Synthesis, characterization and cytotoxicity of some palladium(II), platinum(II), rhodium(I) and iridium(I) complexes of ferrocenylpyridine and related ligands. Crystal and molecular structure of trans-dichlorobis(3-ferrocenylpyridine)palladium(II)

Journal of Organometallic Chemistry 689 (2004) 1553–1568

www.elsevier.com/locate/jorganchem

Synthesis, characterization and cytotoxicity of some palladium(II),

platinum(II), rhodium(I) and iridium(I) complexes of

ferrocenylpyridine and related ligands. Crystal and molecular

structure of trans-dichlorobis(3-ferrocenylpyridine)palladium(II)

a

Jaisheila Rajput , John R. Moss , Alan T. Hutton , Denver T. Hendricks ,

a

b

Catherine E. Arendse , Christopher Imrie

c,

*

a

Department of Chemistry, University of Cape Town, Private Bag, Rondebosch, 7701, South Africa

Department of Medical Biochemistry, University of Cape Town, Private Bag, Rondebosch, 7701, South Africa

b

c

Department of Chemistry, University of Port Elizabeth, P.O. Box 1600, Port Elizabeth, 6000, South Africa

Received 13 November 2003; accepted 27 January 2004

Abstract

The preparation of a series of ferrocenyl nitrogen donor ligands including ferrocenylpyridines, ferrocenylphenylpyridines and

1,1⁰-di(2-pyridyl)ferrocene is described. Coordination studies of the substituted pyridines (L) were carried out with platinum, pal-

ladium, rhodium and iridium. This resulted in the preparation of the following types of complexes: [MCl(CO)₂(L)] and

[M(cod)(L)₂]ClO₄where M ¼ Rh or Ir, cod ¼ 1,5-cyclooctadiene; [M⁰Cl₂(L)₂] where M⁰¼ Pt or Pd. The X-ray crystal structure of

trans-dichlorobis(3-ferrocenylpyridine)palladium was obtained. The complexes were screened for activity against two human cancer

cell lines. At least two of the complexes displayed growth inhibition similar to that of the widely used chemotherapeutic agent,

cisplatin.

Keywords: Ferrocenylpyridines; Ferrocenylphenylpyridines; 1,1⁰-Di(2-pyridyl)ferrocene; Cytotoxicity; Platinum group metals

1. Introduction

anti-cancer drug tamoxifen, a ferrocenium tetraﬂou-

roborate salt containing two ferrocenyl groups and ﬁ-

nally a ferrocene complex based on the anti-cancer drug

cisplatin [7]. Reviewing the literature in connection with

the anti-cancer properties of ferrocenes, it becomes ap-

parent that there are conﬂicting conclusions with re-

gards to the important features that are required in the

molecules to provide anti-cancer properties. In most

cases, ferrocenium salts are reported to be more potent

than the neutral molecules [8]. This eﬀect could arise

from the solubility diﬀerence although recent evidence

by Osella et al. [9] suggests that the reduction of ferr-

ocenium ions in vivo generates active oxygen radicals

such as hydroxyl responsible for its anti-cancer activity

through the formation of radical metabolites that are

responsible for biological damage in the cancer cell.

Several metal complexes most notably those con-

taining platinum such as cisplatin have shown promise

in the treatment of various cancers [1]. Very recently, the

development and cytotoxicity of multinuclear platinum

complexes as anti-cancer drugs have been reviewed [2].

Several metallocenes, including complexes based on

ferrocene [3], titanocene [4], vanadocene [5] and niobo-

cene [6] have also been investigated for their potential

anti-cancer activity. Three of the ferrocene derivatives

that exhibit promising cytotoxic activity are shown in

Scheme 1 and include a neutral ferrocene based on the

^*Corresponding author. Fax: +27-41-504-2573.

E-mail address: chacci@upe.ac.za (C. Imrie).

doi:10.1016/j.jorganchem.2004.01.034

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J. Rajput et al. / Journal of Organometallic Chemistry 689 (2004) 1553–1568

Fe

OH

CH₂

NH

N

CH₃CH₂

Fe

Cl

BF₄

Pt

Fe

NH

OCH₂CH₂N(CH₃)₂

CH₂

Fe

Scheme 1. Ferrocene derivatives with encouraging cytotoxic properties.

In a study combining ferrocene and platinum group

metals, we report on the synthesis of metal complexes

formed between ferrocenylpyridine and related nitrogen

donor ligands and platinum, palladium, iridium and

rhodium centres. The full details on the synthesis of the

ferrocenylpyridine-type complexes of rhodium and

iridium will be provided in a future publication that will

report on their catalytic properties [10]. Cytotoxicity

studies were carried out on a selection of the palladium,

platinum, rhodium and iridium ferrocenylpyridine-type

complexes. The complexes were screened for activity

against oesophageal and cervical cancer cell lines.

Complexes that exhibited signiﬁcant activity in an initial

screening assay, and which were fully soluble in the

culture media, were further tested to determine their

IC₅₀values. These were compared to the IC₅₀value of

cisplatin, determined in the same way and for the same

cell line.

aryl halide. This type of cross-coupling reaction has

been reported to be particularly eﬀective under rela-

tively mild conditions, and oﬀers comparatively good

yields with respect to other synthetic methods [11]. The

synthetic route to 4-ferrocenylpyridine 2 is illustrated

in Scheme 2. A similar methodology was applied to

the preparation of other ferrocenylpyridine com-

pounds.

Bromoferrocene 1, was obtained by the bromination

of chloromercuriferrocene with N-bromosuccinimide

[12]. The synthesis of chloromercuriferrocene was

achieved through metallation of ferrocene with mer-

cury(II) acetate followed by addition of lithium chlo-

ride [13]. The metallation of ferrocene in this case

yields mono- and 1,1⁰-disubstituted chloromercurifer-

rocene, which were separated by Soxhlet extraction.

Unreacted ferrocene was removed by sublimation,

yielding chloromercuriferrocene as the unsublimed

portion which was recrystallised to give a ﬁne golden

powder. Ferrocenylmagnesium bromide was formed in

situ by gradual addition of 1,2-dibromoethane to

magnesium in solution with 1 in diethyl ether. Once

the Grignard reagent was generated, a mixture of the

halogenated pyridine, together with the nickel catalyst,

was added in diethyl ether. The reaction mixture was

heated under reﬂux generating the product 2 which

was puriﬁed by column chromatography. The product

was obtained as yellow ﬂakes in good yield and high

purity.

2. Results and discussion

2.1. Preparation of ligands

2.1.1. Monosubstituted ferrocenylpyridine ligands

The key step in the synthetic route used in the

preparation of monosubstituted ferrocenylpyridine li-

gands involved a nickel–phosphine catalysed cross-

coupling reaction between a Grignard reagent and an

Br

MgBr

N

Br

N

1,2-Dibromoethane

Et₂O

Mg

+

Fe

Ni cat., reflux 16 h

2

1

Ph₂P

Cl

PPh₂

Cl

Ni cat. =

Ni

cis-(1,3-bis(diphenylphosphino)propane)dichloronickel

Scheme 2. Synthesis of 4-ferrocenylpyridine via the Grignard reaction.

J. Rajput et al. / Journal of Organometallic Chemistry 689 (2004) 1553–1568

1555

Yellow flakes,73%

N

Br

Fe

2

N

Br

MgBr

N

Brown flakes,80%

N

Fe

3

N

Orange needles,65%

Br

N

Fe

4

Scheme 3. Preparation of ferrocenylpyridine ligands via a Grignard reaction.

Orange flakes, 33%

N

Br

N

Fe

5

Br

N

Orange-brown flakes, 39%

N

MgBr

Fe

6

N

Br

N

Orange crystals,38%

Fe

7

Scheme 4. Preparation of ferrocenylphenylpyridine ligands via a Grignard reaction.

Using this synthetic route, ligands 3–7 were prepared

(Schemes 3 and 4). Moving the position of the sub-

stituents on the pyridyl ring from the 4- to 3- and

2-positions was performed with the intention of varying

the number of bonds between the ferrocenyl substituent

and the nitrogen donor atom, and consequently ori-

entating the metals in the ligand-coordinated transition

metal complexes spatially closer together. These types

of complexes may allow electrochemical communica-

tion to occur through bond, as well as through space.

Compounds 3 and 4 were similarly obtained from

bromoferrocene and the appropriate halogenated pyri-

dine. Although the preparation of 3 has been achieved

previously by a diazonium reaction [14], the Grignard

reaction described here consistently gave a higher

yield.

appreciably lower. The exact reason for this is unclear

but may be related to the preparation of ferrocenyl-

phenylmagnesium bromide in situ. Although compound

5 has previously been prepared via a palladium-cataly-

sed cross-coupling reaction with an organozinc reagent

[15], the synthetic route described here represents a rel-

atively simple one-pot synthesis.

2.1.2. 1,1⁰-(2-Pyridyl)ferrocene ligand

Despite the fact that 1,1⁰-di(2-pyridyl)ferrocene 8 was

prepared over three decades ago [16], its coordination

behaviour has not been extensively investigated. Studies

have been limited to the preparation and X-ray crystal

structure analysis of novel rhodium and silver complexes

[17]. Recent work has seen the preparation of palladium

and platinum complexes of 8 [18]. The palladium com-

plex has been further studied in carbonyl insertion re-

actions. This type of disubstituted ferrocene oﬀers a

ligand with a relatively ﬂexible conformation and a large

The compounds 5, 6 and 7 were obtained using the

same synthetic route as for the preparation of 2, 3 and 4,

starting from 4-bromophenylferrocene. The yields were

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J. Rajput et al. / Journal of Organometallic Chemistry 689 (2004) 1553–1568

bite angle. Compound 8 was prepared by a palladium

catalysed cross-coupling reaction between a bis(chloro-

zinc)ferrocene and a bromopyridine. The dilithioferro-

cene–TMEDA complex was prepared in n-hexane and

this resulted in a higher conversion to the desired

dilithioferrocene than in the commonly used diethyl

were prepared using this synthetic route and were

obtained in good yield.

The pyridyl proton chemical shifts for all complexes

display downﬁeld shifts on complexation of the palla-

dium metal centre. The proton attached to the carbon

atom adjacent to the nitrogen atom showed the largest

shift on complexation of the palladium metal for com-

plex 14, contrary to the observed ferrocenyl shifts where

very little diﬀerence was observed between the free li-

gand and complex. Complexes 12 and 13 showed small

downﬁeld shifts for both a-H and b-H on complexation

to the palladium metal centre (Scheme 5). Complex 10

was the only complex that displayed upﬁeld shifts on

complexation while complex 14 showed no diﬀerence

between the free ligand and coordinated complex.

Cyclic voltammograms of the palladium complexes

were obtained in acetonitrile using tetrabutylammonium

perchlorate as the background electrolyte and a plati-

num disk as the working electrode (Table 1). The vol-

tammograms were recorded relative to ferrocene using a

scan rate of 100 mV s^ꢀ1and the same conditions

ðE₁₌₂¼ þ75:5 mV). A single ferrocenyl wave was ob-

served for all palladium complexes suggesting that no

electrochemical communication occurred between the

ferrocenyl groups of the complexes through the palla-

dium metal centre.

ether [16].

N

Fe

8

N

2.2. Preparation and properties of palladium complexes

The ligands investigated were soluble in dichlorome-

thane, whereas the palladium starting material was not.

The palladium complexes were prepared using a bi-

phasic system with the ligands in a dichloromethane

solution and the palladium starting material in an eth-

anol–water mixture. The reaction mixture was stirred

vigorously at room temperature to increase the interface

of reaction between the solvent layers. A phase-transfer

reaction was established between the layers, where the

palladium product was found to be either soluble in the

dichloromethane phase or formed as an insoluble pre-

cipitate. The reaction could be monitored as the palla-

dium layer was observed to lighten from dark brown to

colourless. The use of this synthetic route gave a sub-

stantial decrease in reaction time, with the longest re-

action time being 10 h; this constitutes a decrease of

more than half the reaction time when compared with

the previously reported method [19]. Complexes 10–14

With the exception of complex 14, all samples dis-

played a positive potential shift in E₁₌₂indicating that the

ferrocenyl group became harder to oxidise on coordi-

nation of the palladium centre. Complex 13 gave the

largest positive E₁₌₂value as well as the most signiﬁcant

shift on comparison of the free ligand 3 and complex.

Although the half-wave potential for complex 14 is

puzzling, it is consistent with its spectroscopic properties.

R

N

Cl

Pd

Fe

N

Cl

N

Cl

R

Pd

Cl

9 : R = H; yellow powder, 77%

N

Fe

10: R = Fc;red powder, 84%

11: R = Ph; light yellow powder, 83%

12: R = (C₆H₄)Fc; maroon-brown powder, 82%

13: Mustard microcrystals, 84%

N

Cl

Fe

Pd

Cl

Fe

N

14: Dark red microcrystals, 78%

J. Rajput et al. / Journal of Organometallic Chemistry 689 (2004) 1553–1568

1557

Scheme 5. Comparison of ¹H NMR chemical shifts (ppm) for complexes 10, 12, 13 and 14.

Table 1

Electrochemical data for ferrocenyl palladium complexes 10, 12, 13

and 14 in acetonitrile

and angles are listed in Table 2. The observed bond

lengths and angles around the palladium centre are

similar to those reported for complex 9 [20]. The dihe-

dral angle between the plane of the palladium centre and

a pyridyl ring is 131°. The cyclopentadienyl rings in the

ferrocenyl group are almost planar but tilt towards each

other by an angle of 3.1°. The rings are not completely

eclipsed and are observed to rotate by an angle of 5.7°.

The pyridyl ring rotates away from the attached cyclo-

pentadienyl ring by an angle of 12.5°. There are no

Complex Complex

number

Free ligand

E_pa(mV)

E_pc(mV)

E₁₌₂(mV)

10

12

13

14

+253

+176

+256

+136

+187

+107

+190

+32

+220

+142

+223

+84

+206

+134

+168

+155

2.2.1. Crystal structure analysis of trans-dichlorobis(3-

ferrocenylpyridine)palladium

Table 2

ꢀ

Selected bond lengths (A) and angles (°) for 13

The X-ray crystal structure of the palladium complex

13 was obtained using single crystals grown from a

mixture of dichloromethane and pentane. The complex

was observed to crystallise in the monoclinic space

group C2=c (Fig. 1).

The 3-ferrocenylpyridine ligands are equivalent from

a crystallographic point of view, indicating a completely

symmetrical structure. The X-ray analysis conﬁrms the

trans geometry of the complex. Selected bond lengths

Pd(1)–Cl(1)

Pd(1)–N(1)

N(1)–C(5)

N(1)–C(1)

C(5)–C(4)

C(1)–C(2)

C(2)–C(3)

C(3)–C(4)

C(4)–C(6)

2.305 (9)

2.022 (2)

1.343 (3)

1.347 (3)

1.390 (4)

1.380 (4)

1.384 (4)

1.392 (4)

1.464 (3)

N(1)–Pd(1)–N⁰(1)

Cl(1)–Pd(1)–N(1)

Pd(1)–N(1)–C(1)

180.0 (1)

89.8 (6)

122.0 (2)

119.0 (2)

15.7 (4)

12.5 (4)

Pd(1)–N(1)–C(5)

C(3)–C(4)–C(6)–C(7)

C(5)–C(4)–C(6)–C(10)

Fig. 1. Labelled perspective view of molecular structure for complex 13.

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J. Rajput et al. / Journal of Organometallic Chemistry 689 (2004) 1553–1568

signiﬁcant intermolecular contacts between the mole-

cules in the unit cell.

dimer was carried out in a low coordinating solvent with

solvation of the monosubstituted rhodium leading to the

formation of a monomeric species. This was followed by

addition of the ligand with the product formed by dis-

placement of the solvent molecule.

2.3. Preparation and properties of platinum complexes

Since the preparation of cisplatin, a signiﬁcant num-

ber of related platinum complexes have been synthesised

in a bid to discover further platinum complexes exhib-

iting similar or enhanced anti-cancer activity. Both the

cis and trans isomers of complex 15 have been prepared

and their anti-cancer activity investigated [21].

The rhodium cyclooctadienyl dimer, chloro(1,5-cy-

clooctadiene)rhodium(I) 22 was readily prepared by the

reaction of excess cyclooctadiene and rhodium trichlo-

ride trihydrate. Several nitrogen-donor ligands were

coordinated to the rhodium metal centre using by bridge

spliting of the rhodium cyclooctadienyl dimer followed

by addition of the ligand to give a series of complexes

23–28 (Scheme 7(b) and (c)).

The platinum complexes in this study, complexes 15–

19, were prepared using the synthetic route described in

Scheme 6. This methodology is the same as that de-

scribed for the synthesis of the palladium complex 9

where the product was formed as a precipitate over time.

The preparation of the ferrocenyl complexes 18 and 19

was repeated using the biphasic route devised for the

related palladium complexes. The biphasic route pro-

vided faster reaction times usually in the order of 5–10 h,

as opposed to 24 h using the former route. The com-

plexes were all obtained in good yield. Downﬁeld shifts

were observed for the pyridyl protons on complexation

of the platinum metal, for all complexes. No shifts were

observed in the ferrocenyl protons for complex 19 while

upﬁeld shifts were observed for complex 18.

Square planar rhodium(I) cationic complexes were

also prepared. Cationic rhodium complexes are well-

known primarily for their application in the ﬁeld of

catalysis [22]. The complexes examined in this study 29–

32 contain two pyridyl ligands and in the case of those

containing ferrocenylpyridyl ligands constitute the

preparation of trimetallic complexes. The cationic rho-

dium(I) complexes were prepared using the general

synthetic route described in Scheme 7(d). Silver per-

chlorate was added to a solution of the rhodium dimer

in acetone, yielding a solvated complex of general for-

mula [Rh(COD)(Me₂CO)_x]ClO₄. The addition of a ni-

trogen-donor ligand to this complex produced a cationic

complex by displacement of the solvent from the rho-

dium coordination sphere. Complexes were obtained in

good yield through concentration of the reaction mix-

ture followed by addition of solvents such as diethyl

ether or pentane to precipitate the product. The iridium

complexes 33 and 34 are the iridium equivalents of

complex 25 in which the H substituent is replaced by Ph

and Fc, respectively, and were prepared in the same

manner.

2.4. Preparation of rhodium and iridium complexes

An outline of the general synthetic methods used in

the preparation of a series of rhodium(I) complexes is

shown in Scheme 7. The full description of the syntheses

and spectroscopic properties of the rhodium and iridium

complexes will be published elsewhere along with a

study on their catalytic properties [10]. The rhodium(I)

carbonyl monosubstituted pyridyl coordination com-

plex in this study was prepared through a bridge-

splitting reaction of the rhodium carbonyl dimer 20. The

complex 21 was prepared using the synthetic route

shown in Scheme 7(a). A bridge-splitting reaction of the

2.5. Cytotoxicity

Initial screening of complexes for cytotoxic activity

was carried out by means of crystal violet staining of

Scheme 6. Synthesis of platinum complexes 15–19.

J. Rajput et al. / Journal of Organometallic Chemistry 689 (2004) 1553–1568

1559

N

Fe

N

OC

Cl

OC

CO

(a)

(b)

Rh

CH₂Cl₂, RT

Cl

20

21

N

R

23: R = Fc

Cl

N

R

Rh

24: R = (C₆H₄)Fc

Cl

22

R

25: R = H

26: R = Ph

Cl

R

N

Rh

(c)

(d)

27: R = (C₆H₄)Fc

28: R = (C=N)(C₆H₄)Fc

Cl

acetone

+

AgClO₄

[Rh(COD)(Me₂CO)_x]ClO₄

+

AgCl

R

N

2x

29: R = H

30: R = Fc

N

R

ClO₄

Rh

31: R = (C₆H₄)Fc

32: R = (C=N)(C₆H₄)Fc

Scheme 7. Preparation of rhodium complexes.

treated cells [23]. Complexes were tested at three diﬀer-

ent concentrations, and the results of the crystal violet

assays are presented as percentage of untreated cells (see

Table 3). In principle, an active compound would cause

a decrease in cell number (and hence absorbance) with

increasing drug concentration. Some complexes were

not completely soluble, which occasionally resulted in

an increased absorbance reading because the undis-

solved solid contributed to the absorbance. All cells

were carefully examined microscopically prior to stain-

ing to determine the presence of precipitates and also to

estimate cell density.

The next step involved determining the IC₅₀values of

those compounds that were readily soluble. This was

accomplished by treating cells with serial dilutions of

each complex of interest, then assessing for cell viability

with the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphe-

nyltetrazolium bromide] assay [24]. An IC₅₀value was

obtained, indicating the concentration of complex (in

lM) which resulted in a 50% decrease in the number of

cells. This approach allowed a direct comparison of

various metal centres and various substituents on the

activity of the synthesized complexes. The IC₅₀for

cisplatin was also determined so that the activity of the

complexes described here could be compared to this

widely used chemotherapeutic agent (see Table 4).

The use of platinum in anti-cancer drugs has been

well established and cisplatin is the most prominent

member of this class [25]. This drug is known to be 70–

90% eﬀective in cases of testicular cancer and is also

used in the treatment of ovarian cancer. At least two of

the complexes tested here displayed growth inhibitory

activities similar to that of cisplatin (15 and 20 lM for

complexes 23 and 32, respectively, compared to 13 lM

for cisplatin) (Table 4). This is of interest as these were

the only two complexes tested which have ferrocenyl

substituents, the other complexes with ferrocenyl-con-

taining ligands being too insoluble.

Although palladium complexes have generally been

found to be less biologically active than related platinum

complexes [26], we found that complex 9 (containing

trans ligands with a palladium centre) was approxi-

mately twofold more active than complex 15 (an iden-

tical complex with cis ligands and a platinum centre).

Systematic substitution or modiﬁcation of complex

25 allowed a functional comparison of an interesting

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J. Rajput et al. / Journal of Organometallic Chemistry 689 (2004) 1553–1568

Table 3

Cytotoxic activity as determined by crystal violet assay^a

Concentration (lg/ml)

WHCO1^b

1

ME180^b

1

Precipitate^c

10

50

10

50

1

10

50

Pd complexes

9

10

57

108

93

71

11

133

176

111

133

94

15

*

89

116

98

181

116

272

130

123

112

221

121

200

*

11

13

48

Pt complexes

15

107

61

80

31

67

41

51

57

113

67

62

21

67

26

24

47

16

18

*

103

131

Ir complexes

33

113

107

133

74

25

28

100

85

83

85

16

11

34

Rh complexes (one py ligand)

*

21

23

24

25

26

27

28

70

149

140

93

74

53

28

30

77

176

118

72

57

55

24

15

61

34

16

30

33

48

30

77

136

90

*

107

57

100

62

38

136

85

70

108

98

121

43

127

33

*

66

Rh complexes (two py ligands)

29

90

84

21

94

34

97

16

98

34

103

124

148

76

100

36

57

24

30

31

32

112

80

*

97

15

152

0

*

62

^aResults are expressed as [OD_{595 nm}(treated)/OD_{595 nm}(untreated)] ꢁ 100.

^bComplexes were screened against two cancer cells lines (WHCO1 – oesophageal and ME180 – cervical) at three concentrations (1, 10 and 50 lg/

ml).

^cAn asterisk indicates the presence of a precipitate at that concentration.

Table 4

IC₅₀values for soluble complexes against WHCO1 cells^a

a complex with growth inhibitory activity similar or

better than that displayed by cisplatin. In fact, the

crystal violet results for the cationic complex 30 indicate

that this complex is signiﬁcantly more active than

complex 23, even with a reduced solubility. It is clear

that relatively small structural changes to these com-

plexes result in signiﬁcant diﬀerences in cytotoxicity.

Although the rhodium complexes (21, 23–28) were

generally more active in vitro relative to the platinum

complexes (15, 16 and 18), it is diﬃcult at this stage

given our limited study to comment on this diﬀerence.

Complex

IC₅₀(lM)

9

15

33

78

23

25

15

253

33

26

29

147

19

32

33

59

13

cisplatin

^aValues were determined from a dose response curve (assayed with

MTT), and the IC₅₀is the concentration at which OD_{595 nm}is half that

of untreated cells.

3. Conclusion

series of complexes containing a rhodium centre. Add-

ing a phenyl substituent to the 4-position of the pyridyl

ligand in complex 25, generating complex 26, substan-

tially increased the growth inhibitory eﬀect (by a factor

of almost eight). Introducing a ferrocenyl substituent in

the 3-position generated complex 23, the most active

complex tested in this series (approximately 17 times

more active than complex 25). Preliminary evidence

suggests that replacing the chloride ligand in complex 23

with a second ferrocenyl pyridine ligand would result in

In this paper, a series of new multinuclear complexes

containing ferrocenyl groups and platinum group metals

were successfully prepared and characterized using an

array of analytical techniques. Some of the new com-

plexes were tested for cytotoxic activity and a compar-

ison was made to that of cisplatin. Several of the

complexes displayed signiﬁcant cytotoxic activity

against the cancer cell line WHCO1 and two of the

complexes particularly 23 and 32 displayed growth in-

hibitory activities similar to that of cisplatin. We are

J. Rajput et al. / Journal of Organometallic Chemistry 689 (2004) 1553–1568

1561

currently exploring approaches to increase the water

solubility of complexes such as 23, 26, 30 and 32 so that

the growth inhibitory activity of the complexes can be

determined more accurately, as well as investigating

the synthesis and activity of related organometallic

compounds.

Infrared spectra were recorded on a Perkin Elmer Par-

agon 1000 FT-IR spectrometer, with solid samples

prepared as potassium bromide disks and solution

samples in sodium chloride solution cells. Thermal

analyses were conducted on Perkin Elmer Thermo-

gravimetric analyser TGA7 and Diﬀerential Scanning

Calorimeter DSC7. NMR spectra were recorded on ei-

ther a Varian Unity-400 (¹H: 400 MHz; ¹³C: 100.6

MHz) or Varian Mercury-300 (¹H: 300 MHz; ¹³C: 75.5

4. Experimental

1

MHz) spectrometer at ambient temperatures. H NMR

4.1. Puriﬁcation and characterization of the materials

spectra were referenced internally using residual protons

in the deuterated solvent (CDCl₃: d 7.27; C₆D₆: d 7.24,

CD₃OD: d 5.84, CD₃COCD₃: d 2.09) and values re-

ported relative to tetramethylsilane (d 0.00). ¹³C NMR

spectra were similarly referenced internally to the sol-

vent resonance (CDCl₃: d 77.0; C₆D₆: d 128.1, CD₃OD:

d 49.1, CD₃COCD₃: d 30.60 and 205.87) with values

reported relative to tetramethylsilane (d 0.0). UV–Vis

spectra were recorded on a Hewlett–Packard 8452A

diode array spectrophotometer in a range of solvents.

Cyclic voltammograms were obtained on a BAS 100B

electrochemical analyser with a one compartment three-

electrode system consisting of a Ag/AgNO₃(0.01 M)

reference electrode, platinum wire auxiliary electrode

and platinum disc working electrode. Samples (1–2 mM)

were prepared and run at a scan rate of 100 mV s^ꢀ1

under argon at ambient temperature, in anhydrous

acetonitrile with tetrabutylammonium perchlorate (0.1

M) as background electrolyte. Solutions were saturated

with argon by bubbling for several minutes prior to each

run. The system gave ferrocene E₁₌₂¼ þ75:5 mV. The

platinum disc working electrode was polished between

runs as a standard protocol.

All manipulations, unless otherwise stated were car-

ried out under an inert atmosphere of nitrogen using

standard Schlenk techniques. Glass syringes were stored

at 60 °C and all other glassware thoroughly dried at 210

°C for at least four hours prior to use. For the most part,

reaction solvents were puriﬁed, dried and distilled prior

to use according to literature methods. Less commonly

used reagents and solvents such as N,N-dimethylfor-

mamide, pyridine and triethylamine were puriﬁed, dried,

and then stored under nitrogen in dry glass storage

vessels equipped with Teﬂon valve stopcocks. Chroma-

tography solvents were of analytical grade and used

without puriﬁcation, with the exception of dichlorome-

thane and hexane which were of chemically pure grade

and distilled in air prior to use. n-Butyllithium (1.6 M in

hexanes), Superhydride^â(1.0 M in tetrahydrofuran) and

N,N,N⁰,N⁰-tetramethylethylenediamine were purchased

from Sigma–Aldrich and transferred under nitrogen into

a glass storage vessel with a Teﬂon stopcock. All other

commercial reagents were used as obtained without

further puriﬁcation. Rhodium, iridium, platinum, and

palladium were obtained as chloride salts on loan from

Johnson–Matthey and ferrocene was obtained com-

mercially from Sigma–Aldrich. The rhodium complexes

20–32 used in this study were prepared and fully char-

acterized by us and this work will be published elsewhere

[10].

Thin layer chromatography was performed on alu-

minium backed silica gel or aluminium oxide 60 F₂₅₄

plates in a variety of solvent systems using the ascending

technique. Plates were analysed under ultraviolet light.

Column chromatography was conducted either on silica

gel 60, particle size 0.063–0.200 mm (70–230 mesh

ASTM) or neutral alumina, particle size 0.063–0.200

mm (70–230 mesh ASTM). Columns were generally

prepared with 1:100 ratio product to chromatographic

material. Melting points were determined on a Koﬂer

hotstage microscope (Reichart Thermovar). Micro-

analyses were obtained on a Carlo Erba EA 1108 ele-

mental analyser. Fast atom bombardment (FAB) and

high resolution (EI) mass spectra were recorded on a

VG-70SEQ mass spectrometer at the mass spectrometry

unit, Cape Technikon. In all cases the isotopic distri-

bution was checked against the theoretical distribution.

4.2. Cytotoxicity determinations

4.2.1. Cell culture

Cells were routinely maintained at 37 °C, 5% CO₂.

WHCO1 cells were cultured in DMEM supplemented

with 10% fetal calf serum, 100 U/ml penicillin and 100

lg/ml streptomycin. ME180 cells (ATCC #HTB-33)

were maintained in McCoy’s 5A supplemented with 10%

fetal calf serum, 100 U/ml penicillin and 100 lg/ml

streptomycin.

4.2.2. Crystal violet assay [23]

Initial screening for cytotoxicity was carried out by

plating cells at 1500 cells/well in 90 ll medium in Cell-

Star 96 well plates. After 24 h incubation to allow cell

settling, complexes were added in 10 ll medium to a

ﬁnal concentration of 1, 10 and 50 lg/ml, with solvent

(DMSO) at 0.2%. Following 48 h incubation, observa-

tions of cell number and morphology were made, and

the plates were then processed for staining.

Media were discarded, the plates allowed to drain,

and 100 ll absolute methanol applied to each well for 10

1562

J. Rajput et al. / Journal of Organometallic Chemistry 689 (2004) 1553–1568

min. Methanol was discarded and replaced with staining

solution (1% crystal violet, 50% methanol) for 20 min.

Plates were rinsed with water, and 100 ll water added to

each well for 1 h. The water was discarded and replaced

with a further 100 ll water. Plates were read at 595 nm

on an Anthos microplate reader 2001.

served with a small amount of unreacted magnesium. A

mixture of 4-bromopyridine (462.2 mg, 2.6 mmol) and

cis-(1,3-bis(diphenylphosphino)propane)dichloronickel

(16.7 mg, 31 lmol) in diethyl ether (10 ml) was added to

the freshly prepared Grignard reagent. The reaction

mixture was heated under reﬂux under nitrogen for 23 h,

changing to a deep red solution over time. Upon cooling

the reaction mixture, distilled water was added slowly to

destroy any active Grignard reagent remaining. The

two-layer reaction mixture was poured into a separating

funnel and the aqueous layer extracted repeatedly with

diethyl ether. The organic fractions were combined,

washed with brine, dried over anhydrous magnesium

sulfate and the solvent removed in vacuo yielding an

orange residue. The residue was puriﬁed by column

chromatography on silica gel. The product was eluted

with 5% methanol in diethyl ether and isolated as golden

yellow ﬂakes (450 mg, 73%), m.p. 137–139 °C (lit. 136–

138 °C [11]); IR (KBr cm^ꢀ1) 3104, 3069, 3033, 3047,

1612, 1569, 1478, 1436, 1348, 1105, 1093, 1033, 823, 486;

¹H NMR (300 MHz, CDCl₃): d 8.45 (2H, d, J ¼ 6:0 Hz,

C₅H₄N), 7.51 (2H, dd, J ¼ 6:3 Hz, C₅H₄N), 4.82 (2H, t,

J ¼ 1:8 Hz, C₅H₄), 4.61 (2H, t, J ¼ 1:9 Hz, C₅H₄), 4.08

(5H, s, C₅H₅); ¹³C NMR (75 MHz, CDCl₃): d 150.78

(C₅H₄N), 123.85 (C₅H₄N), 72.02 (C₅H₅), 70.46 (C₅H₄)

and 67.96 (C₅H₄).

4.2.3. MTT assay [24]

IC₅₀determinations were carried out using the MTT

kit from Roche (Cat #1465007), according to manu-

facturer’s instructions. Brieﬂy, 1500 cells were seeded

per well in 90 ll medium in Cellstar 96 well plates. Cells

were incubated for 24 h, then complexes were plated at a

range of concentrations in 10 ll medium, with a ﬁnal

concentration of 0.2% DMSO. After 48 h incubation,

observations were made, and 10 ll MTT solution was

added to each well. After a further 4 h incubation, 100 ll

solubilization solution was added to each well, and the

plates incubated again overnight. The following morn-

ing, plates were read at 595 nm on an Anthos microplate

reader 2001.

4.3. Preparation of ferrocenyl ligands

4.3.1. 4-Pyridylimine-4⁰-phenylferrocene

Pyridine-4-carboxaldehyde (0.12 g, 1.08 mmol) was

added to a solution of 4-ferrocenylaniline (0.20 g, 0.72

ꢀ

mmol) in methanol (20 ml) with 4 A molecular sieves (1

4.3.3. 3-Ferrocenylpyridine 3

g). The reaction mixture was heated under reﬂux over-

night. The reaction mixture was then ﬁltered and con-

centrated. The concentrate was cooled to 0 °C to

precipitate the product. The product was collected via

vacuum ﬁltration and obtained as maroon crystalline

ﬂakes (0.24 g, 90%), m.p. 195–196 °C; Anal. Calc. for

C₂₂H₁₈FeN₂: M^þ366.08194. Found: M^þ366.08140; IR

3-Ferrocenylpyridine was prepared according to the

general procedure described in Section 4.3.2. Magne-

sium (183.7 mg, 7.55 mmol), 4-bromoferrocene (500.0

mg, 1.89 mmol), 1,2-dibromoethane (702.0 mg, 0.32 ml,

3.74 mmol), 3-bromopyridine (194.0 mg, 0.12 ml, 1.23

mmol) and cis-(1,3-bis(diphenylphosphino)propane)di-

chloronickel (8.0 mg, 14.7 lmol) in diethyl ether (25 ml)

was heated under reﬂux for 19 h. The product was ob-

tained as large ﬂat brown crystals from dichlorome-

thane–hexane (258.0 mg, 80%), m.p. 60-62 °C (lit. 57-59

°C [27]); IR (KBr cm^ꢀ1) 3853, 3743, 1699, 1652, 1569,

1495, 1419, 1305, 1282, 1215, 1103, 1088, 1007, 887, 808,

702, 668, 523, 498, 404; ¹H NMR (400 MHz, CDCl₃): d

8.75 (1H, br s, C₅H₄N), 8.42 (1H, d, J ¼ 4:3 Hz,

C₅H₄N), 7.73 (1H, dd, J ¼ 8:0 Hz, C₅H₄N), 7.21 (1H,

dd, J ¼ 12:7 Hz, C₅H₄N), 4.67 (2H, t, J ¼ 1:8 Hz,

C₅H₄), 4.37 (2H, t, J ¼ 1:8 Hz, C₅H₄), 4.06 (5H, s,

C₅H₅); ¹³C NMR (101 MHz, CDCl₃): d 145.87

(C₅H₄N), 145.40 (C₅H₄N), 131.41 (C₅H₄N), 121.63

(C₅H₄N), 68.05 (C₅H₅), 67.85 (C₅H₄) and 64.87 (C₅H₄).

1

(KBr cm^ꢀ1) 3506, 1623, 1408, 1105, 846 and 823; H

NMR (400 MHz, CDCl₃): d 8.77 (2H, d, J ¼ 5:9 Hz,

C₅H₄N), 8.54 (1H, s, N@CH), 7.79 (2H, dd, J ¼ 5:9 Hz,

C₅H₄N), 7.55 (2H, dd, J ¼ 6:7 Hz, C₆H₄), 7.22 (2H, d,

J ¼ 8:5 Hz, C₆H₄), 4.68 (2H, t, J ¼ 1:8 Hz, C₅H₄), 4.36

(2H, t, J ¼ 1:8 Hz, C₅H₄), 4.06 (5H, s, C₅H₅); ¹³C NMR

(101 MHz, CDCl₃): d 156.71 (N@C), 150.80 (C₅H₄N),

148.61 (C₅H₄N), 143.26 (C₆H₄), 139.07 (C₅H₄N),

127.00 (C₅H₄N), 122.38 (C₅H₄N), 121.48 (C₆H₄), 69.88

(C₅H₅), 69.42 (C₅H₄) and 66.70 (C₅H₄); MS (EI)

m=z 366 (M^þ, 100%), 301 (8), 245 (9), 139 (8), 121 (8)

and 56 (3).

4.3.2. 4-Ferrocenylpyridine 2

Diethyl ether (5 ml) was added to previously dried

and weighed magnesium (396.0 mg, 16.0 mmol) in a

two-necked 50 ml round bottom ﬂask ﬁtted with a

condenser and dropping funnel. A solution of 1,2-dib-

romoethane (0.7 ml, 7.9 mmol) and bromoferrocene

(792.0 mg, 4.0 mmol) in diethyl ether (10 ml) was added

dropwise. On complete addition, two layers were ob-

4.3.4. 2-Ferrocenylpyridine 4

2-Ferrocenylpyridine was prepared by the general

procedure described in Section 4.3.2. Magnesium (220.6

mg, 9.06 mmol), bromoferrocene (600.9 mg, 2.26 mmol),

1,2-dibromoethane (840.0 mg, 0.39 ml, 4.48 mmol), 2-

bromopyridine (200.0 mg, 0.12 ml, 1.28 mmol) and cis-

(1,3-bis(diphenylphosphino)propane)dichloronickel (6.9

J. Rajput et al. / Journal of Organometallic Chemistry 689 (2004) 1553–1568

1563

mg, 12.8 lmol) in diethyl ether (27 ml) were heated

under reﬂux for 44.4 h. The product was obtained as

orange rod-like microcrystals from dichloromethane–

hexane (218.9 mg, 65%), m.p. 85–87 °C (lit. 87–89 °C

[28]); Anal. Calc. for C₁₅H₁₃FeN: M^þ263.1; Found: M^þ

263.0; IR (KBr cm^ꢀ1) 3608, 3565, 2324, 1843, 1767,

1698, 1622, 1587, 1558, 1495, 1423, 1275, 1106, 892, 824,

stroy any active Grignard reagent remaining. The two-

layer reaction mixture was poured into a separating

funnel and the aqueous layer extracted repeatedly with

diethyl ether. The organic fractions were combined,

washed with brine, dried over anhydrous magnesium

sulfate and the solvent removed in vacuo yielding an

orange residue, which was subjected to column chro-

matography on silica gel. The product was eluted with

5% methanol in diethyl ether and isolated as an orange

solid (156.0 mg, 39%), m.p. 144–147 °C; Anal. Calc. for

C₂₁H₁₇FeN: C, 74.3; H, 5.1; N, 4.1%; M^þ339.1. Found:

1

788, 741, 667, 518, 496, 441, 403; H NMR (300 MHz,

CDCl₃): d 8.49 (1H, br s, C₅H₄N), 7.57 (1H, d, C₅H₄N),

7.41 (1H, dd, J ¼ 7:8 Hz, C₅H₄N), 7.06 (1H, t, C₅H₄N),

4.92 (2H, t, J ¼ 1:8 Hz, C₅H₄), 4.39 (2H, t, J ¼ 1:8 Hz,

C₅H₄), 4.05 (5H, s, C₅H₅); ¹³C NMR (75 MHz, CDCl₃):

d 149.30 (C₅H₄N), 135.87 (C₅H₄N), 120.45 (C₅H₄N),

120.04 (C₅H₄N), 69.87 (C₅H₄), 69.56 (C₅H₅), 67.23

(C₅H₄); MS (FAB) m=z 264 (58%), 263 (M^þ, 100), 198

(M ) Cp, 39), 121 (Cp, 5), 56 (Fe, 6).

C, 74.44; H, 5.06; N, 3.79%; M^þ339.1; IR (KBr cm^ꢀ1

)

3083, 3022, 2913, 2329, 1645, 1609, 1542, 1498, 1436,

1401, 1105, 1087, 1000, 842, 809, 668, 498, 409; ¹H

NMR (400 MHz, CDCl₃): d 8.89 (1H, br s, C₅H₄N),

8.58 (1H, d, J ¼ 4:8 Hz, C₅H₄N), 7.89 (1H, dt, J ¼ 1:8

and 11.7 Hz, C₅H₄N), 7.58 (2H, d, J ¼ 8:4 Hz, C₆H₄),

7.52 (2H, d, J ¼ 8:8 Hz, C₆H₄), 7.36 (1H, dd, J ¼ 12:4

Hz, C₅H₄N), 4.69 (2H, t, J ¼ 1:8 Hz, C₅H₄), 4.36 (2H, t,

J ¼ 2:2 Hz, C₅H₄), 4.07 (5H, s, C₅H₅); ¹³C NMR (101

MHz, CDCl₃): d 148.16 (C₅H₄N), 139.98 (C₅H₄N),

133.81 (C₅H₄N), 126.96 (C₆H₄), 126.65 (C₆H₄), 123.51

(C₅H₄N), 69.61 (C₅H₅), 69.14 (C₅H₄), 66.51 (C₅H₄); MS

(EI) m=z 340 (24%), 339 (M^þ, 100), 218 (M^þ) Cp–Fe,

18), 189 (4), 169 (4), 121 (Cp–Fe, 31) and 56 (Fe, 15).

4.3.5. 4-Ferrocenylphenyl-4⁰-pyridine 5

4-Ferrocenylphenyl-4⁰-pyridine was prepared by the

general procedure described in Section 4.3.2. Magne-

sium (178.2 mg, 7.33 mmol), 4-bromophenylferrocene

(625.4 mg, 1.83 mmol), 1,2-dibromoethane (682.0 mg,

0.31 ml, 3.63 mmol), 4-bromopyridine (188.2 mg, 1.19

mmol) and cis-(1,3-bis(diphenylphosphino)propane)di-

chloronickel (7.8 mg, 14.3 lmol) in diethyl ether (36 ml)

were heated under reﬂux for 21.8 h. The product was

obtained as an orange powder (134.0 mg, 33%), m.p.

225-226 °C; IR (KBr cm^ꢀ1) 3085, 3023, 1645, 1610,

1545, 1500, 1435, 1401, 1105, 1087, 1000, 842, 810, 656,

4.3.7. 4-Ferrocenylphenyl-2⁰-pyridine 7

4-Ferrocenylphenyl-2⁰-pyridine was prepared by the

general procedure described in Section 4.3.2. Diethyl

ether (5 ml) was added to previously dried and weighed

magnesium (129.0 mg, 5.28 mmol) in a two-necked 50

ml round bottom ﬂask ﬁtted with a condenser and

dropping funnel. A solution of 1,2-dibromoethane

(490.0 mg, 0.24 ml, 2.61 mmol) and 4-bromophenylfer-

rocene (450.0 mg, 1.32 mmol) in diethyl ether (10 ml)

was added dropwise. On complete addition, two layers

were observed with a small amount of unreacted mag-

nesium. A mixture of 2-bromopyridine (136.0 mg, 82.0

ll, 0.86 mmol) and cis-(1,3-bis(diphenylphosphino)pro-

pane)dichloronickel (5.6 mg, 10.3 lmol) in diethyl ether

(16 ml) was added to the freshly prepared Grignard re-

agent. The reaction mixture was heated under reﬂux

under nitrogen for 20.1 h, changing to a bright orange-

red solution over time. Upon cooling the reaction mix-

ture, distilled water was added slowly to destroy any

active Grignard reagent remaining. The two-layer reac-

tion mixture was poured into a separating funnel and

the aqueous layer extracted repeatedly with diethyl

ether. The organic fractions were combined, washed

with brine, dried over anhydrous magnesium sulfate and

the solvent removed in vacuo yielding an orange residue,

which was subjected to column chromatography on

silica gel. The product was eluted with 5% methanol in

diethyl ether and isolated as a bright orange-red solid

(112.0 mg, 38%), m.p. 37–39 °C; Anal. Calc. for

C₂₁H₁₇FeN: C, 74.3; H, 5.0; N, 4.1%; M^þ339.1. Found:

1

498, 409; H NMR (400 MHz; CDCl₃): d 8.66 (2H, dd,

J ¼ 5:9 Hz, C₅H₄N), 7.59 (4H, s, C₆H₄), 7.54 (2H, dd,

J ¼ 6:1 Hz, C₅H₄N), 4.70 (2H, t, J ¼ 1:8 Hz, C₅H₄),

4.37 (2H, t, J ¼ 1:8 Hz, C₅H₄), 4.07 (5H, s, C₅H₅);¹³C

NMR (101 MHz, CDCl₃): d 150.45 (C₅H₄N), 127.09

(C₆H₄), 126.86 (C₆H₄), 121.35 (C₅H₄N), 66.83 (C₅H₄),

69.56 (C₅H₄), 69.92 (C₅H₅).

4.3.6. 4-Ferrocenylphenyl-3⁰-pyridine 6

4-Ferrocenylphenyl-3⁰-pyridine was prepared by the

general procedure described in Section 4.3.2. Diethyl

ether (5 ml) was added to previously dried and weighed

magnesium (179.4 mg, 7.38 mmol) in a two-necked 50

ml round bottom ﬂask ﬁtted with a condenser and

dropping funnel. A solution of 1,2-dibromoethane

(682.0 mg, 0.31 ml, 3.63 mmol) and 4-bromophenylfer-

rocene (625.3 mg, 1.83 mmol) in diethyl ether (10 ml)

was added dropwise. On complete addition, two layers

were observed with a small amount of unreacted mag-

nesium. A mixture of 3-bromopyridine (188.2 mg, 0.11

ml, 1.19 mmol) and cis-(1,3-bis(diphenylphosph-

ino)propane)dichloronickel (7.8 mg, 14.3 lmol) in di-

ethyl ether (15 ml) was added to the freshly prepared

Grignard reagent. The reaction mixture was heated

under reﬂux under nitrogen for 20.5 h, changing to a

bright orange solution over time. Upon cooling the re-

action mixture, distilled water was added slowly to de-

1564

J. Rajput et al. / Journal of Organometallic Chemistry 689 (2004) 1553–1568

C, 74.54; H, 5.25; N, 4.10%; M^þ339.1; IR (KBr cm^ꢀ1

)

131.90 (C₅H₄N), 128.39 (C₅H₄N), 120.30 (C₅H₄N),

71.48 (C₅H₄), 68.73 (C₅H₄).

1585, 1467, 1434, 1105, 818, 782, 492, 441, 418, 411, 404;

¹H NMR (400 MHz, CDCl₃): d 8.69 (1H, dd, J ¼ 4:8

Hz, C₅H₄N), 7.93 (2H, dd, J ¼ 8:4 Hz, C₆H₄), 7.74 (2H,

dd, J ¼ 6:2 Hz, C₅H₄N), 7.57 (2H, dd, J ¼ 8:8 Hz,

C₆H₄), 7.21 (1H, dd, J ¼ 6:6 Hz, C₅H₄N), 4.71 (2H, t,

J ¼ 1:8 Hz, C₅H₄), 4.35 (2H, t, J ¼ 2:2 Hz, C₅H₄), 4.05

(5H, s, C₅H₅); ¹³C NMR (101 MHz, CDCl₃): d 149.60

(C₅H₄N), 136.58 (C₅H₄N), 126.22 (C₆H₄), 126.77

(C₆H₄), 121.70 (C₅H₄N), 120.05 (C₅H₄N), 69.60

(C₅H₅), 69.12 (C₅H₄), 66.49 (C₅H₄); MS (FAB) m=z 340

(56%), 339 (M^þ, 100), 274 (M ) Cp, 5), 121 (Cp, 3), 56

(Fe, 3).

4.4. Palladium complexes

4.4.1. Dichlorobis(pyridine)palladium 9

The reaction mixture was observed to change from a

light brown solution to opaque yellow on addition of a

solution of pyridine (54.0 mg, 55.0 ll, 0.68 mmol) in

ethanol (5 ml) to a solution of sodium tetrachloropal-

ladate(II) (100.0 mg, 0.34 mmol) in (1:2) ethanol/water

(3 ml). The reaction mixture was further stirred at room

temperature for 24 h. A precipitate was observed during

this time. The product was collected via vacuum ﬁltra-

tion as a light yellow powder (88.1 mg, 77%); IR (KBr

4.3.8. 1,1⁰-Bis(2-pyridyl)ferrocene 8

1

cm^ꢀ1) 3629, 1636, 1604, 1474, 769, 668, 472; H NMR

n-Butyllithium (6.23 ml, 9.97 mmol, 1.6 M in hexanes)

was added slowly to a solution of N,N,N⁰,N⁰-tetra-

methylethylenediamine (1.16 g, 1.50 ml, 9.97 mmol) in

hexane (5 ml). The mixture was stirred under nitrogen

for at least 10 min at room temperature to allow butyl-

lithium–TMEDA to form. A solution of ferrocene

(0.743 g, 4.0 mmol) in hexane (35 ml) was added slowly

and the mixture further stirred at room temperature for

6 h. Hexane was then removed and the residue taken up

in tetrahydrofuran (30 ml) and cooled to 0 °C. A cold

solution of zinc chloride (1.09 g, 8.0 mmol) in tetrahy-

drofuran (20 ml) was added to the dark solution, which

was further stirred at room temperature for at least an

hour. Meanwhile Superhydride^â(0.40 ml, 0.40 mmol,

1 M in tetrahydrofuran) was added to a suspension of

dichlorobis(triphenylphosphine)palladium (0.140 g, 0.20

mmol) in tetrahydrofuran (10 ml), forming a dark so-

lution that was added via cannula to the ferrocene re-

action mixture. 2-Bromopyridine (1.58 g, 0.95 ml, 9.97

mmol) was added dropwise to the reaction mixture. An

aqueous solution of sodium hydroxide (25 ml, 2.5 M)

was added after 25 h. The two-layer reaction mixture

was poured into a separating funnel. The aqueous phase

was extracted repeatedly with dichloromethane. The

organic fractions were combined and dried over anhy-

drous magnesium sulfate. The solvent was removed in

vacuo and the residue further puriﬁed by column chro-

matography on alumina. Elution with diethyl ether

yielded a yellow band of 2-ferrocenylpyridine (575.5 mg,

55%). Elution with dichloromethane yielded an orange

band of the product. The product was obtained as a

pinkish-red powder (114.0 mg, 10%), m.p. 180–182 °C

(lit. 179–180 °C [16]); IR (KBr cm^ꢀ1) 3568, 2323, 1773,

1700, 1636, 1617, 1586, 1562, 1507, 1457, 1425, 1100,

1025, 984, 668, 420, 405; ¹H NMR (300 MHz, CDCl₃): d

8.35 (2H, d, J ¼ 5:3 Hz, C₅H₄N), 7.67 (2H, t, J ¼ 7:8

Hz, C₅H₄N), 7.50 (2H, dd, J ¼ 6:7 Hz, C₅H₄N), 7.08

(2H, dd, J ¼ 11:6 Hz, C₅H₄N), 4.91 (4H, t, J ¼ 1:8 Hz,

C₅H₄), 4.36 (4H, t, J ¼ 1:8 Hz, C₅H₄); ¹³C NMR (75

MHz, CDCl₃): d 156.97 (C₅H₄N), 136.51 (C₅H₄N),

(400 MHz, CDCl₃): d 8.84 (4H, dd, J ¼ 8:1 and 5.1 Hz,

C₅H₅N), 7.78 (2H, tt, J ¼ 7:7 Hz, C₅H₅N), 7.34 (4H, t,

J ¼ 7:7 Hz, C₅H₅N); ¹³C NMR (101 MHz, CDCl₃): d

153.65 (C₅H₅N), 138.96 (C₅H₅N), 124.95 (C₅H₅N).

4.4.2. Dichlorobis(4-phenylpyridine)palladium 11

A light yellow precipitate was observed to occur im-

mediately on addition of a solution of 4-phenylpyridine

(0.21 g, 1.36 mmol) in dichloromethane (5 ml) to a so-

lution of sodium tetrachloropalladate(II) (0.20 g, 0.68

mmol) in (1:2) ethanol/water (6 ml). The reaction mix-

ture was further stirred at room temperature for 6 h. The

product was collected as a light yellow powder by vac-

uum ﬁltration (0.27 g, 83%); Anal. Calc. for

C₂₂H₁₈Cl₂N₂Pd: C, 54.2; H, 3.7; N, 5.7%. Found: C,

54.52; H, 3.55; N, 5.58%; IR (KBr cm^ꢀ1) 3626, 1760,

1

1699, 1634, 1609, 1480, 667, 503, 431; H NMR (300

MHz, CDCl₃): d 8.69 (4H, d, J ¼ 5:8 Hz, C₅H₄N), 7.48

(4H, d, J ¼ 5:8 Hz, C₅H₄N), 7.32 (10H, m, C₆H₅).

4.4.3. Dichlorobis(4-ferrocenylpyridine)palladium 10

Dichlorobis(4-ferrocenylpyridine)palladium was pre-

pared according to the procedure described in Section

4.4.2. A red precipitate was observed to occur immedi-

ately on addition of a solution of 4-ferrocenylpyridine

(0.50 g, 1.9 mmol) in dichloromethane (5 ml) to a so-

lution of sodium tetrachloropalladate(II) (0.28 g, 0.95

mmol) in (1:2) ethanol–water (6 ml). The reaction mix-

ture was further stirred at room temperature for 8 h. The

product was collected as a red powder by vacuum ﬁl-

tration (0.56 g, 84%); m.p. 250–253 °C dec.; Anal. Calc.

for C₃₀H₂₆Cl₂Fe₂N₂Pd: C, 51.2; H, 3.7; N, 4.0%; M^þ

703.65268. Found: C, 50.76; H, 3.52; N, 4.02%; M^þ

703.92108; IR (KBr cm^ꢀ1) 3568, 1700, 1636, 1611, 1499,

1

1215, 1107, 1039, 825, 494; H NMR (CDCl₃): d 8.59

(4H, d, J ¼ 6:7 Hz, C₅H₄N), 7.30 (4H, br s, C₅H₄N),

4.72 (4H, s, C₅H₄), 4.52 (4H, s, C₅H₄), 4.07 (10H, s,

C₅H₅); MS (FAB) m=z 703.9 (M^þ, 28%), 667 (M ) Cl,

14), 613 (9), 482 (7), 460 (25), 371 (8), 329 (32), 307 (75),

289 (60), 263 (ligand, 77), 176 (58), 107 (70), 89 (86).

J. Rajput et al. / Journal of Organometallic Chemistry 689 (2004) 1553–1568

1565

4.4.4. Dichlorobis(3-ferrocenylpyridine)palladium 13

Dichlorobis(3-ferrocenylpyridine)palladium was pre-

pared according to the procedure described in Section

4.4.2. A yellow precipitate was observed to occur im-

mediately on addition of a solution of 3-ferrocenyl-

pyridine (0.30 g, 1.2 mmol) in dichloromethane (5 ml) to

a solution of sodium tetrachloropalladate(II) (0.17 g,

0.59 mmol) in (1:2) ethanol–water (6 ml). The reaction

mixture was further stirred at room temperature for 6 h.

The product was collected as a ﬁne mustard-yellow

crystalline powder by vacuum ﬁltration (0.35 g, 84%),

m.p. 148–150 °C dec.; Anal. Calc. for C₃₀H₂₆Cl₂

Fe₂N₂Pd requires C, 51.2; H, 3.7; N, 4.0%; M^þ

703.65268. Found: C, 50.86; H, 3.64; N, 3.92%; M^þ

703.92108; IR (KBr cm^ꢀ1) 3626, 1699, 1634, 1615, 1495,

1106, 815, 667, 498; ¹H NMR (300 MHz, CDCl₃): d 8.91

(2H, br s, C₅H₄N), 8.62 (2H, d, J ¼ 5:1 Hz, C₅H₄N),

7.75 (2H, d, J ¼ 6:9 Hz, C₅H₄N), 7.20 (2H, t, J ¼ 6:6

Hz, C₅H₄N), 4.73 (4H, br s, C₅H₄), 4.46 (2H, br s,

C₅H₄), 4.18 (10H, s, C₅H₅); ¹³C NMR (75 MHz,

CDCl₃): d 151.13 (C₅H₄N), 149.76 (C₅H₄N), 138.31

(C₅H₄N), 135.05 (C₅H₄N), 124.20 (C₅H₄N), 70.37

(C₅H₄), 70.28 (C₅H₅) and 67.16 (C₅H₄); MS (FAB) m=z

706 (55), 704 (M^þ, 74%), 702 (30), 669 (M ) Cl, 15),

633 (M ) Cl, 8), 581 (7), 511 (13), 371 (30), 369

(M ) ligand, 39), 263 (ligand, 100), 198 (29), 154 (38),

136 (37), 89 (11).

4.4.6. Dichlorobis(4-ferrocenylphenyl-4⁰-pyridine)palla-

dium 12

Dichlorobis(4-ferrocenylphenyl-4⁰-pyridine)palladium

was prepared according to the procedure described in

Section 4.4.2. 4-Ferrocenylphenyl-4⁰-pyridine (49.5 mg,

0.15 mmol) in dichloromethane (5 ml) was added to a

solution of sodium tetrachloropalladate(II) (21.5 mg,

0.07 mmol) in (1:2) ethanol/water (3 ml). The reaction

mixture was further stirred at room temperature for 8 h.

The product was collected as red-brown microcrystals

by vacuum ﬁltration (49.1 mg, 82%), m.p. 224–226 °C

dec.; Anal. Calc. for C₄₂H₃₄Cl₂Fe₂N₂Pd: C, 58.9; H, 4.0,

N, 3.3%; M^þ855.8. Found: C, 59.25; H, 4.38; N, 2.85%;

M^þ856.1; IR (KBr cm^ꢀ1) 3585, 1750, 1699, 1634, 1615,

1495, 1456, 818, 667, 406; ¹H NMR (300 MHz, CDCl₃):

d 8.84 (4H, d, J ¼ 4:1 Hz, C₅H₄N), 7.56 (8H, br s,

C₆H₄), 7.54 (4H, d, J ¼ 6:1 Hz, C₅H₄N), 4.72 (4H, t,

J ¼ 1:8 Hz, C₅H₄), 4.41 (4H, t, J ¼ 1:8 Hz, C₅H₄), 4.08

(10H, s, C₅H₅); ¹³C NMR (75 MHz, CDCl₃): d 153.10

(C₅H₄N), 127.04 (C₆H₄), 126.75 (C₆H₄), 122.03

(C₅H₄N), 69.72 (C₅H₄), 69.59 (C₅H₄), 66.67 (C₅H₅); MS

(FAB) m=z 856 (M^þ, 4%), 675 (13), 610 (4), 415 (24), 339

(ligand, 100), 278 (7), 149 (25), 85 (60).

4.5. Platinum complexes

4.5.1. Chloro(1,5-cyclooctadiene)(4-pyridylimine-4⁰-phe-

nylferrocene)platinum chloride

4.4.5. Dichlorobis(2-ferrocenylpyridine)palladium 14

Dichlorobis(2-ferrocenylpyridine)palladium was pre-

pared according to the procedure described in Section

4.4.2. A brown two-layer solution was observed on ad-

dition of a solution of 2-ferrocenylpyridine (0.50 g, 1.9

mmol) in dichloromethane (5 ml) to a solution of so-

dium tetrachloropalladate(II) (0.28 g, 0.95 mmol) in

(1:2) ethanol–water (6 ml). The reaction mixture was

further stirred at room temperature for 7.5 h. The two-

layer reaction mixture was separated and the organic

layer was concentrated. The product was precipitated on

addition of pentane and collected as dark red micro-

crystals by vacuum ﬁltration (0.52 g, 78%), m.p. 108–110

°C; Anal. Calc. for C₃₀H₂₆Cl₂Fe₂N₂Pd: C, 51.2; H, 3.7;

N, 4.0%; M^þ703.65268. Found: C, 51.56; H, 3.78; N,

4.07%; M^þ703.92108; IR (KBr cm^ꢀ1) 3626, 1760, 1703,

1634, 1605, 1495, 1435, 1106, 815, 667 and 408; ¹H

NMR (300 MHz, CDCl₃): d 9.25 (2H, d, J ¼ 12:8 Hz,

C₅H₄N), 8.56 (2H, br s, C₅H₄N), 7.47 (2H, d, J ¼ 7:7

Hz, C₅H₄N), 7.16 (2H, d, J ¼ 8:1 Hz, C₅H₄N), 4.92

(4H, t, J ¼ 1:8 Hz, C₅H₄), 4.39 (4H, t, J ¼ 1:8 Hz,

C₅H₄), 4.16 (10H, s, C₅H₅); ¹³C NMR (75 MHz;

CDCl₃): d 157.51 (C₅H₄N), 152.22 (C₅H₄N), 139.08

(C₅H₄N), 125.67 (C₅H₄N), 119.68 (C₅H₄N), 70.94

(C₅H₄), 70.12 (C₅H₄), 67.84 (C₅H₅); MS (FAB) m=z 704

(M^þ, 22%), 666 (M^þ) Cl, 3), 631 (M ) Cl, 17), 565 (5),

510 (4), 370 (18), 368 (M ) ligand, 19), 279 (35), 263

(ligand, 100), 198 (25), 154 (35), 136 (27), 89 (13).

4-Pyridylimine-4⁰-phenylferrocene (23.1 mg, 0.06

mmol) was added to a solution of dichloro(1,5-cyclo-

octadiene)platinum(II) (23.8 mg, 0.06 mmol) in pentane

(6 ml). The reaction mixture was stirred at room tem-

perature for 2 days after which a purple precipitate was

observed. The product was collected via vacuum ﬁltra-

tion as purple crystalline ﬂakes (18.3 mg, 39%), m.p.

200–202 °C; Anal. Calc. for C₃₀H₃₀Cl₂FeN₂Pt: C, 48.6;

H, 4.1; N, 3.8%; M^þ704.97134. Found: C, 48.76; H,

3.87; N, 3.39%; M^þ704.10948; IR (KBr cm^ꢀ1) 3503,

1685, 1624, 1577, 1473, 1406, 847, 668, 552, 418; ¹H

NMR (300 MHz, CDCl₃): d 8.74 (2H, d, J ¼ 5:9 Hz,

C₅H₄N), 8.52 (1H, s, N@CH), 7.76 (2H, dd, J ¼ 5:9 Hz,

C₅H₄N), 7.52 (2H, dd, J ¼ 8:6 Hz, C₆H₄), 7.22 (2H, d,

J ¼ 8:3 Hz, C₆H₄), 5.59 (4H, br s, COD–CH), 4.66 (2H,

t, J ¼ 1:8 Hz, C₅H₄), 4.34 (2H, t, J ¼ 1:8 Hz, C₅H₄),

4.04 (5H, s, C₅H₅), 2.72–2.67 (4H, m, COD–CH₂), 2.27–

2.23 (4H, d, J ¼ 8:3 Hz, COD–CH₂); ¹³C NMR (75

MHz, CDCl₃): d 153.71 (N@C), 150.85 (C₅H₄N), 148.54

(C₅H₄N), 143.24 (C₆H₄), 139.07 (C₅H₄N), 126.72

(C₅H₄N), 122.38 (C₅H₄N), 121.49 (C₆H₄), 69.89

(C₅H₅), 69.39 (C₅H₄), 66.69 (C₅H₄); MS (FAB) m=z 704

(M^þ, 1%), 519 (3), 460 (8), 410 (6), 366 (ligand, 68), 277

(95), 229 (20), 176 (24), 149 (25), 91 (37) and 77 (100).

4.5.2. Dichlorobis(pyridine)platinum 15

A solution of pyridine (95.0 mg, 0.10 ml, 1.20 mmol)

in ethanol (5 ml) was added slowly to a solution of

1566

J. Rajput et al. / Journal of Organometallic Chemistry 689 (2004) 1553–1568

potassium tetrachloroplatinate(II) (0.25 g, 0.60 mmol) in

(1:2) ethanol/water (6 ml). The reaction mixture was

further stirred at room temperature for at least 24 h. A

precipitate was observed to form during this time. The

product was collected as a white powder via vacuum

150.10 (C₅H₄N), 129.02 (C₆H₅), 123.84 (C₆H₅), 121.06

(C₆H₅), 120.78 (C₆H₅); MS (FAB) m=z 630 (M^þ, 10%),

558 (M ) 2Cl, 27), 469 (30), 375 (33), 195 (4), 183 (li-

gand, 100) and 77 (32).

ﬁltration (0.18 g, 72%), m.p. 227–229 °C; IR (KBr cm^ꢀ1

)

4.5.5. Dichlorobis(4-ferrocenylpyridine)platinum 18

Dichlorobis(4-ferrocenylpyridine)platinum was pre-

pared according to the general procedure described in

Section 4.5.2. A solution of 4-ferrocenylpyridine (15.4

mg, 0.06 mmol) in ethanol (2 ml) was added to a solu-

tion of potassium tetrachloroplatinate(II) (12.1 mg, 0.03

mmol) in (1:2) ethanol/water (2 ml). The reaction mix-

ture was stirred under nitrogen at room temperature for

24 h. A precipitate was observed to form during this

time. The product was collected via vacuum ﬁltration as

a pink-red powder (16.7 mg, 72%), m.p. 228–230 °C

dec.; Anal. Calc. for C₃₀H₂₆Cl₂Fe₂N₂Pt: C, 45.5; H, 3.3;

N, 3.5%; M^þ792.27. Found: C, 45.42; H, 3.54; N,

3.15%; M^þ793; IR (KBr cm^ꢀ1) 3629, 1701, 1696, 1653,

1617, 1521, 1437, 833, 501, 423, 416, 410, 406 and 403;

¹H NMR (300 MHz, CDCl₃): d 8.56 (4H, d, J ¼ 5:3 Hz,

C₅H₄N), 7.25 (4H, br s, C₅H₄N), 4.69 (4H, br s, C₅H₄),

4.51 (4H, br s, C₅H₄), 4.02 (10H, s, C₅H₅); ¹³C NMR

(CDCl₃): d 152.98 (C₅H₄N), 125.23 (C₅H₄N), 73.15

(C₅H₅), 70.64 (C₅H₄), 69.96 (C₅H₄); MS (FAB) m=z 793

(M^þ, 4%), 521 (96), 398 (12), 342 (20), 279 (52), 263 (4-

Fcpy, 24) and 223 (21).

3608, 3087, 3023, 2322, 2317, 1843, 1634, 1616, 1607,

1575, 1557, 1482, 1436, 1242, 1207, 1156, 1075, 790, 767,

697, 427, 410 and 404; H NMR (300 MHz, CDCl₃): d

8.76 (2H, d, C₅H₅N), 7.33 (2H, dd, C₅H₅N), 7.84 (1H, t,

C₅H₅N); ¹³C NMR (75 MHz, CDCl₃): d 152.90

(C₅H₅N), 126.31 (C₅H₅N), 138.52 (C₅H₅N).

1

4.5.3. Dichlorobis(4-phenylpyridine)platinum 16

Dichlorobis(4-phenylpyridine)platinum was prepared

according to the general procedure described in Section

4.5.2. A solution of 4-phenylpyridine (64.7 mg, 0.42

mmol) in ethanol (2 ml) was added to a solution of

potassium tetrachloroplatinate(II) (86.5 mg, 0.21 mmol)

in (1:2) ethanol/water (3 ml). The reaction mixture was

stirred under nitrogen at room temperature for 2 days.

A precipitate was observed to form during this time. The

product was collected via vacuum ﬁltration as a cream

powder (90.8 mg, 75%), m.p. 235 °C dec.; Anal. Calc.

for C₂₂H₁₈Cl₂N₂Pt: C, 45.8; H, 3.1; N, 4.9%. Found: C,

46.19; H, 3.26; N, 4.87%; IR (KBr cm^ꢀ1) 3565, 3055,

2349, 2322, 1662, 1616, 1575, 1505, 1498, 1447, 1393,

1292, 1076, 1014, 842, 729, 693, 562, 497, 441, 435, 416,

1

410, 404; H NMR (300 MHz, DMSO–d₆): d 8.61 (4H,

4.5.6. Dichlorobis(4-ferrocenylphenyl-4⁰-pyridine)plati-

num 19

d, J ¼ 5:8 Hz, C₅H₄N), 7.86 (8H, m, C₆H₅), 7.76 (2H, d,

J ¼ 8:0 Hz, C₆H₅), 7.66 (4H, d, J ¼ 5:8 Hz, C₅H₄N);

¹³C NMR (75 MHz, DMSO-d₆): d 149.89 (C₅H₄N),

129.09 (C₆H₅), 128.84 (C₆H₅), 126.99 (C₆H₅), 126.86

(C₅H₄N).

Dichlorobis(4-ferrocenylphenyl-4⁰-pyridine)platinum

was prepared according to the general procedure de-

scribed in Section 4.5.2. A solution of 4-ferrocenylphe-

nyl-4⁰-pyridine (50.0 mg, 0.15 mmol) in dichloromethane

(5 ml) was added to a solution of potassium tetrachlo-

roplatinate(II) (30.6 mg, 0.07 mmol) in (1:2) ethanol/

water (3 ml). The reaction mixture was stirred under

nitrogen at room temperature for 6 h. A two-layer re-

action mixture was obtained with a dark red organic

layer and colourless aqueous layer. The layers were

separated and the solvent removed in vacuo, yielding

dark red crystals (43.0 mg, 65%), m.p. 239–241 °C dec.;

Anal. Calc. for C₄₂H₃₄Cl₂Fe₂N₂Pt: C, 53.4; H, 3.6; N,

3.0%; M^þ944.38395. Found: C, 53.08; H, 3.64; N,

2.85%; M^þ944.04473; IR (KBr cm^ꢀ1) 1601, 1121, 1105,

4.5.4. Dichlorobis(4-phenylimine-4⁰-pyridine)platinum 17

Dichlorobis(4-phenylimine-4⁰-pyridine)platinum was

prepared according to the procedure described in Sec-

tion 4.5.2. A solution of 4-phenylimine-4⁰-pyridine (0.44

g, 2.4 mmol) in ethanol (10 ml) was added to a solution

of potassium tetrachloroplatinate(II) (0.50 g, 1.2 mmol)

in (1:2) ethanol/water (12 ml). The reaction mixture was

stirred under nitrogen at room temperature for 2 days.

A precipitate was observed to form during this time. The

product was collected via vacuum ﬁltration as a mus-

tard-yellow powder (0.53 g, 70%), m.p. 145–146 °C;

Anal. Calc. for C₂₄H₂₀Cl₂N₄Pt: C, 45.7; H, 3.2; N, 8.9%;

M^þ630.42326. Found: C, 45.69; H, 3.12; N, 8.62%; M^þ

630.07145; IR (KBr cm^ꢀ1) 3611, 3054, 2322, 1662, 1645,

1623, 1616, 1575, 1557, 1495, 1429, 1061, 832, 765, 692,

668, 552, 435, 420, 410, 403; ¹H NMR (300 MHz,

DMSO-d₆): d 9.04 (4H, d, J ¼ 6:6 Hz, C₅H₄N), 8.66

(2H, s, N@CH), 8.05 (4H, d, J ¼ 7:3 Hz, C₆H₅), 7.83

(4H, d, J ¼ 5:8 Hz, C₅H₄N), 7.44 (2H, dd, J ¼ 7:6 Hz,

C₆H₅), 7.36 (2H, t, C₆H₅); ¹³C NMR (75 MHz; DMSO-

d₆): d 156.95 (N@C), 153.70 (C₅H₄N), 152.12 (C₅H₄N),

1

1073, 1030, 1002, 887, 854, 815, 524, 504, 444, 425; H

NMR (300 MHz, CDCl₃): d 8.89 (4H, dd, J ¼ 5:9 Hz,

C₅H₄N), 7.62 (4H, dd, J ¼ 6:0 Hz, C₅H₄N), 7.54 (8H, s,

C₆H₄), 4.70 (4H, t, J ¼ 1:8 Hz, C₅H₄), 4.40 (4H, t,

J ¼ 1:8 Hz, C₅H₄), 4.07 (10H, s, C₅H₅); ¹³C NMR (75

MHz, CDCl₃): d 152.82 (C₅H₄N), 126.96 (C₆H₄), 126.80

(C₆H₄), 122.55 (C₅H₄N), 69.82 (C₅H₅), 69.62 (C₅H₄),

66.73 (C₅H₄); MS (FAB) m=z 944 (M^þ, 5%), 908 (M^þ-

Cl, 3), 871 (3), 675 (10), 610 (5), 533 (15), 415 (9), 340

(63), 339 (ligand, 100), 307 (14), 261 (6), 176 (12), 154

(51), 89 (34).

J. Rajput et al. / Journal of Organometallic Chemistry 689 (2004) 1553–1568

1567

€ €

[3] (a) P. Kopf-Maier, H. Kopf, E.W. Neuse, J. Cancer Res. Clin.

5. X-ray crystallography

Oncol. 108 (1984) 336;

(b) V. Scarcia, A. Furlani, B. Longato, B. Corain, G. Pilloni,

Inorg. Chim. Acta. 153 (1988) 67;

5.1. Structural analysis of 13

(c) D.T. Hill, G.R. Girard, F.L. McCabe, R.K. Johnson, P.D.

Stupik, J.H. Zhang, W.M. Reiﬀ, D.S. Eggleston, Inorg. Chem. 28

(1989) 3529;

X-ray diﬀraction data was collected at 173 K using

Nonius Kappa CCD with 1.5 kW graphite monochro-

mated Mo radiation. The strategy for data collection

was evaluated using ^COLLECT[29]. Several sets of data

were collected with both a 199° / scan and x scans to

collect cusp data. The data was scaled and reduced as

well as treated for absorption by a semi-empirical

method using ^DENZO-SMN [30]. Unit cell dimensions

were reﬁned on all data. The structure was solved and

reﬁned using ^SHELX97 [31]. Molecular graphics were

(d) N. Motohashi, R. Meyer, S.R. Gollapudi, K.R. Bhattiprolu,

J. Organomet. Chem. 398 (1990) 205;

(e) A. Houlton, R.M.G. Roberts, J. Silver, J. Organomet. Chem.

418 (1991) 107;

(f) L.V. Popova, V.N. Babin, Yu.A. Belousov, Yu.S. Nekrosov,

A.E. Snegireva, N.P. Borodina, G.M. Shaposhnikova, O.B.

Bychenko, P.M. Raevskii, N.B. Morozova, A.I. Ilyina, K.G.

Shithov, Appl. Organomet. Chem. 7 (1993) 85;

(g) S. Top, J. Tang, A. Vessieres, D. Carrez, C. Provot, G.

Jaouen, Chem. Commun. (1996) 995.

generated using ^ORTEP-III [32], PLATON [33] and

SEED [34], a graphical interface for the SHELX program.

Crystal data for 13: M_r

703.53 g mol^ꢀ1, size

X-

€

[4] (a) H. Kopf, P. Kopf-Maier, Angew. Chem. Int. Ed. Engl. 18

(1979) 477;

€

(b) P. Kopf-Maier, W. Wagner, B. Hesse, H. Kopf, Eur. J. Cancer

17 (1981) 665;

€

¼

0.10 ꢁ 0.10 ꢁ 0.04 mm, monoclinic, space group C2=c,

(c) P. Yang, M. Guo, Coord. Chem. Rev. 185 (1999) 189;

(d) M.A.D. McGowan, P.C. McGowan, Inorg. Chem. Commun.

(2000) 337.

ꢀ

a ¼ 34:606ð7Þ, b ¼ 5:674ð1Þ, c ¼ 13:126ð3Þ A, V ¼

3

ꢀ

2572:8ð9Þ A , T ¼ 203K, Z ¼ 4, l(Mo Ka) ¼ 2.036

mm^ꢀ1, 2950 independent reﬂections, R_int¼ 0:0000,

€

[5] (a) P. Kopf-Maier, H. Kopf, Z. Naturforsch. 34B (1979)

805;

(b) P. Kopf-Maier, W. Wagner, H. Kopf, Cancer Chemother.

R_1obs¼0:0270, R_2obs¼ 0:0537, R_1all¼ 0:0416, xR_2all

0:0641, goodness-of-ﬁt ¼ 0.822.

¼

€

Pharmacol. 5 (1981) 237.

€

[6] P. Kopf-Maier, M. Leiter, H. Kopf, J. Inorg. Nucl. Chem. 42

(1980) 1789.

[7] E.W. Neuse, M.G. Meirim, N.F. Blom, Organometallics 7 (1988)

2562.

6. Supplementary material

€

[8] P. Kopf-Maier, H. Kopf, E.W. Neuse, Angew. Chem. Int. Ed.

Crystallographic data for the structural analysis have

been deposited with the Cambridge Crystallographic

Data Centre, CCDC no. 204897 for compound 13.

Copies of this information may be obtained free of

charge from The Director, CCDC, 12 Union Road,

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Synthesis, characterization and cytotoxicity of some palladium(II), platinum(II), rhodium(I) and iridium(I) complexes of ferrocenylpyridine and related ligands. Crystal and molecular structure of trans-dichlorobis(3-ferrocenylpyridine)palladium(II)

DOI: 10.1016/j.jorganchem.2004.01.034

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