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Single crystals of the title complex, tris(1,6-di­hydro-9H-purine-6-thione-N7,S)­iron(II) tetra­chloro­ferrate(III) chloride, [Fe(C5H4N4S)3][FeCl4]Cl, were grown on the surface of solid 6-mercaptopurine monohydrate pellets in a solution of iron(III) chloride. The solution of the hexagonal structure required the application of twin refinement techniques. All the component ions lie on threefold rotation axes. The complex contains distorted octahedral [Fe(C5H4N4S)3]2+ cations with three N7/S6-chelating neutral 6-mercaptopurine ligands, tetrahedral [FeCl4]- anions with a mean Fe-Cl distance of 2.189 (1) Å, and free chloride ions.

Supporting information

cif

Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270100008118/sk1395sup1.cif
Contains datablocks I, global

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S0108270100008118/sk1395Isup2.hkl
Contains datablock I

CCDC reference: 150322

Comment top

6-mercaptopurine (6-MP), the synthetic thio analogue of the naturally occurring purine derivative hypoxanthine, is a clinical agent routinely administered for the therapy of human leukaemia. 6-MP is converted intracellularly to the corresponding ribonucleotide, which inhibits purine biosynthesis (Elion, 1989). Metal complexes of 6-MP and related drugs are of special interest in view of their possibly enhanced therapeutic effect with respect to the free base, which may also be a consequence of the protection of the molecule from enzymatic biological degradation by metal complexation. Metal complexes of drug molecules could, in addition, be used as slow-release drugs (Farrell, 1989). Preliminary investigations by UV spectroscopy of the enzymatic degradation of 6-MP in aqueous solutions by xanthine oxidase, supported by catalase, show a significant decrease of the decomposition reaction rate of 6-MP in the form of the title iron complex, (I), compared with the corresponding rate of the free ligand. \sch

A review of metal complexes of sulfur-containing purine derivatives has recently been given by Dubler (1996). It has been shown that, depending on the protonation status of the ligand and on the hardness or softness of the corresponding metal atom, 6-MP variously coordinates monodentately through S6, N7 or N3, by chelating through N7/S6 and/or by bridging two metal atoms through S6, S6/N7 or N1/N7. As part of a program elucidating the coordination properties of oxo- and thiopurines (Zhu et al., 1998), we present here the synthesis and structure of the title complex, (I).

There are three building units in the structure (Fig.1): octahedral [Fe(C5H4N4S)3]2+ cations with three N7/S6 chelating neutral 6-MP ligands, tetrahedral [FeCl4] anions and free chloride anions. The FeN3S3-octahedron is significantly distorted, with octahedral angles ranging from 83.39 (5) to 95.44 (5)°. The neutral 6-MP ligand is protonated at N1 and N9, but not at the coordinating N7 atom. A common feature of most coordinating purine bases is a slight non-planarity in the pseudoaromatic ring system. Small deviations from planarity occur also in Fe2(6-MP)3Cl5, where the maximum distances of an atom from the best plane through the nine purine ring atoms are −0.029 (2) for N9 and 0.025 (2) Å for N7. The `bite distance' S6···N7 of the chelating 6-MP ligand is 3.179 (2) Å, compared with the corresponding distance of 3.342 (1) Å for the non-coordinating molecule in 6-mercaptopurine monohydrate (Sletten et al., 1969). This fact is in agreement with the observation that the decrease of the bite distance is more pronounced the smaller the metal atom is. The distance may vary from about 3.32 Å in CdII-complexes to 3.04 Å in CuII complexes (Dubler & Gyr, 1988).

The [Fe(C5H4N4S)3]2+ cations are separated from each other by the [FeCl4] anions, and there is no evidence for stacking interactions between the purine planes. The mean Fe—Cl distance in the [FeIIICl4] anion is 2.189 (1) Å. This distance clearly indicates the FeIII oxidation state of the central atom, since for a tetrahedral [FeIICl4]2− anion the expected mean bonding distance is about 2.30 Å (query) (Pelizzi et al., 1977).

The [Fe(C5H4N4S)3]2+ cations and the free Cl anions are connected through a network of hydrogen bonds of the type N—H···Cl, where the Cl anion acts as a six-coordinated acceptor. In addition, weak interactions of the type C—H···S are observed (Table 2 and Fig. 2).

Experimental top

A solution of FeCl3·6H2O (270 mg, 1 mmol) in ethanol (20 ml) and 1 N HCl (1 ml) was overlaid on a solid pill of 6-MP·H2O and stored at a temperature of 333 K in a closed vessel. After 2 d red-brown hexagonal prismatic crystals of (I) suitable for X-ray analysis had grown on the surface of the pill. Crystals of the same composition were also synthesized by heating a solution of 6-MP·H2O (681 mg, 4 mmol) and FeCl3·6H2O (1081 mg, 4 mmol) in 1 N HCl (2 ml) and ethanol (100 ml). The reaction mixture was filtered and kept at a temperature of 333 K for crystallization. Within a few hours, a red-brown microcrystalline product, (I), could be separated from the solution.

Refinement top

The structure had been refined previously (ref?) with SHELX76 (Sheldrick, 1976) on Fo based on room-temperature measurements (three different crystals were used), with relatively bad R values of about 0.08. Improvement of refinement techniques (e.g. SHELXL97) and the possibility of user-friendly twin refinements with SHELXL97 (Sheldrick, 1997; Herbst-Irmer & Sheldrick, 1998) led us to remeasure one of the example crystals at 173 (1) K with an image-plate detector system (Stoe IPDS) in order to resolve this old problem structure. Repeating the refinement of the known model with the new data set showed the same result for R1 = 0.09, wR2 = 0.143, based on Fo2 using all unique reflections. Application of the twin matrix (010, 100, 00–1) led to a remarkable improvement of the final R values, as shown in the Experimental section; the twinning ratio was 0.286:0.714. The positions of the H atoms were determined from difference electron-density maps but they were finally calculated after each cycle of refinement using a riding model.

Computing details top

Data collection: IPDS (Stoe & Cie, 1999); cell refinement: IPDS; data reduction: X-RED in IPDS; program(s) used to solve structure: SHELXS97 (Sheldrick, 1990); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: PLATON (Spek, 1990) and PLUTON (Spek, 1991); software used to prepare material for publication: SHELXL97.

Figures top
[Figure 1] Fig. 1. The PLATON (Spek, 1990) displacement ellipsoid plot of (I) at the 50% probability level with the atom-numbering scheme. H atoms are drawn as small spheres of arbitrary radii.
[Figure 2] Fig. 2. The PLUTON (Spek, 1991) packing diagram for (I) showing the hydrogen-bonding interactions between the 6-MP ligands and the Cl ion.
tris(1,6-dihydro-9H-purine-6-thione-N7,S)iron(II) tetrachloroferrate(III) chloride top
Crystal data top
[Fe(C5H4N4S)3][FeCl4]ClDx = 1.820 Mg m3
Mr = 745.50Mo Kα radiation, λ = 0.71073 Å
Trigonal, P63Cell parameters from 7998 reflections
Hall symbol: P 6cθ = 3.6–30.4°
a = 10.3499 (6) ŵ = 1.82 mm1
c = 14.6652 (11) ÅT = 173 K
V = 1360.48 (15) Å3Prism, red-brown
Z = 20.28 × 0.25 × 0.24 mm
F(000) = 742
Data collection top
STOE IPDS
diffractometer
2717 independent reflections
Radiation source: fine-focus sealed tube2484 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.031
ϕ rotation scanθmax = 30.4°, θmin = 3.6°
Absorption correction: numerical
(Coppens et al., 1965)
h = 1214
Tmin = 0.630, Tmax = 0.669k = 1414
16156 measured reflectionsl = 2020
Refinement top
Refinement on F2Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: fullH-atom parameters constrained
R[F2 > 2σ(F2)] = 0.021 w = 1/[σ2(Fo2) + (0.01P)2]
where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.038(Δ/σ)max < 0.001
S = 1.10Δρmax = 0.26 e Å3
2717 reflectionsΔρmin = 0.24 e Å3
114 parametersExtinction correction: SHELXL97 (Sheldrick, 1997), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
1 restraintExtinction coefficient: 0.0107 (4)
Primary atom site location: structure-invariant direct methodsAbsolute structure: Flack (1983); 1306 Friedel pairs
Secondary atom site location: difference Fourier mapAbsolute structure parameter: 0.05 (2)
Crystal data top
[Fe(C5H4N4S)3][FeCl4]ClZ = 2
Mr = 745.50Mo Kα radiation
Trigonal, P63µ = 1.82 mm1
a = 10.3499 (6) ÅT = 173 K
c = 14.6652 (11) Å0.28 × 0.25 × 0.24 mm
V = 1360.48 (15) Å3
Data collection top
STOE IPDS
diffractometer
2717 independent reflections
Absorption correction: numerical
(Coppens et al., 1965)
2484 reflections with I > 2σ(I)
Tmin = 0.630, Tmax = 0.669Rint = 0.031
16156 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.021H-atom parameters constrained
wR(F2) = 0.038Δρmax = 0.26 e Å3
S = 1.10Δρmin = 0.24 e Å3
2717 reflectionsAbsolute structure: Flack (1983); 1306 Friedel pairs
114 parametersAbsolute structure parameter: 0.05 (2)
1 restraint
Special details top

Experimental. The crystal represents a twin with twin law (010, 100, 00–1), refined with the twin option of SHELXL97.

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 (Å2) top
xyzUiso*/Ueq
Fe22/31/30.40989 (4)0.02359 (12)
Cl12/31/30.16182 (5)0.01632 (15)
Cl22/31/30.55907 (7)0.0501 (3)
Cl30.43881 (8)0.25114 (9)0.36101 (5)0.0479 (2)
Fe1000.15255 (3)0.01517 (9)
S60.23600 (6)0.12766 (8)0.25433 (3)0.01852 (10)
N30.4658 (3)0.5425 (3)0.07443 (13)0.0312 (5)
N70.1220 (2)0.1982 (2)0.06987 (11)0.0177 (4)
C80.1196 (3)0.2637 (2)0.00670 (13)0.0200 (4)
H80.03900.22120.04870.024*
N10.4545 (2)0.4048 (2)0.20667 (13)0.0254 (4)
H10.50180.40510.25660.030*
C60.3192 (3)0.2824 (3)0.18914 (14)0.0177 (4)
N90.2433 (2)0.3970 (2)0.01909 (12)0.0221 (4)
H90.26270.45640.06630.026*
C50.2565 (2)0.2976 (3)0.10827 (14)0.0168 (5)
C40.3339 (3)0.4234 (3)0.05506 (15)0.0215 (5)
C20.5206 (3)0.5268 (3)0.1512 (2)0.0344 (6)
H20.61440.60710.16990.041*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
Fe20.02305 (17)0.02305 (17)0.0247 (2)0.01152 (8)00
Cl10.0183 (2)0.0183 (2)0.0123 (3)0.00916 (12)00
Cl20.0625 (5)0.0625 (5)0.0252 (4)0.0312 (2)00
Cl30.0291 (4)0.0554 (5)0.0562 (4)0.0188 (4)0.0125 (3)0.0111 (4)
Fe10.01680 (13)0.01680 (13)0.01192 (18)0.00840 (6)00
S60.0209 (2)0.0208 (3)0.01322 (16)0.0099 (3)0.0010 (2)0.0031 (3)
N30.0252 (13)0.0259 (13)0.0347 (10)0.0070 (9)0.0001 (12)0.0135 (12)
N70.0211 (11)0.0191 (9)0.0130 (7)0.0102 (8)0.0003 (7)0.0012 (7)
C80.0256 (14)0.0255 (12)0.0132 (7)0.0159 (11)0.0010 (10)0.0017 (8)
N10.0229 (11)0.0257 (12)0.0213 (8)0.0075 (10)0.0042 (8)0.0056 (9)
C60.0180 (11)0.0200 (11)0.0155 (9)0.0099 (10)0.0020 (9)0.0016 (8)
N90.0269 (10)0.0276 (11)0.0159 (7)0.0167 (9)0.0029 (8)0.0098 (9)
C50.0186 (11)0.0158 (11)0.0171 (10)0.0094 (9)0.0028 (8)0.0032 (8)
C40.0230 (11)0.0207 (12)0.0238 (10)0.0133 (11)0.0044 (10)0.0076 (9)
C20.0223 (14)0.0254 (16)0.0439 (11)0.0034 (12)0.0022 (13)0.0077 (13)
Geometric parameters (Å, º) top
Fe2—Cl22.1878 (11)N7—C81.318 (3)
Fe2—Cl3i2.1892 (7)N7—C51.371 (3)
Fe2—Cl3ii2.1892 (7)C8—N91.345 (3)
Fe2—Cl32.1892 (7)C8—H80.9500
Fe1—N7iii2.1638 (19)N1—C61.363 (3)
Fe1—N72.1638 (19)N1—C21.364 (3)
Fe1—N7iv2.1638 (19)N1—H10.8800
Fe1—S6iv2.5908 (6)C6—C51.398 (3)
Fe1—S62.5908 (6)N9—C41.371 (3)
Fe1—S6iii2.5909 (6)N9—H90.8800
S6—C61.686 (2)C5—C41.380 (3)
N3—C21.307 (3)C2—H20.9500
N3—C41.335 (4)
Cl2—Fe2—Cl3i109.11 (3)C8—N7—Fe1144.36 (17)
Cl2—Fe2—Cl3ii109.11 (3)C5—N7—Fe1111.92 (13)
Cl3i—Fe2—Cl3ii109.83 (2)N7—C8—N9112.9 (2)
Cl2—Fe2—Cl3109.11 (3)N7—C8—H8123.5
Cl3i—Fe2—Cl3109.83 (2)N9—C8—H8123.5
Cl3ii—Fe2—Cl3109.83 (2)C6—N1—C2123.7 (2)
N7iii—Fe1—N791.66 (7)C6—N1—H1118.2
N7iii—Fe1—N7iv91.66 (7)C2—N1—H1118.2
N7—Fe1—N7iv91.66 (7)N1—C6—C5112.0 (2)
N7iii—Fe1—S6iv171.45 (6)N1—C6—S6125.13 (17)
N7—Fe1—S6iv95.44 (5)C5—C6—S6122.85 (19)
N7iv—Fe1—S6iv83.39 (5)C8—N9—C4107.62 (18)
N7iii—Fe1—S695.44 (5)C8—N9—H9126.2
N7—Fe1—S683.39 (5)C4—N9—H9126.2
N7iv—Fe1—S6171.45 (6)N7—C5—C4111.59 (19)
S6iv—Fe1—S690.122 (19)N7—C5—C6128.2 (2)
N7iii—Fe1—S6iii83.39 (5)C4—C5—C6120.2 (2)
N7—Fe1—S6iii171.45 (6)N3—C4—N9129.4 (2)
N7iv—Fe1—S6iii95.44 (5)N3—C4—C5126.5 (2)
S6iv—Fe1—S6iii90.122 (19)N9—C4—C5104.1 (2)
S6—Fe1—S6iii90.123 (19)N3—C2—N1125.5 (2)
C6—S6—Fe193.51 (8)N3—C2—H2117.2
C2—N3—C4112.1 (2)N1—C2—H2117.2
C8—N7—C5103.72 (19)
N7iii—Fe1—S6—C693.98 (10)Fe1—S6—C6—C53.42 (18)
N7—Fe1—S6—C62.93 (9)N7—C8—N9—C40.9 (3)
N7iv—Fe1—S6—C652.0 (4)C8—N7—C5—C40.7 (3)
S6iv—Fe1—S6—C692.53 (8)Fe1—N7—C5—C4179.81 (15)
S6iii—Fe1—S6—C6177.34 (8)C8—N7—C5—C6177.7 (2)
N7iii—Fe1—N7—C880.6 (3)Fe1—N7—C5—C61.4 (3)
N7iv—Fe1—N7—C811.1 (3)N1—C6—C5—N7179.4 (2)
S6iv—Fe1—N7—C894.6 (3)S6—C6—C5—N72.0 (3)
S6—Fe1—N7—C8175.9 (3)N1—C6—C5—C42.4 (3)
S6iii—Fe1—N7—C8135.1 (3)S6—C6—C5—C4176.23 (19)
N7iii—Fe1—N7—C597.90 (18)C2—N3—C4—N9179.0 (3)
N7iv—Fe1—N7—C5170.39 (16)C2—N3—C4—C52.1 (4)
S6iv—Fe1—N7—C586.87 (15)C8—N9—C4—N3177.9 (3)
S6—Fe1—N7—C52.62 (14)C8—N9—C4—C51.3 (3)
S6iii—Fe1—N7—C543.5 (4)N7—C5—C4—N3177.9 (2)
C5—N7—C8—N90.1 (3)C6—C5—C4—N33.6 (4)
Fe1—N7—C8—N9178.45 (19)N7—C5—C4—N91.2 (3)
C2—N1—C6—C50.4 (3)C6—C5—C4—N9177.29 (19)
C2—N1—C6—S6178.2 (2)C4—N3—C2—N10.2 (4)
Fe1—S6—C6—N1178.1 (2)C6—N1—C2—N31.0 (5)
Symmetry codes: (i) y+1, xy, z; (ii) x+y+1, x+1, z; (iii) x+y, x, z; (iv) y, xy, z.
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H1···Cl1v0.882.483.273 (2)150
N9—H9···Cl1vi0.882.383.231 (2)164
C2—H2···S6vii0.952.783.693 (3)161
Symmetry codes: (v) xy1, x1, z+1/2; (vi) x1, y1, z; (vii) x+y1, x1, z.

Experimental details

Crystal data
Chemical formula[Fe(C5H4N4S)3][FeCl4]Cl
Mr745.50
Crystal system, space groupTrigonal, P63
Temperature (K)173
a, c (Å)10.3499 (6), 14.6652 (11)
V3)1360.48 (15)
Z2
Radiation typeMo Kα
µ (mm1)1.82
Crystal size (mm)0.28 × 0.25 × 0.24
Data collection
DiffractometerSTOE IPDS
diffractometer
Absorption correctionNumerical
(Coppens et al., 1965)
Tmin, Tmax0.630, 0.669
No. of measured, independent and
observed [I > 2σ(I)] reflections
16156, 2717, 2484
Rint0.031
(sin θ/λ)max1)0.711
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.021, 0.038, 1.10
No. of reflections2717
No. of parameters114
No. of restraints1
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)0.26, 0.24
Absolute structureFlack (1983); 1306 Friedel pairs
Absolute structure parameter0.05 (2)

Computer programs: IPDS (Stoe & Cie, 1999), X-RED in IPDS, SHELXS97 (Sheldrick, 1990), SHELXL97 (Sheldrick, 1997), PLATON (Spek, 1990) and PLUTON (Spek, 1991), SHELXL97.

Selected geometric parameters (Å, º) top
Fe2—Cl22.1878 (11)N7—C51.371 (3)
Fe2—Cl32.1892 (7)C8—N91.345 (3)
Fe1—N72.1638 (19)N1—C61.363 (3)
Fe1—S62.5908 (6)N1—C21.364 (3)
S6—C61.686 (2)C6—C51.398 (3)
N3—C21.307 (3)N9—C41.371 (3)
N3—C41.335 (4)C5—C41.380 (3)
N7—C81.318 (3)
Cl2—Fe2—Cl3109.11 (3)C6—N1—C2123.7 (2)
Cl3i—Fe2—Cl3109.83 (2)N1—C6—C5112.0 (2)
N7—Fe1—N7ii91.66 (7)N1—C6—S6125.13 (17)
N7—Fe1—S6ii95.44 (5)C5—C6—S6122.85 (19)
N7—Fe1—S683.39 (5)C8—N9—C4107.62 (18)
N7ii—Fe1—S6171.45 (6)N7—C5—C4111.59 (19)
S6ii—Fe1—S690.122 (19)N7—C5—C6128.2 (2)
C6—S6—Fe193.51 (8)C4—C5—C6120.2 (2)
C2—N3—C4112.1 (2)N3—C4—N9129.4 (2)
C8—N7—C5103.72 (19)N3—C4—C5126.5 (2)
C8—N7—Fe1144.36 (17)N9—C4—C5104.1 (2)
C5—N7—Fe1111.92 (13)N3—C2—N1125.5 (2)
N7—C8—N9112.9 (2)
Symmetry codes: (i) y+1, xy, z; (ii) y, xy, z.
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H1···Cl1iii0.8802.4823.273 (2)149.8
N9—H9···Cl1iv0.8802.3753.231 (2)164.2
C2—H2···S6v0.9502.7833.693 (3)160.7
Symmetry codes: (iii) xy1, x1, z+1/2; (iv) x1, y1, z; (v) x+y1, x1, z.
 

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