Cycloauration of pyridyl sulfonamides

Article abstract of DOI:10.1039/b803835j

The pyridyl-2-alkylsulfonamides C₅H₄N(CH ₂)_nNHSO₂R (n = 1,2; R = Me, Ph or p-C ₆H₄Me) and 8-(p-tosylamino)quinoline undergo facile cycloauration reactions with H[AuCl₄] in water, giving metallacyclic complexes coordinated through the pyridyl (or quinolyl) nitrogen atom and the deprotonated nitrogen of the sulfonamide group. The complexes have been fully characterised by NMR spectroscopy, ESI mass spectrometry and elemental analysis. The X-ray crystal structures of two derivatives reveal the presence of non-planar sulfonamide nitrogen atoms. The complexes show low activity against P388 murine leukaemia cells, possibly as a result of their ease of reduction with mild reducing agents.

Full text of DOI:10.1039/b803835j

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PAPER
www.rsc.org/dalton | Dalton Transactions
Cycloauration of pyridyl sulfonamides†
Kelly J. Kilpin, William Henderson* and Brian K. Nicholson
Received 5th March 2008, Accepted 14th May 2008
First published as an Advance Article on the web 19th June 2008
DOI: 10.1039/b803835j
The pyridyl-2-alkylsulfonamides C5H4N(CH2)nNHSO2R (n = 1,2; R = Me, Ph or p-C6H4Me) and 8-(p-
tosylamino)quinoline undergo facile cycloauration reactions with H[AuCl4] in water, giving metallacyclic
complexes coordinated through the pyridyl (or quinolyl) nitrogen atom and the deprotonated
nitrogen of the sulfonamide group. The complexes have been fully characterised by NMR spectroscopy,
ESI mass spectrometry and elemental analysis. The X-ray crystal structures of two derivatives
reveal the presence of non-planar sulfonamide nitrogen atoms. The complexes show low activity against
P388 murine leukaemia cells, possibly as a result of their ease of reduction with mild reducing agents.
known.9 A recent report has described the cycloauration of bis(2-
pyridylmethyl)amine, giving complex 9.10
Introduction
Compared with the extensive chemistry of cyclometallated
gold(III) complexes containing C,N donor ligands,1 little research
has been conducted on analogous cycloaurated complexes sta-
bilised by N,Nꢀ donor ligands. Complexes derived from the
primary amide picolinamide2,3 1 and substituted analogues 24
and 3,5 the dinuclear complex 46 and the substituted 2-(pyrrol-
2-yl)pyridine ligand 57 are examples of the systems prepared. In
addition, the ionic species 6–8 formed by the tridentate coordi-
nation of quinoline-derived ligands have also been investigated8
and related gold(III) complexes containing anionic chelating
N,Nꢀ ligands such as tri- and tetrakis-pyrazolylborates are also
Because C,N stabilised complexes exhibit interesting chem-
istry and biological activity,1 we wished to synthesise related
N,Nꢀ-stabilised species and assess their chemical and biolog-
ical properties. Pyridylsulfonamide compounds [of the type
C5H4N(CH2)nNHSO2R (n = 1,2; R = Me, Ph or p-C6H4Me)] were
attractive ligands for this study due to the ease of synthesis, the
opportunity of introducing variable R groups and the possibility of
variable ring sizes in the subsequent cyclometallated complexes.
In addition, cyclometallated complexes of this type containing
a variety of metals are also known in the literature and show
interesting applications.11 In this paper we describe the synthesis
of six new auracyclic compounds and investigations into the
reactivity and biological activity of these complexes.
Results and discussion
Syntheses
When the ligands HL1 to HL6 (Scheme 1) are refluxed in aqueous
H[AuCl4] in a 1 : 1 mole ratio, the auracyclic compounds L1AuCl2
to L6AuCl2 (Scheme 2) are easily isolated in excellent yields by
filtration of the yellow to brown solid that is present throughout
the reaction, the exception being L3AuCl2 which required cooling
to induce crystallisation. This synthetic procedure is analogous to
Department of Chemistry, University of Waikato, Private Bag 3105,
Hamilton, New Zealand. E-mail: w.henderson@waikato.ac.nz; Fax: +64-
7-838-4219
† CCDC reference numbers 676314 and 676315 for L3AuCl2 and L6AuCl2
respectively. For crystallographic data in CIF or other electronic format
see DOI: 10.1039/b803835j
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was refluxed with H[AuCl4] in either an aqueous or an acetonitrile–
water (1 : 1) solution, or alternatively mixed with HL7 in an
aqueous acetonitrile solution of H[AuCl4] at room temperature,
the only product was the salt [H2L7][AuCl4]. This was identified
1
by H and 13C NMR spectroscopy and the presence of both the
[H2L7]+ and [AuCl4]− ions in positive- and negative-ion ESI mass
spectra respectively.
X-Ray crystal structures of L3AuCl2 and L6AuCl2
Single crystal X-ray structure analyses of L3AuCl2 and L6AuCl2
were carried out in order to confirm the bonding of the ligand
to the gold. In both cases, the ligands are deprotonated at the
sulfonamide nitrogen and bonded to the gold through the two
nitrogen atoms, with the remaining sites on the metal occupied by
two chloride ligands. L3AuCl2 crystallises with two independent
molecules per unit cell. Diagrams of the molecular structures
of L3AuCl2 and L6AuCl2, along with the atom numbering schemes,
are shown in Fig. 1 and 2 respectively. Important bond lengths and
angles are presented in Tables 1 and 2.
For both L3AuCl2 and L6AuCl2, the geometry around the d8
gold centre is essentially square planar, with the bite angle of
Scheme 1
Fig. 1 Molecular structure of L3AuCl2, showing one of the independent
molecules present in the unit cell, and the atom numbering scheme.
Scheme 2
the preparation of 12,3 however, similar reactions of the secondary
amines 10 and 11 only afforded the salts 12 and 13.7 The difference
in the reactivity can be attributed to the decreased acidity of the
NH protons in the ligands 10 and 11 relative to the sulfonamide
counterparts. NMR and IR spectroscopy, along with ESI mass
spectrometry indicate the nitrogen donor ligands are coordinated
to gold through the neutral pyridyl donor and the anionic amido
group. The formulation was confirmed by X-ray crystal structures
of the complexes L3AuCl2 and L6AuCl2.
Fig. 2 Molecular structure of L6AuCl2, showing the atom numbering
scheme, with the dichloromethane solvent omitted for clarity.
Attempted preparation of the analogous four-membered aura-
cyclic system L7AuCl2 from HL7 proved unsuccessful. When HL7
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˚
Table 1 A comparison of selected bond lengths (A) for the crystal
structures of L3AuCl2 (two independent molecules) and L6AuCl2
L3AuCl2
Molecule 1
Molecule 2
L6AuCl2
Au(1)–Cl(1)
Au–Cl(2)
Au–N (ex py)
Au–N (ex NH)
2.2872(10)
2.2720(10)
2.046(3)
2.2807(10)
2.2800(10)
2.037(3)
2.2789(8)
2.2637(9)
2.026(3)
2.038(3)
2.006(3)
2.021(3)
Table 2 A comparison of selected bond angles (◦) for the crystal struc-
tures of L3AuCl2 (including the two independent molecules) and L6AuCl2
L3AuCl2
Molecule 1
Molecule 2
L6AuCl2
Cl(1)–Au(1)–Cl(2)
89.09(4)
90.17(4)
88.13(3)
94.36(8)
81.48(11)
95.88(8)
Cl(1)–Au(1)–N(ex. py)
N(ex py)–Au(1)–N(ex NH)
N(ex NH)–Au(1)–Cl(2)
94.08(10)
78.98(13)
98.02(10)
93.89(10)
82.09(13)
93.79(10)
the sulfonamide ligand less than 90◦ in both cases (Table 2).
In L3AuCl2, the atom with the greatest deviation from the metal
coordination plane [defined by Au(1), N(1), N(2), Cl(1) and Cl(2)]
Fig. 3 (a) Structure of L3AuCl2 (molecule 1) showing the envelope
conformation of the cycloaurated ring with N(2) sitting above the plane
of the ring; (b) crystal structure of L6AuCl2 showing the planarity of the
quinoline group, with Au(1) sitting below the plane. For clarity, only the
ipso carbon of the p-tolyl group of L6AuCl2 is shown and hydrogen atoms
are omitted.
˚
˚
is N(1) [0.0817(15) A] and Au(1) [0.0280(10) A] for molecules 1
and 2 respectively. For L6AuCl2, the gold atom shows the greatest
deviation from the coordination plane [defined by Au(1), N(1),
˚
N(2), Cl(1) and Cl(2)], sitting 0.0514(8) A above the plane.
In all cases, the coordination around the deprotonated sul-
fonamide nitrogen N(2) is not planar, and is slightly distorted
towards tetrahedral geometry, with the ◦angles around the nitrogen
adding to 358.6◦ (molecule 1) and 344.2 (molecule 2) for L3AuCl2,
and 353.7◦ for L6AuCl2. Such distortion has previously been
observed and discussed by Otter et al. for copper(II), cobalt(II)
and palladium(II) compounds of the type ML2 (L = N-(2-
pyridin-2-yl-phenyl)-p-toluenesulfonamide).12 In addition, similar
cyclometallated gold(III)13 and platinum(II)14 compounds also
show this type of behaviour.
the ligands HL1–HL3 appear as a doublet due to coupling to the
NH proton of the sulfonamide group, whereas for HL4 and HL5
a triplet and an apparent quartet arise from the two methylene
groups. Upon coordination to the gold, the methylene signals
become either a singlet (for the five-membered ring systems)
or two triplets (for the six-membered ring systems) providing
unambiguous evidence for loss of the sulfonamide proton.
Coordination to the gold can clearly be seen in com-
pounds L1AuCl2 (Fig. 4) and L2AuCl2. A downfield shift of
approximately 0.7 ppm is seen for H-1 (the proton adjacent to the
coordinated pyridyl nitrogen) upon coordination to the gold, due
to the proximity of the gold atom and the increased deshielding
produced by the electron-withdrawing metal centre.
For the complexes L4AuCl2 and L5AuCl2 there appears to
be fluxionality in the six-membered auracyclic rings at 30 ◦C,
though contribution from inversion of an amide nitrogen which is
distorted from planarity, although unlikely, cannot be discounted.
The two methylene signals are seen as broad triplets; presumably
if the system was not fluxional the multiplets would be much more
complex due to the different stereochemical environment each
proton inhabits.
In both molecules of L3AuCl2, the cycloaurated ring [defined by
Au(1), C(1), C(5), N(1) and N(2)] is in a envelope conformation
˚
˚
with N(2) sitting above the ring (by 0.286(2) A and 0.206(2) A
for molecules 1 and 2 respectively). Due to the increased rigidity
imposed by the aromatic ring system, in L6AuCl2 it is Au(1) that
shows the greatest deviation from the plane [defined by C(1)–C(9),
˚
N(1) and N(2)], sitting 0.339(3) A above the plane of the quinoline
ring system (Fig. 3).
For L3AuCl2 the gold–sulfonamide nitrogen bond length is
shorter than the gold–pyridyl nitrogen bond length, but the
opposite is observed in the structure of L6AuCl2. The rigidity
imposed on the system by the quinoline moiety in L6AuCl2, in
comparison to the flexibility of L3AuCl2 system, is the probable
cause of this discrepancy.
The main points of interest in the IR spectra of the complexes
are the loss of NH stretching frequencies (∼3 100 cm−1) of the free
ligands and a shift to lower wavenumbers for the SO2 stretching
NMR and IR spectroscopic characterisation
=
modes, consistent with lengthening of the S O bonds through
Compounds of the type LAuCl2 were most suited to analysis by
NMR spectroscopy. The effect of coordination of the gold to
the ligand through the deprotonated sulfonamide nitrogen and
pyridyl nitrogen could clearly be seen. The methylene protons of
movement of electrons onto the sulfonyl oxygen atoms. For
example, the SO2 stretches shift from 1164 cm−1 and 1327 cm−1
(for the asymmetric and symmetric stretches respectively) in HL1
to 1146 cm−1 and 1306 cm−1 in the cycloaurated complex L1AuCl2.
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Fig. 4 1H NMR spectra (CDCl3, 300 MHz) of (a) HL1 and (b) L1AuCl2, showing changes in spectra upon coordination of the ligand to gold.
ESI mass spectrometry
bis(cycloaurated) species such as [(L2)2Au]+, dominate the spectra
as a result of their high ionisation efficiency, a phenomenon ob-
served previously in cyclometallated gold(III) dichloride species.16
For example, when L2AuCl2 is analysed without ionisation aids
(Fig. 5a), the spectrum is dominated by the ion at m/z 691 due to
[(L2)2Au]+, although there is no evidence for the presence of this
species in either the 1H NMR spectrum or microanalytical results.
Addition of NaCl to the sample before analysis produces ions at
m/z 537 (21%) and 1051 (10%) corresponding to [L2AuCl2 + Na]+
Analysis of the compounds L1AuCl2–L6AuCl2 by ESI-MS was
not overly effective for two reasons. Firstly, the compounds are
neutral so must either pick up an ion (e.g. H+ or Na+) to be easily
observed in the spectra or alternatively, coordination of a neutral
species (e.g. pyridine) produces an easily detectable cation through
displacement of Cl−.15 Secondly, because of the low ionisation
ability of the neutral species, cationic impurity ions, namely the
Fig. 5 Positive ion ESI mass spectra (cone voltage 20 V, MeOH solvent) of L2AuCl2 showing the observed ions under different ionisation conditions:
(a) neat solution; (b) with addition of NaCl; (c) with addition of pyridine (py).
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and [2(L2AuCl2) + Na]+ respectively, however [(L2)2Au]+ is still
the dominant peak. Addition of strongly coordinating pyridine
(py) to a solution of the compound in methanol forms species
identified as [L2AuCl(py)]+ and [L2Au(OMe)(py)]+ at m/z 558
and 554 respectively, however the ion at m/z 691 (40%) is still
present. Identification and confirmation of these ions is aided by
the presence of chlorine(s) and thus unique isotope patterns. A
similar pattern of behaviour was seen for all members of this
family of compounds.
activity of these complexes against murine leukaemia cell lines is
also low–possibly due to this lack of stability towards reduction.
Experimental
General
All reactions were carried out with no efforts at exclud-
ing air. 2-Picolylamine, 2-(2-aminoethyl)pyridine and 8-(p-
tosylamino)quinoline (Aldrich) were used as supplied, as were p-
toluenesulfonyl chloride (BDH), benzenesulfonyl chloride (BDH)
and methanesulfonyl chloride (Riedel-de Hae¨n). H[AuCl4]·4H2O
was synthesised from gold metal by the literature procedure,20
and yields of the dichloride complexes L1AuCl2–L6AuCl2 are
calculated assuming the above formulation. The sulfonamide
ligands (all previously reported compounds21–23) were synthesised
by the condensation of the appropriate sulfonyl chloride and
amine, following the procedure reported for HL1and HL4.24
ESI mass spectra were obtained on a VG Platform II instrument
operating at a cone voltage of 20 V, using methanol as the
solvent after the compound was dissolved in a small amount of
dichloromethane. IR spectra were recorded as KBr disks on a
Digilab Scimitar FT-IR, and NMR spectra on a Bruker DRX 400
FT-NMR spectrometer, operating at 30 ◦C, with a series of 1H, 13C,
Biological activity
Previously, C,N cycloaurated complexes, in particular the com-
pound (damp)AuCl2, (damp = 2-[(dimethylamino)methyl]phenyl)
and its derivatives have shown promising antitumour activity.17
Little data exist on N,Nꢀ-stabilised cycloaurated complexes and
for this reason complexes L1AuCl2–L5AuCl2 were screened for
antitumour activity against the P388 murine leukemia cell line.
Results indicate an IC50 value of greater than 12 500 ng mL−1 for
all compounds, indicating little activity against this particular cell
line.
Reactivity
When C,N cycloaurated dichloride species are reacted with
tertiary phosphines, the chloride ligands may be displaced by
coordination of the neutral phosphines to the gold or conversely,
cleavage of the Au–N bond may occur with both Au–Cl bonds
remaining intact; in each case gold(III) products are formed. Such
reactions can give an indication of the strength of the gold–
nitrogen bond and are dependent on the cycloaurated ligand
present.1
Reaction of L1AuCl2 with PPh3 in a 1 : 1 molar ratio in
dichloromethane resulted in lightening of the solution from yellow
to pale yellow. ESI-MS of the solution showed ions corresponding
1
DEPT-135, H-1H COSY, HMBC, HSQC and 1D-SELNOESY
experiments utilised in the assignment of the NMR spectra.
Antitumour activities against the P388 murine leukemia cell line
were determined at the University of Canterbury. Methods have
been described previously,25 and samples were analysed as 1 : 1
dichloromethane–methanol solutions.
Synthesis of L1AuCl2
HL1 (0.560 g, 2.13 mmol) and H[AuCl4]·4H2O (0.877 g, 2.13 mmol)
were added to water (75 mL) to give an orange suspension. This
was refluxed with stirring for 3 h and cooled to room temperature.
The orange precipitate that was present throughout the reaction
was filtered, washed with water (2 × 10 mL) and isopropanol (2 ×
10 mL) and air dried to give L1AuCl2 (0.918 g, 82%) as an orange
solid. Found: C 29.6, H 2.5, N 5.3; C13H13N2SO2AuCl2 requires
+
=
to the gold(I) species [Au(PPh3)2] (m/z 721), PPh3 and Ph3P O.
31P-{ H} NMR spectroscopy of the solution gave peaks at d 30
1
=
(br s) and 34 (s) ppm, the first of which arises from Ph3P O, and
the second from an average of rapidly exchanging [Au(PPh3)2]+
with free PPh3.18 Likewise, when L1AuCl2 was reacted with PPh3
in a 1 : 2 ratio, ESI-MS gave ions due to [Au(PPh3)2]+, PPh3 and
1
C 29.6, H 2.5, N 5.3%. NMR (CDCl3): H d 2.40 (s, 3H, H-11),
Ph3P O; the 31P-{ H} NMR spectrum again showed peaks at
1
3
=
4.88 (s, 2H, H-6), 7.26 (d, J9,8 = 8.5 Hz, 2H, H-9), 7.62 (ddd,
d 30 (s) and 34 (s) ppm. Reaction of L1AuCl2 with thiosalicylic
acid using previously established methods19 resulted in immediate
reduction and decomposition of the gold species to elemental
gold. These results indicate that the N,Nꢀ cycloaurated ligands
are not as effective at stabilising the Au(III) centre as are C,N
cycloaurated ligands, so reactions can result in reduction of the
gold(III), suggesting that these complexes may have limited utility.
3J2,1 = 6.1 Hz, 3J2,3 = 7.7 Hz, 4J2,4 = 1.6 Hz, 1H, H-2), 7.73 (dd,
3J4,3 = 7.8 Hz, 4J4,2 = 1.6 Hz, 1H, H-4), 7.87 (d, 3J8,9 = 8.5 Hz, 2H,
3
3
4
H-8), 8.13 (td, J3,2 = 7.7 Hz, J3,4 = 7.8 Hz, J3,1 = 1.5 Hz, 1H,
H-3), 9.22 (dd, 3J1,2 = 6.1 Hz, 4J1,3 = 1.5 Hz, 1H, H-1); 13C-{ H}
1
d 21.7 (C-11), 61.6 (C-6), 121.7 (C-4), 125.5 (C-2), 127.8 (C-8),
129.7 (C-9), 138.0 (C-7), 143.2 (C-3), 143.6 (C-10), 147.5 (C-1),
166.9 (C-5) (see Scheme 3 for NMR numbering scheme). ESI-
MS: (NaCl added) m/z 551 (32%, [L1AuCl2 + Na]+), 719 (100%,
Conclusions
Six new cycloaurated gold(III) complexes containing N,Nꢀ cy-
clometallated ligands have been synthesised and fully charac-
terised, including the X-ray crystal structures of two of these
complexes. Coordination to the gold is through pyridyl and
deprotonated amide nitrogen atoms. Unlike the more common
analogous C,N cyclometallated compounds, these complexes
show lower stability, as reactions with reducing agents leads to
reduction of Au(III) to Au(I) or elemental gold. The biological
Scheme 3 NMR numbering scheme for L1AuCl2–L3AuCl2. For com-
plex L3AuCl2, the methyl carbon is labelled C-7. Hydrogens are labelled
according to the carbon they are directly bonded to.
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[(L1)2Au]+), 1079 (10%, [2(L1AuCl2) + Na]+); (pyridine added) m/z
568 (28%, [L1Au(OMe)(py)]+), 572 (100%, [L1AuCl(py)]+), 719
(25%, [(L1)2Au]+). IR: m(SO2)sym 1306 (s), m(SO2)asym 1146 (vs) cm−1.
(d, 3J10,9 = 8.2 Hz, 2H, H-10), 7.57 (d, 3J9,10 = 8.2 Hz, 2H, H-9),
7.74 (ddd, 3J2,1 = 6.0 Hz, 3J2,3 = 7.7 Hz, 4J2,4 = 1.5 Hz, 1H, H-2),
3
4
7.77 (dd, J4,3 = 7.8 Hz, J4,2 = 1.5 Hz, 1H, H-4), 8.26 (td, 1H,
3J3,2 = 7.7 Hz, 3J3,4 = 7.8 Hz, 4J3,1 = 1.4 Hz, 1H, H-3), 8.91 (dd,
4
1
3J1,2 = 6.0 Hz, J1,3 = 1.4 Hz, 1H, H-1); 13C-{ H} d 20.8 (C-12),
37.6 (C-6), 42.4 (C-7), 126.0 (C-2), 126.8 (C-9), 127.7 (C-4), 129.4
(C-10), 137.8 (C-8), 142.2 (C-11), 143.8 (C-3), 149.7 (C-1), 155.5
(C-5) (see Scheme 4 for NMR numbering scheme). ESI-MS: (NaCl
added) m/z 565 (100%, [L4AuCl2 + Na]+), 747 (91%, [(L4)2Au]+),
1107 (19%, [2(L4AuCl2) + Na]+); (pyridine added) m/z 582 (50%,
[L4Au(OMe)(py)]+), 586 (100%, [L4AuCl(py)]+). IR: m(SO2)sym 1311
(s), m(SO2)asym 1148 (vs) cm−1.
Synthesis of L2AuCl2
As for the synthesis of L1AuCl2, HL2 (0.566 g, 2.28 mmol) was
suspended in an aqueous (50 mL) solution of H[AuCl4]·4H2O
(0.939 g, 2.28 mmol) and refluxed with stirring for 3 h. The
precipitate that was present throughout was filtered and washed
with water (2 × 10 mL) and isopropanol (2 × 10 mL). The
yellow/brown solid was air dried to give L2AuCl2 (0.964 g, 82%).
Found: C 27.9, H 2.1, N 5.4; C12H11N2SO2AuCl2 requires C 28.0,
1
H 2.2, N 5.5%. NMR (CDCl3): H d 4.91 (s, 2H, H-6), 7.47 (t,
3
3
3J9,10 = 8.0 Hz, J9,8 = 7.2 Hz, 2H, H-9), 7.53 (t, J10,9 = 8.0 Hz,
1H, H-10), 7.63 (ddd, 3J2,1 = 6.1 Hz, 3J2,3 = 7.6 Hz, 4J2,4 = 1.6 Hz,
1H, H-2), 7.74 (dd, 3J4,3 = 7.8 Hz, 4J4,2 = 1.6 Hz, 1H, H-4), 7.99
(d, 3J8,9 = 7.2 Hz, 2H, H-8), 8.13 (td, 3J3,2 = 7.6 Hz, 3J3,4 = 7.8 Hz,
4J3,1 = 1.5 Hz, 1H, H-3), 9.22 (dd, 3J1,2 = 6.1 Hz, 4J1,3 = 1.5 Hz, 1H,
1
H-1); 13C-{ H} d 61.6 (C-6), 121.7 (C-4), 125.5 (C-2), 127.7 (C-8),
Scheme 4 NMR numbering scheme for L4AuCl2 and L5AuCl2. Hydro-
gens are labelled according to the carbon they are directly bonded to.
129.0 (C-9), 141.2 (C-7), 143.2 (C-3), 132.7 (C-10), 147.5 (C-1),
166.7 (C-5) (see Scheme 3 for NMR numbering scheme). ESI-
MS: (NaCl added) m/z 537 (21%, [L2AuCl2 + Na]+), 691 (100%,
[(L2)2Au]+), 1051 (10% [2(L2AuCl2) + Na]+; (pyridine added) m/z
554 (40%, [L2Au(OMe)(py)]+), 558 (100% [L2AuCl(py)]+), 691
(40%, [(L2)2Au]+). IR: m(SO2)sym 1313 (s), m(SO2)asym 1155 (vs) cm−1.
Synthesis of L5AuCl2
HL5 (0.329 g, 1.25 mmol) and aqueous (30 mL) H[AuCl4]·4H2O
(0.515 g, 1.25 mmol) were refluxed with stirring for 3 h, resulting
in the formation of a red/orange precipitate. This was filtered,
washed with water (2 × 10 mL) and isopropanol (10 mL).
The crude product was recrystallised by dissolving in minimum
dichloromethane, filtering off the insoluble yellow precipitate, and
adding diethyl ether to the filtrate until the solution went cloudy.
The resulting dark red crystals were filtered and washed with
diethyl ether (2 × 10 mL) and dried to give L5AuCl2 (0.436 g,
66%). Found: C 29.7, H 2.6, N 5.4; C13H13N2SO2AuCl2 requires
Synthesis of L3AuCl2
HL3 (0.200 g, 1.07 mmol) was dissolved in a solution of
H[AuCl4].4H2O (0.441 g, 1.07 mmol) in water (30 mL). Upon
reaching reflux temperature, the yellow solution turned deep
orange and remained this colour for the duration of the reflux
(2 h). The clear solution was cooled in an ice bath which resulted
in the deposition of orange/red microcrystals. These were filtered
and washed with water (2 × 10 mL) and isopropanol (2 × 10 mL)
and air dried to give L3AuCl2 (0.266 g, 55%). Found: C 18.1, H
1.9, N 6.0; C7H9N2SO2AuCl2 requires C 18.6, H 2.0, N 6.2%.
NMR (d6-DMSO): 1H d 3.10 (s, 3H, H-7), 4.96 (s, 2H, H-6), 7.80
1
C 29.5, H 2.5, N 5.3%. NMR (d6-DMSO): H d 3.25 (br t, 2H,
3
3
H-7), 3.48 (t, J6,7 = 6.4 Hz, 2H, H-6), 7.41 (t, J10,11 = 7.5 Hz,
3J10,9 = 7.0 Hz, 2H, H-10), 7.48 (t, J11,10 = 7.5 Hz, 1H, H-11),
3
3
3
4
(ddd, J2,1 = 6.2 Hz, J2,3 = 7.6 Hz, J2,4 = 1.2 Hz, 1H, H-2),
7.70 (d, 3J9,10 = 7.0 Hz, 2H, H-9), 7.75 (ddd, 3J2,1 = 6.0 Hz, 3J2,3
7.8 Hz, 4J2,4 = 1.7 Hz, 1H, H-2), 7.77 (dd, 3J4,3 = 7.7 Hz, 4J4,2
=
=
=
8.05 (dd, 3J4,3 = 7.7 Hz, 4J4,2 = 1.2 Hz, 1H, H-4), 8.33 (td, 3J3,2
7.6 Hz, 3J3,4 = 7.7 Hz, 4J3,1 = 1.4 Hz, 1H, H-3), 9.04 (dd, 3J1,2
=
=
3
3
4
1.7 Hz, 1H, H-4), 8.25 (td, J3,2 = 7.8 Hz, J3,4 = 7.7 Hz, J3,1
4
1
6.2 Hz, J1,3 = 1.4 Hz, 1H, H-1); 13C-{ H} d 41.9 (C-7), 61.1
(C-6), 122.1 (C-4), 125.6 (C-2), 143.8 (C-3), 146.5 (C-1), 166.2 (C-
5) (see Scheme 3 for NMR numbering scheme). ESI-MS: (NaCl
added) m/z 475 (100%, [L3AuCl2 + Na]+), 567 (84%, [(L3)2Au]+),
927 (56%, [2(L3AuCl2) + Na]+); (pyridine added) m/z 492 (45%,
[L3Au(OMe)(py)]+), 496 (100%, [L3AuCl(py)]+). IR: m(SO2)sym 1306
(s), m(SO2)asym 1132 (vs) cm−1.
1.4 Hz, 1H, H-3), 8.95 (dd, 3J1,2 = 6.0 Hz, 4J1,3 = 1.4 Hz, 1H, H-1);
13C-{ H} d 37.6 (C-6), 42.4 (C-7), 126.0 (C-2), 126.7 (C-9), 127.7
1
(C-4), 128.9 (C-10), 131.9 (C-11), 140.6 (C-8), 143.9 (C-3), 149.7
(C-1), 155.5 (C-5) (See Scheme 4 for NMR numbering scheme).
ESI-MS: (NaCl added) m/z 547 (55%, [L5Au(OMe)Cl + Na]+),
551 (100%, [L5AuCl2 + Na]+), 1079 (25%, [2(L5AuCl2) + Na]+);
(pyridine added) m/z 568 (100%, [L5Au(OMe)(py)]+), 572 (78%,
[L5AuCl(py)]+). IR: m(SO2)sym 1320 (s), m(SO2)asym 1149 (vs) cm−1.
Synthesis of L4AuCl2
To an aqueous (30 mL) solution of H[AuCl4]·4H2O (0.531 g,
1.29 mmol), HL4 (0.357 g, 1.29 mmol) was added and the yellow
solution refluxed with stirring for 3.5 h. During this time a brown
solid formed, which after cooling was filtered, dried and washed
with water (2 × 10 mL) and ether (10 mL) to give L4AuCl4 (0.542 g,
78%). Found: C 31.1, H 2.9, N 5.3; C14H15N2SO2AuCl2 requires
Synthesis of L6AuCl2
8-(p-Tosylamino)quinoline (0.176 g, 0.590 mmol) was suspended
in aqueous (30 mL) H[AuCl4]·4H2O (0.243 g, 0.590 mmol)
and refluxed with stirring for 8 h. When the mixture reached
reflux temperature, a brown solid formed that remained present
throughout the duration of the reaction. The mixture was allowed
to cool before being filtered, washed with H2O (2 × 10 mL) and
1
C 31.0, H 2.8, N 5.2%. NMR (d6-DMSO): H d 2.31 (s, 3H, H-
3
12), 3.23 (br t, 2H, H-7), 3.47 (t, J6,7 = 6.3 Hz, 2H, H-6), 7.19
3904 | Dalton Trans., 2008, 3899–3906
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isopropanol (2 × 10 mL) and dried under vacuum, to give L6AuCl2
as a brown solid (0.241 g, 72%). Found: C 33.9, H 2.3, N 5.0;
C16H13N2SO2AuCl2 requires C 34.0, H 2.3, N 5.0%. NMR (d6-
When cool, the solution was filtered and the solid washed with
water (2 × 10 mL) and isopropanol (10 mL) to give 0.188 g (26%)
of a brown solid, which was identified as the salt [H2L7][AuCl4].
1
3
DMSO): H d 2.30 (s, 3H, H-14), 7.26 (d, J12,11 = 8.3 Hz, 2H,
H-12), 7.67 (d, 3J11,12 = 8.3 Hz 2H, H-11), 7.76 (t, 3J6,7/5 = 7.7 Hz,
1H, H-6), 7.81 (dd, 3J7,6 = 7.7 Hz, 4J7,5 = 1.6 Hz, 1H, H-7), 7.86
NMR (CDCl3): 1H d (ppm) 2.38 (s, 3H, H-10), 6.80 (ddd, 3J2,1
=
3
4
3
5.9 Hz, J2,3 = 7.1 Hz, J2,4 = 1.1 Hz, 1H, H-2), 7.24 (d, J8,7
=
8.1 Hz, 2H, H-8), 7.40 (dd, 3J4,3 = 8.9 Hz, 4J4,2 = 1.1 Hz, 1H, H-4),
7.64 (ddd, 3J3,2 = 7.1 Hz, 3J3,4 = 8.9 Hz, 4J3,1 = 1.9 Hz, 1H, H-3),
3
4
3
(dd, J5,6 = 7.7 Hz, J5,7 = 1.6 Hz, 1H, H-5), 7.93 (dd, J2,1
=
=
5.6 Hz, 3J2,3 = 8.3 Hz, 1H, H-2), 8.92 (dd, 3J3,2 = 8.3 Hz, 4J3,1
7.79 (d, 3J7,8 = 8.1 Hz, 2H, H-7), 8.34 (dd, 3J1,2 = 5.9 Hz, 4J1,3
=
1.1 Hz, 1H, H-3), 9.21 (dd, 3J1,2 = 5.6 Hz, 4J1,3 = 1.1 Hz, 1H, H-
1.9 Hz, 1H, H-1), NH not observed; 13C-{ H} d 21.6 (C-10), 114.7
(C-2), 115.1 (C-4), 127.0 (C-7), 129.7 (C-8), 138.8 (C-6), 141.5 (C-
1), 141.9 (C-3), 143.1 (C-9), 155.0 (C-5) (see Scheme 6 for NMR
numbering scheme). ESI-MS: (positive ion, cone voltage 20 V):
m/z 249 (100%, [H2L7]+); (negative ion, cone voltage 20 V): m/z
339 (100%, [AuCl4]−).
1
1); 13C-{ H} d 21.1 (C-14), 123.5 (C-2), 124.3 (C-5), 125.9 (C-7),
1
126.8 (C-11), 129.7 (C-12), 130.0 (C-6), 130.7 (C-4), 138.8 (C-
10), 143.3 (C-13), 143.7 (C-9), 144.0 (C-3), 146.0 (C-8), 148.1 (C-
1) (see Scheme 5 for NMR numbering scheme). ESI-MS: (NaCl
added) m/z 587 (100%, [L6AuCl2 + Na]+); (pyridine added) m/z
608 (100%, [L6AuCl(py)]+), 604 (35%, [L5Au(OMe)(py)]+). IR:
m(SO2)sym 1326 (s), m(SO2)asym 1158 (vs) cm−1.
Scheme 6 NMR numbering scheme for [H2L7][AuCl4]. Hydrogens are
labelled according to the carbon they are directly bonded to.
(ii) Standing with H[AuCl4] in MeCN–H2O solution. HL7
(0.108 g, 0.43 mmol) was dissolved in MeCN (5 mL) and
added dropwise to aqueous (20 mL) H[AuCl4]·4H2O (0.177 g,
0.43 mmol). The solution was left to stand and after 2 weeks a
light brown solid had formed. This was filtered and washed with
water (2 × 10 mL) and ether (1 × 10 mL), to give 0.078 g (31%)
of [H2L7][AuCl4], which was identified by ESI-MS and 1H NMR
spectroscopy.
Scheme 5 NMR numbering scheme for L6AuCl2. Hydrogens are labelled
according to the carbon they are directly bonded to.
Attempted preparation of L7AuCl2
(i) Reflux with H[AuCl4] in water. HL7 (0.310 g, 1.25 mmol)
was refluxed with stirring in aqueous (30 mL) H[AuCl4]·4H2O
(0.515 g, 1.25 mmol) for 1 h, after which a brown solid had formed.
(iii) Refluxing in 1 : 1 MeCN–H2O. HL7 (0.050 g, 0.20 mmol)
and H[AuCl4]·4H2O (0.082 g, 0.20 mmol) were refluxed in aqueous
(20 mL) MeCN (1 : 1) with stirring for 3 h. The solution was left
Table 3 Crystal and refinement data for the complexes L3AuCl2 and L6AuCl2
Complex
L3AuCl2
L6AuCl2
Formula
Mr
C7H9AuCl2N2O2S
453.09
89
Triclinic
¯
P1
7.3424(1)
9.2813(1)
17.2700(2)
99.383(1)
95.785(1)
102.127(1)
1124.06(2)
4
C16H13AuCl2N2O2S·CH2Cl2
650.14
93
T/K
Crystal system
Space group
Monoclinic
P21/n
˚
a/A
14.1782(6)
10.6792(5)
14.4771(6)
90
115.147(2)
90
1984.2(2)
4
2.176
˚
b/A
˚
c/A
a/◦
b/◦
c /◦
3
˚
V/A
Z
D
calc/g cm−3
2.677
Max., min, transmission
Number of unique reflections
Number of observed reflections [I > 2r(I)]
R [I > 2r(I)]
0.1699, 0.1138
4562
4360
0.0203
0.0512
0.2950, 0.0597
6252
5476
0.0293
0.0868
1.046
wR2 (all data)
Goodness of fit
1.117
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to stand overnight and brown crystals were formed. These were
subsequently identified as [H2L7][AuCl4] (0.037 g, 31%).
3 D. Fan, C.-T. Yang, J. D. Ranford and J. J. Vittal, Dalton Trans., 2003,
4749.
4 T. Yang, J.-Y. Zhang, C. Tu, J. Lin, Q. Liu and Z.-J. Guo, Chin. J. Inorg.
Chem., 2003, 19, 45.
X-Ray crystal structure determinations of L3AuCl2 and L6AuCl2†
5 T.-C. Cheung, T.-F. Lai and C.-M. Che, Polyhedron, 1994, 13, 2073.
6 A. Dogan, B. Schwederski, T. Schleid, F. Lissner, J. Fiedler and W.
Kaim, Inorg. Chem. Commun., 2004, 7, 220.
7 S. Schouteeten, O. R. Allen, A. D. Haley, G. L. Ong, G. D. Jones and
D. A. Vicic, J. Organomet. Chem., 2006, 691, 4975.
8 T. Yang, C. Tu, J. Zhang, L. Lin, X. Zhang, Q. Liu, J. Ding, Q. Xu and
Z. Guo, Dalton Trans., 2003, 3419.
9 J. Vicente, M. T. Chicote, R. Guerrero, U. Herber and D. Bautista,
Inorg. Chem., 2002, 41, 1870.
10 L. Cao, M. C. Jennings and R. J. Puddephatt, Inorg. Chem., 2007, 46,
1361.
SinglecrystalsofL3AuCl2 andL6AuCl2 suitableforX-raystructure
analysis were obtained by slow diffusion of diethyl ether into a
dichloromethane solution of the compounds, at room temperature
◦
and −20 C respectively. L3AuCl2 crystallised as orange prisms
with two independent molecules per unit cell, and L6AuCl2 as
brown cubes as a CH2Cl2 solvate.
Intensity data and unit cell dimensions were obtained at the
University of Auckland on a Bruker Smart CCD diffractometer
(L3AuCl2) and at the University of Canterbury on a Bruker Apex II
diffractometer (L6AuCl2). The data were corrected for absorption
using SADABS.26
11 For recent examples see: B. Mac´ıas, M. V. Villa, M. Salgado, J. Borra´s,
´
M. Gonza´lez-Alvarez and F. Sanz, Inorg. Chim. Acta, 2006, 359, 1465;
M. H. Lim and S. J. Lippard, J. Am. Chem. Soc., 2005, 127, 12170; B.
Mac´ıas, M. V. Villa, I. Garc´ıa, A. Castin˜eiras, J. Borra´s and R. Cejudo-
Marin, Inorg. Chim. Acta, 2003, 342, 241; P. Jiang, L. Chen, J. Lin, Q.
Liu, J. Ding, X. Gao and Z. Guo, Chem. Commun., 2002, 1424.
12 C. A. Otter, S. M. Couchman, J. C. Jeffery, K. L. V. Mann, E. Psillakis
and M. D. Ward, Inorg. Chim. Acta, 1998, 278, 178.
13 K. J. Kilpin, W. Henderson and B. K. Nicholson, Polyhedron, 2007, 26,
434.
The structures of L3AuCl2 and L6AuCl2 were solved using
the Patterson and Direct methods options of SHELXS-9727
respectively. The gold atom was initially located, followed by the
location of all other non-hydrogen atoms by a series of difference
maps. Full-matrix least-squares refinement (SHELXL-97)28 was
14 C. Evans, W. Henderson and B. K. Nicholson, Inorg. Chim. Acta, 2001,
2
314, 42.
based upon Fo with all non-hydrogen atoms anisotropic, and
15 W. Henderson and C. Evans, Inorg. Chim. Acta, 1999, 294, 183.
16 M. B. Dinger and W. Henderson, J. Organomet. Chem., 1998, 560, 233.
17 R. G. Buckley, A. M. Elsome, S. P. Fricker, G. R. Henderson, B. R. C.
Theobald, R. V. Parish, B. P. Howe and L. R. Kelland, J. Med. Chem.,
1996, 39, 5208.
hydrogen atoms in calculated positions.
Crystal and refinement data for the complexes are presented in
Table 3. CCDC reference numbers 676314 and 676315 for L3AuCl2
and L6AuCl2 respectively. For crystallographic data in CIF or
other electronic format see DOI: 10.1039/b803835j
18 B. D. Alexander, P. D. Boyle, B. J. Johnson, J. A. Casalnuovo, S. M.
Johnson, A. M. Mueting and L. H. Pignolet, Inorg. Chem., 1987, 26,
2547.
19 W. Henderson, B. K. Nicholson, S. J. Faville, D. Fan and J. D. Ranford,
J. Organomet. Chem., 2001, 631, 41.
20 Synthetic Methods of Organometallic and Inorganic Chemistry, ed.
W. A. Herrmann, Thieme, Stuttgart, 1999, vol. 5, p. 60.
21 L. Gutierrez, G. Alzuet, J. Borra´s, M. Liu-Gonza´lez, F. Sanz and A.
Castin˜eiras, Polyhedron, 2001, 20, 703.
22 W. J. Houlihan, S. H. Cheon, D. A. Handley and D. A. Larson, J. Lipid
Mediators, 1991, 3, 91.
23 M. Doering, E. Mueller, E. Uhlig and B. Undeutsch, Z. Anorg. Allg.
Chem., 1987, 547, 7.
Acknowledgements
We thank the University of Waikato for financial support of this
work and the Tertiary Education Commission for a Top Achievers
Doctoral Scholarship (KJK). We also thank Dr Tania Groutso
(University of Auckland) and Dr Jan Wikaira (University of
Canterbury) for collection of X-ray intensity data and Gill Ellis
(University of Canterbury) for biological assay data. Mr Bevan
Jarman is also thanked for helpful discussions.
24 M. H. Klingele, B. Moubaraki, K. S. Murray and S. Brooker, Chem.–
Eur. J., 2005, 11, 6962.
25 W. Henderson, B. K. Nicholson and A. L. Wilkins, J. Organomet.
Chem., 2005, 690, 4971.
26 R. H. Blessing, Acta Crystallogr., Sect. A, 1995, A51, 33.
27 G. M. Sheldrick, SHELXS-97, Program for solution of crystal struc-
tures, University of Go¨ttingen, Germany, 1997.
28 G. M. Sheldrick, SHELXL-97, Program for refinement of crystal
structures, University of Go¨ttingen, Germany, 1997.
References
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3906 | Dalton Trans., 2008, 3899–3906
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The Royal Society of Chemistry 2008
©