Synthesis of gold(I), silver(I) and copper(I) complexes containing substituted (2-aminophenyl)phosphines. Molecular structures of [AuI(2-H2NC6H4PPh2)], [AuI{(±)-2-H2NC6H4PMePh}]

Article abstract of DOI:10.1039/a702757e

Linear gold(I) complexes of type [AuI(L)] and [AuL₂]I (L = 2-H₂NC₆H₄PPhR, R = Me or Ph) have been prepared by the reaction of the appropriate ligand with [NBuⁿ₄][AuI₂] in ethanol

Full text of DOI:10.1039/a702757e

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Synthesis of gold(I), silver(I) and copper(I) complexes containing
substituted (2-aminophenyl)phosphines. Molecular structures of
[AuI(2-H2NC6H4PPh2)], [AuI{(±)-2-H2NC6H4PMePh}] and (±)-
[Cu(2-H2NC6H4PPh2)2]PF6
Peter Papathanasiou,a Geoffrey Salem,a Paul Waringb and Anthony C. Willisc
a
Chemistry Department, The Faculties, Australian National University, Canberra, A.C.T. 0200,
Australia
b John Curtin School of Medical Research, Australian National University, Canberra, A.C.T. 0200,
Australia
c Research School of Chemistry, Australian National University, Canberra, A.C.T. 0200, Australia
Linear gold() complexes of type [AuI(L)] and [AuL2]I (L = 2-H2NC6H4PPhR, R = Me or Ph) have been prepared
by the reaction of the appropriate ligand with [NBun ][AuI2] in ethanol. The neutral ligand L is co-ordinated to
4
the metal centre via the phosphorus donor atom. The structures of the complexes [AuI(2-H2NC6H4PPh2)]
and [AuI{(±)-2-H2NC6H4PMePh}] have been confirmed by X-ray analyses with the latter, but not the former,
complex exhibiting auriophilicity. Metathesis of these compounds with NH4PF6 gave the corresponding
hexafluorophosphate salts [AuLn]PF6 (n = 1 or 2). Tetrahedral complexes of the type [MLn]PF6 (L = 2-
H2NC6H4PPhR; R = Ph, M = Ag or Cu, n = 2 or 3; R = Me, M = Cu, n = 2 or 3; R = Me, M = Ag, n = 3) have also
been prepared via reaction of the appropriate ligand with [Cu(NCMe)4]PF6 in acetonitrile or AgNO3 in ethanol
followed by metathesis with NH4PF6. The molecular structure of (±)-[Cu(2-H2NC6H4PPh2)2]PF6 has been
confirmed by X-ray crystallography. All of the complexes have been shown by NMR spectroscopy to undergo
facile ligand-exchange reactions in solution. These complexes are seen as potential anticancer agents. Preliminary
biological studies have shown them to be active against three mouse tumour cell lines in vitro with cytotoxicities of
certain of these complexes being comparable to that of cis-diamminedichloroplatinum(), cisplatin, and bis[1,2-
bis(diphenylphosphino)ethane]gold() iodide.
The coinage metals of Group 11 readily form bis(bidentate)
complexes with di(tertiary phosphines) in which the univalent
metal centre has a tetrahedral stereochemistry. Complexes of
this type containing the dissymmetric di(tertiary phosphine)
(R*,R*)-1,2-bis(methylphenylphosphino)benzene were found to
undergo intermolecular ligand-redistribution reactions in solu-
tion, the rate of exchange increasing in the order gold() <
copper() < silver().1,2 In the case of gold() these reactions were
slow enough to allow the separation by fractional crystal-
lisation of racemic and meso complexes. Furthermore, the
stereogenic metal centre in related tetrahedral complexes con-
taining the (R*,S*) form of C6H4(PMePh)2-1,2 underwent
facile inversion, the low barriers to inversion precluding reso-
lution of the complexes. Similar results have been reported
for related tetrahedral complexes containing symmetrical di-
(tertiary phosphines) such as 1,2-bis(diphenylphosphino)-
ethane, dppe, 1,2-bis(diphenylphosphino)propane, dppp, cis-
1,2-bis(diphenylphosphino)ethene, dppey, and 1,2-bis(diethyl-
phosphino)ethane, depe; the unsymmetrical di(tertiary phos-
dichloroplatinum(), cisplatin.9 Whilst cisplatin has been highly
successful in the treatment of certain cancers, there are a num-
ber of side-effects associated with the use of this drug such as
nephrotoxicity, myelosuppression, ototoxicity, nausea and
vomiting.10 Continuing research into the development of other
platinum-based anticancer agents as well as alternative metal-
based drugs is geared to overcoming these problems. Despite
the early promise of [Au(dppe)2]Cl and its derivatives, the com-
pounds have subsequently been shown to be too toxic for clin-
ical use due to side-effects related to the disruption of mito-
chondrial function in hepatocytes.11,12
This paper describes the synthesis of gold(), silver() and
copper() complexes containing the mixed-donor ligands (2-
aminophenyl)diphenylphosphine, adpp, and (±)-(2-aminophen-
yl)methylphenylphosphine, (±)-ampp.† The molecular struc-
tures of [AuI(2-H2NC6H4PPh2)], [AuI{(±)-2-H2NC6H4PMe-
Ph}] and (±)-[Cu(2-H2NC6H4PPh2)2]PF6 have been confirmed
by X-ray crystallography. The solution behaviour of these com-
plexes and their in vitro cytotoxic properties against three
mouse tumour cell lines are also reported.
phine)
1-(diethylphosphino)-2-(diphenylphosphino)ethane,
eppe;3–7 the di(tertiary arsine) (R*,R*)- and (R*,S*)-1,2-bis-
(methylphenylarsino)benzene;1,2 and the mixed-donor ligands
(R*,R*)- and (R*,S*)-1-(methylphenylarsino)-2-(methylphenyl-
phosphino)benzene, and 1-(diphenylphosphino)-2-(2-pyridyl)-
ethane, ppye.1,8 In the latter case, only the complexes of
copper() and silver() had a tetrahedral stereochemistry; the
gold() complex was digonal.
Bis(ditertiary phosphine) complexes of gold(), silver() and
copper() have attracted much interest over the past decade as
certain of these complexes, for example, bis[1,2-bis(diphenyl-
phosphino)ethane]gold() chloride, [Au(dppe)2]Cl, and its sil-
ver() and copper() derivatives, have been shown to display
antitumour activities comparable to those of cis-diammine-
Experimental
Synthetic procedures and materials
Reactions involving air-sensitive reagents were performed
under argon using Schlenk techniques. Solvents were dried and
purified by distillation under argon. The NMR spectra were
recorded on a Varian Gemini II spectrometer operating at 300
(1H) or 121 MHz (31P-{1H}). Chemical shifts are reported as δ
† A paper on the synthesis of related gold() complexes containing the
ligand adpp has very recently appeared.13
J. Chem. Soc., Dalton Trans., 1997, Pages 3435–3443
3435

View Article Online
values relative to SiMe4 (1H) or 85% H3PO4 (31P-{1H}). Molar
conductivities were measured on 10Ϫ3 mol dmϪ3 solutions at
25 ЊC using a Radiometer Copenhagen CDM 80 conductivity
meter. Elemental analyses were performed within the Research
School of Chemistry.
C26H28AuIN2P2: C, 41.4; H, 3.7; N, 3.7%). 1H NMR (CDCl3): δ
2.26 (d, 6 H, JPH 8.5 Hz, PMe), 4.31 (s, 4 H, NH2) and 6.63–
7.67 (m, 18 H, aromatics).
2
(T-4)-Bis[1,2-bis(diphenylphosphino)ethane]gold(I)
iodide,
The compounds (2-aminophenyl)diphenylphosphine,14 (±)-
(2-aminophenyl)methylphenylphosphine,15 (L-2)-tetra-n-butyl-
ammonium diiodoaurate()16 and (T-4)-tetrakis(acetonitrile)-
copper() hexafluorophosphate17 were prepared by literature
procedures.
[Au(dppe)2]I. This was prepared as for [Au(adpp)2]I except
using tetra-n-butylammonium diiodoaurate() (0.30 g, 0.43
mmol) and dppe (0.35 g, 0.88 mmol). The product was
recrystallised from methanol (3 cm3) by the addition of water
(20 cm3) to give white crystals (0.33 g, 68%), m.p. 94 ЊC (Found:
1
C, 55.4; H, 3.9. Calc. for C52H48AuIP4: C, 55.7; H, 4.3%). H
NMR (CDCl3): δ 2.51 (s, 4 H, CH2) and 7.21–7.38 (m, 20 H,
Preparations
aromatics).
(L-2)-[(2-Aminophenyl)diphenylphosphine]iodogold(I), [AuI-
(adpp)]. Tetra-n-butylammonium diiodoaurate() (0.25 g, 0.36
mmol) was dissolved in ethanol (15 cm3) and adpp (0.10 g, 0.36
mmol) slowly added with stirring. The resulting white crystal-
line product was filtered off, washed with ethanol and dried in
vacuo (0.15 g, 69%), m.p. 210 ЊC (Found: C, 35.9; H, 2.8; N, 2.0.
Calc. for C18H16AuINP: C, 36.0; H, 2.7; N, 2.3%). H NMR
(CDCl3): δ 4.40 (s, 2 H, NH2) and 6.73–7.61 (m, 14 H,
aromatics).
(L-2)-Bis[(2-aminophenyl)diphenylphosphine]gold(I)
hexa-
fluorophosphate, [Au(adpp)2]PF6. This was prepared as for
[Au(adpp)]PF6 except using [Au(adpp)2]I (0.25 g, 0.28 mmol) to
give a white crystalline product (0.23 g, 90%), m.p. 190 ЊC
(Found: C, 48.6; H, 3.2; N, 2.7. Calc. for C36H32AuF6N2P3: C,
48.2; H, 3.6; N, 3.1%). H NMR (CDCl3): δ 4.32 (s, 4 H, NH2)
and 6.68–7.48 (m, 28 H, aromatics).
1
1
(L-2)-Bis[(±)-(2-aminophenyl)methylphenylphosphine]gold(I)
hexafluorophosphate, [Au{(±)-ampp}2]PF6. This was prepared
as for [Au(adpp)]PF6 except using [Au{(±)-ampp}2]I (0.42 g,
0.57 mmol) to afford a white crystalline product (0.39 g, 91%),
m.p. 186 ЊC (Found: C, 40.6; H, 3.6; N, 3.4. Calc. for
C26H28AuF6N2P3: C, 40.4; H, 3.7; N, 3.6%). 1H NMR (CDCl3):
δ 2.19 (d, 6 H, 2JPH 6.2 Hz, PMe), 4.28 (s, 4 H, NH2) and 6.67–
7.71 (m, 18 H, aromatics).
(L-2)-[(±)-(2-Aminophenyl)methylphenylphosphine]iodo-
gold(I), [AuI{(±)-ampp}]. A solution of the racemic ligand (±)-
ampp (0.17 g, 0.79 mmol) in ethanol (5 cm3) was added to a
solution of tetra-n-butylammonium diiodoaurate() (0.55 g,
0.79 mmol) in ethanol (20 cm3) with stirring. The white crystal-
line product was filtered off, washed with ethanol and dried in
vacuo (0.33 g, 77%), m.p. 164 ЊC (Found: C, 29.4; H, 2.9; N, 2.4.
1
Calc. for C13H14AuINP: C, 29.0; H, 2.6; N, 2.6%). H NMR
(CDCl3): δ 2.13 (d, 3 H, 2JPH 10.4 Hz, PMe), 4.28 (s, 2 H, NH2)
(T-4)-Bis[(2-aminophenyl)diphenylphosphine]silver(I) nitrate–
dichloromethane (2/1), [Ag(adpp)2]NO3ؒ0.5CH2Cl2. Silver
nitrate (0.07 g, 0.41 mmol) was dissolved in ethanol (20 cm3)
and adpp (0.23 g, 0.83 mmol) slowly added with stirring.
n-Pentane (10 cm3) was added dropwise to give white crystals
which were subsequently filtered off, washed with n-pentane,
dried in vacuo and stored in the dark (0.25 g, 84%), m.p. 222 ЊC
(Found: C, 56.8; H, 4.4; N, 5.6. Calc. for C36.5H33AgClN3O3P2:
and 6.81–7.83 (m, 9 H, aromatics).
(L-2)-[(2-Aminophenyl)diphenylphosphine]gold(I) hexafluoro-
phosphate, [Au(adpp)]PF6. The complex [AuI(adpp)] (0.15 g,
0.25 mmol) was dissolved in acetone (15 cm3) and a solution of
NH4PF6 (0.10 g, 0.61 mmol) in water (5 cm3) slowly added with
stirring. The resulting white crystalline product was filtered off
and dried in vacuo (0.11 g, 72%), m.p. 210 ЊC (Found: C, 35.5;
H, 2.5; N, 2.4. Calc. for C18H16AuF6NP2: C, 34.9; H, 2.6; N,
1
C, 57.1; H, 4.3; N, 5.5%). H NMR (CDCl3): δ 4.61 (s, 4 H,
NH2) and 6.58–7.50 (m, 28 H, aromatics).
1
2.3%). H NMR (CDCl3): δ 4.40 (s, 2 H, NH2) and 6.68–7.59
(m, 14 H, aromatics).
(T-4)-Tris[(2-aminophenyl)diphenylphosphine]silver(I)
nitrate–dichloromethane (2/1), [Ag(adpp)3]NO3ؒ0.5CH2Cl2. This
was prepared as for [Ag(adpp)2]NO3 except using silver nitrate
(0.07 g, 0.41 mmol) and adpp (0.46 g, 1.66 mmol) to give a
white crystalline product (0.31 g, 59%), m.p. 200 ЊC (Found: C,
63.0; H, 4.3; N, 5.0. Calc. for C36.5H33AgClN3O3P2: C, 62.7;
(L-2)-[(±)-(2-Aminophenyl)methylphosphine]gold(I)
hexa-
fluorophosphate–acetone (2/1), [Au{(±)-ampp}]PF6ؒ0.5Me2CO.
This was prepared as for [Au(adpp)]PF6 except using [AuI{(±)-
ampp}] (0.11 g, 0.20 mmol) to give a white crystalline product
(0.09 g, 79%), m.p. 168 ЊC (Found: C, 29.4; H, 2.7; N, 2.4. Calc.
1
H, 4.7; N, 5.4%). H NMR (CDCl3): δ 4.61 (s, 6 H, NH2) and
6.39–7.40 (m, 42 H, aromatics).
1
for C14.5H20AuF6NOP2: C, 29.7; H, 2.9; N, 2.4%). H NMR
(CDCl3): δ 2.31 (d, 3 H, 2JPH 10.5 Hz, PMe), 4.28 (s, 2 H, NH2)
and 6.88–7.76 (m, 9 H, aromatics).
(T-4)-Bis[(2-aminophenyl)diphenylphosphine]silver(I)
hexa-
fluorophosphate, [Ag(adpp)2]PF6. Silver nitrate (0.15 g, 0.89
mmol) was dissolved in ethanol (100 cm3) and adpp (0.51 g,
1.84 mmol) was slowly added with stirring. The solution was
filtered, the solvent evaporated, the residue dissolved in dichloro-
methane (100 cm3) and a solution of NH4PF6 (0.50 g, 3.05
mmol) in water (20 cm3) added. The organic layer was separated
off, dried over anhydrous MgSO4, filtered and the solvent again
evaporated. The residue was redissolved in dichloromethane (5
cm3) and diethyl ether (25 cm3) added to give a white crystalline
product. The product was collected, washed with diethyl ether
(5 cm3), dried in vacuo and stored in the dark (0.58 g, 81%), m.p.
172–174 ЊC (Found: C, 54.0; H, 3.7; N, 3.2. Calc. for C36-
H32AgF6N2P3: C, 53.6; H, 4.0; N, 3.5%). 1H NMR [(CD3)2CO]:
δ 4.99 (s, 4 H, NH2) and 6.82–7.55 (m, 28 H, aromatics).
(L-2)-Bis[(2-aminophenyl)diphenylphosphine]gold(I) iodide,
[Au(adpp)2]I. Tetra-n-butylammonium diiodoaurate() (0.40 g,
0.56 mmol) was dissolved in ethanol (20 cm3) and adpp (0.32 g,
1.15 mmol) slowly added with stirring. The resulting white crys-
talline product was filtered off, washed with ethanol and dried
in vacuo (0.41 g, 81%), m.p. 192–194 ЊC (Found: C, 49.6; H, 3.6;
N, 2.9. Calc. for C36H32AuIN2P2: C, 49.2; H, 3.7; N, 3.2%). H
NMR (CDCl3): δ 4.29 (s, 4 H, NH2) and 6.72–7.59 (m, 28 H,
aromatics).
1
(L-2)-Bis[(±)-(2-aminophenyl)methylphenylphosphine]gold(I)
iodide, [Au{(±)-ampp}2]I. A solution of (±)-ampp (0.15 g, 0.70
mmol) in ethanol (5 cm3) was added to a solution of tetra-n-
butylammonium diiodoaurate() (0.24 g, 0.35 mmol) in ethanol
(15 cm3) with stirring. The white crystalline product was filtered
off, washed with ethanol and dried in vacuo (0.14 g, 54%),
m.p. 168 ЊC (Found: C, 41.8; H, 3.6; N, 3.4. Calc. for
(T-4)-Tris[(2-aminophenyl)diphenylphosphine]silver(I) hexa-
fluorophosphate, [Ag(adpp)3]PF6. This was prepared as for
[Ag(adpp)2]PF6 except using silver nitrate (0.07 g, 0.41 mmol)
3436
J. Chem. Soc., Dalton Trans., 1997, Pages 3435–3443

View Article Online
and adpp (0.35 g, 1.26 mmol) to give a white crystalline pro-
Biological procedures and materials
duct (0.25 g, 56%), m.p. 228 ЊC (Found: C, 59.3; H, 4.4; N,
3.5. Calc. for C54H48AgF6N3P4: C, 59.8; H, 4.5; N, 3.9%). H
NMR [(CD3)2CO]: δ 4.69 (s, 6 H, NH2) and 6.76–7.55 (m, 42 H,
aromatics).
The P815 mastocytoma cells were cultured in Eagle’s Minimum
Essential Medium F15 with 10% foetal bovine serum, B16 cells
in McCoy’s medium RPMI 1640 with 10% foetal bovine serum
and P388 leukaemia cells in Dulbecco’s Modified Eagle
Medium H16 with 10% horse serum (herein EC 10). All cells
were cultured and incubated in a Forma Scientific Infrared CO2
incubator at 37 ЊC in 5% CO2. Cell suspensions were centri-
fuged using a model CR 4 22 Jouan centrifuge. Linbro 96
round-bottom-well tissue-culture plates were used for the thy-
midine incorporation assay. Cells were harvested using a Phar-
macia Version 1.02 Micro Cell Harvester and incorporated
thymidine was counted using a Pharmacia 1205 Betaplate
liquid scintillation counter. Thymidine incorporation assays
were performed following a literature procedure.18 The com-
pounds tested were dissolved in dimethyl sulfoxide (0.2 cm3) to
give a concentration of 0.02 mol dmϪ3 and then diluted to
2 × 10Ϫ5 mol dmϪ3 using EC 10.
1
(T-4)-Tris[(±)-(2-aminophenyl)methylphenylphosphine]-
silver(I) hexafluorophosphate, [Ag{(±)-ampp}3]PF6. A solution
of (±)-ampp (0.30 g, 1.39 mmol) in ethanol (10 cm3) was added
dropwise to a solution of silver nitrate (0.08 g, 0.47 mmol) in
ethanol (90 cm3). The solution was filtered, the solvent evapor-
ated, the residue redissolved in dichloromethane (40 cm3) and a
solution of NH4PF6 (0.50 g, 3.05 mmol) in water (20 cm3)
added. The organic layer was separated, dried over anhydrous
MgSO4, filtered and the solvent again evaporated. The residue
was redissolved in methanol (20 cm3) and gave a white crystal-
line product on standing. The product was collected, washed
with diethyl ether (5 cm3), dried in vacuo and stored in the dark
(0.34 g, 81%), m.p. 164–166 ЊC (Found: C, 52.0; H, 4.1; N, 4.4.
Calc. for C39H42AgF6N3P4: C, 52.1; H, 4.7; N, 4.7%). 1H NMR
(CDCl3): δ 1.82 (br s, 9 H, PMe), 4.75 (s, 6 H, NH2) and 6.80–
7.54 (m, 27 H, aromatics).
X-Ray crystallography
Crystal data. Complex [AuI(adpp)] A. C18H16AuINP,
M = 601.18, orthorhombic, space group P212121 (no. 19),
a = 10.220(2), b = 12.689(4), c = 14.112(4) Å, U = 1830(1) Å3
(by least-squares analysis of the setting angles of 24 reflec-
tions 38.69 < 2θ < 42.27Њ), Mo-Kα radiation λ = 0.710 69 Å
(T-4)-Bis[(2-aminophenyl)diphenylphosphine]copper(I) hexa-
fluorophosphate, [Cu(adpp)2]PF6. Tetrakis(acetonitrile)copper()
hexafluorophosphate (1.00 g, 2.68 mmol) was dissolved in
acetonitrile (50 cm3) and adpp (1.49 g, 5.38 mmol) was slowly
added with stirring. The solution was filtered, the solvent evap-
orated and the residue dissolved in dichloromethane (2 cm3). A
white crystalline product was obtained upon the addition of
diethyl ether (25 cm3). The product was collected, washed
with diethyl ether (5 cm3) and dried in vacuo (1.90 g, 93%),
m.p. 186 ЊC (Found: C, 56.3; H, 4.0; N, 3.7. Calc. for
C36H32CuF6N2P3: C, 56.2; H, 4.2; N, 3.7%). 1H NMR
[(CD3)2CO]: δ 5.82 (s, 4 H, NH2) and 7.31–7.50 (m, 28 H,
aromatics).
with a graphite monochromator, Z = 4, Dc = 2.182 g cmϪ3
,
F(000) = 1112.00, specimen 0.37 × 0.28 × 0.09 mm, µ(Mo-
Kα) = 98.38 cmϪ1
.
Complex [AuI{(±)-ampp}] B. C13H14AuINP, M = 539.11, tri-
¯
clinic, space group P1 (no. 2), a = 11.109(3), b = 11.892(4),
c = 13.244(3) Å, α = 72.24(2), β = 78.31(2), γ = 62.12(2)Њ,
U = 1469.0(8) Å3 (by least-squares analysis of the setting angles
of 24 reflections 35.02 < 2θ < 41.50Њ), Mo-Kα radiation
λ = 0.710 69
Dc = 2.437 g cmϪ3, F(000) = 984.00, specimen 0.25 × 0.13 × 0.12
mm, µ(Mo-Kα) = 121.51 cmϪ1
Complex (±)-[Cu(adpp)2]PF6
Å with a graphite monochromator, Z = 4,
.
C.
C36H32CuF6N2P3,
(T-4)-Tris[(2-aminophenyl)diphenylphosphine]copper(I) hexa-
fluorophosphine, [Cu(adpp)3]PF6. This was prepared as for
[Cu(adpp)2]PF6 except using tetrakis(acetonitrile)copper()
hexafluorophosphate (1.00 g, 2.68 mmol) and adpp (1.73 g, 6.24
mmol) to give a white crystalline product (2.00 g, 98%), m.p.
218–220 ЊC (Found: C, 62.0; H, 4.6; N, 3.7. Calc. for
C54H48CuF6N3P4: C, 62.3; H, 4.7; N, 4.0%). 1H NMR
[(CD3)2CO]: δ 5.82 (s, 6 H, NH2) and 7.42–7.78 (m, 42 H,
aromatics).
¯
M = 763.12, triclinic, space group P1 (no. 2), a = 11.298(6),
b = 11.877(4), c = 14.798(4) Å, α = 66.52(2), β = 88.91(3),
γ = 74.52(3)Њ, U = 1747(1) Å3 (by least-squares analysis of
the setting angles of 18 reflections 82.28 < 2θ < 86.54Њ), Cu-Kα
radiation λ = 1.541 78 Å with a graphite monochromator,
Z = 2, Dc = 1.451
g
cmϪ3
,
F(000) = 780.00, specimen
0.49 × 0.21 × 0.08 mm, µ(Cu-Kα) = 27.15 cmϪ1
.
Data collection and processing. A unique data set was meas-
ured in each case at 296(1) K using the ω–2θ scan technique to a
maximum 2θ value of 50.1 and 55.1Њ for A and B, respectively,
on a Rigaku AFC6S diffractometer, and a maximum 2θ value
of 120.5Њ for C on a Rigaku AFC6R diffractometer. Scans of
width (1.78 ϩ 0.34 tan θ), (1.52 ϩ 0.34 tan θ) and (1.52 ϩ 0.30
tan θ)Њ were made at a speed (in ω) of 8.0, 4.0 and 32.0Њ minϪ1
for A, B and C, respectively. The weak reflections [I < 10.0σ(I)]
were rescanned (maximum of four scans) and the counts were
accumulated to ensure good counting statistics. The number of
unique reflections was 1889 for A, 6814 for B and 5200 for C.
The intensities of three representative reflections were measured
after every 150. No decay correction was required. Analytical
absorption corrections were applied which resulted in transmis-
sion factors ranging from 0.14 to 0.44 for A, 0.24 to 0.37 for B
and 0.56 to 0.81 for C. The data were corrected for Lorentz-
polarisation effects.
(T-4)-Bis[(±)-(2-aminophenyl)methylphenylphosphine]gold(I)
hexafluorophosphate, [Cu{(±)-ampp}2]PF6. A solution of (±)-
ampp (0.30 g, 1.39 mmol) in acetonitrile (10 cm3) was added to
a solution of tetrakis(acetonitrile)copper() hexafluorophos-
phate (0.26 g, 0.70 mmol) in acetonitrile (25 cm3). The colour-
less solution was filtered, the solvent evaporated and the residue
dissolved in methanol (2 cm3). Diethyl ether (20 cm3) was added
dropwise to give a white crystalline product which was col-
lected, washed with diethyl ether (5 cm3) and dried in vacuo
(0.31 g, 70%), m.p. 188 ЊC (Found: C, 51.8; H, 4.9; N, 4.4. Calc.
for C26H28CuF6N2P3: C, 51.4; H, 4.6; N, 4.6%). 1H NMR
(CDCl3): δ 1.61 (s, 6 H, PMe), 4.40 (s, 4 H, NH2) and 7.00–7.42
(m, 18 H, aromatics).
(T-4)-Tris[(±)-(2-aminophenyl)methylphenylphosphine]gold(I)
hexafluorophosphate, [Cu{(±)-ampp}3]PF6. This was prepared
as for [Cu{(±)-ampp}2]PF6 except using tetrakis(acetonitrile)-
copper() hexafluorophosphate (0.50 g, 1.34 mmol) and (±)-
ampp (0.86 g, 4.00 mmol) to give a white crystalline product
(0.62 g, 72%), m.p. 180 ЊC (Found: C, 54.7; H, 5.1; N, 4.8. Calc.
for C39H42CuF6N3P4: C, 54.8; H, 5.0; N, 4.9%). 1H NMR
(CDCl3): δ 1.67 (s, 9 H, PMe), 5.05 (s, 6 H, NH2) and 7.00–7.43
(m, 27 H, aromatics).
Structure analysis and refinement. The structures were solved
by direct methods and expanded using Fourier techniques.19–21
The non-hydrogen atoms were refined anisotropically for A and
B. These atoms were refined with isotropic displacement factors
and then anisotropically for C. The hexafluorophosphate ion in
C was found to be rotationally disordered to some degree.
J. Chem. Soc., Dalton Trans., 1997, Pages 3435–3443
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(i )
(ii )
[AuIL]
[AuL]PF6
NH2
NH2
P
H2N
P
[NBu4][AuI2]
PPh2
R
S
Ph
(iii )
[AuL2]I
Ph
Me
Me
(iv )
adpp
(±)-ampp
[Ag(adpp)2]NO3
(vi )
(v )
[ML2]PF6
[ML3]PF6
(vii )
Hydrogen atoms attached to carbon atoms of the cations were
included at calculated positions but were not refined. Similarly
the amine hydrogens of C. Amine hydrogen atoms of A and B
were not located unambiguously and have not been included.
The final cycle of full-matrix least-squares refinement was
based on 1223 (for A), 4087 (for B) and 3954 (for C) observed
reflections [I > 3.0σ(I)] and 203 (for A), 307 (for B) and 452 (for
C) variable parameters and converged [largest shift was 0.04
(for A), 0.01 (for B) and 0.22 (for C) times its estimated stand-
ard deviation (e.s.d.)] with final R and RЈ values being 0.031 an
0.030 for A, 0.030 and 0.031 for B and 0.050 and 0.060 for C,
respectively. The maximum and minimum peaks on the final
Fourier-difference map corresponded to 1.02 and Ϫ0.73 (for
A), 1.07 and Ϫ0.90 (for B) and 0.49 and Ϫ0.62 e ÅϪ3 (for C),
respectively. The absolute structure of A was also established by
refining a model with coordinates transformed by (Ϫx, Ϫy, Ϫz)
which yielded a higher R factor of 0.059 and RЈ of 0.062 and
thereby showed that the original model was correct. Neutral
atom scattering factors were taken from Cromer and Waber.22
Anomalous dispersion effects were included in Fc;23 the values
for ∆fЈ and ∆fЉ were those of Creagh and McAuley.24 The
values for the mass-attenuation coefficients were those of Cre-
agh and Hubbell.25 All calculations were performed using the
TEXSAN package.26
AgNO3
[Cu(NCMe)4]PF6
(ix )
(viii )
(x )
[Ag(adpp)3]NO3
Scheme 1 (i) L, EtOH; (ii) acetone, NH4PF6 in water; (iii) 2 L, EtOH;
(iv) acetone, NH4PF6 in water; (v) 2 L, MeCN; (vi) 2 adpp, EtOH,
NH4PF6 in water; (vii) 2 adpp, CH2Cl2; (viii) 3 L, MeCN; (ix) 3 L,
EtOH, NH4PF6 in water; (x) 3 adpp, CH2Cl2
CCDC reference number 186/600.
Results and Discussion
Synthesis of complexes
A number of gold(), silver() and copper() complexes have
been synthesized containing the ligands (2-aminophenyl)-
diphenylphosphine, adpp, and (±)-(2-aminophenyl)methyl-
phenylphosphine, (±)-ampp. Gold() complexes of the type
[AuI(L)] were prepared by treating equimolar quantities of the
Fig. 1 Molecular structure of [AuI(adpp)] [both locations of the dis-
ordered amine nitrogen atom are shown, vis-à-vis N(1) and N(2)]
molar conductance data are entirely consistent with the given
formulations;27 the complexes [AuI(L)] behaving as non-
electrolytes in nitromethane and acetonitrile and those of the
type [MLn]X as 1:1 electrolytes in the same solvents. A linear
geometry about the metal centre is proposed for the gold()
complexes and a tetrahedral stereochemistry for their copper()
and silver() counterparts. The related complex [Au(ppye)2]PF6
has been structurally authenticated and shown to have a
two-co-ordinate gold() centre with the ppye ligands bound
in a monodentate fashion via the phosphorus donor atom.8
Complexes of the type [ML3]PF6 [M = CuI or AgI, L = adpp or
(±)-ampp] are believed to contain one bidentate ligand and two
ligands bound in a monodentate fashion via the phosphorus
donor atom.
appropriate ligand
L [adpp or (±)-ampp] with tetra-n-
butylammonium diiodoaurate() in ethanol (Scheme 1). When 2
equivalents of L were used in the reaction the complexes
[AuL2]I were isolated. Further reaction of [AuI(L)] and [AuL2]I
with aqueous NH4PF6 gave the corresponding salts [AuLn]PF6
(n = 1 or 2). Copper() complexes of the type [CuLn]PF6 (n = 2
or 3) were prepared by treating 2 or 3 equivalents of L [adpp
or (±)-ampp] with tetrakis(acetonitrile)copper() hexafluoro-
phosphate in acetonitrile. The analogous silver() complexes
[AgLn]PF6 (where n = 2 or 3) were obtained from the appro-
priate form of the ligand and silver nitrate in ethanol followed
by treatment with aqueous NH4PF6. In the case of adpp the
intermediate nitrate salts were also isolated. The complex
[Ag{(±)-ampp}2]PF6, however, could not be isolated in a pure
form; the product was invariably contaminated with [Ag{(±)-
ampp}3]PF6.
Crystal structures of complexes [AuI(adpp)], [AuI{(±)-ampp}]
and (±)-[Cu(adpp)2]PF6
No evidence was found for the co-ordination of more than 2
equivalents of adpp or (±)-ampp to gold() or of 4 equivalents
to copper() and silver(). Furthermore, the complex [Cu{(±)-
ampp}2]PF6 was unstable in the solid state and particularly so
in solution. This, coupled with the failure to prepare the analo-
gous complex of silver(), suggests that these two metal centres
preferentially bind 3 equivalents of (±)-ampp. The greater steric
bulk of adpp probably accounts for the enhanced stability of
(±)-[M(adpp)2]PF6 (where M = CuI or AgI).
The molecular structures of [AuI(adpp)], [AuI{(±)-ampp}] and
(±)-[Cu(adpp)2]PF6 have been confirmed by X-ray analyses.
The stereochemistries of the gold() complexes and the cation
(±)-[Cu(adpp)2]ϩ are shown in Figs. 1, 2 and 3, respectively; and
selected bond lengths and angles in Table 2.
It is clear from the structural data that the molecular struc-
tures of the two gold() complexes are significantly different.
Only one molecule of [AuI(adpp)] was present in the asym-
metric unit whereas two were found for [AuI{(±)-ampp}]. In
Selected data for the complexes are given in Table 1. The
3438
J. Chem. Soc., Dalton Trans., 1997, Pages 3435–3443

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Table 1 Selected data for the ligands adpp and (±)-ampp, and their gold(), silver() and copper() complexes
ΛM a/S cm2 molϪ1
1H NMR,b δ
31P-{1H} NMR b
δ
Compound
MeNO2
MeCN
PMec
NH2
adpp
(±)-ampp
[AuI(adpp)]
[Au(adpp)]PF6
[Au(adpp)2]I
[Au(adpp)2]PF6
[AuI{(±)-ampp}]
[Au{(±)-ampp}]PF6
[Au{(±)-ampp}2]I
[Au{(±)-ampp}2]PF6
(±)-[Ag(adpp)2]NO3
[Ag(adpp)3]NO3
(±)-[Ag(adpp)2]PF6
[Ag(adpp)3]PF6
[Ag{(±)-ampp}3]PF6
(±)-[Cu(adpp)2]PF6
[Cu(adpp)3]PF6
[Cu{(±)-ampp}2]PF6
[Cu{(±)-ampp}3]PF6
—
—
0.4
91
90
91
0.8
93
92
92
82
80
83
80
84
89
86
90
89
—
—
0.5
91
90
90
0.8
93
93
93
83
80
82
81
84
92
89
91
91
—
3.90 (br s)
4.07 (br s)
4.40 (s)
4.40 (s)
4.29 (s)
4.32 (s)
4.28 (s)
4.28 (s)
4.31 (s)
4.28 (s)
4.61 (s)
4.61 (s)
4.99 (s)
4.69 (s)
4.75 (s)
5.82 (s)
5.82 (s)
4.40 (br s)
5.05 (br s)
Ϫ20.9 (s)
Ϫ42.8 (s)
28.1 (s, 1P)
28.2 (s, 1P)
19.9 (s, 2P)
23.4 (s, 2P)
13.7 (s, 1P)
15.5 (s, 1P)
1.56 (d, 3.5)
—
—
—
—
2.13 (d, 10.4)
2.13 (d, 10.5)
2.26 (d, 8.5)
2.19 (d, 6.2)
—
—
—
—
1.82 (br s)
—
—
1.61 (s)
1.67 (s)
11.1 (s, 2P)
14.2 (s, 2P)
Ϫ2.3 (br s, 2P)d
Ϫ5.1 (br s, 2P)d
Ϫ1.1 (s, 2P)
Ϫ1.9 (s, 3P)
Ϫ24.2 (s, 3P)
Ϫ10.6 (br s, 2P)
Ϫ9.0 (br s, 3P)
Ϫ24.6 (br s, 2P)
Ϫ23.8 (br s, 3P)
d
d
d
d
a
Molar conductance for 10Ϫ3 mol dmϪ3 solutions at 298 K. b In CDCl3. c Coupling constants (2JPH /Hz) are given in parentheses. d In (CD3)2CO.
Fig. 2 Molecular structure of [AuI{(±)-ampp}]
Fig. 3 Molecular structure of the cation (±)-[Cu(adpp)2]ϩ
the latter case a weak interaction between the Au(1) and Au(2)
centres was present. Auriophilicity has been observed in a num-
ber of gold() complexes;28 the absence of this effect in the
crystal structure of [AuI(adpp)] is presumably a direct result of
the greater steric bulk of the adpp ligand. The geometry about
the gold() centres is essentially linear in the two structures, the
largest deviation from linearity being found for [AuI{(±)-
ampp}] {where the P᎐Au᎐I angle was 170.9 and 173.2Њ com-
pared with 177.9Њ for [AuI(adpp)]}. The Au᎐P and Au᎐I bond
lengths in the two structures were similar and comparable to
other values in the literature.24 Furthermore, the complex
[AuI{(±)-ampp}] is racemic with both (R,R) and (S,S) dimeric
units being present in the unit cell. Only the former is shown in
Fig. 2. In addition, the NH2 group, which was not co-ordinated
to the gold() metal centre, was found to be disordered over two
sites in the crystal lattice of [AuI(adpp)]. For 70% of the time
this group was found bound to the C(2) atom [vis-à-vis N(1)]
while for the other 30% it was bound to the C(8) atom [vis-à-vis
N(2)].
parable to other values in the literature.24 Furthermore, the
complex (±)-[Cu(adpp)2]PF6 is a racemic compound with both
R and S forms of the cation being present in the unit cell. Only
the S form is shown in Fig. 3.
NMR spectra
Selected NMR data for adpp and (±)-ampp and their gold(),
silver() and copper() complexes are given in Table 1. In all
cases singlet NH2 and single PMe [for (±)-ampp and its com-
plexes] resonances were observed in the 1H NMR spectra at 293
K and singlet 31P resonances in the 31P-{1H} NMR spectra at
the same temperature. The chemical shifts of the singlet NH2
resonances for the gold() complexes were very similar to those
recorded for the free phosphines, this being consistent with the
interpretation that the ligands bind to the gold() centre in a
monodentate fashion through the phosphorus donor atom. For
the silver() and copper() complexes the NH2 resonances
occurred further downfield indicating some degree of metal–
nitrogen interaction. Both these results were consistent with the
solid-state structures of the gold() and copper() complexes
and indicated that the configuration about the metal centre was
retained in solution. Ligand-redistribution reactions, however,
are rife for these complexes in solution.
The structural data for the cation (±)-[Cu(adpp)2]ϩ revealed a
distorted tetrahedral co-ordination geometry with angles about
the copper() centre of P(1)᎐Cu᎐P(2) 129.11(5), P(1)᎐Cu᎐N(1)
84.2(1), P(2)᎐Cu᎐N(2) 86.0(1), P(1)᎐Cu᎐N(2) 119.0(1),
P(2)᎐Cu᎐N(1) 134.9(1) and N(1)᎐Cu᎐N(2) 104.6(1). The Cu᎐P
and Cu᎐N bond lengths in this structure were similar and com-
J. Chem. Soc., Dalton Trans., 1997, Pages 3435–3443
3439

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Fig. 4 Diastereomerism in the cations (i) [Au{(±)-ampp}2]ϩ, (ii) [M{(±)-ampp}2]ϩ and (iii) [M{(±)-ampp}3]ϩ (M = CuI or AgI)
1
The observation of singlet 31P resonances for the silver()
complexes in the 31P-{1H} NMR spectra at 293 K is only con-
sistent with rapid intermolecular exchange of the ligands. For
kinetically inert complexes containing silver() two doublets
should be observed for each 31P resonance in the 31P-{1H}
NMR spectrum as a result of coupling of the 31P nucleus to
107Ag and 109Ag nuclei.29 The observation of single NH2 and
PMe resonances for the cations [M{(±)-ampp}2]ϩ and [M{(±)-
pair of doublets centred at δ Ϫ3.38 [with J(107Ag᎐31P) Ϫ312
and 1J(109Ag᎐31P) Ϫ361 Hz]. The sign of the coupling constants
was assumed to be negative by analogy with other silver()
complexes containing tertiary phosphine ligands.29 In the case
of [Ag(adpp)3]PF6 two pairs of doublet 31P resonances (in the
ratio of 1:2) would be expected in the 31P-{1H} NMR spectrum
at the slow-exchange limit (assuming the spectrum is amenable
to first-order analysis). The 31P-{1H} NMR spectrum of the
complex at 213 K exhibited a pair of doublets centred at δ
1
ampp}3]ϩ in the respective H NMR spectra and singlet 31P
resonances in the 31P-{1H} NMR spectra at 293 K was also
indicative of the species undergoing facile rearrangement in
solution. Whereas complexes of the type [AuI(L)], [AuL]PF6
and [M(adpp)n]X can only exist as a single stereoisomer, or as a
pair of enantiomers in the case of tetrahedral [M(adpp)2]X, two
diastereomers are possible for [M{(±)-ampp}2]PF6 and three for
[M{(±)-ampp}3]PF6. The diastereomeric forms of the cations
[M{(±)-ampp}2]ϩ and [M{(±)-ampp}3]ϩ are depicted in Fig. 4.
Similarly, two distinct NH2 resonances and 31P resonances
would be expected for kinetically inert cations of the type
[M(adpp)3]ϩ in the appropriate spectra.
Variable-temperature NMR spectroscopy has been used to
probe the dynamic behaviour of certain of these complexes
in solution. For example, 31P-{1H} NMR spectra of (±)-
[Ag(adpp)2]PF6 and [Ag(adpp)3]PF6 in CD2Cl2 were recorded
over the temperature range 183–298 K (Fig. 5). The slow-
exchange limit for (±)-[Ag(adpp)2]PF6 was attained at 213 K:
the 31P-{1H} NMR spectrum at this temperature exhibited a
Ϫ3.31 [with J(107Ag᎐31P) Ϫ313 and J(109Ag᎐31P) Ϫ361 Hz] as
well as unresolved signals at δ Ϫ0.47 and Ϫ4.70, respectively.
On further cooling of the NMR sample to 183 K a second pair
1
1
of doublets centred at δ Ϫ2.87 [with J(107Ag᎐31P) Ϫ491 and
1
1J(109Ag᎐31P) Ϫ567 Hz] was observed in the 31P-{1H} NMR
spectrum. Presumably the upfield signal arose from the phos-
phorus donor atom of the chelating adpp ligand and the other
signal from the equivalent phosphorus nuclei of the two uni-
dentate adpp ligands. The 31P-{H} NMR spectrum of the
related complex [Ag{(±)-ampp}3]PF6 in CD2Cl2 at 183 K simi-
larly contained a number of peaks, however they were insuffi-
ciently well resolved for an unequivocal assignment to be made.
A series of 31P-{1H} NMR spectra was similarly recorded for
each of the complexes [Cu(adpp)3]PF6, [Cu{(±)-ampp}3]PF6
and [Au{(±)-ampp}2]PF6 in CD2Cl2 over the temperature range
183–298 K. For the two copper() complexes singlet 31P reson-
₁
ances were observed with ν decreasing from 90 to 50 Hz for
[Cu(adpp)3]PF6 and 170 to 80 Hz for [Cu{(±)-ampp}3]PF6 on
₂
3440
J. Chem. Soc., Dalton Trans., 1997, Pages 3435–3443

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Table 2 Selected non-hydrogen interatomic distances (Å) and inter-
atomic angles (Њ) for [AuI(adpp)], [AuI{(±)-ampp}] and (±)-
[Cu(adpp)2]PF6
Table 3 The IC50 values for gold(), silver() and copper() complexes
against P815 mastocytoma, B16 melanoma, and P388 leukaemia mouse
tumour cell models
[AuI(adpp)]
IC50/mmol dmϪ3
Au᎐P
2.260(4)
177.9(1)
Au᎐I
2.553(1)
Complex
P815
B16
2.12
P388
I᎐Au᎐P
[AuI(adpp)]
[Au(adpp)]PF6
[Au(adpp)2]I
[Au(adpp)2]PF6
[AuI{(±)-ampp}]
[Au{(±)-ampp}]PF6
[Au{(±)-ampp}2]I
[Au{(±)-ampp}2]PF6
8.00
10.00
8.50
4.50
18.00
4.80
5.50
5.50
8.00
5.80
9.50
3.00
0.97
1.65
0.80
2.50
2.60
15.00
[AuI{(±)-ampp}]
5.00
Au(1)᎐P(1)
Au(1)᎐I(1)
Au(2)᎐P(2)
Au(2)᎐I(2)
2.262(2)
2.5644(9)
2.256(2)
2.5708(7)
Au(1)᎐Au(2)
Au(1) ؒ ؒ ؒ I(2)
Au(2) ؒ ؒ ؒ I(1)
3.1709(5)
3.7891(9)*
4.0820(7)*
32.40
40.00
9.25
7.80
I(1)᎐Au(1)᎐P(1) 173.13(6)
(±)-[Cu(adpp)2]PF6
I(2)᎐Au(1)᎐P(2) 170.86(6)
(±)-[Ag(adpp)2]NO3
[Ag(adpp)3]NO3
(±)-[Ag(adpp)2]PF6
[Ag(adpp)3]PF6
4.25
4.00
3.40
2.25
9.50
1.75
1.35
1.48
1.54
5.00
3.90
3.20
5.00
3.20
4.40
Cu᎐P(1)
Cu᎐P(2)
2.256(1)
2.207(2)
Cu᎐N(1)
Cu᎐N(2)
2.131(4)
2.152(4)
[Ag{(±)-ampp}3]PF6
P(1)᎐Cu᎐P(2)
P(1)᎐Cu᎐N(1)
P(2)᎐Cu᎐N(2)
129.11(5)
84.2(1)
86.0(1)
P(1)᎐Cu᎐N(2)
P(2)᎐Cu᎐N(1)
N(1)᎐Cu᎐N(2)
119.0(1)
134.9(1)
104.6(1)
(±)-[Cu(adpp)2]PF6
[Cu(adpp)3]PF6
[Cu{(±)-ampp}2]PF6
[Cu{(±)-ampp}3]PF6
4.20
2.50
49.00
6.00
2.22
2.18
25.00
5.00
11.00
6.00
17.90
9.00
* Non-bonded interatomic distance.
[Au(dppe)2]I
cis-[PtCl2(NH3)2]
0.22
14.50
5.20
0.90*
0.10
5.00
adpp
dppe
19.50
1.75
—
—
—
—
* Data taken from ref. 9.
the complexes in the absence of free phosphine. Clearly inter-
molecular ligand exchange was taking place for all three com-
plexes in the presence of free phosphine.
1
Variable-temperature H NMR spectra were also recorded
for the complexes [M{(±)-ampp}3]PF6 (M = AgI or CuI) and
[Au{(±)-ampp}2]PF6 in CD2Cl2 over the temperature range
183–298 K. The low-temperature (183 K) spectra contained
poorly resolved multiplets for the PMe and NH2 resonances of
the copper() and silver() complexes. Separate PMe and NH2
resonances similarly could not be discerned for the racemic and
meso diastereomers of [Au{(±)-ampp}2]PF6 in CD2Cl2 at 213 K.
Preliminary biological studies
The in vitro cytotoxic properties of gold(), silver() and cop-
per() complexes have been assessed by measuring the effect on
proliferation of three mouse tumour cell lines, P815 mastocy-
toma, B16 melanoma and P388 leukaemia. The IC50 values
(concentrations resulting in 50% inhibition of labelled thymi-
dine) for these complexes and for the reference compounds cis-
platin and [Au(dppe)2]I are given in Table 3. Several trends are
evident from these results.
(i) The nature of the metal ion made very little difference to
the cytotoxicity of the complexes, although it was generally
seen that silver() compounds may be marginally more potent
than gold() and copper() complexes. This trend is illustrated
for complexes of the type [M(adpp)2]PF6 in Fig. 6(a).
(ii) As the number of ligands co-ordinated to the metal ion
increased the cytotoxicity of the complex also increased as
reflected in the decrease in IC50 value. This trend was seen when
the number of ligands co-ordinated was increased from one to
two [for gold()] and similarly from two to three [for silver()
and copper()]. Fig. 6(b) shows this trend for the complexes
[CuLn]PF6.
(iii) Complexes containing adpp generally had lower IC50
values, and hence were more active, than their (±)-ampp ana-
logues. Fig. 6(b) also illustrates this trend.
(iv) Toxicity was independent of the counter anion. This is
shown for the complexes [Ag(adpp)2]X in Fig. 6(c).
Fig. 5 Variable-temperature 31P-{1H} NMR spectra for the complexes
(a) (±)-[Ag(adpp)2]PF6 and (b) [Ag(adpp)3]PF6 in CD2Cl2
cooling the respective NMR samples from 298 to 183 K, con-
sistent with the complexes undergoing facile ligand redistribu-
tion in solution. In the case of [Au{(±)-ampp}2]PF6 two singlet
resonances at δ 13.40 and 14.05 were observed in the 31P-{1H}
NMR spectrum at 213 K, consistent with the presence of
racemic and meso diastereomers. The observation of facile
racemic–meso interconversion in the room-temperature spec-
trum of [Au{(±)-ampp}2]PF6 in CD2Cl2 is only consistent with
rapid intermolecular ligand exchange. Furthermore, when a
trace of free phosphine was added to either of the three NMR
samples a single 31P resonance was observed in the respective
31P-{1H} NMR spectrum at 293 K, upfield of that recorded for
J. Chem. Soc., Dalton Trans., 1997, Pages 3435–3443
3441

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cells.11,12 The latter possess an electric field gradient across their
membrane thereby having a high affinity for positively charged
species. It is the accumulation of such species in the mito-
chondria of cells, and in particular of hepatocytes, which may
be responsible for the cytotoxicity of these compounds.
Conclusion
A number of gold(), silver() and copper() complexes have
been prepared containing the substituted (2-aminophenyl)-
phosphines adpp and (±)-ampp. These ligands were chosen for
study as completely chemoselective cleavage of the phenyl
group(s) from adpp and (±)-ampp is readily achieved and thus
the ligands are readily derivatised.15 This may be important in
modifying the solubility, toxicity and anticancer activity of
these complexes. Furthermore, chiral ligands of this type are
readily resolved and will thereby allow the synthesis of enan-
tiomerically pure copper(), silver() and gold() complexes.
Since the biological targets of such complexes will invariably be
chiral, an enhanced spectrum of activity may result from the
use of optically pure compounds.
A preliminary study on the in vitro cytotoxic properties of
these complexes against three mouse cell lines has shown them,
in general, to have comparable activities to those of cisplatin
and [Au(dppe)2]I. This augurs well for the role of related com-
plexes containing optically active ligands of this type with
stereogenic phosphorus donor atoms as potential anticancer
agents. Future work will also involve an investigation into the
relationship between the antiproliferative properties of these
complexes and their effects on mitochondria.
Acknowledgements
We wish to thank Mr. A. Sjaarda for his technical assistance in
relation to the preliminary biological studies described herein.
References
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Fig. 6 Graphical representation of IC50 values for the complexes (a)
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Received 22nd April 1997; Paper 7/02757E
J. Chem. Soc., Dalton Trans., 1997, Pages 3435–3443
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