atoms of the CBDCA. All Pt /N and Pt /O bond lengths are in the range normally observed for platinum(II) com˚ is plexes. The average Pt /N bond length of 2.06(9) A consistent with the length of those found in other monodentate and bidentate amine ligand-containing ˚ in complexes. For instance, this length is 1.99(2) A II [Pt (1-methylhomopiperazine)(methylmalonato)] ×/2H2O ˚ in [PtII(hpip)(pentadecanoato)2] [25], [18], 2.02(10) A ˚ 2.038(8) A in [PtII(3-methylpiperidine)(malonato)] ×/H2O ˚ in [Pt(trans -l-1,2-DACH)(CBDCA)] ×/H2O [28], 2.03 A ˚ in [Pt(cis- 1,4-DACH)(CBDCA)] [30], [29], 2.043(2) A ˚ and 2.02 A in [Pt(cis- 1,4-DACH)(malonato)] [31]. ˚ is normal as The average Pt /O bond length of 2.02 A compared with the values observed in other Pt(II) ˚ in [Pt(trans -lcarboxylate complexes, e.g. 2.01(9) A ˚ in [PtII(11,2-DACH)(CBDCA)] ×/H2O [29], 2.02(2) A methylhomopiperazine)(methylmalonato)] ×/2H2O [18], ˚ in [Pt(3-methylpiperidine)2(malonato)] ×/H2O 2.014(7) A ˚ in [PtII(hpip)(pentadecanoato)2] [28], and 2.038(10) A [25].
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Fig. 3. ORTEP representation of the structure [PtII(HMI)2(CBDCA)]×/H2O with atom numbering scheme.
of
Table 4 ˚ ) and angles (8) for [PtII(HMI)2(CBDSelected bond lengths (A CA)]× H2O Bond lengths Pt(1) O(2) Pt(1) O(1) Pt(1) N(2) Pt(1) N(1) Pt(2) O(22) Pt(2) O(21) Pt(2) N(22A) Pt(2) N(21)
2.015(8) 2.033(9) 2.036(10) 2.067(8) 2.013(8) 2.028(8) 2.054(9) 2.059(10)
Bond angles O(2) Pt(1) O(1) O(2) Pt(1) N(2) O(1) Pt(1) N(2) O(2) Pt(1) N(1) O(1) Pt(1) N(1) N(2) Pt(1) N(1) C(18A) N(1) Pt(1) C(13A) N(1) Pt(1) C(5) O(1) Pt(1) C(6) O(2) Pt(1) C(7) N(2) Pt(1) C(12) N(2) Pt(1) O(22) Pt(2) O(21) O(22) Pt(2) N(22A) O(21) Pt(2) N(22A) O(22) Pt(2) N(21) O(21) Pt(2) N(21) N(22A) Pt(2) N(21) C(32) N(21) Pt(2) C(27) N(21) Pt(2) C(25) O(21) Pt(2) C(26) O(22)-Pt(2) C(38) N(22A) Pt(2) C(33A) N(22A) Pt(2)
89.9(3) 89.3(4) 178.8(4) 177.0(4) 87.8(4) 93.0(4) 109.3(8) 108.3(6) 119.2(8) 119.5(7) 111.7(7) 112.2(6) 88.3(3) 89.1(4) 177.1(4) 176.6(4) 89.6(4) 93.0(4) 110.8(8) 111.3(8) 119.3(7) 121.5(8) 109.7(8) 109.5(8)
The coordination structure of the platinum complex with two ring nitrogens of HMI is considerably strained.
The N(2) /Pt(1) /N(1) bond angle is expanded to an average value of 93.08 due to geometric constraints imposed by the ligand. These angles are close to the 98.8(4)8 reported for [Pt(cis- 1,4-DACH)(CBDCA)] [30] and the 100.0(2)8 reported for [Pt(cis- 1,4-DACH)(malonato)] [31]. The bond between HMI and the metal ion are also considerably strained as evidenced by the average C /N /Pt angle of 109.1(8)8. These angles are 112.1(9)8, 114.2(7)8, and 122.3(7)8 in [Pt(trans -l -1,2DACH)(CBDCA)] [29], [Pt(3methylpiperidine)2(malonato)] ×/H2O [28], and [Pt(cis1,4-DACH)(CBDCA)] [30], respectively. The expansion of the N(2) /Pt(1) /N(1) bond angle was compensated for by the contraction of the O(1) /Pt(1) /O(2) angle to 89.9(3)8 and the O(21) /Pt(2) /O(22) angle to 88.3(3)8. The molecules in the crystal show a system of N/H O hydrogen bonds (Fig. 4). The hydrogen bond interactions were examined using the program CRYSTALS [32]. The hydrogen bond lengths were found to range from ˚ , with the average N /H O interaction 2.039 to 2.413 A ˚ in length and possessing a bond angle of being 2.207 A approximately 158.38. In summary, we have synthesized and characterized a series of new platinum(II) and (IV) complexes containing HMI as nonleaving amine ligands and different groups as leaving ligands. The crystal structure of [PtII(HMI)2(CBDCA)] ×/H2O was determined by X-ray crystallography.
Fig. 4. Packing diagram of [PtII(HMI)2(CBDCA)]×/H2O Hydrogen bonds are shown by dashed lines.
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4. Supplementary material Full lists of bond lengths and bond angles, atomic coordinates and equivalent isotropic displacement parameters, anisotropic displacement parameters, and hydrogen coordinates have been deposited at the Cambridge Crystallographic Data Centre (CCDC). Supporting information is available from The Director, CCDC, 12 Union Road, Cambridge, CB2 1EZ, UK (fax: /44-1223-336033; e-mail: [email protected] or www: http://www.ccdc.cam.ac.uk) on request, quoting the deposition number 181721. Any request to the CCDC for this material should quote the full literature citation.
Acknowledgements This work was supported by grants by CA-77332 and CA-82361 from National Cancer Institute, Robert A. Welch Foundation (C-0976), and the National Science Foundation (CHE9983352).
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[10] R. Perez-Soler, G. Lopez-Berestein, J. Luthersztain, S. Al-Baker, K. Francis, D. Macias-Kiger, M.N. Raber, A.R. Khokhar, Cancer Res. 50 (1990) 4254. [11] L.R. Kelland, in: S.P. Fricke (Ed.), Metal Compounds in Cancer Therapy: Platinum Anticancer Drugs, Chapman & Hall, London, 1994, p. 32. [12] G.R. Gibbons, J.D. Page, S.K. Mauldin, I. Hussain, S.G. Chaney, Cancer Res. 50 (1990) 6497. [13] P.M. Takahara, C.A. Fredrick, S.J. Lippard, J. Am. Chem. Soc. 118 (1996) 12309. [14] A. Gelasco, S.J. Lippard, Biochemistry 37 (1998) 9230. [15] S.U. Dunham, C.J. Turner, S.J. Lippard, J. Am. Chem. Soc. 120 (1998) 5395. [16] E.D. Scheef, S.B. Howell, Proc. Am. Assoc. Cancer Res. 39 (1998) 158 (Abstract). [17] S. Shamsuddin, M.S. Ali, A.R. Khokhar, J. Coord. Chem. 49 (2000) 291. [18] M.S. Ali, K.H. Whitmire, T. Toyomasu, Z.H. Siddik, A.R. Khokhar, J. Inorg. Biochem. 77 (1999) 231. [19] Z.H. Siddik, G.S. Hagopian, G. Thai, S. Tomisaki, T. Toyomasu, A.R. Khokhar, J. Inorg. Biochem. 77 (1999) 65. [20] G. Scheldrick, SHELXTL. 6.10, Go¨ttingen, Go¨ttingen, Germany, 2001. [21] The scattering factors are part of the SHELXTL package and can be found in the international Tables for X-ray Crystallography, vol. C, Kluwer, Dordrecht, The Netherlands, 1992. [22] A.L. Spek, PLATON */A Multipurpose Crystallographic Tool, Utrecht, The Netherlands, 2002. [23] S.C. Dhara, Indian J. Chem. 8 (1970) 193. [24] S. Shamsuddin, I. Takahashi, Z.H. Siddik, A.R. Khokhar, J. Inorg. Biochem. 61 (1996) 291. [25] M.S. Ali, C.A. Powers, K.H. Whitmire, I. Guzman-Jimenez, A.R. Khokhar, J. Coord. Chem. 52 (2001) 273. [26] S.R. Ali Khan, A.R. Khokhar, J. Coord. Chem. 52 (2000) 119. [27] S.R. Ali Khan, S. Shamsuddin, S. Inutsuka, K.H. Whitmire, Z.H. Siddik, A.R. Khokhar, Bioorg. Med. Chem. 8 (2000) 515. [28] S.R. Ali Khan, I. Guzman-Jimenez, K.H. Whitmire, A.R. Khokhar, Polyhedron 19 (2000) 983. [29] P. Bitha, G.O. Morton, T.S. Dunne, E.F. Delos Santos, Y. Lin, S.T. Boone, R.C. Haltwanger, C.G. Pierpont, Inorg. Chem. 29 (1990) 645. [30] S. Shamsuddin, A.R. Khokhar, J. Coord. Chem. 33 (1994) 83. [31] J.D. Hoeshele, H.D. Hollis Showalter, A.J. Krakar, W.L. Illiott, B.J. Roberts, J.W. Kamp, J. Med. Chem. 37 (1994) 2630. [32] D.J. Watkin, C.K. Prout, J.R. Carruthers, P.W. Betterridge, R.I. Cooper, CRYSTALS, Issue 11, Chemical Crystallography Laboratory, University of Oxford, Oxford, 2002.
Synthesis and characterization of platinum(II) and (IV) complexes containing hexamethyleneimine ligand: crystal structure of [PtII(hexamethyleneimine)2(cyclobutanedicarboxylato)] × H2O /
Mohammad S. Ali a, John H. Thurston b, Kenton H. Whitmire b, Abdul R. Khokhar a, a
Department of Experimental Therapeutics, M.D. Anderson Cancer Center, The University of Texas, Box 353, 1515 Holcombe Boulevard, Houston, TX 77030, USA b Department of Chemistry, MS-60, Rice University, 6100 Main Street, Houston, TX 77005, USA Received 16 March 2002; accepted 15 September 2002
Abstract A series of new platinum(II) and platinum(IV) complexes of the type [PtII(HMI)2X] (where HMI /hexamethyleneimine, X/ dichloro, sulfato, 1,1-cyclobutanedicarboxylato [CBDCA], oxalato, methylmalonato, or tatronato) and [PtIV(HMI)2Y2Cl2] (where Y /hydroxo, acetato, or chloro) were synthesized and characterized by infrared (IR) spectroscopy, 13C and 195Pt nuclear magnetic resonance (NMR) spectroscopy and elemental analysis. Among the complexes synthesized, [PtII(hexamethyleneimine)2(1,1cyclobutanedicarboxylato)] ×/H2O was examined by single-crystal X-ray diffraction. The slightly distorted square planar coordination environment of the platinum metal includes the amino group of the hexamethyleneimine (HMI) molecule and the oxygen atoms of the carboxylato ligand. The cyclobutanedicarboxylic acid (CBDCA) molecule adopts six-member chelating rings with platinum. Hydrogen bonding plays an important part in holding the crystal lattice together. # 2002 Elsevier Science Ltd. All rights reserved. Keywords: Platinum; Hexamethyleneimine; 1,1-Cyclobutanedicarboxylato; Synthesis; Crystal structure
1. Introduction In chemotherapy, a major obstacle to extend treatment with platinum anticancer drugs is the development of acquired and intrinsic tumor resistance [1,2]. Possible mechanisms of cisplatin resistance have been studied in a wide variety of murine and human cell lines and have recently been reviewed [3,4]. Platinum anticancer agents with different carrier amino ligands (such as 1,2diaminocyclohexane, 1,4-diaminocyclohexane, homopiperazine) and leaving non-amino ligands (such as choloro, mono and dicarboxylato, and hydroxo) have been developed in an attempt to overcome this problem. Platinum(II) and (IV) complexes containing 1,2-diaminocyclohexane carrier ligands (such as ormaplatin (tetrachlolro-trans -dl -1,2-diamminocyclohexane-plati-
Corresponding author. Tel.: /1-713-792-2837; fax: /1-713-7451176 E-mail address: [email protected] (A.R. Khokhar).
num(IV)), oxaliplatin (trans -l -1,2-diamminocyclohexane-oxalatoplatinum(II)), and liposomal-entrapped ci sbis(neodecanoato)(trans -1(R ),2(R )-diamminocyclohexane)platinum(II) (L-NDDP) and cyclohexylamine carrier ligands (such as JM216 (bis(acetato)amminedicholoro(cyclohexanamine)platinum(IV)) are often effective in overcoming cell resistance to platinum complexes containing cis -diammine carrier ligands (such as cisplatin (cis -diamminedicholorplatinum(II)) and carboplatin (diammine-1,1-cyclobutanedicarboxylatoplatinum(II)) [5 /11]. Once inside the cell, the compounds lose the nonamine ligands, bind to cellular DNA, and form several stable Pt /DNA adducts. The majority of these adducts are represented by intrastrand cross-links between adjacent guanosines [12]. Both nuclear magnetic resonance (NMR) and crystallographic structural studies have revealed that when a platinum complex such as cisplatin or JM216 binds to adjacent guanine residues on duplex DNA, it distorts the double helix by causing a
0277-5387/02/$ - see front matter # 2002 Elsevier Science Ltd. All rights reserved. PII: S 0 2 7 7 - 5 3 8 7 ( 0 2 ) 0 1 2 6 3 - 9
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bend toward the major groove and a widening and flattening of the minor groove. Studies showing significant differences in the effectiveness of EN /Pt (EN / 1,2-ethylenediamine) and DACH/Pt (DACH/1,2-diaminocyclohexane) adducts in inhibiting transformation efficiency in a repair-deficient strain of Escherichia coli suggest that some carrier ligand effects on resistant cell lines arise from differences in the ability of certain Pt / DNA adducts to inhibit other processes like replication or transcription [5,6,12 /14]. These structural distortions and differences in carrier ligand effects in turn likely affect the ability of the platinum drugs to block DNA replication and transcription [15,16]. A series of compounds with 1,2-DACH, 1,4-DACH and homopiperazine as carrier ligands have been synthesized in our laboratory [17,18]. Here at the M.D. Anderson Cancer Center, DACH /acetate / Pt(IV) complexes have been identified as circumventing cisplatin resistance [19]. This led us to design and synthesize platinum complexes of a monodentate seven-member hexamethyleneimine (HMI) ligand as a stable amine with different leaving groups. We wish to report here the synthesis, and characterization of new platinum complexes and the crystal structure of [PtII(hexamethyleneimmine)2(cyclobutanedicarboxylato)] ×/H2O complex.
2. Experimental 2.1. Chemicals K2PtCl4 and silver sulfate were purchased from Johnson Matthey, Seabrook, NH. HMI, 1,1-cyclobutanedicarboxylic acid (CBDCA), sodium oxalate, malonic acid disodium salt, and acetic anhydride were purchased from Aldrich Chemical Co., Milwaukee, WI. Silver nitrate and HCl were obtained from Fisher Scientific Co., Houston, TX. All chemicals obtained from commercial sources were used as supplied. 2.2. Physical measurements Elemental analyses of the complexes were performed by Robertson Laboratory Inc., Madison, NJ. Infrared (IR) spectra in the range of 600 /4000 cm 1 and far-IR spectra in the range of 150 /600 cm 1 were recorded in KBr and polyethylene pellets, respectively, on a Perkin/ Elmer 2000 spectrophotometer. 13C and 195Pt NMR spectra in methanol were recorded using a Bruker Advance 300 spectrometer. 13C spectra were recorded with a 5 mm tunable probe at 75.13 MHz, 195Pt spectra were recorded at 43.055 MHz, and the shifts were measured relative to an external standard of 2.2 M Na2PtCl6 in D2O at 0.00 ppm.
2.3. Synthesis 2.3.1. Preparation of [Pt(HMI)2Cl2] (complex 1) K2PtCl4 (20.00 g, 48.19 mmol) was dissolved in 300 ml of deionized water and filtered. A solution of KI (63.99 g, 385.54 mol) in 150 ml of water was added to it, and the reaction mixture was stirred for 10 min. Next, HMI (9.55 g, 96.38 mmol) was added dropwise to the mixture while stirring to obtain a yellow precipitate of [Pt(HMI)2I2] (1a). The stirring was continued for a further 30 min, and the precipitate was then collected by filtration. This compound was stirred in 100 ml of dimethylformamide, filtered, washed with water, ethanol, and acetone, and dried under vacuum (yield, 95%). [Pt(HMI)2I2] (13.00 g, 20.08 mmol) was suspended in an aqueous solution of silver nitrate (6.87 g, 40.16 mmol) in 400 ml of water. The reaction mixture was stirred for 24 h at room temperature (r.t.) in the dark. The AgI precipitate was filtered off, and a solution of 1:1 concentrated HCl was added to the filtrate with constant stirring until a yellow precipitate of 1 formed. It was filtered washed with water and acetone and dried under vacuum. Complex 1 was used as a precursor for Pt(IV) complexes 7 /9 (see below). 2.3.2. [PtII(HMI)2(OSO3)H2O] (complex 2) To a suspension of 1a (3.1 g, 4.79 mmol) in 250 ml of water Ag2SO4 (1.49, 4.79 mmol) was added. The reaction mixture was then stirred in the dark at r.t. for 24 h. The dark yellow precipitate was filtered off, and the filtrate was evaporated to dryness under reduced pressure at 35 8C. A pale yellow solid was obtained. The product was recrystallized from water, to yield a white compound. Complex 2 was used as a precursor for Pt(II) complexes 3/6 (see below). 2.3.3. [PtII(HMI)2(CBDCA)] ×/H2O (complex 3) Complex 2 (0.40 g, 0.84 mmol) was dissolved in 50 ml of water and then added to 50 ml of sodium salt of CBDCA (0.067 g, 1.68 mmol) prepared in situ. The reaction mixture was stirred for 24 h, filtered, and evaporated to 10 ml under reduced pressure. It was cooled at 0 8C for 24 h in a refrigerator. A white precipitate of 3 was obtained. The final product was filtered, washed with cold water, and dried in vacuum. Recrystallization of 3 was achieved by dissolving 0.025 g of the compound in 100 ml of methanol, after which the volume of the solution was reduced to 50 ml and filtered. The filtrate was allowed to evaporate slowly at r.t. Within 2 weeks, colorless needle-shaped crystals were separated from the solution and used for singlecrystal X-ray diffraction. Complexes 4 /6 were prepared by the same procedure as described for the complex 3.
M.S. Ali et al. / Polyhedron 21 (2002) 2659 /2665
2.3.4. [Pt1V(HMI)2trans -(OH)2Cl2] (complex 7) To a suspension of 1 (2.00 g, 4.30 mmol) in 200 ml of water was added 30 ml of 30% H2O2. The reaction mixture was then stirred for 3 h at 70 8C and thereafter continuously stirred for 24 h at r.t. It was filtered and evaporated to dryness and precipitated with acetone. A pale yellow precipitate of 7 formed and was filtered, washed with acetone, and dried in vacuo. 2.3.5. [Pt1V(HMI)2trans -(acetato)2Cl2] (complex 8) Complex 7 (1.00 g, 2.00 mmol) was suspended in 25 ml of acetic anhydride and stirred at r.t. for 24 h. Methanol (25 ml) was added to the reaction mixture and stirred. A clear solution formed, which was filtered and evaporated to dryness. The crude product was dissolved in acetone, supplemented with activated carbon, and filtered. The resulting solution was then evaporated to dryness. A pale yellow compound was obtained and dried in vacuo. 2.3.6. [Pt1V(HMI)2Cl4] (complex 9) Complex 7 (1.00 g, 2.20 mmol) was suspended in 20 ml of water supplemented with 15 ml of concentrated HCl. A clear solution was obtained. The stirring was continued for 4 days at r.t. to obtain a yellow crystalline compound. This was filtered and washed with water. The solid was recrystallized from acetone and dried in vacuo. 2.4. Single-crystal X-ray crystallographic study The experimental details of the X-ray data collection, the structure solution, and refinement of the title compound are compiled in Table 1. A single-crystal of [PtII(HMI)2(CBDCA)] ×/H2O was coated with a thin layer of epoxy cement and mounted on the goniometer of a Bruker SMART 1K diffractometer equipped with a CCD area detector. The data was corrected for Lorentz and polarization effects. An empirical absorption correction was applied using the program SADABS [20]. No appreciable decay of the crystal was detected during data collection. The structure was solved using direct methods with the SHELXTL software package [20]. Scattering factors were taken from the literature [21]. Heavy atoms were located initially to set the correct phases for the model. All other atoms were located by successive Fourier maps and were refined using the full-matrix least-squares method on F2. Two complete molecules were found to occupy the asymmetric unit of the crystal lattice. Attempts to transform the crystallographic data to a space group that possessed higher symmetry and would presumably only contain a single molecule in the asymmetric unit, did not result in successful solution of the data. The choice of the space group Pc was confirmed through symmetry software in the PLATON
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Table 1 Crystal data and structure refinement for [PtII(HMI)2(CBDCA)]× H2O Empirical formula Formula weight Temperature (K) ˚) Wavelength (A Crystal system Space group Unit cell dimensions ˚) a (A ˚) b (A ˚) c (A b (8) ˚ 3) V (A Z Dcalc (Mg m 3) Absorption coefficient F (000) (mm 1) Crystal size (mm) u Range for data collection (8) Limiting indices
C18H32N2O4Pt× H2O 552.54 293(2) 0.71073 monoclinic Pc
13.144(3) 11.285(2) 14.483(3) 98.42(3) 2125.3(7) 4 1.724 6.630 1084 0.30 0.27 0.25 1.57 /23.29 14 5 h 5 14, 125 k 5 9, 16 5 l 5 16 Reflections collected 8948 Independent reflections 5697 [Rint 0.0305] Completeness to u 23.298, 99.4% Absorption correction empirical Max/min transmission 1.000000, 0.603765 Refinement method full-matrix least-squares on F2 Data/restraints/parameters 5697/53/438 Goodness-of-fit on F2 1.040 Final R indices [I 2s (I )] R1 0.0348, wR2 0.0916 R indices (all data) R1 0.0367, wR2 0.0927 Absolute structure parameter 0.017(13) Largest difference peak and hole 1.480 and 1.411 ˚ 3) (e A
crystallographic package [22]. Hydrogen atoms were placed in calculated positions and allowed to ride on the adjacent atom. Toward the end of the refinement it was discovered that one of the amine ligands on each platinum atom was disordered over two positions. The disorder was modeled and the structure was refined accordingly. Carbon /carbon bonds in the disordered ligands were constrained to the same distances. Disordered atoms were allowed to refine isotropically. All other non-hydrogen atoms were refined anisotropically. Refinement of positional and anisotropic parameters led to convergence.
3. Results and discussion 3.1. Synthesis of platinum complexes The steps involved in the synthesis of platinum(II) and platinum(IV) complexes are shown in Schemes 1 and 2. Compound 1 was prepared according to the method described by Dhara [23], which was adopted because it is rapid and easy and provides a much higher yield than when K2PtCl4 is treated directly with HMI.
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Scheme 1. Where HMI/hexamethyleneimine; X/1,1-cyclobutyldicarboxylato (CBDCA), methylmalonato, oxalato, or tartronato; Y/ chloro or acetato.
Scheme 2. Where HMI/hexamethyleneimine; X/1,1-cyclobutyldicarboxylato (CBDCA), methylmalonato, oxalato, or tartronato; Y/ chloro or acetato.
Complexes 1 and 2 were used as precursors for both [PtII(HMI)2X]- and [PtIV(HMI)2trans -(Y)2Cl2]-type complexes. In Scheme 1, K2PtCl4 mixed with an excess of KI produced K2PtI4 in solution. K2PtI4 was then treated with 2 equiv. of HMI to precipitate [PtII(HMI)2I2]. The reaction of [PtII(HMI)2I2] with AgNO3 led to the formation of [PtII(HMI)2(H2O)2](NO3)2 in solution, which was further converted to [PtII(HMI)2Cl2] by treating it with a concentrated 1:1 HCl solution. The reaction of [PtII(HMI)2Cl2] with Ag2SO4 formed [PtII(HMI)2(OSO3)H2O]. The reaction of [PtII(HMI)2(OSO3)H2O] with 1 equiv. of corresponding sodium salt of dicarboxylic acids in methanol produced [PtII(HMI)2X] type complexes (complexes 3 /6). In Scheme 2, Pt(II) complexes of the type [PtII(HMI)2X] were oxidized with 30% H2O2 to form corresponding axial dihydroxyplatinum(IV) complex 7 [PtIV(HMI)2trans -(OH)2Cl2]. By substitution of the hydroxo group with acetate using acetic anhydride, complex 8 [PtIV(HMI)2trans -(acetato)2Cl2] was produced. Hydroxide was substituted with chloride by reacting trans -hydroxy complex with conc. HCl to form complex 9 [PtIV(HMI)2Cl4]. 3.2. Characterization of platinum complexes The complexes were characterized by elemental analysis and IR, 13C NMR, and 195Pt NMR spectroscopy. The composition of each complex as determined by elemental analysis showed good agreement between the
theoretical and actual values. The analytical results are summarized in Table 2. The results of characterization by IR, 13C NMR, and 195Pt NMR are shown in Table 3. These values are close to the values reported for similar types of platinum complexes [18,24 /27]. The IR spectra of the complexes in general showed a broad absorption between 3204 and 3009 cm 1, which was due to the nNH stretching vibrations of coordinated HMI. The carboxyl groups in complexes 3 /6 displayed a band in the range of 1580/1610 cm 1 corresponding to the nas(COO ) band. The ns(COO ) band appeared in the range of 1360 /1390 cm 1. Two intense bands at 620 and 1130 cm 1 in complex 2 indicated the presence of an SO4 group in the complex. The Pt /N, Pt /Cl, and Pt /O stretching frequencies showed peaks in the range of 520/525, 325 /360, and 420/430 cm1, respectively. The proton-decoupled 13C NMR spectra showed a signal in the range of 180 /190 ppm for magnetically equivalent carbonyl carbons in complexes 3 /7. The values of the free acids and platinum complexes are shown in the Table 3. Complexation shifts (DC / d [complex]/d[ligand]) fell between 1.8 and 2.5 ppm. The 195Pt NMR data shown in Table 3 further confirmed the structures of these platinum complexes. [PtII(HMI)2Cl2] showed a signal at /2210 ppm, which is characteristic of the square planar platinum(II) complex in which the two adjacent corners are occupied by two nitrogen and the other two positions by two chlorides. Two peaks were observed at /1623 and /1666 ppm in the spectrum of complex 2. Complexes 3 /7 showed signals in the range of /1802 through /1821 ppm. Such chemical shifts are characteristic of square planar platinum(II) complexes having two nitrogens and two oxygen atoms as donor ligands. As oxidation of platinum(II) to platinum(IV) leads to a large shift, complex 7 showed a singlet at 1069 ppm and complex 8 a singlet at 1150 ppm. These values are close to those of the related platinum(IV) complexes having two nitrogen atoms, two oxygen atoms, and two chloride ions as donor ligands. In these complexes (7 and 8), the chloride ions occupied the equatorial positions. Complex 9 showed a signal at /150 ppm, consistent with the values of platinum(IV) complexes having two nitrogen atoms and four chloride ions as donor ligands. Figs. 1 and 2 show the general structure of the complexes.
3.3. Crystal structure Fig. 3 shows a view of the crystal structure of [PtII(HMI)2(CBDCA)] ×/H2O. Selected bond lengths and bond angles are given in Table 4. In this molecule, the coordination environment around the platinum atom is a slightly distorted square plane, with the angles ranging from 88.0(4)8 to 92.9(4)8. The distortion is caused by limitation in the bite distances of the chelating ligand.
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Table 2 Elemental analysis of platinum complexes Complex
Complex name
Observed (calculated) C
II
[Pt (HMI)2Cl2] [PtII(HMI)2(OSO3)H2O] [PtII(HMI)2(CBDCA)]× H2O [Pt(HMI)2(methylmalonato)] [PtII(HMI)2(oxalato)] [PtII(HMI)2(tartronato)] [PtII(HMI)2(trans -(OH)2Cl2] [PtII(HMI)2trans- (acetato)2)Cl2] [PtIV(HMI)2Cl4]
1 2 3 4 5 6 7 8 9
31.62 27.50 39.04 36.27 34.45 35.04 28.64 32.54 26.76
Yield (%)
H (32.77) (28.04) (39.05) (36.42) (34.92) (35.22) (28.91) (32.(98) (26.91)
5.70 5.47 5.99 5.58 5.30 5.47 5.70 5.51 4.98
N (5.46) (5.52) (6.14) (6.07) (5.40) (5.47) (5.62) (5.49) (4.85)
6.00 5.41 5.05 5.44 5.64 5.31 5.35 4.72 4.83
Cl (5.88) (5.52) (5.06) (5.31) (5.82) (5.47) (5.62) (4.81) (5.23)
14.88 (14.91)
61.53 90.90 64.22 52.00 46.00 53.84 48.00 36.45 87.00
14.00(14.25) 21.32 (21.19) 26.90 (26.54)
HMI, hexamethlyeneimine.
Table 3 IR, 13C NMR, and Complex
195
3182 3165 3076 3170 3189 3180 3168 3180 3145 a b c d
a 13
IR (cm 1) n (N H)
1 2 3 4 5 6 7 8 9
Pt NMR spectroscopic data for platinum complexes
195
C (C O)
na(C O)
ns(C O)
1610 1644 1637 1655
1367 1374 1371 1380
1649
1382
n (Pt N)
n (Pt O)
525 518 560 578 553 536 565 545 530
448 465 466 445 440 471 457
n (Pt Cl)
Ligand
Pt
Complex
DC
327
332 341 320, 334
177.3 175.8 176.4 172.7
180.8 179.7 181.4 177.0
3.5 3.8 5.0 4.3
178.2
181.6
3.4
2267b 1666, 1623c 1802c 1821c 1872c 1890c 1069c 1245d 150d
See Figs. 1 and 2 for structures. Recorded in N ,N -dimethylformamide. Recorded in methanol. Recorded in acetone; DC d [complex]d [ligand].
The platinum coordination environment contains two adjacent corners occupied by the two nitrogen atoms of
Fig. 1. Structure of [PtII(HMI)2X]; HMI/hexamethyleneimine; X/ dichloro in complex 1; sulfato in complex 2; CBDCA, methylmalonato, oxalato, or tatronato in complexes 3 /6, respectively.
Fig. 2. Structure of [PtII(HMI)2(CBDCA)]×/H2O; X/chloro in complexes 7 /9; Y/OH in complex 7, acetato in complex 8, and chloro in complex 9.
the HMI ligand, whereas the remaining two cis positions are coordinated with two of the oxygen atoms of the CBDCA. All Pt /N and Pt /O bond lengths are in the range normally observed for platinum(II) com˚ is plexes. The average Pt /N bond length of 2.06(9) A consistent with the length of those found in other monodentate and bidentate amine ligand-containing ˚ in complexes. For instance, this length is 1.99(2) A II [Pt (1-methylhomopiperazine)(methylmalonato)] ×/2H2O ˚ in [PtII(hpip)(pentadecanoato)2] [25], [18], 2.02(10) A ˚ 2.038(8) A in [PtII(3-methylpiperidine)(malonato)] ×/H2O ˚ in [Pt(trans -l-1,2-DACH)(CBDCA)] ×/H2O [28], 2.03 A ˚ in [Pt(cis- 1,4-DACH)(CBDCA)] [30], [29], 2.043(2) A ˚ and 2.02 A in [Pt(cis- 1,4-DACH)(malonato)] [31]. ˚ is normal as The average Pt /O bond length of 2.02 A compared with the values observed in other Pt(II) ˚ in [Pt(trans -lcarboxylate complexes, e.g. 2.01(9) A ˚ in [PtII(11,2-DACH)(CBDCA)] ×/H2O [29], 2.02(2) A methylhomopiperazine)(methylmalonato)] ×/2H2O [18], ˚ in [Pt(3-methylpiperidine)2(malonato)] ×/H2O 2.014(7) A ˚ in [PtII(hpip)(pentadecanoato)2] [28], and 2.038(10) A [25].
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Fig. 3. ORTEP representation of the structure [PtII(HMI)2(CBDCA)]×/H2O with atom numbering scheme.
of
Table 4 ˚ ) and angles (8) for [PtII(HMI)2(CBDSelected bond lengths (A CA)]× H2O Bond lengths Pt(1) O(2) Pt(1) O(1) Pt(1) N(2) Pt(1) N(1) Pt(2) O(22) Pt(2) O(21) Pt(2) N(22A) Pt(2) N(21)
2.015(8) 2.033(9) 2.036(10) 2.067(8) 2.013(8) 2.028(8) 2.054(9) 2.059(10)
Bond angles O(2) Pt(1) O(1) O(2) Pt(1) N(2) O(1) Pt(1) N(2) O(2) Pt(1) N(1) O(1) Pt(1) N(1) N(2) Pt(1) N(1) C(18A) N(1) Pt(1) C(13A) N(1) Pt(1) C(5) O(1) Pt(1) C(6) O(2) Pt(1) C(7) N(2) Pt(1) C(12) N(2) Pt(1) O(22) Pt(2) O(21) O(22) Pt(2) N(22A) O(21) Pt(2) N(22A) O(22) Pt(2) N(21) O(21) Pt(2) N(21) N(22A) Pt(2) N(21) C(32) N(21) Pt(2) C(27) N(21) Pt(2) C(25) O(21) Pt(2) C(26) O(22)-Pt(2) C(38) N(22A) Pt(2) C(33A) N(22A) Pt(2)
89.9(3) 89.3(4) 178.8(4) 177.0(4) 87.8(4) 93.0(4) 109.3(8) 108.3(6) 119.2(8) 119.5(7) 111.7(7) 112.2(6) 88.3(3) 89.1(4) 177.1(4) 176.6(4) 89.6(4) 93.0(4) 110.8(8) 111.3(8) 119.3(7) 121.5(8) 109.7(8) 109.5(8)
The coordination structure of the platinum complex with two ring nitrogens of HMI is considerably strained.
The N(2) /Pt(1) /N(1) bond angle is expanded to an average value of 93.08 due to geometric constraints imposed by the ligand. These angles are close to the 98.8(4)8 reported for [Pt(cis- 1,4-DACH)(CBDCA)] [30] and the 100.0(2)8 reported for [Pt(cis- 1,4-DACH)(malonato)] [31]. The bond between HMI and the metal ion are also considerably strained as evidenced by the average C /N /Pt angle of 109.1(8)8. These angles are 112.1(9)8, 114.2(7)8, and 122.3(7)8 in [Pt(trans -l -1,2DACH)(CBDCA)] [29], [Pt(3methylpiperidine)2(malonato)] ×/H2O [28], and [Pt(cis1,4-DACH)(CBDCA)] [30], respectively. The expansion of the N(2) /Pt(1) /N(1) bond angle was compensated for by the contraction of the O(1) /Pt(1) /O(2) angle to 89.9(3)8 and the O(21) /Pt(2) /O(22) angle to 88.3(3)8. The molecules in the crystal show a system of N/H O hydrogen bonds (Fig. 4). The hydrogen bond interactions were examined using the program CRYSTALS [32]. The hydrogen bond lengths were found to range from ˚ , with the average N /H O interaction 2.039 to 2.413 A ˚ in length and possessing a bond angle of being 2.207 A approximately 158.38. In summary, we have synthesized and characterized a series of new platinum(II) and (IV) complexes containing HMI as nonleaving amine ligands and different groups as leaving ligands. The crystal structure of [PtII(HMI)2(CBDCA)] ×/H2O was determined by X-ray crystallography.
Fig. 4. Packing diagram of [PtII(HMI)2(CBDCA)]×/H2O Hydrogen bonds are shown by dashed lines.
M.S. Ali et al. / Polyhedron 21 (2002) 2659 /2665
4. Supplementary material Full lists of bond lengths and bond angles, atomic coordinates and equivalent isotropic displacement parameters, anisotropic displacement parameters, and hydrogen coordinates have been deposited at the Cambridge Crystallographic Data Centre (CCDC). Supporting information is available from The Director, CCDC, 12 Union Road, Cambridge, CB2 1EZ, UK (fax: /44-1223-336033; e-mail: [email protected] or www: http://www.ccdc.cam.ac.uk) on request, quoting the deposition number 181721. Any request to the CCDC for this material should quote the full literature citation.
Acknowledgements This work was supported by grants by CA-77332 and CA-82361 from National Cancer Institute, Robert A. Welch Foundation (C-0976), and the National Science Foundation (CHE9983352).
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