The interaction of antitumor active vanadocene dichloride with sulfur-containing amino acids

Article abstract of DOI:10.1016/j.jorganchem.2007.05.026

Vanadocene dichloride (1) reacts with sulfur-containing amino acids, cysteine and methionine, giving new complexes with five- or six-membered chelate ring, but the structure of isolated compounds is affected by the pH value of the reaction mixture. Methio

Full text of DOI:10.1016/j.jorganchem.2007.05.026

Journal of Organometallic Chemistry 692 (2007) 3758–3764
www.elsevier.com/locate/jorganchem
The interaction of antitumor active vanadocene dichloride with
sulfur-containing amino acids
a
a,
a
b
a
*
´ˇ
´
´
´
´
´ ˇ
´
Hana Palackova , Jaromır Vinklarek , Jana Holubova , Ivana Cısarova , Milan Erben
a
ˇ
Department of General and Inorganic Chemistry, University of Pardubice, na´m. Cs. legiı´ 565, 532 10 Pardubice, Czech Republic
b
Department of Inorganic Chemistry, Charles University, Hlavova 2030, 128 40 Prague 2, Czech Republic
Received 16 January 2007; received in revised form 3 April 2007; accepted 15 May 2007
Available online 26 May 2007
Abstract
Vanadocene dichloride (1) reacts with sulfur-containing amino acids, cysteine and methionine, giving new complexes with five- or six-
membered chelate ring, but the structure of isolated compounds is affected by the pH value of the reaction mixture. Methionine reacts
with aqueous 1 in the pH range of 3–8 affording chelate structure [Cp2V(N,O-met)]Cl (4). Similar reaction with cysteine gives two dif-
ferent products depending on pH. In the acidic solution, the complex [Cp2V(O,S-cys)]Cl (2) is present, whereas in neutral media the com-
pound [Cp2V(N,S-cys)] (3) could be identified. On inspection of spectroscopic measurements, particularly EPR and vibrational
spectroscopy, it is evident that sulfur atom of amino acid is bonded directly to the vanadium atom of [Cp2V]2+ moiety. For the purpose
of comparison the complexes [Cp2V(O,S-mpa)] (5) and [Cp2V(N,S-csam)]+ (6a) with related chelating ligands, 3-mercaptopropionic acid
(mpa) and cysteamine (csam), respectively, were prepared and spectroscopically characterized. The structure of the complex [Cp2V(N,S-
csam)]BPh4 (6b) was also determined by X-ray diffraction analysis.
ꢀ 2007 Published by Elsevier B.V.
Keywords: Antitumor drugs; Vanadocene dichloride; Cysteine; Methionine; EPR; X-ray
1. Introduction
acids. Although Cp2TiCl2 and Cp2MoCl2 form stable
complexes with alkylated nucleobases and nucleotides
[5,7,13–16], no such complexes were found for VDC [11].
The interaction of bent metallocenes with proteins was
widely studied on the series of model amino acid complexes
and it was found that the chemistry of each metallocene
compound strongly depends on the nature of central metal
atom. Highly oxophilic fragment [Cp2Ti]2+ prefers monod-
entate bonding of two amino acid (aa) via the oxygen atoms
of carboxylic group [17–20]. The reaction of Cp2TiCl2 with
sulfur-containing amino acids such as methionine or cys-
teine gives the same type of complexes [Cp2Ti(O-aa)2]Cl2
(aa = met, cys) with O-bounded amino acid ligands
[28,29].
Vanadocene dichloride Cp2VCl2 (VDC, 1) belongs to
the class of metallocene dihalides Cp2MX2 (M = Ti, Mo,
Nb, V and X = halide), which show high antiproliferative
properties against various animal or human tumors [1–4].
Extensive studies have evidenced that the cytostatic activity
of metallocene compounds is related with their interaction
toward DNA molecule or proteins responsible for DNA
replication (e.g. proteinkinase C or topoisomerase II)
[5–11]. Investigation of the interactions between the metal-
locenes and DNA was performed using so-called ‘‘model
compounds’’. When various metallocenes are compared,
there are some distinct differences in their hydrolysis chem-
istry [12], interactions with DNA fragment and amino
On the other hand, Cp2MoCl2 and Cp2VCl2 generally
give N,O-chelated amino acid complexes [21–27]. Similarly,
methionine complex [Cp2Mo(N,O-met)]Cl has typical che-
late bond previously described for molybdenocene deriva-
tives with sulfur-free amino acids [22]. However, from the
*
Corresponding author. Tel.: +420 46603 7164; fax: +420 46603 7068.
´
E-mail address: jaromir.vinklarek@upce.cz (J. Vinklarek).
0022-328X/$ - see front matter ꢀ 2007 Published by Elsevier B.V.
doi:10.1016/j.jorganchem.2007.05.026

H. Pala´cˇkova´ et al. / Journal of Organometallic Chemistry 692 (2007) 3758–3764
3759
reaction of Cp2MoCl2 with cysteine two different com-
pounds were isolated. Chelate structure of the complex
[Cp2Mo(N,S-cys)]Cl has been proved by X-ray diffraction
analysis [23] whereas the structure of the second complex,
[Cp2Mo(S-cys)2], was proposed only on the basis of
NMR spectra [30].
occurred; pH value of this solution was found to be 2.5.
Successive addition of carbonate-free NaOH solution led
to the diminishing of diaquacomplex signal and increasing
of the signal of 2. Further increasing of pH to a value of 5
leads to the appearance of new paramagnetic compound 3
(Aiso = 59.9 · 10ꢀ4 cmꢀ1, giso = 1.994). In the pH range
As a part of broad investigation vanadocene chemistry,
we recently described vanadocene complexes with simple
amino acids [25,26]. Present work deals with the study of
interaction of 1 with sulfur-containing biogenic amino
acids, cysteine and methionine, respectively. We have also
prepared related complexes with 3-mercaptopropionic acid
(mpa) and cysteamine (csam). All isolated compounds were
characterized by spectroscopic techniques (IR and Raman
spectroscopy), electrospray ionization mass spectrometry
(ESI-MS), electron paramagnetic resonance spectroscopy
(EPR) and X-ray diffraction with the view to elucidate
bonding pattern in these complexes. Obtained results can
contribute to the understanding of the antiproliferative
activity of VDC at the molecular level. In addition, pre-
pared amino acid derivatives are air-stable and highly
water-soluble analogues of 1. This fact could be advanta-
geously used in clinical studies.
2. Results and discussion
2.1. The reaction of vanadocene dichloride with L-cysteine in
aqueous solutions at different pH
The behavior of L-cysteine in aqueous solution of vana-
docene dichloride at various pH was investigated by isotro-
pic electron paramagnetic resonance spectroscopy; see
Scheme 1 and Fig. 1.
Freshly prepared aqueous solution of 1 gives simple
eight-line EPR spectrum of vanadocene diaquacomplex
[Cp2V(H2O)2]2+ (Aiso = 74.5 · 10ꢀ4 cmꢀ1
,
giso = 1.979)
[31]. After the addition of one equivalent of L-cysteine to
this solution the new paramagnetic species (2) with EPR
parameters Aiso = 65.8 · 10ꢀ4 cmꢀ1 and giso = 1.986 was
Fig. 1. EPR spectra of aqueous solutions of 1 with L-cysteine at different
pH (m0 = 9.46 GHz). (a) pH 2.6, (b) pH 3.6, (c) pH 5, and (d) pH 7.4.
+
O
S
NH2
O
S
OH-
O
V
V
O
NH3
H3O+
HS
OH
O
NH2
2+
H3O+
pH = 2.3 - 6
pH = 4.5 - 9
OH2
OH2
2H2O
2 Cl-
Cl
Cl
2
3
O
V
V
S
OH
NH2
H3C
+
H3O+
pH < 4
O
O
1
V
CH3
NH2
S
pH = 3 - 8
4
Scheme 1. Behavior of L-cysteine and L-methionine in aqueous solution of vanadocene dichloride at different pH.

3760
H. Pala´cˇkova´ et al. / Journal of Organometallic Chemistry 692 (2007) 3758–3764
from 6 to 8.5 only one EPR active species in the reaction
mixture is complex 3.
thiolic group is deprotonised and participates in bond to
the vanadocene moiety [33].
By the integration of the EPR spectra measured during
the reaction was evidenced that the starting diaquacomplex
was completely transformed into cysteine products. No
other vanadium species (e.g. EPR inactive oxidized or
reduced reaction products) were observed and the signal
intensity was constant up to pH value 8.5. At higher pH
the EPR silent vanadium compounds are formed.
The study of reaction mixtures containing an excess of
L-cysteine (molar ratios 2:1, 5:1 or 10:1) did not evidence
formation of another complexes and observed EPR spectra
were identical to those recorded for stoichiometric mixtures
of VDC and L-cysteine.
For the purpose of identification of complex 2, we
prepared and spectroscopically characterized vanadocene
complex with 3-mercaptopropionic acid, [Cp2V(O,S-
mpa)] (5). 3-mercaptopropionic acid contains exactly
two donor groups (carboxylic and thiolic function) that
are can be used for chelate bond realized via oxygen
and sulfur atoms. Since EPR parameters of 5 with 2 are
very similar, we anticipate identical coordination environ-
ment around the vanadium(IV) atom in these complexes,
see Table 1.
2.3. Synthesis and identification of 3
2.2. Synthesis and characterization of 2
Neutralization of equimolar mixture of 1 and L-cysteine
by 2 equiv. of NaOH led to the formation of [Cp2V(N,S-
cys)] (3). EPR parameters of compound 3 isolated from
methanolic solution are similar to those observed in aque-
ous solution of 1 and L-cysteine at neutral pH.
Complex [Cp2V(O,S-cys)]Cl (2) was synthesized in
methanol by the reaction of vanadocene dichloride (1) with
an equimolar amount of L-cysteine after neutralization by
one equivalent of sodium hydroxide. When the reaction
was carried out in water, inseparable mixture of 2 and 3
was obtained.
EPR parameters of isolated compound 2 dissolved in
methanol are similar to those observed during above-men-
tioned study, see Table 1.
Observation of the base peak [Cp2V(cys)]+ in positive-
ion ESI mass spectrum and results of elemental analysis
showed that 3 contains only one molecule of L-cysteine.
IR and Raman spectra proved the presence [Cp2V]2+
fragment and L-cysteine in the molecule of 3. Similarly as
in the case of 2, the absence of strong SH vibration at
ꢁ2540 cmꢀ1 in vibrational spectra indicates that the sulfur
atom of thiolic group participates in chelate bond to the
vanadium(IV) centre [33].
For the purpose of identification of complex 3, related
compound with cysteamine, [Cp2V(N,S-csam)]Cl, (6a)
was prepared and characterized. The molecule of cyste-
amine contains only two donor functions (amino and thio-
lic group) and preferential formation of N,S-chelate bond
could be expected. This presumption was unambiguously
validated by X-ray diffraction analysis on the single crystal
of tetraphenylborate salt, [Cp2V(N,S-csam)]BPh4 (6b), see
below. An agreement of EPR parameters for 6a, 6b and
3 evidenced that coordination environment at the VIV+
center is identical and we can assume that all these com-
plexes contain five-membered N,S-chelate ring.
Both the base peak [Cp2V(cys)]+ in positive-ion ESI
mass spectrum and results of elemental analysis of 2
showed that only one molecule of L-cysteine is presented.
The infrared (IR) and Raman spectra (Ra) of 2 con-
firmed the presence of vanadocene fragment as well as
amino acid ligand. The presence of g5-bonded cyclopenta-
dienyl ring is evident from medium to strong bands of
ma(C–H) (IR: ꢁ3140 cmꢀ1), ms(C–H) (IR: ꢁ3096 cmꢀ1
,
Ra: ꢁ3105 cmꢀ1), d(C–H) (IR: ꢁ1025 cmꢀ1) and c(C–H)
(IR: ꢁ840 cmꢀ1) modes, the integrity of bent vanadocene
moiety [Cp2V]2+ verifies observed very strong Raman lines
ms(C–C) (Ra: ꢁ1132 cmꢀ1, ring breathing) and j(Cp) (Ra:
ꢁ285 cmꢀ1, Cp rings tilting). These vibrations are typical
for bent bis(g5-cyclopentadienyl)metal complexes [32].
Very intensive IR band of ma(COO) vibration at
ꢁ1640 cmꢀ1 proved the presence of amino acid carboxylic
group in 2. The absence of strong vibration m(SH) at
ꢁ2545 cmꢀ1 in both IR and Raman spectra indicates that
2.4. Interaction of vanadocene dichloride with L-methionine
in aqueous solutions at different pH
Table 1
The behavior of L-methionine in aqueous solution of 1
at different pH was investigated by EPR spectroscopy
(Scheme 1, Fig. 2).
The isotropic EPR parameters Aiso (10ꢀ4 cmꢀ1) and giso for studied
complexes
Solvent
Aiso
giso
Addition of L-methionine to the aqueous solution of 1
does not change its EPR spectrum and signal correspond-
ing to [Cp2V(H2O)2]2+ was solely observed. Adjusting of
pH to a value of 3 led to the appearance of new paramag-
2
3
4
CH3OH
H2O
CH3OH
H2O
CH3OH
H2O
CH3OH
CH3OH
CH3OH
65.9
65.8
59.6
59.9
62.5
62.5
66.0
60.3
60.1
1.984
1.986
1.992
1.994
1.985
1.984
1.988
1.992
1.990
netic vanadocene complex 4 (Aiso = 62.5 · 10ꢀ4 cmꢀ1, giso
=
1.984). When pH value of 4.5 was reached, the signal of
diaquacomplex disappeared and complex 4 was only one
the EPR active specie in the solution. The complex 4 is sta-
ble in the solution at the pH up to 8.
5
6a
6b

H. Pala´cˇkova´ et al. / Journal of Organometallic Chemistry 692 (2007) 3758–3764
3761
Fig. 3. ORTEP drawing of the molecular structure and atom numbering
scheme of the cationic part of 6b (ellipsoids: 30% probability). Selected
˚
bond distances (A) and angles (deg): Cg(1)–V(1) 1.9685(11), Cg(2)–V(1)
1.9597(10), Cg(1)–V(1)–Cg(2) 132.52(5), V(1)–N(1) 2.181(2), V(1)–S(1)
2.3997(7), N(1)–V(1)–S(1) 76.25(5).
Table 2
Crystal data of 6b, measurement and refinement detailsa
Fig. 2. EPR spectra of aqueous solutions of 1 with L-methionine at
different pH (m0 = 9.46 GHz). (a) pH 2.6, (b) pH 4, and (c) pH 6.5.
Compound
6b
Moiety formula
Crystal system
Space group
C
12H16NSV, C24H20
B
2.5. Synthesis and characterization of 4
Orthorhombic
Pna21 (No. 33)
20.18700(10)
14.6480(2)
9.8000(3)
4
2897.85(10)
1.321
0.5 · 0.25 · 0.15
Green
˚
a (A)
Complex [Cp2V(N,O-met)]Cl (4) was prepared analo-
gously to compound 2. Its structure was proposed on the
basis of spectroscopic measurements (IR, Raman and
EPR), mass spectrometry and elemental analysis.
Raman and IR spectroscopies validated the presence of
both [Cp2V]2+ fragment and amino acid, additionally, ESI-
MS spectrum and elemental analysis of 4 confirmed the
presence of one L-methionine molecule.
The EPR spectrum recorded in methanol is identical to
those observed in aqueous solution during above-men-
tioned acidobasic study (Table 1). The agreement of EPR
parameters of 4 with those known vanadocene amino acid
complexes [Cp2V(O,N-aa)]Cl (aa = gly, ala, val, leu, ile,
phe, his, trp; Aiso = 62.6 0.2 · 10ꢀ4 cmꢀ1, giso = 1,986
0.006) evidenced the presence of N,O-chelate bond in 4
[25,26].
˚
b (A)
˚
c (A)
Z
3
˚
V (A )
Dcalc (g cmꢀ3
)
Crystal size (mm)
Color
Shape
Prism
0.441
l (mmꢀ1
h Range
k Range
l Range
)
ꢀ26, 26
ꢀ18, 19
ꢀ12, 12
49013
6425(0.050)
5737
370
1.071
0.034, 0.081
0.249, ꢀ0.297
Reflections measured
– Independent (Riant
)
– Observed [I > 2r(I)]
Number of parameters
GOFb
Rc, wRc
ꢀ3
˚
Dq (e A
)
P
P
a
2
2
2
Rint
=
jFo ꢀFo,mean j/ Fo
P
.
2.6. Crystal structure of [Cp2V(N,S-csam)]BPh4 (6b)
P
b
2
GOF = [ (w(Fo ꢀ Fc2)2)/(Ndiffrs ꢀ Nparams)]1/2 for all data.
P
P
c
2
R(F) = iFoj ꢀ jFci/ jFoj for observed data, wR(F2) = [ (w(Fo
ꢀ
P
Fc2)2)/( w(Fo2)2)]1/2 for all data.
A typical bent metallocene structure of the cationic part
of 6b is shown in Fig. 3, crystallographic data summarizes
Table 2. In this structure the vanadium(IV) atom is pseudo-
tetrahedrally coordinated by sulfur and nitrogen atoms of
cysteamine and two g5-bonded Cp rings. The structural
features of the vanadocene core (V–Cg of 1.968 and
is constrained by the presence of five-membered chelate
ring to a value of 76.25ꢁ when compared to vanadocene
dichloride (Cl–V–Cl 87.2ꢁ). The V–N bond length
˚
˚
2.181 A is close to the values found in chelate vanadocene
1.960 A, Cg–V–Cg angle 132.5ꢁ) are in good agreement
or 1,10-dimethylvanadocene amino acids complexes
˚
with other vanadocene compounds (Cg–V ꢁ1.96–1.97 A;
˚
(ꢁ2.14–2.18 A) [26,38] and is longer than in vanadocene
Cg–V–Cg ꢁ131–135ꢁ) [26,34–37]. The S–V–N bond angle

3762
H. Pala´cˇkova´ et al. / Journal of Organometallic Chemistry 692 (2007) 3758–3764
complexes with monodentate sp-nitrogen bonded ligands
Cp2V(NCNCN)2 (2.05 A) [39], (MeCp)2V(NCO)2 (2.03
excess of water under argon atmosphere. The a-amino
acids (L-cysteine, L-methionine), 3-mercaptopropionic acid
and cysteamine were obtained commercially (Fluka) and
used without further purification. Vanadocene dichloride
(1) was prepared by published method [45] and purified
by crystallization from dichloromethane. Elemental anal-
ysis, IR, Raman and EPR spectroscopy checked its
purity.
˚
˚
˚
˚
A) [40], Cp2V(N3)2 (2.08 A) [41]. The V–S distance 2.40 A
is slightly shorter than corresponding one reported for
˚
˚
Cp2V(SPh)2 (2.445 A) [42] and Cp2V(SMe)2 (2.442 A)
[43]. The structural parameters for 6b and its molybdeno-
˚
cene analogues [Cp2Mo(N,S-csam)]I (Mo–N = 2.21 A;
˚
Mo–S = 2.44 A; N–Mo–S = 78.4ꢁ) and [Cp2Mo(N,S-
˚
˚
cys)]Cl (Mo–N = 2.26 A; Mo–S = 2.44 A; N–Mo–S =
78.4ꢁ) are comparable [23,44].
4.2. Measurements
3. Conclusions
IR spectra were recorded in the 4000–350 cmꢀ1 region
on a Perkin–Elmer 684 using KBr pellets. Raman spectra
of solid samples at 50–3500 cmꢀ1 were recorded on a Bru-
ker IFS 55 equipped with FRA 106 extension.
The interaction of vanadocene dichloride with sulfur-
containing a-amino acids (L-cysteine and L-methionine)
was studied. The prepared amino acid complexes [Cp2V-
(O,S-cys)]Cl, [Cp2V(N,S-cys)] and [Cp2V(N,O-met)]Cl
were isolated and characterized by spectroscopic tech-
niques (EPR, IR, Raman, MS). Obtained results confirmed
that both L-cysteine and L-methionine are able to coordi-
nate the vanadocene(IV) moiety by stable chelate bond.
The reaction of 1 with cysteine gives two different
products whose structure depends on pH of the reaction
mixture. In acidic media, complex [Cp2V(O,S-cys)]Cl
was identified, but from mixture of neutral pH the com-
pound [Cp2V(N,S-cys)] could be isolated. The reaction
with methionine afforded only [Cp2V(N,O-met)]Cl in the
pH range 3–8. Since the methionine contains the sulfur
atom involved in sulfidic bond, possibility of its transfor-
mation into highly nucleophilic thiolate anion is disabled.
This fact explains observation, that no N,S- or O,S-che-
late complexes of L-methionine were observed during this
study.
The bonding manner of polydentate ligands such as
aforesaid amino acids, cysteamine and 3-mercaptoprop-
ionic acid in prepared complexes was determined particu-
larly by EPR spectroscopy using the comparison of EPR
parameters of amino acid complexes with model vanado-
cene compounds containing a known bond. On the basis
of agreement of EPR parameters of amino acid complexes
2, 3 and 4 with related compounds [Cp2V(O,S-mpa)],
[Cp2V(N,S-csam)]Cl and [Cp2V(O,N-aa)]Cl (aa = gly, ala,
val, leu, ile, phe, his, trp), respectively, structures of each
of them were proposed. The structure of related complex
[Cp2V(N,S-cysam)]BPh4 was unambiguously determined
by X-ray diffraction analysis.
EPR spectra were run on ERS 221 (ZWG Berlin)
apparatus in microwave X-band (ꢁ9.5 GHz) in flat quartz
cuvettes (width 0.3 mm) at room temperature. The appa-
ratus was calibrated with DPPH value (g = 2.0036 2).
Obtained EPR spectra were simulated using EPR simula-
tion software SimFonia v.1.2 (Bruker). A second-order
perturbation theory for interaction of unpaired electronic
spin with vanadium nuclear spin, anisotropic line widths
and mixed Lorentzian/Gaussian lineshapes were used.
Positive-ion electrospray ionization (ESI) mass spectra
were measured on an Esquire 3000 ion trap analyzer
(Bruker Daltonics, Bremen, Germany) in the m/z range
50–1000. The samples were dissolved in methanol and ana-
lyzed by direct infusion at a flow rate 1 ll/min. The selected
precursor ions were further analyzed by MS/MS analyses
under the following conditions: the isolation width
m/z = 4, the collision amplitude 0.9 V, the ion source tem-
perature 300 ꢁC, the flow rate and the pressure of nitrogen
4 l/min and 10 psi, respectively.
The pH adjustments of aqueous solutions were made
with carbonate-free NaOH solution (c = 0.5 mol lꢀ1). The
pH measurements were performed on Hanna pH 211
pH-meter using a glass electrode HI 1131.
4.3. Synthesis of compounds
4.3.1. [Cp2V(O,S-cys)]Cl (2)
To a solution of 1 (0.5 g, 1.98 mmol) in 20 ml of deoxy-
genated methanol L-cysteine (0.24 g, 1.98 mmol) was added
and neutralized by addition of NaOH solution (3.96 ml,
c = 0.5 mol lꢀ1, 1.98 mmol). Solvent was evaporated in
vacuo and the solid residue was crystallized from the ace-
tone–methanol mixture. The brown-green solid was then
washed with 10 ml acetone and dried in vacuo. Yield:
0.62 g (1.84 mmol, 93%). Anal. Calc. for C13H16ClNO2SV
(MW 336.7): C, 49.4; H, 4.8; N, 4.2; Cl, 10.5. Found: C,
49.3; H, 4.9; N, 4.0; Cl, 10.5%. EPR (CH3OH solution):
Aiso = 71.1 G, giso = 1.984. IR (KBr): 3104m, 3068w,
3032w, 2962w, 2930w, 2346w, 1734w, 1647m, 1635s,
1506m, 1436m, 1394m, 1340m, 1286w, 1260m, 1187w,
1130m, 1103m, 1024m, 971m, 839s, 665w, 615m, 565w,
553w, 512m, 488w, 419s, 380m. Raman: 3256(2), 3231(1),
4. Experimental
4.1. Methods and materials
All operations were routinely carried out using con-
ventional Schlenk-line and vacuum techniques. The sol-
vents were purified and deoxygenated by standard
methods. Water was deionised, double distilled and satu-
rated with argon. Carbonate-free sodium hydroxide was
prepared by the reaction of pure sodium metal with the

H. Pala´cˇkova´ et al. / Journal of Organometallic Chemistry 692 (2007) 3758–3764
3763
3187(2), 3115(3), 3095(3), 2964(2), 2919(1), 1130(10),
496(2), 353(3), 287(7), 273(8). Positive-ion MS: m/z 301
[MꢀCl]+ (100%), 284 [MꢀClꢀNH3]+. Positive-ion MS/
MS of 284: m/z 268; 240 [MꢀClꢀNH3ꢀCO2]+; 198; 181
[Cp2V]+ (100%), 127.
666m, 594w, 542w, 442w. Raman: not measured due to
fluorescence.
4.3.5. [Cp2V(N,S-csam)]Cl (6a)
The reaction was carried out as described for complex 4
using 0.22 g (1.98 mmol) of cysteamine. Yield: 0.52 g
(1.76 mmol, 89%). Anal. Calc. for C12H16ClNSV (MW
292.7): C, 49.2; H, 5.5; N, 4.8; Cl, 12.1. Found: C, 49.1;
H, 5.5; N, 4.9; Cl, 12.4%. EPR (CH3OH solution):
Aiso = 64.8 G, giso = 1.992. IR (KBr): 3093w, 3040w,
2965m, 2928w, 1734w, 1622vs, 1506m, 1487m, 1456m,
1384m, 1322m, 1262s, 1128w, 1095m, 1020vw, 979vs,
877vw, 803m, 712s, 667w, 623w, 453w, 396w. Raman:
not measured due to fluorescence.
4.3.2. [Cp2V(N,S-cys)] (3)
Complex 3 was prepared via the procedure described
for 2 using 0.5 g of 1, 0.24 g of L-cysteine. After neutral-
ization by 7.98 ml (3.96 mmol) of NaOH solution (c =
0.5 mol lꢀ1) and evaporation of solvent was obtained
dark-brown solid. Yield: 0.58 g (1.72 mmol, 87%). Anal.
Calc. for C13H16NO2SV Æ NaCl (MW 359.7): C, 43.4; H,
4.5; N, 3.9; Cl, 9.9. Found: C, 43.6; H, 4.4; N, 4.0; Cl,
9.9%. EPR (CH3OH solution): Aiso = 64.1 G, giso = 1.992.
IR (KBr): 3126w, 3112w, 2965m, 2929m, 2856w, 2380w,
2346w, 1772m, 1645m, 1635s, 1539m, 1506m, 1436m,
1394m, 1340w, 1260m, 1102m, 1024m, 960m, 876w,
806s, 755w, 701w, 667w, 544w, 448w. Raman: 3269(6),
3252(7), 3164(2), 3141(2), 3112(5), 3096(5), 2978(3),
2930(5), 2916(1), 1452(4), 1298(4), 1182(3), 1129(10),
632(4), 293(8), 275(6), 165(1), 121(4). Positive-ion MS:
m/z 323 [MꢀCl+Na]+ (100%), 301 [MꢀCl]+, 284
[MꢀClꢀNH3]+; 258 [MꢀClꢀCp+Na]+. Positive-ion
MS/MS of 284: m/z 240 [MꢀClꢀNH3ꢀCO2]+; 198; 181
[Cp2V]+ (100%).
4.3.6. [Cp2V(N,S-csam)]BPh4 (6b)
Complex 6a (0.2 g, 0.68 mmol) was dissolved in 2 ml of
methanol and saturated methanolic solution (1 ml) of
NaBPh4 was added. After stirring of the mixture for several
minutes the crystals suitable for X-ray diffraction analysis
were grown. Yield: 0.16 g (0.29 mmol, 42%). Anal. Calc.
for C36H20BNSV (MW 566.3): C, 76.3; H, 3.6; N, 2.5%.
Found: C, 76.1; H, 3.5; N, 2.5%. EPR (CH3OH solution):
Aiso = 64.7 G, giso = 1.990. IR (KBr): 3093w, 3041w,
2965w, 1734w, 1635m, 1580m, 1558w, 1539w, 1506w,
1480s, 1444m, 1428s, 1384w, 1366w, 1263m, 1185m,
1154m, 1121w, 1099m, 1071m, 1030s, 1020m, 971w,
884w, 842s, 832m, 806m, 747vs, 735vs, 714vs, 667w,
626m, 614 m, 602s, 487m, 464w. Raman: 3321(<1),
3250(<1), 3202(<1), 3168(<1), 3121(1), 3081(1), 3037(5),
2964(<1), 2946(1), 2929(1), 2829(1), 2703(<1), 2435(<1),
2313(<1), 1581(3), 1183(1), 1132(4), 1071(<1), 1030(1),
1000(10), 671(<1), 603(2), 531(<1), 494(<1), 354(1),
307(1), 280(3), 255(1), 189(1), 123(3).
4.3.3. [Cp2V(O,N-met)]Cl (4)
The reaction was carried out as described for complex 2
using 0.5 g of 1 and 0.30 g (1.98 mmol) L-methionine. The
dark-green solid was obtained. Yield: 0.65 g (1.78 mmol,
90%). Anal. Calc. for C15H20ClNO2SV (MW 364.8): C,
49.4; H, 5.5; N, 3.8; Cl, 9.7. Found: C, 49.3; H, 5.4; N,
3.6; Cl, 9.8%. EPR (CH3OH solution): Aiso = 67.5 G,
giso = 1.985. IR (KBr): 3103m, 3090w, 3079w, 2965w,
2919m, 2856w, 1733w, 1645s, 1635s, 1435s, 1386s, 1362w,
1336m, 1303w, 1263m, 1227w, 1187w, 1149w, 1129m,
1094m, 1017m, 969m, 855s, 802m, 665w, 557s, 455w,
396w. Raman: 3113(4), 2983(1), 2917(5), 1435(3), 1369(2),
1350(<1), 1132(10), 1067(2), 717(<1), 700(<1), 598(<1),
436(2), 421(2), 280(9), 237(1), 117(1). Positive-ion MS:
m/z 329 [MꢀCl]+ (100%). Positive-ion MS/MS of 329:
m/z 263 [MꢀClꢀCpH]+; 219 [MꢀClꢀCpHꢀCO2]+; 181
[Cp2V]+ (100%), 104.
4.4. X-ray crystallography
The X-ray data for 6b was obtained at 150 K using
Oxford Cryostream low-temperature device on a Nonius
KappaCCD diffractometer with Mo Ka radiation
˚
(k = 0.71073 A), a graphite monochromator, and the /
and x scan mode. Data reductions were performed with
DENZO-SMN [46]. The absorption was neglected. The
structures were solved by direct methods (Sir92) [47] and
refined by full matrix least-square based on F2 (SHELXL97)
[48]. The symmetry of the crystal is non-centrosymetric,
however the chirality parameter was close to 0.5 and there-
fore crystal was refined as racemic twin. Crystal data are
summarized in Table 2.
4.3.4. [Cp2V(O,S-mpa)] (5)
Complex 5 was prepared according the procedure
described for compound 2 from 1 (0.5 g), 3-mercaptoprop-
ionic acid (0.17 ml, 1.98 mmol) and NaOH (3.96 mmol).
Yield: 0.47 g (1.64 mmol, 83%). Anal. Calc. for C13H14-
O2SV (MW 285.2): C, 54.7; H, 5.0. Found: C, 54.7; H,
5.1%. EPR (CH3OH solution): Aiso = 71.2 G, giso = 1.988.
IR (KBr): 3110s, 3102w, 2934w, 2925w, 2903w, 1733w,
1714w, 1700w, 1589vs, 1575w, 1569w, 1554m, 1506w,
1495w, 1435s, 1386s, 1305m, 1272m, 1199m, 1188m,
1151w, 1130m, 1067m, 1023m, 980w, 959m, 827vs, 673w,
Acknowledgements
This work was financially supported within the frame-
work of Research Project MSM0021627501 and Grant
3310/75/FR361135 of the Ministry of Education of the
Czech Republic.

3764
H. Pala´cˇkova´ et al. / Journal of Organometallic Chemistry 692 (2007) 3758–3764
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Appendix A. Supplementary material
CCDC 625114 contains the supplementary crystallo-
graphic data for 6b. These data can be obtained free of
charge
via
http://www.ccdc.cam.ac.uk/conts/retriev-
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Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax:
(+44) 1223-336-033; or e-mail: deposit@ccdc.cam.ac.uk.
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.jorganchem.
2007.05.026.
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