purine complexes of platinum: synthesis, nmr, and crystal and molecular structures of cis...

Purine complexes of platinum: synthesis, nmr, and crystal and molecular structures of cis-chloro(caffeine)bis(triethylphosphine)platinum(II) fluoroborate and cis-bis(isocaffeine)bis(triethylphosphine)platinum (11) fluoroborate

GORDON WILLIAM BUSHNELL, RODERICK JAMES DENSMORE, KEITH ROGER D I X O N , A N D ARTHUR CHARLES RALFS D e p c w t ~ n u ~ t of' Cht~r~zisrry. Urlir~er.sirv of Vic.rorrtr, Vic,ro~.rtr, B.C.. C(orcctkr V8W 2 Y2

Rcccivcd Scptcmbcr 24, 1982

GORDON WILLIAM BUSHNELL, RODERICK JAMES DENSMORE, KEITH ROGER DIXON, and ARTHUR CHARLES RALFS. Can. J. Chem. 61, I132 (1983).

Synthcsis and "P nmr spcctra of the complex cations, c.1.s-[PtCI(L)(PEtl),I', L = theophylline, caffcinc, or isocaffeine. and ( . is - l~t( isocaff)~(PEt~)~]" arc rcportcd. The crystal structure of cis-[PtCl(caffein~)(PEt~)~][BF,I is dctcrminctl, spacc group PT. o = 1.1766(6), b = 1.4428(5), t . = 0.9002(4) nm, a = 97.28(4)". P = 97.69(4)". y = 100.96(5)", D,, , = 1.649 g cm?. the bond lengths are Pt-CI = 233.4(4) pm. Pt-N = 215(l) pm, Pt-P = 225.4(5) pm (mean), and the rcsidual R = 0.071. The crystal structure of c~i~-[Pt(isocaffeine)~(PEt~)~I[BF,]~ is orthorhombic. spacc group Pbc,tr. tr = 2.317(3). b = 1.717(3), t. = 2.130(3) nm, D,,, = 1.574 g cm-'. with an opposing isocaffcinc conformation. bond lcngths Pt-N = 21 l(2) pm, Pt-P = 227.6(9) pm (mean), and R = 0.073. Both crystal structures contain approximately square planar Pt(1l) coordination with the purine coordinated via an imidazole nitrogen. The structures are discussed as models for the possible involvement of N7---O6 chelation of guanine to platinum when platinum drugs act as antitumour agents, but thcrc is no evidcnce that isocaffeine acts as an N7---0, chelate.

GORDON WILLIAM BUSHNELL, RODERICK JAMES DENSMORE, KEITH ROGER DIXON et ARTHUR CHARLES RALFS. Can. J . Chem. 61, 1 132 (1983).

On rapporte la synthhsc ct les spectrcs dc rmn du "P des cations complexes: [PtCI(L)(PEt,),]+ cis , L = thkophylline, cafeine ou isocafkine et [ ~ t ( i s o c a f ) ~ ( ~ ~ t ~ ) ~ ] " + cis. On a determink la structure du composk [PtCl(caft?inc)PEt,),IIBF,I. LC cristal appartient au groupe d'espace PT avec a = 1,1766(6), b = 1,4428(5), c = 0,9002(4) nm, a = 97,28(4)", P = 97,69(4)", y = 100,96(5)", D,,, = 1,649 g ~ m - ~ . Les longucurs de liaison sont de Pt-CI = 233,4(4) pm, Pt-N = 215(l) pm. Pt-P = 225,4(5) pm (moyenne) et la valcur convcntionnellc de R est de 0.071. La structure cristalline du compost? [Pt(isocafkine)z(PEtr)z]LBF,]z cis est orthorhombique et appartient au groupc d'espace Pbc~r avec n = 2,3 17(3), 1) = 1,7 17(3), t . = 2,130(3) nm, D,,, = 1,574 g cm-' avec une conformation isocafkine opposke. Les longucurs de liaison sont de Pt-N = 2 1 l(2) pm, Pt-P = 227,6(9) pm (moyenne) et R = 0,073. Dans chacunc des dcux structures cristallincs, on retrouve du Pt(ll) avec h e coordination approximativement plan carrCe avec la purinc coordonnCc au moyen de I'azotc de I'imidazolc. On discute des structures en tant que modele pour l'implication de la chklation N7---Oh de la guanine sur le platine lorsque les drogues contenant du platine agissent comme agents antitumkreux, mais il n'y a pas de prcuvc du fait que I'isocafkine agit comme un chklate N7---0,.

[Traduit par Ic journal]

Introduction The use of platinum complexes as anti-tumour drugs is now

well known and the subject has been extensively covered in recent reviews ( 1 -5). One such complex, c~s-[P~CI,(NH,)~], has passed into widespread clinical use (recent reports of the clinical status of the drug appear in a two-part issue (6)) but the design of more effective analogues, for example with greater solubility in body fluids and reduced toxicity, is hampered by the lack of detailed understanding of the mechanism of action of these drugs. It is widely accepted that the platinum becomes attached to DNA, most probably via coordination to the N7 position of a guanine base, but the details of the attachment and the mechanism of its effect on the cancer cell are unknown. Several different models have been proposed (5, 7) and an especially important point is to account for the activity of cis-[PtClz(NH3),] relative to the corresponding trans isomer which is essentially inactive. An early proposal (8- 12) which is still under discussion ( 5 , 7, 13) involves chelation of the platinum by the N7 and o6 atoms of a guanine base attached to DNA. Assuming that it is the chloride ligands which are displaced by base coordination, such chelation is possible only for cis-[PtCI,(NH,),] and not for the trans isomer (8- 12).

Studies on model complexes have shown that unsubstituted purines normally coordinate to metals via the imidazole nitrogen atom which is protonated in the free, neutral ligand, i.e.,

Caffeine' Isocaffeine' (I ,3,7-trimethylxanthine) (I ,3,9-trimethylxanthine)

Theophylline' Guanine'

N, for adenine, guanine, xanthine, and hypoxanthine and N7 for theophylline. However, when N, is blocked, as it would be by the deoxyribose residue in DNA bound guanosine, N7 is indeed the normal site of metal coordination (3).

Unfortunately no platinum purine complexes have provided

'For a discussion of nomenclature and numbcring of purincs. see ref. 36.

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BUSHNELL ET AL. 1133

TABLE I . Nuclear magnetic I.csonancc parameters for platinum-purine c o ~ n p l c x e s

"P spcctrum"

rrtrns to N/ ' t~.co~.s to CI" ' H spectrum"

6 6 Conlplcx ' J (P~-P) ' J (P~-P) 'J(P-P) S(Hn) 'J(Pt-H,)

"Chemical shifts in parts per niillion and couplin? constants in Hertz. Positive shifts are downfield from the references: LP(OCH,),] for "P and [Si(CH<),] for 'H.

"The assignment of thcsc resonances is discussed in the Results sections. ' CHIOH solution. "CH:CI: solution. 'CD2CI, solurion with CH,CI: lock. 'SO(CD,), solution with CH:CI: lock.

any structural evidence for metal interaction with O6 in addition to N,, although chelation has been suggested several times from spectroscopic evidence (8- 12). Indeed the only crystallographic demonstration of a direct 0,-metal interaction is in a copper complex of the theophyllinate anion and even here the bond is very weak, Cu-0 = 292 pm (14). More definite chelate interactions have been observed in 6-thio-purine complexes of both copper, Cu-S = 242 prn (15), and palladium, Pd-S = 23 1 pm (16).

We have chosen to study this problem by a structural comparison of platinum complexes of the caffeine and isocaffeine molecules. lsocaffeine is a close model for the guanine base with the same possibilities for N7-O6 chelation but with the other sites blocked by methylation. Caffeine is isomeric but the different methylation pattern limits coordination to N, where no possibility of oxygen chelation exists. At the same time the presence of the methyl group on N, in caffeine permits a direct comparison of the Pt-0 distance in the isocaffeine complex with the Pt-C(N,) distance in the caffeine complex. This comparison is expected to reveal any shortening of Pt-0, or other geometrical distortions caused by Pt-Oh bonding interactions.

Several crystallographic studies of transition metal caffeine complexes have been reported previously ( 17, 18). Structures of isocaffeine complexes are very few, but a recent paper ( 19) gives two crystal structures containing the ion [Pt(en)(isocaff),]" .

Results ( A ) Sjltzthesis cl17d spectroscopy

The bridge cleavage reaction represented by eq. [ I ] is a convenient route to complexes of the general type [PtC1(L)(PEt3)2][BF,1, and under controlled conditions usually leads to exclusively cis stereochemistry (20).

[ 11 [Pt2(1~,-C1),(PEt,),lLBF,12 + 2L + 2cis-[PtCI(L)(PEt,),][BF,]

Our preliminary results with a range of purines (L = guanine, hypoxanthine, adenine, and theophylline) indicated that crystals suitable for X-ray diffraction study were likely to be obtained only if L was highly substituted. Moreoever, "P nmr studies showed that complex mixtures, apparently involving coordination to several different nitrogen sites, resulted from reac- tions of unsubstituted purines. Even when L was theophylline several minor products were formed in addition to cis-

[PtCl(the~)(PEt,)~][BF,l which was identified as the main product by "P nmr (see Table 1). In view of these results we decided to focus our structural studies on the trimethylated purines, caffeine and isocaffeine.

Reaction of caffeine according to eq. [ I ] proceeded smooth- ly under mild conditions to yield cis-[PtCl(cafQ(PEt3),l[BF4] which was initially identified by microanalysis, and by infrared and nmr spectroscopy and finally by a full structure deter- mination as described below. The infrared spectrum showed the expected caffeine, triethylphosphine, and fluoroborate absorptions together with v(Pt-CI) at 290 cm-'. The "P nmr spectrum recorded at 24.3 MHz showed an AB quartet (SAB = 38.5 Hz) with 'J(P-P), 20 Hz, typical of a cis-P,Pt arrange- ment (21). Sidebands attributable to the 33.8% of molecules containing "'Pt were also observed and, as is expected in this type of spin system (22), the sideband patterns were not identical to the centre-band. The effective chemical shifts in- troduced by the different phosphorus coupling constants to platinum (SEFF = SAU 2 (1/2){'J(Pt-PA) - IJ(Pt-Pe))) result in a low-field sideband which is essentially an AX double doublet, and an up-field sideband which is an AB system so closely coupled that only a single line is observed. The spectra of cis-[PtCl(theo)(PEt,)21[BF4] and cis-[PtCl(isocaff)(PEt,)21- [BF,] which were identified only by nmr, were closely similar to that for the structurally characterised cis-[PtCl(cafQ(PEt,),]- [BF4] complex and nmr parameters for all these molecules are collected in Table I. The assignment of phosphorus resonances in this table is based on the assumption that the nmr trnus- influence of nitrogen ligands is generally greater than that of chloride and hence the phosphorus tra~zs to chloride will be the one with the larger 'J(Pt-P) value (23). In the present case where the platinum-phosphorus coupling constants are fairly closely similar, the assignment should be treated with caution. The 'H nmr of cis-[PtCl(caff)(PEt,)II[BF,l showed the expected caffeine and triethylphosphine resonances in the correct relative intensities and is mainly notable for the Iy5Pt sidebands observed on the caffeine Hx resonance. The coupling constant (,J(P~-H) = 11.7 Hz) is a typical value for a proton a to a coordinated nitrogen (24) and confirms that the platinum is attached in the imidazole ring.

The reaction of isocaffeine with [Pt2C12(PEt3)4.1[BF4], was slightly more complex. "P nmr of the initial crude products showed the presence of a small amount of cis-[PtC12(PEt,)l] (Sp - 130.7 ppm, 'J(Pt-P) 3509 Hz) together with two new compounds in an approximately 2: 1 ratio. The more intense new

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1134 CAN. J . CHEM. VOL. 61. 1983

FIG. I. Thc molecular structure of cis-lPt(PEtl)?(cafijCIIIBF,J.

FIG. 2. The molecular structure of ~is-[Pt(PEt~)~(isocaff)~][BF~]~.

spectrum was very similar to that described above for the caffeine complex and is assigned to cis-[PtCl(i~ocaff)(PEt,)~]' while the less intense spectrum was a singlet with "'Pt sidebands consistent with cis-[Pt(isocaff),(PEt,),]". An infrared spectrum of the mixture showed a v(Pt-CI) absorption at 275 cm-' . However, various attempts at recrystallization to obtain high quality product for further analytical and crystallographic study resulted only in crystals of cis-[Pt(isocaff),(PEt,)21[BF,I2 and we were unable to obtain pure cis-[PtCl(isocaff)(PEt3)21- [BF,]. Mother liquors from these crystallizations contained no cis-[Pt(is~caftj~(PEt~),]'~'. but only cis-[PtCl(i~ocaff)(PEt~)~]' together with a much increased quantity of c i ~ - [ P t C l ~ ( P E t ~ ) ~ ] .

eters (Tables S 12 and S 13), mean plane coefficients (Tables S5 and S9). and bond lengths ant1 angles of the BF, and PEt, groups (Tables S3, S4, S7, and S8) have been deposited for both structures.'

(i) cis-[P~C/(~L!~)(PE~~)~][BF,] The caffeine ligand is coordinated, as expected, through N,

and is inclined at 97-98' (depending on the plane chosen for the ligand) to the coordination plane defined by the PtCIP, unit. The platinurn aton1 is significantly displaced (41.0 pm) from the plane of the imidazole ring. Similar displacements are not uncommon (e.g. [PtCI,(caftj]-, 4.9 pm (18). cis-IPtCI- (naphthyridine)(PEtZ)ll ' , 14.3 pni (2.51, and [CuCI2(H20)- (caftjl, 3 1 pni ( 17)) but the present example seems unusually large. We have recently observed a similarly large displacement (34.8 pni) in a palladium pyrazole complex, cis- [PdCl(dimethyIpyraz~le)(PEt~)~I ' (26). These displacements lnay sinlply be the result of steric factors such as interaction between the five-membered rings and the cis-PEt, ligands, but could also be indicative of sorne rehybridisation of the coordinating nitrogen. All the caffeine ligands in the crystal are parallel by symmetry and it may be seen in Fig. 3 that there is an internlolecular caffeinelcaffeine contact halfway along the 6-axis.

The bond lengths and bond angles within the caffeine ligand are essentially identical within experimental error with those reported previously in the complexes, [CuCI,(H20)(caff)l ( 17) and [PtCl,(caff)l- (18), the conlparison with the latter being especially exact. The only slight discrepancy concerns the N7-C8-N,, angle in the imidazole ring, where the present value of 109" is close to that found in [H(caff)] ' (109.6") rather than to the more usual value of 112- 113" found in caffeine itself and in other N-bonded caffeine complexes (18). As in previous examples the caffeine shows significant departures from planarity, notably a slight dihedral angle (2.3") between the 5- and 6-membered rings.

Within the platinum coordination sphere, the Pt-N distance is longer, 215 pnl, in the present complex than in [PtC17(caftjl-, 202 pm (18), reflecting the greater tr-arzs influence of phosphorus relative to chlorine. On the basis of tr-at1.s-Pt-CI bond lengths, the tr-mls intluence of caffeine itself has been suggested to be similar to that of simple nitrogen donors (18) and this view is confirmed by the Pt-P bond length trurls to caffeine in the present complex. The value of 225.3 pm is very close to lengths observed tr-mls to phenanthroline (27), naphthyridine (25), and phthalazine (28) ligands. Indeed, as Table 10 shows, the geometry of the cis- PtCI(PEt,), fragment remains very constant in a range of complexes and the cis-PdCl(PEt3), fragment in cis- [PdCl(dimethyIpyraz~le)(PEt~)~] + is also similar (26). The con- formations of the triethylphosphine ligands are also the same in .all these complexes.

Evidently cis-[PtCI(i~ocaff)(PEt~)~] ' tends to disproportionate during crystallization and only the least soluble complex cis- (ii) cis-[Pt(is~cafl)flEt.~)~/[BFII. [ P t ( i s ~ c a f f ) ~ ( P E t ~ ) ~ J[BF,]: is obtained.

The two isocaffeine ligands are coordinated through N7 and are inclined at 88.2 and 87.9" to the coordination plane defined

(B) Descrip~iotz of str-uctures by the PtP2N2 unit. The isocaffeines are arranged so that their Both structures consist of discrete, essentially square planar 6-membered rings are away from each other, one above and

cations and fluoroborate anions. The structures of the cis- one below the coordination plane. As in the cis- [PtCl(~aff)(PEt,)~] ' and cis-[Pt(i~ocaff)~(PEt,)~]'+ cations are shown in Figs. I and 2 and the packing diagrams are given in he structure factor tables for both I and I1 are available, at a Figs. 3 and 4. Fractional atomic coordinates, bond lengths, nominal charge, from the Depository of Unpublished Data, CISTI, bond angles, and results of mean plane calculations are col- National Research Council of Canada, Ottawa, Ont., Canada K I A lected in Tables 2-9. Tables of anisotropic temperature param- 0S2.

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BUSHNELL ET I\L.

FIG. 3. Thc stcrcoscopic packing drawing for thc caffcinc complcx. I

FIG. 4. Thc stcrcoscopic packing drawing for thc isocaffcinc complcx. I1

[PtCl(caftj(PEt,),] ' structure the platinum atom is significantly displaced from the planes of the imidazole rings, by 22.6 pm from the more planar and by 44.7 pm from the less planar isocaffeine.

The bond lengths and bond angles in the isocaffeine ligands are generally similar within experimental error to those reported for the free ligand (29) but the puckering of the rings appears to be affected by coordination. One isocaffeine is fairly closely planar while the 5- and 6-membered rings in the other isocaffeine are inclined at -8.9" to each other, possibly because of steric interactions with a PEt, ligand. Both base ligands of the conlplex are involved in intern~olecular contacts with their planes parallel, as may be seen in Fig. 4. The hexafluorophosphate and nitrate salts of cis-[Pt(en)(isocaff),]" studied by Orbell et (11. (19) show structures similar to our isocaffeine conlplex in the general conformation of the cis- isocaffeine ligands and in departures of them from planarity, but differ in the baselbase dihedral angles 70.6" (nitrate), 87.3" (hexafluorophosphate), 65.4" (this work). Hydrogen bonding cannot occur in our complex as it does in the structures containing ethylenediamine.

Within the platinum coordination sphere the Pt-N(isocaff) distances reported by Orbell et 01. (19) are shorter than in cis-[~t(isocaff)?(PEt~),]'+ owing to the greater trans influence of PEt, over en, the mean values being 201.9(7) pm (19) and 21 1 ( l ) pm (this work). The latter value is still slightly shorter than the corresponding distance, 215(1) pm, in the caffeine complex. If this is a reflection of greater donor strength towards platinum then i t may explain the formation of the 2 : 1 complex in the isocaffeine/platinum case whereas we were able to ob-

tain only the I : I complex for caffeine. Finally, we note that the geometry of the Pt(PEt,), unit in cis-[Pt(isocaff),(PEt,),]'' is very similar to that in the conlplexes containing PtCI(PEt,), units (Table 10) and indeed the entire PtP,N, geometry is closely comparable with other complexes containing PtCINP, and PtCI,P, coordination spheres. The principal variable in these structures is the displacement of the coordinating nitrogen atom from the otherwise planar coordination geometry. In the phthalazine, naphthyridine, and phenanthroline complexes (Table lo), the displacement varies from 4 p n ~ in cis- [PtCl(phth)(PEt,),]+ to 37 pm in cis-[PtCI(phen)(PEt,),] b. It correlates with the rate of-metal shuttling between the two

L

ligand nitrogens and serves as an index of potentially bidentate character (28). However, this does not appear to be a useful concept in the present case since the displacement (23 pm) in the caffeine complex, where there is no possibility of a chelate interaction, is larger than the displacements (4- 15 and - 10 pm) in the isocaffeine complex.

Discussion As noted in the Introduction, a primary motivation for this

study was to seek evidence for or against the possibility of O6-N7 chelation in the isocaffeine complex. Two principal lines of evidence bear on this question.

Firstly, the Pt---O6 distances in cis-[Pt(isocaff),(PEt3),]" are 334 pm and 322 pm. Szalda, Kirstenmacher, and Marzilli ( 14) have collected data for several 6-oxopurine complexes of copper in which they consider there is no Cu---Oh interaction and the distances range from 328 to 383 pm. In contrast a complex with a weak Cu---O6 interaction has a distance of 292 pm (14).

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BUSHNELL ET AL

TABLE 4. Bond angles (deg) for c.i.~-[PtCl(caff)(PEt~)~][BF,I~ ( ( I ) Platinum coordination

Bonds Angle Bonds Angle

( b ) The caffcinc ligand

Bonds Angle Bonds Angle

TABLE 5. Mean plane results for c~is-[PtCl(~aff)(PEt~)~I[BF,]~'

Plane Description Number of atoms x2 I The heavy atoms ( Z = 15-78) 4 196 2 The 5-membered ring plus attached

C-methyl 6 10 3 The 6-membered ring plus its 4

peripheral atoms 10 3.9 4 The caffeine ligand less N( I ) 13 8.2

Perpendicular distances of atoms from the mean planes (pm)

Plane Atorn/distance list

I Pt, -0.15(5); Cl, 4.8(5); P(1). 0.4(4); P(2), 3 .34) ; N(I) , -23(1) 2 Pt, 40.96(5); C(3). -6(3); N(3). 6(1) 3 N(1)- -8(1); N(2), l(2); C( I ) , 2(2); Pt, 26.74(5) 4 Pt, 25.60t5); N(I), -10(1)

"Angles between planes: 1.2 = 97.3": 1,3 = 98.3": 1.4 = 98.0": 2.3 = 2.3": 2.4 = 2.2": 3.4 = 0.3".

x2 = 2 (Pf /u2(P , ) ) where P, = the perpendicular distance of atom i from the plane (atom

i belongs to the plane defining set of atoms).

C20H40BCIF,N402P2Pt: C 32. I , H 5.39, N 7.49%; found: C 32.0, H 5.42, N 7.58%.

(ii) cis-[P~CI(isocnff)(PEt.~)~][BF,] nr~d cis-[Pt(isocc~f)~(PEr,)Z]- [BFJIz

A solution of isocaffeine (0. I00 g. 0.515 mmol) in acetone (60 rnL) was added dropwise to a stirred solution of [Pt2CI2(PEtz),][BF4]~ (0.285 g, 0.257 rnmol) in acetone (15 mL) under a nitrogen atmo- sphere at 25OC. After stirring for 90 min, the solution was evaporated under reduced pressure to about 15 mL and diethyl ether slowly added to give a white precipitate (0.350 g). As detailed in the Results sec- tion, "P nrnr showed this precipitate to be an approximately 2: 1 mixture of cis-[PtCl(iso~aft)(PEt~)~][BF,J and cis-[Pt(i~ocaft)~- (PEt,)4[BF4II. Recrystallization by vapour diffusion of diethyl ether into a solution of the mixture in methanol resulted in colourless crystals, which were identified as cis-[Pt(iso~aff)~(PEt~)~][BF& by "P

nmr and then fully characterised by an X-ray diffraction study. Atrnl. calcd. for CzxHs11BZFxNu04P2Pt: C 33.9, H 5.07, N 11.3%; found: C 32.9, H 5.1 1, N 10.6%.

A "P nmr spectrum of the mother liquors from the recrystallization showed only c i ~ - [ P t C l ~ ( P E t ~ ) ~ ] and cis-[PtCl(i~ocaff)(PEt~)~][BF,].

(B) Cqstcrl rnensuremer~~.~ Crystals of cis-[PtCl(~aftj(PEt~)~l[BF,I (I) and (.is-[Pt(isocaffjz-

(PEt1)2][BF,]2 (11) were prepared as described above and examined by photographic methods,using CuK, radiation and Weissenberg and precession cameras. For I a primitive unit cell was chosen and then changed by use of the Delaunay reduction procedure. Both crystals were mounted approximately along the c-axis. The crystals were then transferred to a Picker 4-circle diffractometer automated with a PDP- I I computer and the orientation matrices were refined by least squares

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1138 CAN. J . CHEM. VOL. 61. 108.1

TABLE 6. Atomic parameters X 10' ( x 10' for Pt and P)" for cis- TABLE 7. Bond lengths (pm) for (,is-1Pt(isocaff),(PEt,),I[BF4lz" [Pt(isocaff),(PEt,),II BF& (11) Platinum coordination

Atom .v j' U,,<, ( p i l 1 2 ~ I0 -') Bond Length Bond Length

Pt 1250(1) 2168(1) 1576(l) - Pt-P(I ) 225.7(8) Pt-P(2) 229.4(9) p(1) 1745(4) 224 l(5) 2486(4) - Pt-N(3 1 ) 2 12(2) Pt-N(41) 2 1 O(2)

p(2) 1929(4) 1557(5) 965(4) -

"Estimated standard deviations are given in parentheses. Temperature factor = exp (-~T'u,,, , sin' €)/A2).

using pairs of centred reflections and MoK,, radiation. The unit cell of I was refined by least squares from 20 measurements in the range 26-45", and that of I1 was obtained photographically. Crystal data for I are as follows: C2oH4(1BCIF4N,OzPzPt mw = 747.90 Triclinic, space group PT (No. 2), a = 1.1766(6), b = 1.4428(5), c

( b ) Isocaffeine ligands

Bond Length Bond Length

N(3 I)-C(3 I ) 128(3) N(4 1 )-C(4 1 ) 138(3) C(3 I)-N(32) 135(3) C(4 1 )-N(42) 143(4) N(32)-C(32) 134(3) N(42)-C(42) 134(3) C(32)-N(33) 138(3) C(42)-N(43) 128(3) N(33)-C(33) 137(4) N(43)-C(43) 134(3) C(33)-N(34) 143(4) C(43)-N(44) 138(3) N(34)-C(34) 138(4) N(44)-C(44) 146(4) C(34)-C(35) 143(4) C(44)-C(45) 138(4) C(35)-N(3 I ) 141(3) C(45)-N(4 1 ) 134(3) C(35)-C(32) 135(4) C(45)-C(42) 145(4) N(32)-C(36) 145(4) N(42)-C(46) 157(4) N(33)-C(37) 154(4) N(43)-C(47) 164(4) C(33)-0(3 I ) 123(4) C(43)-0(4 I ) 125(3) N(34)-C(38) 1 56(4) N(44)-C(48) 154(4) C(34)-O(32) 121(3) C(44)-O(42) 127(3)

"Estimated standard deviations in parentheses.

= 0.9002(4) nm, cu = 97.28(4)". P = 97.69(4)", y = 100.96(5)". cell volume 1.469( 1) nm3, D,,, = 1.694 g cm-' (flotation), D , = 1.690 g c m - - 3 . z = 2 .

Crystal data for I1 are as follows:

CIHHSOBZFHNHOIP~P~ mw = 993.40 Orthorhombic, space group PDc(7 (NO. 61). o = 2.317(3). b = 1.717(3), c = 2.130(3) nm, cell volume 8.472(3) nm'. D,,, = 1.574 g cm-', D , = 1.557, Z = 8.

Intensity measurements were obtained for the hemisphere 11 2 0 up to 48" in 20 for I and up to 40' for 11. Stepped scans with 50 steps of 0.04" in 20 were used, counting for I s per step with a 25 s background count at each end. Each batch of 50 reflections was preceded by the measurement of three standard reflections (I: 4,O.O; 0.6.0; 0.0.4. 11: 16,0,0; 2,5,0; 0,O.lO). Thc Lorentz and polarisation factors were applied and each batch was scaled to maintain the sum of the standards constant. There was no marked decrease in the standard intensities during the measurements. An instrument instability constant of 0.020 was used to estimate u(1). Absorption corrections were applied using numerical integration over 8 X 8 X 8 Gaussian grids with absorption coefficients 52.78 cm-' (I) and 36.93 cm-' (11) for MoK,, radiation. The crystal shapes were defined by perpendicular distances to seven crystal faces froni central origins as follows: I , *(1,0.0) 0.181 nim, ?(O,I,O) 0.087 mm, (0,O.l) 0.279 mm, (0 . - ] , - I ) 0.104 mm, (0.1,- I) 0.145 mm; 11, *(1,0,0) 0,055 nim, ?(0,1,0) 0.105 mm, (0.0,- I ) 0.350 mm,' (0, I , 1 ) 0.267 mm, (0,- I , I ) 0.297 mm. The correction factors were in the ranges 0.16-0.43 (I) and 0.48-0.68 (11). The measurements were sorted and any duplicates averaged to give files containing 3749 (I) and 1893 (11) independent reflections.

( C ) Ctystc~l structure solution and refinement" A set of programmes supplied by Penfold (34) was manly used.

The programnies are based on ORFLS, ORFFE, ORTEP. and FORD- AP. Platinum coordinates were found from the Patterson function and lighter atoms were located by means of difference maps. The refinement was by the method of least squares minimising CIV(IF,( - IF,()'. The atomic scattering factors were corrected for dispersion (35).

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BUSHNELL ET AL

TABLE 8. Bond anglcs (deg) for ci.s-IPt(iso~aff)~(PEt~)~]IBF~]~ ( ( I ) Platinum coordination

Bonds Anglc Bonds Anglc

( b ) lsocaffcinc ligands

Bonds Angle Bonds Anplc

TABLE 9" ( ( I ) Mean plane rcsults for 1Pt(iso~aftj~(PEt~)ZI(BF,]~

Plane Description Atoms X ?

I Coordination plane Pt, P(I ) , P(2). N(31), N(41) 5 70.3

2 1st isocaffeine 14 36.4 3 2nd isocaffeine 14 252.0 4 5-ring and methyl substituent of

2nd isocaffeinc 6 6.1 5 6-ring of the 2nd isocaffeine 6 24.1

( b ) Perpendicular distances of atoms from the mean planes (pm)

Plane Atomldistance list

1 Pt, -0.03(11); P ( l ) , -0.9(8); P(2). 1.7(8); N(3l). - lO(2); N(41), 15(2)

2 0 (32) , -6(2); C(36), -8(3); Pt, -22.6(1) 3 N(4l), - 1 o(2); N(441, lO(2); C(45), - l4(3); C(46), 27(3);

(347). -24(3); C(48), 24(4); Pt, 19.0(1) 4 Pt, 44.7(1) 5 C(42), 7(3); C(4.5). -9(3); 0 (41) , -9(2); 0(42) , - 1 l(2);

C(47), - 14(3); C(48). 7(4)

( i ) cis-[PrCl(cnff)(PEt,b][BF,] The 35 non-hydrogen atoms werc treated anisotropically and the

refinement was done using altcrnatc cyclcs which refined thc hcavy atoms and the caffeinc ligands, then thc hcavy atoms. thc fluoroborate group, and thc triethylphosphine ligands. The weighting schcnic finally used was of thc form = [A + B.r + C.r2 + D.Y']-' wherc x = IF,,^, with valucsA = 57.82. B = -2.006. C = 4.793 X lo-', D = - I .04 X lo-". This gave approximately constant C\r1A2 as a function of IF,,(, thc summations being over subsets of reflections. At con- vergence the maximum changelerror ratio was 1.16. thc mean change/error ratio was 0.13, the largcr ratios bcing associated with the BF4 group. The final difference map gave no evidencc for any further atoms, the major peaks and troughs bcing closc to thc Pt atom. The final R-value was 0.07 1 and R,,. = ~ ( c ( I ~ A ' ) / c I ~ ~ F , , ) ) was 0.087. 2wA' = 822 for 3749 observations and 316 variables, hcnce ~ ( C ( W A ' ) / ( N O - NV) = 0.489.

( i i ) cis-[Pt(i~ocnfSj~(PEb)][B~]~ Both BF4 groups were subjected to the contraints B-F = 136 *

10 pm. F-F = 222 + 10 pm, which werc significant but did not totally dominate the X-ray intensities. Therc were 1893 X-ray observations and 228 parameters in the refinement. The weighting scheme was kv = 0 . 3 3 4 6 / ( ~ ( ~ ) ' + 0 . 0 1 6 6 ~ ' ) . Thc R-value was 0.0731 and H,, = d ( ~ . k v ~ ' / C w F , , ' ) ) = 0.1010. Thc rcfincment converged and the maximum (shiftlsigma) was 0.15 in the final cycle. The final difference map had a maximum of 2.3 x lo-" e pm-' closc to the

"Angles between planes 1.2 = 88.2"; 1 ,3 = 87.9"; 1,4 = 92.3":2,3 = 65.4": position of thc Pt atom; there were only 4 peaks above l .O x lo-" e 2.4 = 62.0"; 2.5 = 66.0"; 4.5 = 8.9". X' has been defined in Table 5. pm-' and these were unsuitable as positions of new atoms.

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1140 CAN. 1. CHEM VOL. 61. 1983

TABLE 10. Comparison of mctal coord~nat ion gcomctry

Dktancc (pni)

M = P t M = Pt M = P t M = P t M = P t M = P d Bond ~ " = ~ h ~ ~ " L=naphC L= phth" L=caff ' L=CI ' L = ~ ~ ~ \ ~ i , s - [ P t ( i s o c a f f j ~ ( ~ ~ t , ) ~ ] ~ + "

~ . ; S - [ M C I ( L ) ( P E ~ , ) , ] + ~ "' 'I

M = Pt M = P t M = P t M = P t M = Pt M = Pd Bonds ~ " = ~ h c n " L = n a p h t ~ = ~ h t h " L=caff ' L=CI1 L = D M P V c,is-[~t(isocaff)~(~~t,)~]~+ "

"phen = I . 10-phenanthroline: naph = 1 -8-naphthyridine; phth = phlhalazine: cuff = caffeine: DMP = 3,s-dimetliylpyrazole: isocaff = isocaffeine. "Reference 27. ' Reference 25. "Reference 28. "Present work. 'Lj. Manojlovic-Muir, K. W. Muir, and T. Solornun. Private co~umunication. 'Reference 26.

TABLE I I . Bond angles as a criterion of chelation in metal purine complcxcs X - - - - - - M

df l c b/f a x = o . s , ~ ~ c H . /Y'+N'\ Y = c or N

Anglcs (dcg)

Complex n b c r l e

Caffeine" [PtCl,(caff)]- " cis-[PtCl(caff)(PEt,)21+ I'

c i . s - [ ~ t ( i s o c a f f ) ~ ( ~ ~ t ~ ) ~ ] ~ + ' I . '

cis-[~t(en)(isocaff)~]~+ 'I.'

[Cu(thcophyllinato)(SME)]" [C~(NO,)(H~O)~(theophylline)~]+ ' [Cu(theophyllinato)(BDE)]' [CuC1,(6-thio-9-nicthy lpurine)]'' [Pd(6-thio-9-benzylpurine]""

"Reference 18. "Present work. ' Average values. "Reference 19. "Reference 3 1. SME = N-salicylidene-N'-methylethylenediamine. 'Reference 32. Only the parameters for the theophylline which is not involved in hydrogen bonding are shown 'Reference 14. BDE = N-3.4-Benzosalicylidene-N'.N'-dimethyl-ethylenediumine. "Reference 15. 'Rcfercnce 16.

Acknowledgements Kathy Beveridge for technical assistance, and Mr. B. Brandon We thank the Natural Sciences and Engineering Research for chemical contributions.

Council of Canada, and the University of Victoria for operating grants, Mr. Blaine Hawkins for illustrative photography, Mrs. 1. M . J . CLEARE. Coord. Chem. Rev. 12, 349 (1974).

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BUSHNELL ET AL. 1141

2. S . J . LIPPARD. Accts. Chcm. Rcs. 11. 21 1 (1978). 3. D. J. HODGSON. Prog. Inorg. Chcm. 23, 21 1 (1977). 4 . L. G. MARZILLI. Prog. Inorg. Chcrn. 23. 255 (1977). 5. T . G. SPIRO. Nucleic acid: mctal ion interactions. Wilcy. Ncw

York. 1980. 6. J . Clin. Hcn~atol. Oncol. 7 (1977). 7. R. FAGGIANI, C. J . L. LOCK. and B. LIPPERT. J. Am. Chcm. Soc.

102, 5418 (1980). and rcfercnccs thcrcin. 8. J . P. MACQUET and T. THEOPHANIDES. lnorg. Chim. Acta. 18.

189 (1976). 9 . M. M. MILLARD. J. P. MACQUET. and T. THEOPHANIDES. Bio-

chirn. Biophys. Acta. 402, 166 (1975). 10. J . P. MACQUET and T. THEOPHANIDES. Bio. Inorg. Chcm. 5. 59

( 1975). I I . D. M. L. GOODGAME. L. JEEVES. F. L. P I~ILLIPES, and A. C.

SKAPSKE. Biochim. Biophys. Acta. 378. 153 (1975). 12. J. DEHAND and J. JORDANOV. J . Chcnl. Soc. Chcm. Cornn~un.

598 ( 1976). 13. B. ROSENBERG. Papcr prescntcd at thc International Confcrencc

on thc Chemistry of thc Platinum Group Metals. Bristol, En- eland. July 1981.

14. b. J. SZALDA, T . J . KIRSTENMACHER, and L. G. MARZILLI. J . Am. Chcm. Soc. 98. 8371 (1976).

15. E. S L E T ~ E N and A. APELAND. Acta. Crystallogr. B31. 2019 ( 1975).

16. H. J . HEITNER and S. J . LIPPARD. Inorg. Chem. 13. 815 ( 1974). 17. G. BANDOLI, M. C. BIAGINI. D. A. CLEMENTE. and G. RIZZARDI.

Inorg. Chim. Acta, 20, 71 (1976). 18. R. E. CRAMER. D. M. HO. W. V A N DORNE. J. A. IBERS, T .

NORTON. and M. KASHIWAGI. Inorg. Chcrn. 20, 2457 (1981). and rcfcrences therein.

19. J. D. ORBELL, K. WILKOWSKI. B. DE CASTRO. L. G. MARZILLI, and T . J. KISTENMACHER. Inorg. Chcm. 21. 813 (1982).

20. K . R. DIXON, K. C. MOSS, and M. A. R. SMITH. Can. J. Chcrn. 52. 692 (1974). and rct'crcnccs thcrcin.

21. R. J. GOODFELLOW and B. F. TAYLOR. J. Chcnl. Soc. Dalton Trans. 1676 ( 1974).

22. K. R. DIXON and T. W. DINGLE. Inorg. Chcn~. 13. 846 (1974). 23. T . G. APPLETON. H. C. CLARK, and L. E. MANZER. Coord.

Chcm. Rcv. 10. 335 (1973). 24, K. R. DIXON. Inorg. Chcrn. 16, 2618 ( 1977). 25. G. W. BUSHNELL. K. R. DIXON. and M. A. KHAN. Can. J .

Chcm. 56. 450 (1978). 26. G. W . BUSHNELL. K. R. D I X ~ N . D. T. EADIE. and S. R. STO-

BART. Inorg. Chcrn. 20. 1545 (1981). 27. G. W. BUSHNELL, K. R. DIXON. and M. A. KHAN:^^^. J .

Chcm. 52. 1367 (1974). 28. G. W. BUSHNELL and K. R. DIxON. Can. J. Chcrn. 56. 878

(1978). 29. H. RASMUSSEN and E. SLETEN. Acta Chcm. Scand. 27. 2757

( 1973). 30. F. A. COTTON and G. WILKINSON. Advanccd inorganic chcrn-

istry. 2nd cd. Intcrscicncc. Ncw York. 1966. p. 115. 31. T. J. KIRSTENMACHER. D. J. SZALDA, and L. G. MARZILLI.

Inorg. Chern. 14, 1686 ( 1975). 32. B. L. KINDBERG, E. A. H. GRIFFITH. E. L. AMMA, and E. R.

JONES, JR. Cryst. Struct. Commun. 5. 533 (1976). 33. K. R. DIXON and D. J. HAWKE. Can. J. Chcm. 49. 3252 (1971). 34. B. R. PENFOLD. University of Cantcrbury crystallographic pro-

grams. Christchurch, Ncw Zealand. 35. International Tables for X-ray Crystallography. Vol IV. The

Kynoch Press, Birmingham, England. p. 71 (f-curves). and p. 148 (dispersion).

36. J. H. LISTER. 117 Thc chemistry of heterocyclic compounds - fused pyrimidines. Part 11. Purines. Edited!? A. Wcissberger arrd E. C. Taylor. Wiley, New York. 1971. pp. 4-7.

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purine complexes of platinum: synthesis, nmr, and crystal and molecular structures of cis...

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