Reactions of palladium and gold complexes with zinc-thiolate chelates using electrospray mass spectrometry and X-ray diffraction: Molecular identification of [Pd(bme-dach)], [Au(bme-dach]+ and [ZnCl(bme-dach)]2Pd

Article abstract of DOI:10.1039/b917748p

The reaction between the complexes [MCl(L)]Cl_x (L = 2,2′,2′′-terpyridine, terpy and dien, diethylenetriamine; M = Pd, x = 1; M = Au, x = 2) and [Zn(bme-dach)]₂, an N₂S ₂-Zn-thiolate bridged dimer used to mimic zinc finger protein sites, was studied by Electrospray Ionisation Mass Spectrometry and the structures of some of the products confirmed by X-ray crystallography. All reactions investigated in this work gave heteronuclear (Zn-thiolate)-metal products, the predominant species being the trinuclear dithiolate-bridged aggregate {[Zn(bme-dach)]₂M}ⁿ⁺ (M = Pd, Au). X-Ray diffraction studies verified the molecular structure of [{ZnCl(bme-dach)}₂Pd], and further confirmed that the zinc within the [Zn(bme-dach)]₂ unit was retained within the N₂S₂ binding site. The Zn-bound thiolates form stable thiolate bridges to Pd²⁺ in a stair-step shape, held together by a planar PdS₄ center. In addition, both zinc atoms maintained penta-coordinate coordination with apical chloride ligands rather than the more commonly observed tetrahedral geometry. Further, [Pd(bme-dach)] was directly synthesized for X-ray structural characterization of the metal exchanged product observed in mass spectrometry experiments. In the case of Au compounds, the reactions were very fast and the products were similar for both [AuCl(L)]Cl₂ (L = terpy and dien) starting materials. In addition to the multimetallic Zn,Au,Zn aggregate formation, the predominant species from the reaction between [Zn(bme-dach)]₂ and both Au compounds was the [Au(bme-dach]⁺ cation observable via ESI-MS, suggesting Zn/Au metal exchange immediately after mixing the compounds. The direct synthesis of [Au(bme-dach)]BPh₄ confirmed the molecular structure of this species through X-ray crystallography. The reactivity profile of Pd²⁺ and Au³⁺ species is compared with previous studies using the isostructural Pt compounds and the biological relevance of the results discussed. The Royal Society of Chemistry 2009.

Full text of DOI:10.1039/b917748p

View Article Online / Journal Homepage / Table of Contents for this issue
This paper is published as part of a Dalton Transactions themed issue on:
Metal Anticancer Compounds
Guest Editor Peter Sadler
University of Warwick, UK
Published in issue 48, 2009 of Dalton Transactions
Image reproduced with permission of Chi-Ming Che
Articles published in this issue include:
PERSPECTIVES:
Non-traditional platinum compounds for improved accumulation, oral bioavailability, and tumor
targeting
Katherine S. Lovejoy and Stephen J. Lippard, Dalton Trans., 2009, DOI: 10.1039/b913896j
Metal complexes as photochemical nitric oxide precursors: Potential applications in the treatment
of tumors
Alexis D. Ostrowski and Peter C. Ford, Dalton Trans., 2009, DOI: 10.1039/b912898k
Novel and emerging approaches for the delivery of metallo-drugs
Carlos Sanchez-Cano and Michael J. Hannon, Dalton Trans., 2009, DOI: 10.1039/b912708a
HOT ARTICLE:
Iron(III) complexes of fluorescent hydroxamate ligands: preparation, properties, and cellular
processing
Antonia J. Clarke, Natsuho Yamamoto, Paul Jensen and Trevor W. Hambley, Dalton Trans., 2009,
DOI: 10.1039/b914368h
Visit the Dalton Transactions website for more cutting-edge inorganic and bioinorganic research
www.rsc.org/dalton

PAPER
www.rsc.org/dalton | Dalton Transactions
Reactions of palladium and gold complexes with zinc-thiolate chelates using
electrospray mass spectrometry and X-ray diffraction: molecular
identification of [Pd(bme-dach)], [Au(bme-dach]+ and [ZnCl(bme-dach)]2Pd†
Queite A. de Paula,a Qin Liu,a Elky Almaraz,b Jason A. Denny,b John B. Mangrum,a Nattamai Bhuvanesh,b
Marcetta Y. Darensbourgb and Nicholas P. Farrell*a
Received 27th August 2009, Accepted 10th November 2009
First published as an Advance Article on the web 17th November 2009
DOI: 10.1039/b917748p
The reaction between the complexes [MCl(L)]Clx (L = 2,2¢,2¢¢-terpyridine, terpy and dien,
diethylenetriamine; M = Pd, x = 1; M = Au, x = 2) and [Zn(bme-dach)]2, an N2S2-Zn-thiolate bridged
dimer used to mimic zinc finger protein sites, was studied by Electrospray Ionisation Mass
Spectrometry and the structures of some of the products confirmed by X-ray crystallography. All
reactions investigated in this work gave heteronuclear (Zn-thiolate)-metal products, the predominant
n+
species being the trinuclear dithiolate-bridged aggregate {[Zn(bme-dach)]2M} (M = Pd, Au). X-Ray
diffraction studies verified the molecular structure of [{ZnCl(bme-dach)}2Pd], and further confirmed
that the zinc within the [Zn(bme-dach)]2 unit was retained within the N2S2 binding site. The Zn-bound
thiolates form stable thiolate bridges to Pd2+ in a stair-step shape, held together by a planar PdS4 center.
In addition, both zinc atoms maintained penta-coordinate coordination with apical chloride ligands
rather than the more commonly observed tetrahedral geometry. Further, [Pd(bme-dach)] was directly
synthesized for X-ray structural characterization of the metal exchanged product observed in mass
spectrometry experiments. In the case of Au compounds, the reactions were very fast and the products
were similar for both [AuCl(L)]Cl2 (L = terpy and dien) starting materials. In addition to the
multimetallic Zn,Au,Zn aggregate formation, the predominant species from the reaction between
[Zn(bme-dach)]2 and both Au compounds was the [Au(bme-dach]+ cation observable via ESI-MS,
suggesting Zn/Au metal exchange immediately after mixing the compounds. The direct synthesis of
[Au(bme-dach)]BPh4 confirmed the molecular structure of this species through X-ray crystallography.
The reactivity profile of Pd2+ and Au3+ species is compared with previous studies using the isostructural
Pt compounds and the biological relevance of the results discussed.
including Cd2+, Hg2+, Pb2+, Ni2+, Pt2+, Co2+, and Fe2+ have been
Introduction
shown to substitute Zn2+ in zinc finger domains.6,7
Zinc finger (ZF) proteins are the most frequently used class of
Inactivation of zinc fingers may also be a mechanism
transcription factors, accounting for 3% of genes in the human
of action for metallodrugs. Specifically, platinum-nucleobase
genome.1,2 These structural elements are associated with protein-
nucleic acid and protein-protein interactions. They display many
diverse functions, including DNA recognition, RNA packaging,
protein folding and assembly, transcriptional activation as well as
cell differentiation and growth.3,4 The most common ligands for
Zn2+ in zinc finger proteins are cysteine (S donor) and histidine
(N donor) in Cys2His2, Cys3His and Cys4 coordination motifs.
The Cys residues of Zn2+ are reactive and changes in the cellular
redox state and/or exposure to electrophilic agents can alter DNA
binding activities of ZF transcription factors.5 Several metals,
compounds such as trans-[PtCl(9-EtGua)(pyr)2]+ and SP-
4-2-[PtCl(9-EtGua)(NH3)(quinoline)]+ have moderate antivi-
ral selectivity and can form ternary adducts with the
C-terminal finger of HIV NCp7 (F2) with eventual ejection of
Zn2+ and incorporation of Pt2+ into the binding site.8,9 Zinc-
Finger-Pt-DNA interactions may also be relevant for those
proteins which recognize platinated DNA (Sp1, UVrABC).10 The
anti-arthritic gold compound, aurothiomalate, diminishes OB2-1
dependent c-erbB-2 transcription by inhibiting the binding of this
positively acting transcription factor to DNA.11 The purported
zinc site of OB2-1 was suggested as the target. More specifically,
aurothiomalate interacts with the Cys2His2 zinc fingers of TFIIIA
and Sp1 with subsequent inhibition of the DNA-binding activity
of the protein.5 Studies using a model peptide based on the
third zinc finger of Sp1 confirmed that Au1+ binding triggered
zinc release.5 It has been found that the formation of Au1+ aqua
complexes are often unstable and may disproportionate to form
Au0 and Au3+ species.12 It has been suggested that certain side
effects brought about during gold(I) anti-arthritic therapy are due
aDepartment of Chemistry, Virginia Commonwealth University, Richmond,
Virginia 23284-2006, USA. E-mail: npfarrell@vcu.edu; Fax: 804-828-8599;
Tel: 804-828-6320
bDepartment of Chemistry, Texas A&M University, College Station, TX
77842, USA
† Electronic supplementary information (ESI) available: Ball and stick
images of the [Pd(bme-dach)] structural disorder, mass spectral data of
Au3+ compounds with Zn compounds. CCDC reference numbers 743609–
743611. For ESI and crystallographic data in CIF or other electronic
format see DOI: 10.1039/b917748p
10896 | Dalton Trans., 2009, 10896–10903
This journal is
The Royal Society of Chemistry 2009
©

to the formation of Au3+ complexes. Further, evidence has been
presented for Au3+ reduction followed by release of the bound
ligand and eventual coordination of a Au1+ ion to a protein side
chain when Au3+ anticancer compounds are allowed to react with
ubiquitin and cytochrome c.13 To explore Au3+ reactivity with the
[Zn(bme-dach)]2 model, the present work supports the possible
products resulting from Zn2+-S-Au3+ interactions. Additionally,
antiparasitic antimony compounds also trigger zinc release in
model zinc fingers, a potentially novel mechanism of action for
these drugs.14
The details of metal and ligand displacement on biomolecules
such as zinc fingers are thus of general interest. We have
therefore begun a biomimetic project to understand the molecular
mechanism of zinc ejection by platinum and platinum-metal
compounds using small molecule models.15,16 In this respect, we
have drawn an analogy between alkylation and platination of
biological substrates.8,15 Thiolate-bridged penta-coordinate zinc
chelates such as [Zn(bme-dach)]2, a Zn(N2S2) dimer, are models
for zinc proteins and are functional in terms of their S-alkylation
reactivity. S-methylation of zinc-tethered thiolates occurs in the
closely related [Zn(bme-daco)]2 complex and its Cd analog.17
The electrophilic reactivity of a similar Zn(N2S2) complex was
explored by Grapperhaus et al., where S-alkylation by MeI and
S-oxygenation with H2O2 indicate the reactivity of zinc-bound
thiolates.18,19
In reactions with representative monofunctional complexes
[PtCl(dien)]Cl or [PtCl(terpy)]Cl with [Zn(bme-dach)]2, monoth-
iolate and dithiolate-bridged heteronuclear Zn-(m-SR)-Pt species
as well as trinuclear Zn-(m-SR)2-Pt-(m-SR)2-Zn aggregates were
structurally characterized and the products are a result of initial
platination of the zinc cysteinate.16 The product of direct displace-
ment of Zn, [Pt(bme-dach)], was also characterized. In the case of
[PtCl(terpy)]+, a novel ligand exchange occurred with formation of
[ZnCl(terpy)]+, whereas the [PtCl(dien)]Cl reaction did not yield
the corresponding [ZnCl(dien)]+ ion. Thus, the nature of the ligand
(dien, terpy) on the Pt moiety dictates to some extent the reactivity
pattern. Platination with the [Pt(dien)] and [Pt(terpy)] moieties
further strengthens the analogy between alkylation and platination
of the Zn-thiolate bond.
To check the generality of the chemistry described above
between Pt complexes and Zn models, we have now examined
the isostructural compounds of Pd2+ and Au3+. This allows
comparison of the effects of isostructural d8 complexes that
differ in substitution kinetics. In addition, ligand (pyridine)
substitution reactions have been shown to be significantly faster
for [PtCl(terpy)]+ than for [PtCl(dien)]+.20 The propensity for p-
stacking of the terpy ligand with other p systems allows for
comparison of structural effects with the dien ligand.21 It is
further relevant that a square planar Pd2+ complex of bis(2-
mercaptoethyl)-1,4-diazacyclooctane, [Pd(bme-daco)], has been
characterized and probed for its thiolate reactivity with small
molecules.17,22,23 The daco derivative contains one more carbon
atom in the diazacyclo backbone than the H2bme-dach (bis(2-
mercaptoethyl)-1,4-diazacycloheptane) ligand system which has
been used in this study.17,22 In this contribution, we report mass
spectrometry (ESI-MS) studies of the reactions of Pd2+ and
Au3+ compounds with the Zn-thiolate dimer, with complementary
MS/MS data to indicate the structure of new species formed.
X-ray crystallography of {[ZnCl(bme-dach)]2Pd} and the directly
synthesized [Au(bme-dach)]BPh4 and [Pd(bme-dach)] confirmed
the proposed structures. The structural parameters of the latter
species were further compared with isostructural analogs of Ni2+
and Pt2+.
Experimental
Chemical synthesis and physical methods
The complexes [Zn(bme-dach)]2,16 [PdCl(terpy)]Cl,24 [AuCl-
(terpy)]Cl2 and [AuCl(dien)]Cl2 were prepared as described in
the literature.24,25 Elemental analysis (C,H,N) for each precursor
corresponded to the expected calculated values. The ESI-MS
spectra for each starting material is shown in Figures S1 and S2.†
Synthesis
Modified synthesis of chloro(diethylenetriamine)palladium chlo-
ride, [PdCl(dien)]Cl (1). This is a new method for the synthesis
of this compound compared to that reported.24 The salt K2PdCl4
(130 mg, 0.40 mmol) was dissolved in 5 mL of deionized H2O
and the solution was filtered to remove impurities. The diethylen-
etriamine (dien) ligand (43.5 mL, 0.04 mmol) was dissolved in
1.0 mL of H2O and the resulting solution was heated to 30 ◦C. The
Pd solution was added drop wise to the ligand solution while
stirring. A yellow precipitate formed initially, which dissolved in
the course of the subsequent drop-wise addition. The temperature
of the reaction solution was increased slowly during a 3 h period
◦
and then maintained at 100 C for 20 min. The resulting yellow
solution was reduced in vacuo to a small volume and stored
overnight at 2 ◦C. Yellow crystals were filtered off, washed
with ether/chloroform, and vacuum-dried; yield 90%. ESI-Mass
Spectrum in MeOH [M]+ m/z = 244.87 ([PdCl(dien)]+); Anal.
Calcd. for C4H13N3Cl2Pd1 (Mr = 280.49 g mol-1): C, 17.13; H,
4.67; N, 14.98. Found: C, 17.20; H, 4.60; N, 14.87.
Synthesis of N,N¢-bis(2-mercaptoethyl)-1,4-diazacycloheptane-
zincchloropalladate, [{ZnCl(bme-dach)}2Pd] (2). [Zn(bme-
dach)]2 (5.60 mg, 0.010 mmol) was partially dissolved in 10.0 mL
of MeOH and the mixture was heated for 10 min at 90 ◦C. Upon
slow addition of a methanolic solution of [PdCl(terpy)]Cl in
either 1 : 1 or 2 : 1 Pd : Zn stoichiometry, a yellow solid appeared
immediately. The yellow product has low solubility in CH3CN
and CHCl3, but was completely soluble in DMSO. The crystals
of the [{ZnCl(bme-dach)}2Pd] were obtained by layering of
CHCl3/ether solvents. Anal. Calcd. for C18H36N4Cl2S4Zn2Pd1
(Mr = 744.90 g mol-1): C, 29.02; H, 4.87; N, 7.52. Found: C,
29.47; H, 4.83; N, 7.24.
Direct synthesis of N,N¢-bis(2-mercaptoethyl)-1,4-diazacyclo-
heptane palladium(II), [Pd(bme-dach)] (3). Under an inert atmo-
sphere, a solution of NaOMe (0.470 g, 0.870 mmol) in 10 mL
of MeOH was added to H2bme-dach (0.188 g, 0.853 mmol) in
15 mL of MeOH and allowed to stir for 1.5 h at 22 ◦C. The PdCl2
(0.151 g, 0.852 mmol) was dissolved in a mixture of 7 mL deionized
H2O and 20 mL MeOH, and cannulated into the stirring ligand
solution. After 2 d of stirring at 22 ◦C under an Ar blanket, a
black precipitate was removed via filtration; the yellow filtrate
was concentrated in vacuo and purified through silica column
chromatography (5 cm ¥ 25 cm) with MeOH as the eluent. The air-
stable product was collected from the mobile pale yellow band and
This journal is
The Royal Society of Chemistry 2009
Dalton Trans., 2009, 10896–10903 | 10897
©

dried in vacuo to yield 0.100 g (0.309 mmol, 36.2%) of [Pd(bme-
dach)]. Large, needle-shaped X-ray quality crystals were acquired
by slow N2 flow over a MeOH solution of product. ESI-Mass
Spectrum in MeOH: [M + H+]+ m/z = 325; Anal. Calcd. for
C9H18N2S2Pd0H2O (Mr = 342.80 g mol-1): 31.58; H, 5.89; N, 8.19.
Found: C, 31.98; H, 5.29; N, 7.57.
appropriate ratios of H2O–MeOH to maintain solubility of both
compounds. After mixing in an ultrasonic bath and vortex, the
solution obtained was directly injected into the ESI source. Each
sample was incubated at 37 ◦C until the next injection.
1H-NMR spectroscopy. Measurements were carried out on a
Varian 300 MHz NMR Spectrometer at 20 ◦C. Samples were
prepared using D2O 98%.
Direct synthesis of N,N¢-bis(2-mercaptoethyl)-1,4-diazacyclo-
heptane gold(III) tetraphenylborate, [Au(bme-dach)]BPh4 (4). Un-
der Ar, H2bme-dach (0.096 g, 0.436 mmol) was dissolved in 15 mL
MeOH, and KOH (0.050 g, 0.891 mmol) in 15 mL MeOH was
slowly added. The solution was vigorously stirred for 1 h at
22 ◦C. KAuCl4 (0.166 g, 0.439 mmol) dissolved in a mixture of
5 mL deionized H2O and 10 mL MeOH was rapidly added to
the stirring ligand solution, immediately forming a cloudy, peach
suspension. After 18 h of stirring under an Ar blanket, the white
solid was anaerobically filtered to yield a clear, light yellow-orange
solution. The solution was reduced in volume and ether was added
to precipitate a peach colored solid. The isolated solid was washed
three times each with MeOH and ether and dried under an Ar flow
to yield 0.161 g [Au(bme-dach)]Cl (0.356 mmol, 81.1% yield).
X-ray diffraction. Data for [Au(bme-dach)]BPh4 and
{[ZnCl(bme-dach)]2Pd} were collected on a Bruker D8 GADDS
general-purpose three-circle X-ray diffractometer (Cu-Ka
˚
radiation, l = 1.54178 A) operating at 110 K. The [Pd(bme-
dach)] single crystal data were collected on a Bruker SMART 1000
CCD based diffractometer27 (Mo-Ka radiation, l = 0.71073 A),
˚
also at 110 K. The structures were solved by direct methods. H
atoms were added at idealized positions and refined with fixed
isotropic displacement parameters equal to 1.2 times the isotropic
displacement parameters of the atoms to which they were
attached. Anisotropic displacement parameters were established
for all non-H atoms. The following programs were employed:
data collection and cell refinement for [Au(bme-dach)]BPh4 and
{[ZnCl(bme-dach)]2Pd}, Bruker FRAMBO, CELL-NOW, and
SAINT;28-30 data collection and cell refinement for [Pd(bme-
dach)], APEX-II;28 absorption correction, SADABS;31 structure
solution and structure refinement for all structures, SHELXS-97
and SHELXL-97;32 and molecular graphics and preparation
of material for publication, SHELXTL-PLUS, version 6.14.32
X-seed was used for the final data presentation and structure
plots.33
Counterion exchange
A solution of NaBPh4 (0.122 g, 0.356 mmol) in 15 mL of
MeOH was added to a yellow-orange solution of [Au(bme-
dach)]Cl (0.161 g, 0.356 mmol) in 25 mL of MeOH, and allowed
to stir at 22 ◦C for 16 h. The resulting reaction mixture was
anaerobically filtered to separate the peach solid from the clear,
colorless solution. The solid was redissolved in MeCN, filtered
to remove residual NaCl, and ether added to precipitate solid
product, [Au(bme-dach)]BPh4. The solid was washed three times
each with MeOH and ether before drying in vacuo to yield 0.122 g
(0.166 mmol, 37.8% yield). X-ray quality crystals were obtained by
slow evaporation from a MeCN solution. ESI-Mass Spectrum in
MeCN: M+, 415; Anal. Calcd. for C33H38N2S2Au1 (Mr = 723.77 g
mol-1): C, 54.76; H, 5.29; N, 3.87. Found: C, 55.61; H, 5.77; N,
4.15.
Crystallographic data and the crystallographic data summaries
are listed in the Supplementary Information.† Please note that the
crystal used for the [Au(bme-dach)]BPh4 data collection was very
small (max dimension < 20 microns), resulting in weak data and
high R-factors.
Results and discussion
Previous studies on the interaction of platinum complexes with
zinc chelates employed a tandem approach of chemical syn-
thesis and crystallographic characterization (millimolar scale)
with biomolecule and mass spectral studies (micro-nanomolar
scale).15,16 The same approach was applied here and in this
work we have examined the reaction pathways of Pd2+ and Au3+
compounds with [Zn(bme-dach)]2 and structurally characterized
the new mononuclear [Pd(bme-dach)] and [Au(bme-dach)]+ and
heteronuclear Pd-Zn adducts formed. ESI-MS is a powerful
technique for the characterization of inorganic and organometallic
complexes and it is a promising approach to identify reaction paths
and compositions from which possible bonding arrangements
might be inferred in solution. Care must be taken in interpreting
this mass spectral data due to possible formation of new species in
the gas phase under the conditions of the mass spectral acquisition.
In the present case the mass spectra of the starting materials
showed in all cases only one predominant peak for the molecular
ion. The reactions (carried out in H2O–MeOH mixtures) were
monitored under the same conditions to minimize adventitous
reactions. The major peaks corresponding to those isolated
synthetically are discussed. The structures of the complexes are
shown in Fig. 1.
Apparatus and procedures
Electrospray Ionisation Time of Flight Mass Spectrometry, ESI-
TOFMS. Mass spectra were acquired on a Waters-Micromass
Qtof-2 for higher resolution. Electrospray conditions were main-
tained throughout the experiment. Samples were flowed pneu-
matically using a Harvard syringe pump at 5.0 mL min-1 with
an ESI source temperature ranging from 90–120 ◦C to provide
efficient dissolution. Capillary voltage was operated in positive
ionization mode at 2.8 kV and a cone voltage of 40 V was used
throughout the experiment. The ESI-MS data for the reaction
between the complexes [PtCl(dien)]Cl and [Zn(bme-dach)]2 were
collected using the ThermoFinnigan LCQ electrospray ion-trap
(LCQ-MS) in positive mode. Acquired spectra were compared
to the predicted isotope distribution patterns for each of the
compounds calculated using IsoPro 3.0 Program.26
Solutions employed in ESI-TOFMS. The conditions followed
those previously described.16 Stock solutions of palladium and
gold compounds (10-3 mol L-1) were made up by dissolving the
accurately weighed amount in H2O. The Zn chelate was dissolved
in MeOH and dilution and mixing were carried out to obtain
10898 | Dalton Trans., 2009, 10896–10903
This journal is
The Royal Society of Chemistry 2009
©

Fig. 1 Structures of the complexes [MCl(dien)]n+, [MCl(terpy)]n+ (M = Pd, n = 1; M = Au, n = 2) and [Zn(bme-dach)]2, a small molecule model of the
zinc coordination motif in zinc finger proteins.
ESI-MS studies. Reaction of [Zn(bme-dach)]2 with [PdCl(terpy)]Cl
formed when the compound [PdCl(terpy)]Cl reacts with the dimer
[Zn(bme-dach)]2, the product precipitating from solution (See
Experimental Section). Crystallisation of the product confirmed
the structure (see X-ray data). After 22 h, the intensity of the
spectrum decreased considerably with concomitant formation
of a yellow precipitate. The formation of the trinuclear species
is analogous to the formation of similar heteronuclear adducts
observed during the reaction of [PtCl(terpy)]Cl and [PtCl(dien)]Cl
with [Zn(bme-dach)]2.16
ESI-MS was used to analyze the reaction between [PdCl(terpy)]Cl
and [Zn(bme-dach)]2 over 22 h at different molar ratios (1 : 1
and 2 : 1, Pd : Zn). Both stoichiometries gave analogous products.
Fig. 2A shows the spectrum from the 1 : 1 reaction after 1 h
incubation at a concentration of ~10 mM in 90% MeOH. It is
clear that multiple species are formed and even at this early
time point. The peak at m/z = 346.92 may be assigned to
+
the species {[Pd(bme-dach)]/Na+} , which is consistent with the
monoisotopic peak of the above species at m/z = 344.88. The
isotopic distribution was consistent with the Zn–Pd exchange and
the presence of a small peak at m/z = 331.99 corresponding to the
[ZnCl(terpy)]+ ion (more intense in the 2 : 1 reaction), confirmed
the ligand scrambling, also observed for platinum.16 The main
heteronuclear aggregate observed at m/z 672.80 corresponded to
Reaction of [Zn(bme-dach)]2 and [PdCl(dien)]Cl
We next extended our study to [PdCl(dien)]Cl, a square planar
complex with a tridentate ligand coordinated to palladium,
similar to [PdCl(terpy)]Cl. The intensity of the spectrum is again
greatly affected by precipitation of products from solution. Fig. 3
illustrates the mass spectrum of the mixture after incubation for
five minutes. Evidence for the formation of the trinuclear aggregate
is seen by the presence of the peak at m/z = 709.13, assigned to the
+
the {[Zn(bme-dach)]2Pd/H+} cation. Fig. 2B shows the MSMS
spectrum and the fragmentation pattern of the m/z = 672.80
+
peak giving the main product ion [Pd(bme-dach)]/Na+} at m/z
+
348.88. In addition, we observed the existence of a higher-order
{[Zn(bme-dach)2]PdCl} ion. The peak at 530.20 may be assigned
+
multinuclear aggregate such as the {Zn(bme-dach)3Pd2}/H+} ion
+
to {[Zn(bme-dach)Pd(dien)]} , corresponding to attack of the
at m/z = 996.79. Interestingly, the MS/MS fragmentation pattern
of this species was consistent with the proposed composition with
loss of a [Pd(bme-dach)] moiety and the daughter peak at m/z =
Pt(dien) electrophile on the nucleophilic zinc-bound thiolate. A
similar species was identified by MS and also NMR spectroscopy
in the Pt reaction.16 Interestingly, no evidence for formation of the
[ZnCl(dien)]+ cation was observed. The general pathways of the
Pd compounds followed those previously observed with platinum.
+
672.80 observed being assigned to {[Zn(bme-dach)]2Pd/H+} ,
Fig. 2C. The {[ZnCl(bme-dach)]2Pd} species is the main species
Fig. 2 (A) ESI-MS full scan (positive mode) of the reaction between [PdCl(terpy)]Cl and [Zn(bme-dach)]2 recorded after one hour at 1 : 1 molar ratio.
+
+
+
Species assigned: a) {[Pd(bme-dach)]/Na+} , b) {[Zn(bme-dach)]2Pd/H+} cation, and c) {Zn(bme-dach)3Pd2}/H+} ion. (B) The MS2 of the peak
672.80 and (C) MS2 of the peak 995.75 from Fig. 2A. The charge outside the brackets indicates the overall charge observed in the mass spectra.
This journal is
The Royal Society of Chemistry 2009
Dalton Trans., 2009, 10896–10903 | 10899
©

+
to the metal exchanged ion {[Au(bme-dach)} , Figure S4.† The
main heteronuclear aggregate is a small peak at m/z = 763.09
+
corresponding to {[Zn(bme-dach)]2Au} , which after 40 h is the
main species observed.
Structural characterization of Pd2+ and Au3+ substituted chelates
In general, the reactivity profile for the Pd2+ and Au3+ compounds
follows that of platinum. Incorporation of M into the bme-dach
chelate with liberation of Zn2+ is seen. It is also of interest that the
heterotrinuclear dithiolate-bridged Zn,M,Zn species appears to be
the predominant multinuclear aggregate in all cases. As expected,
the reactions appeared to be faster for the Pd2+ and Au3+ species.
To confirm the structural assignments the principal products were
synthesized on a macro scale, in contrast to the nano scale of the
MS experiments.
Fig.
3
The ESI-MS full scan (positive mode) of the reaction
between [PdCl(dien)]Cl and [Zn(bme-dach)]2 after
5
min of reac-
+
+
tion. Species: a) {[Zn(bme-dach)Pd(dien)]} , b){[Zn(bme-dach)]2} , c)
{[Zn(bme-dach)]2PdCl} , and d) {[Zn(bme-dach)]2PdCl/H2O/Na+} .
+
+
Synthesis and X-ray results for the {[Zn(bme-dach)Cl]2Pd}
Reactions of gold compounds [AuCl(dien)]Cl2 and
[Au(Cl(terpy)]Cl2 with [Zn(bme-dach)]2
complex
In order to isolate and quantify this compound, the same reaction
as described above was carried out on a larger scale. The
yellow product was characterized as the heteronuclear [ZnCl(bme-
dach)]2Pd] complex, confirmed by elemental analysis and X-ray
diffraction analysis of a single crystal. Cell parameters and data
collection summaries for {[ZnCl(bme-dach)]2Pd}, [Pd(bme-dach)]
and [Au(bme-dach)]BPh4] are given in Table 1, with selected metric
parameters listed in Table 2.
The molecular structure shown in Fig. 5 illustrates the Zn2Pd
trimetallic stair-step product resulting from the 2Pd:1Zn reac-
tion. The ball and stick X-ray crystal structure of {[ZnCl(bme-
dach)]2Pd} shows the zinc coordinated to two sulfurs, two
nitrogens and an apical chloride in a penta-coordinate geometry.
The N2S2 atoms (without Zn) form a plane with a mean deviation
The reactions with the gold species (1 : 1 and 2 : 1 Au : Zn) appeared
to be very fast. The spectra are remarkably simple and the profiles
were very similar for both stoichiometries. The spectrum obtained
immediately upon incubation of a 1 : 1 mixture of [AuCl(dien)]+
and [Zn(bme-dach)]2 is shown in Fig. 4. The main peak at
m/z = 437.26 is assigned to the species with a sodium ion
+
{[Au(bme-dach)]-H+ +Na+} (Fig. 4, species (a)). The peak at
m/z = 873.53 may be assigned to the heteronuclear aggregate
{[{Zn(bme-dach)Cl}2Au/Na+/H2O]} respectively (Fig. 4, species
(c)). In the 2 : 1 incubation of [AuCl(dien)]Cl2 and [Zn(bme-
dach)]2, a companion peak at m/z = 849.09 is attributed to
+
loss of the Na+ ion, {[{Zn(bme-dach)Cl}2Au/H2O]} , Figure
S3.† An interesting peak seen for both 1 : 1 and 2 : 1 incubations
with [AuCl(dien)]+ is that of m/z = 655.40 (Fig. 4, species (b)),
corresponding to {[Au(bme-dach)2]/Na+/-H+}. This may suggest
some form of a gold dimer as a precursor and the species may
also contain disulfide bonds. In this respect it is noteworthy,
as stated, that evidence has been presented for Au3+ reduction
followed by release of the bound ligand and eventual coordination
of a Au1+ ion to a protein side chain when Au3+ anticancer
compounds are allowed to react with ubiquitin and cytochrome
c.13 Further studies are underway to confirm this suggestion. For
[AuCl(terpy)]+, the spectrum taken immediately after the 1 : 1
incubation yielded a peak at m/z = 415.09 which was assigned
˚
of 0.0120 A. In contrast to the {[ZnCl(bme-dach)]2Pt}structure,
which contains some asymmetry, the {[ZnCl(bme-dach)]2Pd}
complex is symmetric with half of its molecule as a symmetry
generated duplicate of the other half. The hinge angles, as defined
above, are larger for the Pt2+ derivative as well as asymmetrical,
104.5◦ and 99.0◦.
The molecular structure of the isolated product confirms the
reactivity of the Zn-bound thiolates to form stable bridges to Pd2+,
while retaining the Zn–S bond. This Zn-(m-SR)2-Pd2+ complex is
relevant to possible interactions between heavy metal compounds
and Zinc fingers from NCp7.
Fig. 4 The ESI-MS full scan (positive mode) of the reaction between [AuCl(dien)]Cl2 and [Zn(bme-dach)]2 immediately upon incubation. Species: a)
+
{[Au(bme-dach)]-H+ +Na+} , b) {[Au(bme-dach)2]/Na+/-H+}, and c) {[{Zn(bme-dach)Cl}2Au/Na+/H2O]}.
10900 | Dalton Trans., 2009, 10896–10903
This journal is
The Royal Society of Chemistry 2009
©

Table 1 Crystal data for {[ZnCl(bme-dach)]2Pd}, [Pd(bme-dach)] and [Au(bme-dach)][BPh4]
{[ZnCl(bme-dach)]2Pd}
[Pd(bme-dach)]
[Au(bme-dach)]BPh4
Empirical formula
Formula weight
T/K
C9.5H18.5Cl12.5N2S2Pd0.5Zn
432.08
110(2)
C9H18 N2 S2Pd
324.77
110(2)
C33 H38 B N2 S2 Au
734.55
110(2)
˚
Wavelength/A
1.54178
0.71073
1.54178
Crystal system
Space group
Unit cell dimensions
Monoclinic
P21/c
Orthorhombic
Pnma
Monoclinic
P21/c
◦
◦
◦
˚
˚
˚
˚
˚
˚
˚
a = 7.4293(2) A; a = 90
a = 9.961(5) A; a = 90
a = 10.643(4) A; a = 90
◦
◦
◦
˚
b = 12.400(8) A; b = 97.128(2)
b = 15.105(7) A; b = 90
b = 14.184(5) A; b = 117.051(18)
◦
◦
◦
˚
c = 16.645(3) A; g = 90
c = 7.514(4) A; g = 90
c = 21.407(7) A; g = 90
Z
4
4
4
Absorption coefficient/mm-1
13.312
1521.66(8)
1.040
1.974
1130.5(9)
1.098
11. 149
2878.1(18)
1.062
3
˚
Volume/A
Goodness-of-fit on F2
Final R indices [I > 2s(I)]
R indices (all data)
R1 = 0.0295, wR2 = 0.0769
R1 = 0.0618, wR2 = 0.1614
R1 = 0.0948, wR2 = 0.2289
R1 = 0.0349, wR2 = 0.0769
R1 = 0.0905, wR2 = 0.1809
R1 = 0.1704, wR2 = 0.2721
˚
Table 2 Selected bond lengths (A) for {[ZnCl(bme-dach)]2Pd}, [Pd(bme-dach)] and [Au(bme-dach)] complexes
{[ZnCl(bme-dach)]2Pd}
[Pd(bme-dach)]
Pd(1)-S(1)
[Au(bme-dach)]+
Pd(1)-S(1)
Pd(1)-S(2)
Zn(1)-S(1)
Zn(1)-S(2)
Zn(1)-N(1)
Zn(1)-N(2)
Zn(1)-Cl(1)
2.3510(8)
2.3543(8)
2.4373(9)
2.4219(9)
2.157(2)
2.185(2)
2.2415(9)
2.2825(2)
2.074(7)
Au(1)-S(1)
Au(1)-S(2)
Au(1)-N(1)
Au(1)-N(2)
—
—
—
2.290(6)
2.293(6)
2.18(2)
2.12(2)
Pd(1)-N(1)
—
—
—
Fig. 5 Molecular structure of {[ZnCl(bme-dach)]2Pd}. The second half
of the molecule is generated by inversion through palladium.
Molecular structures of [Pd(bme-dach)] and [Au(bme-dach)]BPh4
The larger scale direct syntheses of [Pd(bme-dach)] and [Au(bme-
dach)]BPh4 were executed to support the Zn/Pd and Zn/Au
metal exchange within the aforementioned ESI-MS monitored
reactions and MS/MS fragmentations. Table 1 includes the
crystallographic data for both complexes. Fig. 6 displays the ball
and stick representations of the [Pd(bme-dach)] and [Au(bme-
dach)]+ molecular structures, with selected bond distances and
angles denoted within the figure.
Fig. 6 (a) Ball and stick illustration of [Pd(bme-dach)] in a bird’s eye view
of the molecule. (b) Ball and stick representation of [Au(bme-dach)]+ with
-
the BPh4 counterion omitted for clarity.
Both complexes are highly regular square planes and con-
tain similar metric parameters to those of the Pt(bme-dach)
derivative.16 Reminiscent of the Pt2+ analogue, the [Pd(bme-dach)]
is comprised of a perfect N2S2 plane, where one half of the molecule
is the symmetry-generated product of the other. Furthermore, the
Pd2+ is displaced from the N2S2 best plane by 0.0176 A, whereas
˚
the Pt2+ resides within the same ligand set with a lesser deviation
˚
(0.0003 A). The crystal packing of the Pd(bme-dach) molecule
This journal is
The Royal Society of Chemistry 2009
Dalton Trans., 2009, 10896–10903 | 10901
©

19
16
Table 3 Comparison of selected bond angles and distances within [M(bme-dach)] structures, where M = Ni2+
,
Pd2+, Pt2+
,
and Au3+
[Au3+
]
+
[M(bme-dach)], M =
Ni2+
Pd2+
Pt2+
˚
M–N (A)
1.940(4)
2.164(1)
82.5(2)
95.4(1)
n/a
2.074(7)
2.283(2)
79.0(4)
101.7(1)
0.0176
2.089(1)
2.298(3)
80.6(8)
102.4(2)
0.0003
2.18(2), 2.12(2)
2.290(6), 2.293(6)
79.2(8)
99.5(2)
0.0016
˚
M–S (A)
∠ N–M–N (◦)
∠ S–M–S (◦)
˚
M displacement from N2S2 plane (A)
displays disorder of the C(2) atom within the pendant thiolate
arm (see Figure S5†). Note that disorder of only the prominent
(elbow) carbon was modelled in the structure refinement. The
ripple effect of this disorder causing disorder in C(3) and C(5) and
other associated carbon atoms was not modelled.
Pd(dien) species, while for Au3+, only species corresponding to
complete ligand displacement (dien, terpy) were seen even at
the earliest time points. As stated, the development of the Pd2+
and Au3+ derivatives adds to the library of existing M(bme-dach)
compounds (Table 3). Further, the exploration of the interactions
of [Zn(bme-dach)]2 with Pt2+, Pd2+, and Au3+ complexes has amply
demonstrated the capability of such species to form stable thiolate-
bridged heteronuclear aggregates. Indeed, the thermodynamic
“sink” appears to be the trinuclear dithiolate-bridged {Zn,M,Zn}
aggregate. Interestingly, analogous [Ni(N2S2)]2M2+ (M = Ni, Pd,
Pt) have also been reported.35,36
The [Au(bme-dach)]+ structure contains an N(1)N(2)S(1)S(2)
3+
˚
plane with a mean deviation of 0.0228 A, and the Au shifted
˚
only 0.0016 A outside of this plane. As previously mentioned, the
bond distances and angles closely parallel those found within the
[Pt(bme-dach)], displayed in Table 3 along with comparisons to
the Ni2+ analogue.16,19
As revealed in Table 3 above, the development of the Pd2+
and Au3+ derivatives adds to the library of existing M(bme-dach)
compounds. The Zn/Au metal exchange reported in the present
work rendered the first indication of possible formation of an
Au3+ derivative to exist in this bme-dach collection. As expected,
the M–N and M–S bond distances lengthen as the central metal
ion descends from a first to second to third row transition metal.
In terms of the ∠ N–M–N and ∠ S–M–S, both the size of the
central metal ion and the flexibility of the ligand play a role in the
angles ultimately observed. With regard to the metal ion, as the size
increases, the ∠ S–M–S normally increases within this tetradentate
ligand set. Such an “opening” of the ∠ S–M–S is associated with a
concomitant “pinching” or decrease in the ∠ N–M–N. This trend
is observed between the Ni2+, Pd2+, and Pt2+ complexes. The Au3+
complex, however, does not continue to show an increase in ∠
S–M–S with a corresponding decrease in ∠ N–M–N. Although it
is a third row transition metal, the higher oxidation state and thus
decrease in ionic radii may contribute to its detected angles being
more comparable to those found within the Pd2+ complex.
One reason for this investigation has been to use the chemistry
of model zinc chelates as predictors of structure and reactivity on
zinc fingers. Metal ion replacement reactions of zinc in zinc finger
proteins are well documented and may have important biological
implications. Replacement of Zn by metal ions such as Pb2+
and Ni2+ may contribute to their “toxic” effects.37,7 Modification
of the zinc finger Zn–S sites, through alkylation, oxidation, or
metalation, may disrupt zinc protein conformation, thus altering
and/or inhibiting their critical biological functions.8,38 An anal-
ogous study has investigated the reactions of the [MCl(chelate)]
compounds of this study (M = Pt2+, Pd2+ or Au2+ and chelate =
diethylenetriamine, dien or 2,2¢,2¢¢-terpyridine, terpy) with the C-
terminal finger of the HIV nucleocapsid NCp7 zinc finger.39 In
the case of [M(dien)] species, Pt2+ and Pd2+ behaved in a similar
fashion with evidence of adducts caused by displacement of Pt–Cl
or Pd–Cl by zinc-bound thiolate. Labilization, presumably under
the influence of the strong trans influence of thiolate, resulted in
loss of ligand (dien) as well as zinc ejection and formation of
species with only Pd2+ or Pt2+ bound to the finger. For both Au3+
compounds the reactions were very fast and only “gold fingers”
with no ancillary ligands were observed.39 For all terpyridine
compounds, ligand scrambling and metal exchange occurred with
formation of [Zn(terpy)]2+. Thus, as with the platinum case,15 the
chemistry and structures described in this paper also represent
viable descriptions for the reactions of metal complexes with zinc
fingers. In the present case, the isolation and characterization
of an Au3+ chelate suggests that Au3+, as well as Au1+ could be
incorporated into a zinc protein site – further studies will address
this question.
Conclusions
The reactions of isostructural Pd2+ and Au3+ compounds with
[Zn(bme-dach)]2 showed similar behavior to that of previously
studied Pt.16 Zinc preservation of cysteine thiolate nucleophilic-
ity renders the sulfur sufficiently reactive towards electrophilic
platinum moieties to yield Zn-(m-SR)-Pt bridged, multi-metallic,
and metal-exchanged species. In the case of Pt2+, intermediate
species containing the Pt(dien) moiety could be identified by both
NMR and crystallographic methods. The Zn-(m-SR)-Pt-bridged
species, [(ZnCl(bme-dach))(Pt(dien))]Cl, is, to our knowledge, the
first structurally isolated Zn–Pt bimetallic thiolate-bridged model
demonstrating the interaction between Zn-bound thiolates and
Pt2+. Most recently, the -W(CO)4 residue has also been shown
to form dinuclear dithiolate-bridged species with the advantage
that IR spectral reporting via n(CO) stretching frequencies is
possible.34 In the present study, the faster reactions on Pd2+
only allowed limited mass spectrometric evidence for analogous
Acknowledgements
The authors gratefully acknowledge the financial support of The
National Science Foundation (CHE-0616695/CHE-0910679 to
MYD and CHE-0616768 to NPF). Q.A.P. and N.P.F. acknowledge
contributions from Conselho Nacional de Pesquisa e Desenvolvi-
mento (CNPq-210265/2006-0) for supporting the International
Postdoctoral Fellowship of Dr. Queite A. de Paula. MYD also
10902 | Dalton Trans., 2009, 10896–10903
This journal is
The Royal Society of Chemistry 2009
©

acknowledges contributions from the R. A. Welch Foundation
(A-0924).
18 C. A. Grapperhaus, M. J. Maguire, T. Tuntulani and M. Y. Darens-
bourg, Inorg. Chem., 1997, 36, 1860.
19 J. J. Smee, M. L. Miller, C. A. Grapperhaus, J. H. Reibenspies and M. Y.
Darensbourg, Inorg. Chem., 2001, 40, 3601.
20 F. Basolo, H. B. Gray and R. G. Pearson, J. Am. Chem. Soc., 1960, 82,
References
4200.
1 W. Maret and Y. Li, Chem. Rev., 2009, 109, 4682–4707.
2 J. M. N. Hoovers, M. Mannens, R. John, J. Bliek, V. van Heyningen,
D. J. Porteous, N. J. Leschot, A. Westerveld and P. F. R. Little, Genomics,
1992, 12, 254.
3 K. Sakaguchi, N. Zambrano, E. T. Baldwin, B. A. Shapiro, J. W.
Erickson, J. G. Omichinski, G. M. Clore, A. M. Gronenborn and E.
Appella, Proc. Natl. Acad. Sci. U. S. A., 1993, 90, 5219.
4 J. W. Bess Jr., P. J. Powell, H. J. Issaq, L. J. Schumack, M. K. Grimes,
L. E. Henderson and L. O. Arthur, J. Virol., 1992, 66, 840.
5 J. L. Larabee, J. R. Hocker and J. S. Hanas, Chem. Res. Toxicol., 2005,
18, 1943.
6 J. M. Berg and H. A. Godwin, Annu. Rev. Biophys. Biomol. Struct.,
1997, 26, 357.
7 A. Witkiewicz-Kucharczyk and W. Bal, Toxicol. Lett., 2006, 162, 29.
8 A. I. Anzellotti, Q. Liu, M. J. Bloemink, J. N. Scarsdale and N. Farrell,
Chem. Biol., 2006, 13, 539.
21 S. D. Cummings, Coord. Chem. Rev., 2009, 253, 449.
22 T. Tuntulani, G. Musie, J. H. Reibenspies and M. Y. Darensbourg,
Inorg. Chem., 1995, 34, 6279.
23 M. Y. Darensbourg, T. Tuntulani and J. H. Reibenspies, Inorg. Chem.,
1995, 34, 6287.
24 S. Morgan and F. H. Burstall, J. Chem. Soc., 1937, 1649.
25 L. S. Hollis and S. J. Lippard, J. Am. Chem. Soc., 1983, 105, 4293.
26 Isopro3.1 Program.
27 SMART 1000 CCD, Bruker Analytical X-ray Systems, Madison, WI,
1999.
28 Bruker-Nonius Inc., FRAMBO, Version 4.1.13, Madison, Wisconsin,
USA, 2003.
29 G. Sheldrick, CELL-NOW, University of Go¨ttingen, Germany, 2003.
30 Bruker-Nonius Inc., SAINT, Madison, Wisconsin, USA, 2003.
31 Bruker-Nonius, APEX II. Version, 2008.6-0. Bruker-Nonius Inc.,
Madison, Wisconsin, USA, 2008.
9 D. A. Sartori, B. Miller, U. Bierbach and N. Farrell, JBIC, J. Biol. Inorg.
Chem., 2000, 5, 575.
32 G. Sheldrick, Acta Cryst., 2008, A64, 112-122, and related references
therein.
10 Y. Zou, B. Van Houten and N. Farrell, Biochemistry, 1993, 32, 9632.
11 M. L. Handel, A. de Fazio, C. W. Watts, R. O. Day and R. L. Sutherland,
Mol. Pharmacol., 1991, 40, 613.
12 W. Kaim and B. Schwederski, in Bioinorganic Chemistry: Inorganic
Elements in the Chemistry of Life, G. Meyer and A. Nakamura, Eds.,
Wiley, New York, 1994, pp. 374-375.
33 L. J. Barbour, J. Supramol. Chem., 2001, 1, 189.
34 E. Almaraz, W. S. Foley, J. A. Denny, J. H. Reibenspies, M. L. Golden
and M. Y. Darensbourg, Inorg. Chem., 2009, 48, 5288.
35 M. V. Rampersad, S. P. Jeffery, J. H. Reibenspies, C. G. Ortiz, D. J.
Darensbourg and M. Y. Darensbourg, Angew. Chem., Int. Ed., 2005,
44, 1217.
13 A. Casini, C. Hartinger, C. Gabbiani, E. Mini, P. J. Dyson, B. K.
Keppler and L. Messori, J. Inorg. Biochem., 2008, 102, 564.
14 C. Demicheli, F. Frezard, J. B. Mangrum and N. P. Farrell, Chem.
Commun., 2008, 4828.
15 Q. Liu, M. Golden, M. Y. Darensbourg and N. Farrell, Chem.
Commun., 2005, 4360.
16 E. Almaraz, Q. A. de Paula, Q. Liu, J. H. Reibenspies, M. Y.
Darensbourg and N. Farrell, J. Am. Chem. Soc., 2008, 130, 6272.
17 C. A. Grapperhaus, T. Tuntulani, J. H. Reibenspies and M. Y.
Darensbourg, M., Inorg. Chem., 1998, 37, 4052.
36 M. L. Golden, C. M. Whaley, M. V. Rampersad, J. H. Reibenspies,
R. D. Hancock and M. Y. Darensbourg, Inorg. Chem., 2005, 44,
875.
37 J. C. Payne, M. A. ter Horst and H. A. Godwin, J. Am. Chem. Soc.,
1999, 121, 6850.
38 J. S. Hanas, J. L. Larabee and J. R. Hocker, in Zinc Finger Proteins:
From Atomic Contact to Cellular Function, S. Iuchi and N. Kuldell,
Eds., Landes Bioscience, Austin, TX, 2005, pp. 39-46.
39 Q. A. de Paula, J. B. Mangrum and N. P. Farrell, J. Inorg. Biochem.,
2009, 103, 1347.
This journal is
The Royal Society of Chemistry 2009
Dalton Trans., 2009, 10896–10903 | 10903
©