New organotin(IV) ascorbates: Synthesis, spectral characterization, biological and potentiometric studies

Article abstract of DOI:10.1016/j.saa.2004.03.018

New organotin(IV) ascorbates of the general formulae R₃Sn(HAsc) (where R = Me, n-Pr, n-Bu and Ph) and R₂Sn(Asc) (where R = n-Bu and Ph) have been synthesized by the reaction of R_nSnCl_4-n (where n = 2 or 3) with monosodium-L-ascorbate. The bonding and coordination behaviour in these complexes are discussed on the basis of UV-Vis, IR, Far-IR, ¹H and ¹³C NMR, and ¹¹⁹Sn Moessbauer spectroscopic studies. L-Ascorbic acid acts as a monoanionic bidentate ligand in R₃Sn(HAsc) coordinating through O(1) and O(3). The Moessbauer studies together with IR and NMR studies suggest that for these polymeric derivatives, the polyhedron is trigonal bipyramidal around tin with three organic groups in the equatorial positions. In R₂Sn(Asc), L-ascorbic acid acts as dianionic tetradentate ligand and a polymeric structure with octahedral geometry around tin with trans organic groups has been tentatively proposed. The complexes have been assayed for their anti-inflammatory and cardiovascular activity. Ph₂Sn(Asc) has been found to show the highest activity among the studied complexes. It is suggested on the basis of potentiometric studies of Me₂Sn(IV) and Me₃Sn(IV) systems with L-ascorbic acid that under physiological conditions (pH = 7.0) Me ₂Sn(HAsc)(OH) (～60%), Me₂Sn(OH)₂ (～40%) and Me₃Sn(HAsc) (～60%), Me₃Sn(OH) (～40%), respectively, are existing, which may be responsible for their biological activities.

Full text of DOI:10.1016/j.saa.2004.03.018

Spectrochimica Acta Part A 61 (2005) 77–86
New organotin(IV) ascorbates: synthesis, spectral characterization,
biological and potentiometric studies
a,∗
a
b
b
c
Mala Nath , Ruchi Jairath , George Eng , Xueqing Song , Ashok Kumar
a
Department of Chemistry, Indian Institute of Technology-Roorkee, Roorkee 247 667, India
b
Department of Chemistry and Physics, University of the District of Columbia, Washington, DC 20008, USA
c
Department of Pharmacology, LLRM Medical College, Meerut 250004, India
Received 21 January 2004; accepted 22 March 2004
Abstract
New organotin(IV) ascorbates of the general formulae R
and Ph) have been synthesized by the reaction of R
SnCl4−n (where n = 2 or 3) with monosodium-l-ascorbate. The bonding and coordination
behaviour in these complexes are discussed on the basis of UV–Vis, IR, Far-IR, H and C NMR, and Sn Mössbauer spectroscopic studies.
l-Ascorbic acid acts as a monoanionic bidentate ligand in R Sn(HAsc) coordinating through O(1) and O(3). The Mössbauer studies together
with IR and NMR studies suggest that for these polymeric derivatives, the polyhedron is trigonal bipyramidal around tin with three organic
groups in the equatorial positions. In R Sn(Asc), l-ascorbic acid acts as dianionic tetradentate ligand and a polymeric structure with octahedral
geometry around tin with trans organic groups has been tentatively proposed. The complexes have been assayed for their anti-inflammatory
and cardiovascular activity. Ph Sn(Asc) has been found to show the highest activity among the studied complexes. It is suggested on the
basis of potentiometric studies of Me Sn(IV) and Me
Sn(IV) systems with l-ascorbic acid that under physiological conditions (pH = 7.0)
Me Sn(OH) (∼40%) and Me Sn(HAsc) (∼60%), Me Sn(OH) (∼40%), respectively, are existing, which may
Sn(HAsc)(OH) (∼60%), Me
be responsible for their biological activities.
2004 Elsevier B.V. All rights reserved.
3
Sn(HAsc) (where R = Me, n-Pr, n-Bu and Ph) and R
2
Sn(Asc) (where R = n-Bu
n
1
13
119
3
2
2
2
3
2
2
2
3
3
©
Keywords: l-Ascorbic acid; Organotin(IV); Potentiometric; Anti-inflammatory agent; Cardiovascular; Mössbauer
1
. Introduction
and bidentate complexes [4–7]. l-Ascorbic acid has been
proposed to bind a transition metal at two hydroxy groups
at the 2- and 3-positions, but in addition to these it also uses
the carbonyl C(1)=O group as well as chain OH groups for
coordination [7,8]. It means that it utilizes practically all
donor oxygen [C(1)–O to C(6)–O] atoms for coordination
[7,8]. In view of this, several studies have been focussed on
the interaction of l-ascorbic acid with transition and inner
transition elements [9–19] as well as with non-transition
metals [7,8,20,21] during the last decade.
l-Ascorbic acid (vitamin C; H2Asc), one of the most im-
portant biomolecule, acts as an anti-oxidant, pH regulator
and a two-electron reductant in vitro and in vivo [1]. It is
present in all foods of plant origin and is an essential mi-
cronutrient in man due to absence of l-gulonolactine oxi-
dase [2]; its deficiency causes a disease known as scurvy.
l-Ascorbic acid is a weak acid in water and forms mono-
and dianionic forms, C(3)–O (HAsc ) and C(2)–O (Asc ),
respectively (Scheme 1). Its activity may be due to the fact
that it possesses four tautomeric forms and its metabolites
are radicals with two different structures ( i.e. open and
closed) [3] (Scheme 2).
−
2−
Further, metal ascorbates have received considerable
attention due to their potential antitumor [22,23], an-
tibacterial [13,20], antifungal [13], antioxidant [24], an-
tihypoxic [24], plant-growth regulatory [25], and cat-
alytic [26] activities. Reduction of water-soluble iproplatin
The interaction between the metal ions and l-ascorbic
acid results in simple ascorbate salts and rather weak mono-
i
[PtCl2(OH)2(NH2Pr )2], currently used as antitumor drug
[10,27], when given orally, in chemotherapy by sodium
∗
ascorbate or ascorbic acid and reduction of some plat-
inum(IV) ammine complexes by ascorbic acid, and the an-
titumor activities of several platinum diammine ascorbates
Corresponding author. Tel.: +91-1332-285797;
fax: +91-1332-73560.
E-mail address: malanfcy@iitr.ernet.in (M. Nath).
1
386-1425/$ – see front matter © 2004 Elsevier B.V. All rights reserved.
doi:10.1016/j.saa.2004.03.018

7
8
M. Nath et al. / Spectrochimica Acta Part A 61 (2005) 77–86
Scheme 1.
ence of oxygen were taken at every stage. Solvents were
purified, dried, and stored under nitrogen before use.
l-Ascorbic acid (Loba Chemie), monosodium-l-ascorbate
(Fluka), tri-n-butyltin(IV) chloride, trimethyltin(IV) chlo-
ride, tri-n-propyltin(IV) chloride, and triphenyltin(IV) chlo-
ride (Merck-Schudardt) and diphenyltin(IV) dichloride
(Sigma-Aldrich) were used as received.
Scheme 2.
[
28] and some organotitanium and organotin ascorbate com-
2
2
.2. Synthesis of organotin(IV) ascorbates
plexes [29] have added more attention to the biochemistry
of this sugar molecule.
.2.1. Synthesis of triorganotin(IV) ascorbates
The chemistry of organotins has been a topic of research
interest since past few decades, owing to their potential bi-
ological and industrial applications. Inorganic tin has been
evaluated as the third most important pollutant in the ecosys-
tem, which has raised the concern that tin may enter into the
human food chain, get accumulated in the environment, and
finally in biological systems. l-Ascorbic acid is naturally oc-
curring in most of the foods of plant origin and being often
added to various food products, beverages, and pharmaceu-
ticals, potentially makes it highly relevant for Sn bio-uptake.
Therefore, it becomes indispensable to study the interaction
of l-Ascorbic acid with organotins. A few dialkyltin(IV)
complexes of l-ascorbic acid have been reported previously
[
R3Sn(HAsc)], where R = n-Bu, n-Pr, and Ph)
To a suspension of monosodium-l-ascorbate (0.59 g;
3
.0 mmol) in methanol (25 ml) was added drop wise a
methanolic solution of R3SnCl (where R = n-Bu, n-Pr, and
Ph) (3.0 mmol) with stirring. The resulting solution was
stirred at room temperature for 10 min and then refluxed
for 6 h. It was filtered and the volatiles were removed
in vacuum. The yellow crude product was washed with
dichloromethane and dried in vacuum which on recrystal-
lization from methanol afforded yellow powder.
2
=
.2.2. Synthesis of Me3Sn(IV) and R2Sn(IV) (where R
n-Bu and Ph) derivatives of l-ascorbic acid
To a suspension of monosodium-l-ascorbate (1.19 g;
.0 mmol) in methanol (100 ml) was added drop wise a
[29,30].
Here, we report the synthesis and spectral characteri-
zation of six new complexes of l-ascorbic acid with di-
6
solution of Me3SnCl (6.0 mmol) or Bu2SnCl2 (3.0 mmol)
or Ph2SnCl2 (3.0 m mol) in 10 ml methanol at 0 C with
◦
and triorganotin(IV) moieties by using UV–Vis, IR, Far IR,
1
13
119
H and C NMR, and
Sn Mössbauer spectral studies.
constant stirring. After allowing it to warm up to room tem-
perature, the mixture was heated under reflux for 3 h. The
resulting solution was filtered and concentrated in vacuum
leaving a yellow solid. It was washed with dichloromethane
and recrystallized from methanol and collected as yellow
powder.
The anti-inflammatory and cardiovascular activities of these
compounds are also reported. Potentiometric studies relating
to the identification of the stability of the species formed in
MenSn(IV)-l-ascorbic acid (where n = 2 or 3) in aqueous
solution have also been carried out so that they could be used
(
4−n)+
in modeling studies of the interactions between RnSn
n = 2 or 3) cation and l-ascorbic acid, in vivo.
(
2
.2.3. Synthesis of di-n-butyltin(IV) and di-n-octyltin(IV)
ascorbate
l-Ascorbic acid (0.59 g; 3.0 mmol) dissolved in 20 ml
2
. Experimental
of methanol was slowly added, with constant stirring, to
Oct2SnO or Bu2SnO (3.0 mmol) suspended in 40 ml of the
same solvent. The mixture was refluxed for 20 h but the un-
reacted reactants were obtained. Another attempt to synthe-
size diorganotin(IV)-l-ascorbate by azeotropic removal of
2
.1. Materials and methods
All the syntheses were carried out under an anhydrous
nitrogen atmosphere and precautions to avoid the pres-
ꢀ
water method was made by adding 2,2 -dimethoxypropane

M. Nath et al. / Spectrochimica Acta Part A 61 (2005) 77–86
79
to a mixture of l-ascorbic acid and diorganotin(IV)oxide
prior to refluxing, but it also did not result in complexation.
Anti-inflammatory and blood-pressure lowering studies
were carried out at LLRM Medical College, Meerut, India.
2
.3. Measurements and biological studies
2.4. Potentiometric studies
The melting points of the synthesized compounds were
The protonation and coordination equilibria were investi-
gated by potentiometric titrations in aqueous medium (ionic
determined on a Toshniwal capillary melting point appara-
tus and were uncorrected. Carbon, hydrogen, and tin were
determined as reported previously [31]. UV–Vis spectra of
the compounds were recorded in methanol on a Shimadzu
UV-1601, UV–Vis spectrophotometer. IR and Far-IR spec-
tra of the solid compounds were recorded on the same in-
strument as reported previously [31]. Conductance measure-
ments were carried out on the same instrument as reported
−
3
strength, I = 0.1 mol dm KNO and T = 298 ± 0.1 K)
3
using an Orion 960 plus autotitroprocessor equipped with
Orion Ross flow combined glass electrode. The autotitro-
processor and electrode were calibrated with standard buffer
solutions (Merck; pH = 4.0 ± 0.05 and 9.2 ± 0.05). The
titrations were carried out in a purified nitrogen atmosphere
using a titration vessel. The following mixtures (A−C) were
titrated potentiometrically with standardized NaOH solution
(0.2 M) in aqueous medium:
1
13
previously [31]. H and C NMR spectra were recorded
on a Bruker DRX-300 (300 MHz FTNMR) spectrometer at
the CDRI, Lucknow, India, using DMSO-d or CDCl3 or
6
119
(A) 50 ml of a solution containing 0.004 M ascorbic acid
and 0.1 M KNO3.
CD3OD as solvent and TMS as the internal standard. Sn
Mössbauer spectra were recorded on Mössbauer spectrome-
ter model MS-900 according to the procedure reported pre-
viously [31], at the Department of Chemistry and Physics,
University of The District of Columbia, Washington, DC.
(B) 50 ml of a solution containing 0.004 M Me3SnCl/Me2-
SnCl2 and 0.1 M KNO3.
(C) 50 ml of a solution containing 0.004 M ascorbic acid,
0.004 M Me3SnCl/Me2SnCl2, and 0.1 M KNO3.
2
.3.1. Anti-inflammatory activity
A freshly prepared suspension of carrageenan (0.2 ml;
.0% in 0.9% saline) was injected subcutaneously into the
The acid dissociation constants of ascorbic acid and
formation constants of hydroxo organotin species were de-
termined by titrating mixtures (A) and (B), respectively,
whereas the formation constants of the trimethyltin- or
dimethyltin(IV) ascorbates were determined by titrating
mixture (C). The species formed in the systems were char-
acterized by the following general equilibrium:
1
plantar aponeurosis of the hind paw of the rats of both sexes
body weight 120–160 g) by the method of Winter et al. [32].
(
One group of five rats was kept as a control and the animals
of the other group of five; each was pretreated with the test
drugs given orally (p.o.) 30 m before the carrageenan injec-
tion. The paw volume was measured by a water plethys-
mometer socrel at the time of treatment and then at an inter-
val of 1 h for 4 h. The mean increase of paw volume at each
time interval was compared with that of the control group
pM + qL + rOH ↔ M L (OH)
p
q
r
where M denotes the dimethyl- or trimethyltin cation and L
denotes non-protonated ligand (l-ascorbic acid), r is negative
for a protonated species and positive for hydroxo species.
Protonation constants of the ligands and formation constants
of the complexes were determined by SCOGS program [33].
Tentative values of the constants along with ionic product
of water at experimental temperature and activity coefficient
of hydrogen ion at experimental ionic strength [34] were
supplied as inputs. The constants were refined for several
cycles of operations and the values corresponding to the
minimum standard deviations were accepted. The complex
formation equilibria were elucidated with the help of the
speciation curves obtained as outputs.
(five rats treated with carrageenan, but not treated with test
compounds) and percent anti-inflammatory value was cal-
culated as given below:
ꢀ
ꢁDT ꢂꢃ
Percent anti-inflammatory activity = 1 −
× 100
DC
where DT and DC are the volumes of paw edema in drug
treated and control groups, respectively.
2
.3.2. Blood pressure lowering activity
The study was carried out on either adult mongrel dogs
(
body weight 10−20 kg) or on cats (body weight 3−4 kg)
of either sex. The animals were anesthetized with chloralose
−1
(80 mg kg ) injected intravenously (i.v.). The right femoral
3. Results and discussion
vein was cannulated in each case with an indwelling poly-
thene tube. All the animals were maintained on artificial
positive pressure ventilation by cannulation of the trachea
in order to avoid reflex changes in respiration. The blood
pressure was recorded from the left common carotid artery
by means of a mercury manometer on smoked kymograph
paper.
The reactions of triorganotin(IV) chloride with monos-
odium-l-ascorbate in a 1:1 molar ratio led to the forma-
tion of the compounds according to Eq. (1). Diorganotin(IV)
dichloride reacted with monosodium-l-ascorbate in a 1:2
molar, ratio but the product was found to contain only one
ascorbate anion as suggested by the elemental analysis of

8
0
M. Nath et al. / Spectrochimica Acta Part A 61 (2005) 77–86
Table 1
Characteristic properties of organotin(IV) complexes of l-ascorbic acid
◦
Compound number
Complex (empirical formula)
Yield (%)
m.p. (d) ( C)
Analysis percent:found (cal.)
Sn
C
H
1
2
3
4
5
6
Me3Sn(HAsc)[C9H16O6Sn]
Pr3Sn(HAsc)[C15H28O6Sn]
Bu3Sn(HAsc)[C18H34O6Sn]
Ph3Sn(HAsc)[C24H22O6Sn]
Bu2Sn(Asc)[C14H25O6Sn]
Ph2Sn(Asc)[C18H17O6Sn]
20
20
23
47
20
50
185–190
165–170
175–180
180–185
155–160
195–200
36.01 (35.02)
29.63 (28.05)
24.52 (25.52)
23.60 (22.61)
30.07 (29.09)
25.14 (26.50)
31.18 (31.89)
41.73 (42.58)
45.33 (46.48)
52.72 (54.89)
40.15 (41.21)
47.19 (48.25)
4.85 (4.76)
6.12 (6.67)
7.06 (7.37)
3.99 (4.22)
5.98 (6.18)
3.79 (3.82)
the products Eq. (2). Ascorbic acid coordinates as monoan-
ion in triorganotin(IV) ascorbates but as dianion in diorgan-
otin(IV) ascorbates.
and its organotin(IV) derivatives recorded in methanol are
given in Table 2. The ultraviolet spectrum of l-ascorbic acid
exhibits two strong absorption bands at 246 nm (ε 11,000)
∗
The complexes are produced by the nucleophilic substitu-
tion at the tin by either C(3) (in triorganotin(IV) ascorbates)
or both C(3) and C(2) (in diorganotin(IV) ascorbates) al-
coholic groups (or its sodium derivatives) of ascorbic acid.
The greater acceptor properties of the tin in the diorgan-
otin(IV) dichlorides presumably favor the coordination at
both C(3)–O and C(2)–O positions. The reactions involved
in the synthesis of di- and triorganotin(IV) ascorbates were
found to be quite feasible and required 3−6 h of reflux. How-
ever, even prolonged refluxing of 20 h of a mixture contain-
ing dibutyl/dioctyltin(IV) oxide and l-ascorbic acid did not
result in complexation.
and 201 nm (ε 1900), which have been assigned to n–␲
∗
and ␲–␲ transitions of –(C=O) chromophore, respectively.
∗
A bathochromic shift of ∼24 nm in the n–␲ transition is
observed, indicating extended conjugation upon complexa-
tion, as apparent from the proposed structures (Figs. 1 and
3) of the complexes.
3.2. IR spectral studies
The IR spectral data of l-ascorbic acid, its sodium salts,
and organotin(IV) derivatives together with the assignments
made following references [7,15,29,30] are presented in
All the complexes are yellow powders and sparingly sol-
uble in methanol, water, and dimethylsulphoxide and in-
soluble in chloroform. The yield of the purified organotin
ascorbates is low (20−50%), and they are hygroscopic in
nature and decompose on exposure in air. They slowly de-
compose even on standing under dry nitrogen. The analyt-
ical data of the complexes are presented in Table 1 and
correspond to the proposed stoichiometry. The compounds
are non-electrolytes as suggested by their low molar con-
−1
Table 3. Six sharp bands in the region 3000−3526 cm
obtained in the spectra of ascorbic acid and sodium ascor-
bate are assigned to the –OH stretching vibrations [30]. In
the spectra of the complexes, it is difficult to assign the
exact position of each hydroxyl group; however, all the
complexes show a shift in the position of these bands, and
few peaks are shifted to higher wave numbers while some
to lower. A shift of –OH stretching vibration to higher
wave number may be due to breaking down of extensive
H-bonding present in the crystal structure of l-ascorbic acid
upon complexation, while a shift to lower wave number
indicates participation of –OH group in coordination.
−
1
2
−1
ductance values (0.00–0.40 ꢀ cm mol ) determined in
methanol.
3
.1. Electronic spectral studies in solution
=
The carbonyl C(1) O stretching vibration in l-ascorbic
−1
acid appears as a medium intensity band at 1753 cm
.
The electronic spectral bands (in nm) together with their
ε (molar extinction coefficient) values for l-ascorbic acid
Upon complexation, this band is bathochromically shifted
−
1
−1
by 31−46 cm in compounds 1–5 and by 15 cm in com-
pound 6, indicating the participation of carbonyl (C(1)=O)
group in coordination [7,8,15,29,30]. In the triorganotin(IV)
ascorbates, as observed in sodium ascorbate [7,8], there is a
Table 2
a
Electronic spectral bands of l-ascorbic acid and its organotin(IV) deriva-
tives
∗
∗
␲–␲ (C=O)
Compound number Ligand/complex n–␲ (C=O)
l-Ascorbic acid 246.0 (11000) 201.0 (1900)
1
2
3
4
5
6
Me3Sn(HAsc)
Pr3Sn(HAsc)
Bu3Sn(HAsc)
Ph3Sn(HAsc)
Bu2Sn(Asc)
Ph2Sn(Asc)
269.0 (8100)
203.0 (1600)
270.5 (16500) 203.0 (3400)
269.0 (13800) 203.0 (2800)
270.5 (15700) 206.0 (10400)
268.5 (8400)
268.5 (11900) 203.5 (5500)
202.5 (2000)
a
−1
−1
)
λmax in nm, values of molar extinction coefficient (in L mol cm
are given in parenthesis.
Fig. 1. Octahedral polymeric structure of Bu2Sn(Asc).

M. Nath et al. / Spectrochimica Acta Part A 61 (2005) 77–86
81
Table 3
Characterstic IR frequenciesa (in cm ) of l-ascorbic acid, sodium-l-ascorbate, and its organotin(IV) derivativesb
−1
H2(Asc)c
Na(HAsc)c
1
2
3
4
5
6
Assignments
3526s
3410s
3316s
3217s
3030s
3000sh
3437sh
3360sh
3312vs
3260vs
3187sh
3495s
3452s
3379m
3280s
3065m
3482s
3540sh
3450m
3386w
3275s
3201m
3137s
3484vs
3411vs
3228m
3028m
3460m
3367m
3279m
3224m
3073m
3470m
3400s
3370m
3260m
v(OH)
3441m
3369m
3326m
3246m
3162m
3002m
1
1
753m
1703s
1722s
1707m
1718m
1596vs
1716m
1601vs
1720m
1650sh
1738s
v(C=O)
1632s
672s,b
1599s
1596vs
1602vs
1632vs
ν(C=O) +
δ(C=C)
1627vs
1
1
1
1
363w
321s
275m
221m
1360m
1308vs
1280sh
1233m
1419vs
1321sh
1270sh
1412m
1314m
1275sh
1422m
1314m
1260sh
1412s
1314w
1275 w
1422sh
1337m
1422w
1380vs
ν(C–O) +
δ(C–OH) +
δ(C–H)
1199m
1140vs
1119vs
1076m
1157m
1128s
1076s
1051m
1150m
1126sh
1062m
ν(C–O) +
ν(C–C)
1130s
1075m
1128m
1074m
1128s
1072m
1126m
1070w
1130m
–
–
–
–
601s
579m
603w
587m
596m
494m
590w
550w
610w
560w
579m
502vw
v(Sn–O)+
vSn ← O
v(Sn−C)
505m
500m
281m
506m
280m
220m
217s
a
vs, very strong; s, strong; m, medium; w, weak; sh, shoulder.
Complex numbers as indicated in Table 1.
b
c
[30].
larger shift than in the diorganotin(IV)ascorbates, which may
be due to the intramolecular hydrogen [C(1)O · · · H–C(2)O]
bonding [15].
otin(IV) ascorbates, suggesting deprotonation of O(2)–H
also.
There is a reduction in the number of bands in the
sugar ring C–O and C–C stretching vibration region
The combination band due to v(C=O) + δ(C=C),
−
1
−1
which appear at 1672 cm
as a strong broad band in
(1200−900 cm ) followed by accompanying shift upon
l-ascorbic acid, is also shifted towards lower frequency
complexation [15]. The skeletal deformations of C–O–C
and C–C–C bands in this region are also reduced in intensity
upon complexation [15]. The ionization of the C(3)O–H
and C(2)O–H groups will drastically alter the electron
distribution within the lactone ring. New peaks in the re-
−
1
(
1596−1632 cm ) upon complexation [15,29,30]. This
may be due to the delocalization of electronic charge among
C–1, C–2, and C–3 atoms as indicated in Figs. 1 and 3. Fur-
ther, the lowering of v(C=O) + δ(C=C) in the triorganotin
−
1
−1
ascorbates 1–4 (1596−1602 cm ) is much larger than in 5
gion 610−217 cm are assigned to v(Sn–O) and v(Sn–C)
−
1
and 6 (1627−1632 cm ) and in fact it is close to that of
(Table 3), which also confirm coordination. The ␯s(Sn–C2)
in R2Sn(Asc) and ␯as(Sn–C3) in R3Sn(HAsc) could not
be identified with reasonable certainty, which indicates the
presence of trans organic groups in the proposed octahedral
geometry (Fig. 1) and equatorial organic groups in the pro-
posed trigonal bipyramidal geometry (Fig. 3), respectively.
These spectral investigations reveal that complexation oc-
curs through O(1) and O(3) atoms in the triorganotin(IV)
ascorbates, whereas through O(1), O(2), O(3), and some
contribution of O(5) in the diorganotin(IV) ascorbates.
−
1
monosodium ascorbate (1599 cm ), where a monoanionic
ligand is present.
In the region 1500−1200 cm 1, there are several bands
which are assigned to strongly coupled C–O–C, CH2, and
OH bending modes [15]. They are overlapped by the very
strong, broad C(3)–O stretching vibrations which appear
−
−
1
at 1417 ± 5 cm in the complexes studied. A consider-
−
1
able shift (49−59 cm ) of C(3)–O to higher wave num-
bers in the complexes, as compared to the free ligand, in-
dicates participation of C(3)–O in coordination. Disappear-
ance of δ[O(3)–H] in all of the complexes, which appears
3.3. 1H and 13C NMR solution spectral studies
−
1
at 1221 cm in free ascorbic acid, also confirms the re-
placement of O(3)–H proton by the organotin moiety in all
the di- and triorganotin(IV) ascorbates. δ[O(2)–H] occurring
1H and 13C NMR spectral data of l-ascorbic acid [29,35]
and its organotin(IV) derivatives are presented in Tables 4
and 5, respectively.
−
1
at 1321 cm in the ascorbic acid is absent in the diorgan-

8
2
M. Nath et al. / Spectrochimica Acta Part A 61 (2005) 77–86
Table 4
1
H NMR spectral data of l-ascorbic acid and its organotin(IV) derivatives
a
Compound number
Ligand/complex (solvent)
δ (ppm)
b
l-Ascorbic acid [CD3OD]
4.80 (d, 1H, H-4); 3.90 (m, 1H, H-5); 3.69 (m, 2H, H-6).
4.75 (s, 1H, H-4); 3.82 (t, 1H, H-5); 3.55 (m, 2H, H-6);
l-Ascorbic acidc [CDCl3 + DMSO-d6]
8.01 (s, 1H, O(2)-H).
1
2
Me3Sn(Hasc) [DMSO-d6]
4.14 (s, 1H, H-4); 3.80 (mbr, 1H, H-5); 3.43 (m, 2H,
H-6); 0.45 (s, 6H, H-␣); [83.0 Hz] ; 8.40 (s, 1H, O(2)-H).
4.06 (s, 1H, H-4); 3.81 (mbr, 1H, H-5); 3.43 (m, 2H,
d
Pr3Sn(HAsc) [DMSO-d6]
H-6); 1.59 (t, 6H, H-␣); 1.24–1.18 (mbr, 6H, H-␤); 0.90
(tbr, 9H, H-␥); 8.40 (s, 1H, O(2)-H).
3
4
Bu3Sn(HAsc) [CD3OD]
Ph3Sn(HAsc) [CD3OD]
4.06 (s, 1H, H-4); 3.77 (m, 1H, H-5); 3.65 (m, 2H, H-6);
1
6
.21 (t, 6H, 8.4 Hz, H-␣); 1.66 (m, 6H, H-␤); 1.37 (m,
H, H-␥); 0.93 (t, 9H, 7.5 Hz, H-␦); 8.40 (s, 1H, O(2)-H).
4.50 (d, 1H, 2.4 Hz, H-4); 3.85 (td, 1H, 6.5 Hz, 2.4 Hz,
H-5); 3.65 (d, 2H, 6.6 Hz, H-6); 7.82 (d, 6H, 6.3 Hz,
d
H-␤) [70.0/58.5 Hz] ; 7.42 (m, 9H, H-␥ and H-␦); 8.40
(s, 1H, O(2)-H).
5
6
a
Bu2Sn(Asc) [CD3OD]
Ph2Sn(Asc) [DMSO-d6]
4.78 (d, 1H, 1.5 Hz, H-4); 3.92 (td, 1H, 5.1 Hz, 1.5 Hz,
H-5), 3.68 (d, 2H, 7.0 Hz, H-6); 1.60 (br, 4H, H-␤); 1.48
(br, 4H, H-␣); 1.28 (br, 4H, H-␥); 0.88 (tbr, 6H, H-␦).
4.61 (d, 1H, 2.4 Hz, H-4); 3.75 (t, 1H, 6.0 Hz, H-5); 3.50
(
m, 2H, 7.0 Hz, H-6); 7.90 (d, 4H, 6.3 Hz, H-␤)
d
[73.2/58.2 Hz] ; 7.38 (mbr, 6H, H-␥ and H-␦).
s, singlet; d: doublet; t: triplet; q: quartet; dd: doublet doublet; sbr: singlet broad: dbr, doublet broad; tbr: triplet broad; m: multiplet; mbr: multiplet
broad; td: triplet doublet.
b
[
29].
c
[35].
d
2
J ( H−119/117Sn) (
1
).
Table 5
1
3C NMR spectral data of l-ascorbic acid and its organotin(IV) derivatives
Compound number
Ligand/complex (solvent)
δ (ppm)
a
l-Ascorbic acid [CDCl3 + DMSO-d6]
C-1: 170.67; C-2: 118.31; C-3: 152.47; C-4: 75.03; C-5:
6
8.90; C-6: 62.37.
C-1: 173.00; C-2: 114.00; C-3: 154.00; C-4: 78.40; C-5:
1.30; C-6: 63.40; C-␣: 11.00.
C-1: 173.20; C-2: 113.50; C-3: 152.00; C-4: 79.00; C-5:
1.80; C-6: 63.60; C-␣: 22.00; C-␤: 29.00; C-␥: 18.10.
C-1: 169.00; C-2: 119.00; C-3: 153.00; C-4: 74.30; C-5:
1
2
3
Me3Sn(HAsc) [DMSO-d6]
Pr3Sn(HAsc) [DMSO-d6]
Bu3Sn(HAsc) [CDCl3]
7
7
b
7
1.44; C-6: 64.50; C-␣: 19.49; C-␤: 29.13 [30.2 Hz] ;
c
C-␥: 27.99 [75.0 Hz] ; C-␦: 14.00.
4
5
6
a
Ph3Sn(Hasc) [CD3OD]
Bu2Sn(Asc) [CDCl3]
Ph2Sn(Asc) [CDCl3]
C-1: 171.00; C-2: 118.00; C-3: 151.20; C-4: 78.90; C-5:
b
7
1.50; C-6: 64.00; C-␣: 140.01; C-␤: 137.4 [37.8 Hz] ;
c
C-␥: 129.60 [75.5 Hz] ; C-␦: 130.50.
C-1: 173.90; C-2: 119.50; C-3: 156.30; C-4: 77.20; C-5:
70.70; C-6: 63.60; C-␣: 20.04; C-␤: 28.00; C-␥: 27.00;
C-␦: 13.00.
C-1: 171.90; C-2: 117.60; C-3: 164.4; C-4: 76.00; C-5:
b
6
9.50; C-6: 62.70; C-␣: 140.01; C-␤: 136.70 [36.0 Hz] ;
c
C-␥: 128.70 [75.5 Hz] ; C-␦: 129.30.
[
35].
b
2
J ( H−119/117Sn).
1
c
3
J ( H−119/117Sn) (
1
).

M. Nath et al. / Spectrochimica Acta Part A 61 (2005) 77–86
83
1
Octahedral, cationic [37], neutral [37,38], and anionic
39] tin complexes containing two organic residues and four
In the H NMR spectrum of l-ascorbic acid O(2)–H and
[
O(3)–H signals appear at δ 8.01 ppm and δ 11.3 ppm, respec-
electronegative ligands possess a mutually trans geometry
for the tin−carbon bonds (with a few exceptions). In this
context, the magnitude of the 1 Sn Mössbauer Q.S. is a
useful parameter. Point change calculations [40] for octa-
hedral diorganotin(IV) derivatives with two organic groups
predict that the Q.S. for the trans isomer will be twice
tively, in DMSO-d [30]. In all the studied triorganotin(IV)
6
ascorbates the signal due to O(3)–H disappears and a weak
signal of O(2)–H appears at δ 8.4 ppm, suggesting deproto-
nation of O(3)–H and participation of O(2)–H in hydrogen
bonding in these complexes, whereas in the diorganotin(IV)
complexes, both the signals are absent suggesting deproto-
nation of both the hydroxyl groups of the lactone ring. The
ascorbic acid spectrum consists essentially of three groups
of resonances assigned to the protons on C(4), C(5), and
C(6), respectively, in order of increasing field [29]. Greater
change is expected in C(4)–H signals [29] when complex
formation is achieved either through C(3)–O– in the tri-
organotin(IV) ascorbates or both C(3)–O and C(2)–O– in
the diorganotin(IV) ascorbates. This is reflected by the
fact that C(4)–H signals for all the complexes have a sig-
nificant shift in comparison to the C(5)–H and C(6)–H2
signals. Further, the resonances of the organotin(IV)
moieties have also been assigned in the spectra of the
complexes.
19
−
1
−1
(
∼4.0 mm s ) than that of the cis isomer (∼2.0 mm s ).
However, the dibutyltin(IV) ascorbate exhibits I.S. value
−
1
−1
of 1.17 mm s and Q.S. value of 2.83 mm s . The data
can not be directly interpreted in terms of the structure,
since other diorganotin(IV) complexes with similar param-
eters have been assigned as 5-coordinate with monodentate
carboxyl in R2SnL (L = dianion of tridentate dipeptides)
[41,42] or cis octahedral structures [43–45]. Indeed, where
the other ligands have high electronegativity, the Q.S. is
governed mainly by C–Sn–C bond angle [44,45] and dis-
tortion from regular 6-coordination can give values similar
to those for 5-coordination [46]. Further, it has been re-
2
−
ported [47] that I.S. values for cis-[R2SnX4] are less than
−
1
All the 13C resonances of the ascorbate anion are slightly
shifted towards higher δ values upon complexation. The
characteristic signals for alkyl- or aryl-carbons of the organ-
otin moieties have also been assigned which are in good
agreement with the reported values [31].
1
.0 mm s while trans compounds have I.S. values approx-
−
1
imately 1.2−1.3 mm s . For dibutyltin(IV) ascorbate, the
Mössbauer parameters are best interpreted in terms of dis-
torted trans octahedral configuration in which dibutyltin(IV)
complex has ascorbate-bridged linear polymeric structure
and O(1), O(2), O(3) as well as O(5) take part in coordi-
nation (Fig. 1). This proposed structure also explains very
low solubility of the complex and is also consistent with the
Goldanskii–Karyagin effect [48] observed in its Mössbauer
spectrum. Similar structure can also be proposed for Ph2Sn
analogue.
Due to insufficient solubility of the organotin(IV) ascor-
bates their 1 Sn NMR spectra could not be recorded. Ready
oxidation of the complexes prevents collection of crystals,
suitable for single crystal X-ray study. All other studies of
these ascorbates were done within minimum possible time
after their synthesis and isolation. There still remains con-
troversy about the structures of metal ascorbates both in so-
lution and the solid state. The metal ascorbates are weaker
than those with other chelating ligands [36] and moreover,
isolation of the analytically pure compounds from solution
is difficult due to the instability of the ascorbate anion to ox-
idation. Only a few of such compounds have been analyzed
by X-ray crystallography [9–12].
19
Mössbauer spectrum of Bu3Sn(HAsc) exhibits Q.S.
−
1
−1
at 3.25 mm s
and I.S. at 1.24 mm s and pronounced
line-intensity asymmetry (the Goldanskii–Karyagin effect),
suggesting an intermolecularly associated lattice [48]. Each
of the three isomer (Fig. 2) of R3SnL has been reported
[
49,50] to have different Q.S. values: Q.S for isomer
−
1
−1
(a) 1.7−2.3 mm s ; for (b) 3.0−3.9 m ms ; and for (c)
−
1
3
.5−4.1 mm s
.
The observed value of Q.S. of Bu3Sn(HAsc) lies in the
3
.4. 119Sn Mössbauer spectral studies
range of trans trigonal bipyramidal structure ((b) of Fig. 2).
A possible geometry around the tin in Bu3Sn(HAsc) is a
distorted trigonal bipyramid in which ascorbate anion is
monofunctional and bidentate coordinating through O(1)
The spectra of Bu2Sn(Asc) and Bu3Sn(HAsc) could be
taken as representative in assignment of the structure of the
studied ascorbates on the basis of 1 Sn Mössbauer spectra.
The spectra of rest of the compounds could not be recorded
due to their ready decomposition.
19
The di-n-butyltin(IV) and tri-n-butyltin(IV) ascorbates
−
1
−1
show Q.S. value of 2.83 mm s and 3.25 mm s , respec-
tively, indicating that the electric field gradient around the
tin nucleus is produced by the inequalities in the tin−oxygen
σ bonds and is also due to geometric distortions. The ρ
(
QS/IS) values [Bu2Sn(Asc) = 2.42; Bu3Sn(HAsc) =
.62] in these compounds indicate a coordination number
greater than four with either 5- or 6-coordinated tin.
2
Fig. 2. Structures of different isomers of R3SnL.

8
4
M. Nath et al. / Spectrochimica Acta Part A 61 (2005) 77–86
bition), but lower than that of the standard drug phenylbu-
tazone (38.4% inhibition). A number of studies [52,53] of
the triorganotin compounds, R3SnX, and diorganotin com-
pounds, R2SnXY, indicated that the marked biological ac-
tivity of the organotins may be due to the transport of ei-
(
4−n)+
ther more active species (RnSn
, where n = 2 or 3)
or the molecule as a whole across the cellular membrane,
and X or XY group influences only the readiness of deliv-
+
++
ery of the active part R3Sn /R2Sn into the cell [52]. Fur-
ther, the studies on structure–activity correlation of organ-
otin(IV) compounds reveal that the biologically active com-
pounds should have available coordination positions at tin
and relatively stable ligand–Sn bonds viz., Sn–N [54] (bond
length > 2.39 Å) and Sn–S bonds. These bonds should have
low hydrolytic decomposition. Thus, it can be proposed that
the same mechanism may be involved in the observed ac-
tivity of the studied organotin(IV) derivatives. The analysis
of data in Table 6 indicates that the anti-inflammatory ac-
tivity of the studied compounds is influenced by the nature
of ligand environment and organic groups attached to tin.
Diorganotin(IV) derivatives have been found to show better
activity than the triorganotin(IV) derivatives.
Fig. 3. Trigonal bipyramidal polymeric structure of R3Sn(HAsc), where
R = Me, n-Pr, n-Bu, and Ph.
and O(3). The structure as shown in Fig. 3 is proposed for
Bu3Sn(HAsc). Intramolecular hydrogen bonding between
O(1) and H(2) is also supported by IR spectra. This arrange-
ment is the conventional one (i.e. the most electronegative
axial structure) found in organotin chemistry similar to that
reported for Me3Sn(Gly) [48] and R3SnL [51]. Therefore,
the other triorganotin ascorbates have also been proposed to
have the same ascorbate bridged linear polymeric structure.
3.6. Cardiovascular activity
The cardiovascular (blood-pressure lowering) activity of
the synthesized complexes was carried out on either adult
mongrel dogs (body weight 10−20 kg) or on cats (body
weight 3−4 kg) of either sex.
The compounds exhibited mild hypotensive activity which
−1
lasted for 3−5 min at a dose of 5.0 mg kg i.v., without
affecting the carotid occlusion and noradrenaline response.
Such a profile of pharmacological effect is indicative of di-
rect vasodilator action of these compounds. The results are
presented in Table 6.
3
.5. Anti-inflammatory activity
The anti-inflammatory activity (percent inhibition) of the
complexes was conducted on adult albino rats (body weight
1
20−160 g) of Froster Charles species against carageenan
−1
induced edema in the doses of 50 mg kg given orally. The
anti-inflammatory activities of the complexes are reported
in Table 6.
3.7. Potentiometric studies
Di- and trimethyltin(IV) cations are known to form
stable and water-soluble mono- and polynuclear hydroxo
complexes [55] in the whole pH range studied. Since the
hydroxide ion and ascorbate anion are in strong competition
The test compounds showed mild anti-inflammatory ac-
tivity (15.2−31.0% inhibition). Among the studied ascor-
bates, the Ph2Sn(Asc) showed good activity (31.0% inhi-
Table 6
Biological activity of the organotin(IV) complexes of l-ascorbic acid
Compound numbera
Percent decrease in paw
edema (percent inhibition)
Cardiovascular activity (5 mg kg i.v.)
−1
−
1
Fall in b.p. (mm Hg)
Duration (min)
(50 mg kg , p.o.)
1
2
3
4
5
6
21.0
15.3
25.4
23.3
25.7
31.0
38.4
−10
−6
−7
−10
−10
−8
–
3
4
5
5
3
5
–
Phenylbutazone
a
Complex number as mentioned in Table 1.

M. Nath et al. / Spectrochimica Acta Part A 61 (2005) 77–86
85
Table 7
system, while the analogous complex, Me Sn(HAsc), is
formed in case of the trimethyltin system below pH 5.0.
3
Proton (log K) and organotin(IV) complex formation constants (log
β) of l-ascorbic acid at 298 ± 0.1 K,
I
=
0.1 M KNO3, βpqr
In both the cases the ascorbate anion coordinates the metal
through one of the enol oxygens, probably C(3)–O. De-
protonation of the other enolic hydrogen of MenSn(HAsc)
(where n = 2 or 3) complexes starts from as early as
pH 3.0 for dimethyltin system and from pH 4.5 for the
trimethyltin system. The speciation curves show two ad-
ditional equilibria for the dimethyltin system, where the
Me2Sn(HAsc) and Me2Sn(OH) take up more OH to give
rise to Me2Sn(HAsc)(OH) and Me2Sn(OH)2 in the pH
region 5.0−9.5.
p
q
r
=
MpLqHr/[M] [L] [H]
log βpqr
Me2Sn(IV)
Me3Sn(IV)
1
1
1
1
1
1
11
10
1-1
0-1
0-2
0-3
16.084
11.876
6.135
3.25
8.48
19.52
14.282
8.347
–
6.18
17.80
–
pK1 and pK2 for l-ascorbic acid are 3.96 (reported 4.04 [15]) and 11.52
reported 11.34 [15]), respectively.
(
The species distribution curves for Me2Sn(IV) system in-
dicate that the major species at physiological pH, in aqueous
medium, is Me2Sn(HAsc)(OH) (∼60%) along with some
Me2Sn(OH)2 (∼40%). Whereas, for Me3Sn(IV)–ascorbic
acid system, the major species is Me3Sn(HAsc) (∼60%)
along with some Me3Sn(OH) (∼40%) under same condi-
tions.
It can be concluded from the potentiometric studies that
Me2Sn(Asc), which was isolated in solid state, when ad-
ministered in vivo, hydrolyses at physiological pH to form
hydroxo-mixed ascorbic acid complex, Me2Sn(HAsc)(OH).
Whereas, Me3Sn(HAsc) does not form the hydroxo-mixed
ligand complex under similar conditions. The better ac-
tivity (Table 6) of diorganotins may be attributed to the
hydroxo-mixed ligand complex formation. The OH group is
labile and provide more coordinating ability to the complex
with cellular constituents, thereby showing greater activity.
Fig. 4. Speciation curves for 1:1 Me2Sn(IV)–ascorbic acid system: (1) M,
2) M(OH), (3) M(OH)2, (4) M(OH)3, (5) M(LH), (6) ML, (7) ML(OH).
(
for the metal ion, these hydroxo compounds were always
taken into consideration in the equilibrium systems. Proto-
nation constants of ascorbic acid and stability constants of
the complexes formed with dimethyl- and trimethyltin(IV)
are summarized in the Table 7. The speciation curves
Acknowledgements
This work is part of a major research project sponsored
by the UPCST, Lucknow, (Grant No. CST/SERC/D-1909,
26/10/1998) sanctioned to Dr. M. Nath. R. Jairath is thank-
ful to UPCST, Lucknow, India, for the financial support.
Thanks are also due to the Director, CDRI, Lucknow, India,
for carrying out elemental analysis and NMR spectral mea-
surements. Financial support for Mössbauer work from the
National Institute of Health Minority Biomedical Research
Support Program (MBRS/SCORE, GM08005) is gratefully
acknowledged.
(Figs. 4 and 5) indicate that the monoprotonated complex,
Me2Sn(HAsc), is the predominant species for dimethyltin
References
[
[
[
1] J.C. Deutsch, J. Chromatogr. A 802 (1998) 385.
2] H.R. Griffiths, J. Lunec, Environ. Toxicol. Pharmacol. 10 (2001) 173.
3] N. Kagayama, M. Sekiguchi, Y. Inada, H.D. Tallagi, S. Funahashi,
Inorg. Chem. 33 (1994) 1881.
[4] M. Cieœlak-Golonka, M. Raczko, Z. Staszak, Polyhedron 11 (1992)
2549.
[5] M.B. Davies, Polyhedron 11 (1992) 285.
[
6] W. Jabs, W. Gaube, C. Fehl, R. Lukowski, Inorg. Chim. Acta 175
Fig. 5. Speciation curves for 1:1 Me3Sn(IV)–ascorbic acid system: (1)
M, (2) M(OH), (3) M(OH)3, (4) M(LH), (5) ML.
(1990) 273.

8
6
M. Nath et al. / Spectrochimica Acta Part A 61 (2005) 77–86
[7] H.A. Tajmir-Riahi, J. Inorg. Biochem. 40 (1990) 181; I.G. Sayce, V.S. Sharma, Talanta 19 (1972) 831.
H.A. Tajmir-Riahi, J. Inorg. Biochem. 42 (1991) 47;
H.A. Tajmir-Riahi, J. Inorg. Biochem. 44 (1991) 39.
[34] E.M. Wolleym, D.G. Hurkot, L.G. Hepler, J. Phys. Chem. 74 (1970)
3908;
[
[
8] H.A. Tajmir-Riahi, D.M. Boghai, J. Inorg. Biochem. 45 (1992) 73.
9] H. Yuge, T.K. Miyamoto, Inorg. Chim. Acta 329 (2002) 66.
H.S. Harned, B.B. Owen, Physical Chemistry of Electrolytic Solution,
Reinhold, New York, 1958.
[
10] M.J. Arendse, G.K. Anderson, R.N. Majola, N.P. Rath, Inorg. Chim.
[35] C.J. Pouchert, J. Behnke (Eds.), The Aldrich Library of 13C and
1
Acta 340 (2002) 65.
H FTNMR Spectra, vol. 1, Aldrich Chemical Company, Inc., USA,
[
[
11] H. Yuge, T.K. Miyamoto, Chem. Lett. 5 (1996) 375.
12] M.J. Arendse, G.K. Anderson, N.P. Rath, Inorg. Chem. 38 (1999)
1993, p. 1149C.
[36] A. Martell, in: P.A. Seib, B.M. Tolbert (Eds.), Ascorbic Acid
Chemistry, Metabolism and Uses, Advances in Chemistry Series
200, American Chemical Society, Washington, DC, 1982, pp. 152–
157.
[37] M.M. Mugrady, R.S. Tobias, J. Am. Chem. Soc. 87 (1968) 1909.
[38] N.W. Isaacs, C.H.L. Kennard, W. Kitching, Chem. Commun. 820
(1968).
[39] M.K. Das, J. Buckle, P.G. Harrison, Inorg. Chim. Acta 6 (1972) 17.
[40] B.W. Fitzsimmons, N.J. Seeley, A.W. Smith, J. Chem. Soc. (A) 143
(1969).
[41] M. Vornefeld, F. Huber, H. Preut, G. Ruisi, R. Barbieri, Appl.
Organometal. Chem. 6 (1992) 75.
5864.
[
[
13] J.A. Obaleye, C.L. Orjiekwe, Int. J. Chem. 4 (1993) 37.
14] B. Zumreoglu-Karan, A.N. Ay, C. Unaleroglu, Synth. Reac. Inorg.
Met.-Org. Chem. 32 (2002) 1071.
[
[
[
15] M. Cieœlak-Golonka, M. Raczko, D. Łasut, I. Ma s´ lanka, Spec-
trochim. Acta Part A 55 (1999) 421.
16] C. Ünalero g˘ lu, B. Zümreo g˘ lu-Karan, Y. Zencir, T. Hökelek, Polyhe-
dron 16 (1997) 2155.
17] N.A. Skorik, V.M. Plotnikov, V.V. Kozik, Zhurnal Neorganicheskoi
Khimii 41 (1996) 1146.
[18] W. Yin, Z. Lu, Ziran Kexueban 16 (1998) 46.
[19] D.T. Pham, Hoa Hoc Va Cong Nghiep Hoa Chat 8 (2001) 16.
[20] A.E. Koziol, K. Stepniak, T. Lis, Carbohydr. Res. 226 (1992) 43.
[21] X. Yang, Q. Miao, T. Yu, J. Hu, Z. Yang, S. Bi, Spectrochim. Acta
Part A 59 (2003) 2655.
[42] B. Mundus-Glowacki, F. Huber, H. Preut, G. Ruisi, R. Barbieri,
Appl. Organometal. Chem. 6 (1992) 83.
[43] M. Nath, S. Goyal, C.L. Sharma, Main Group Met. Chem. 18 (1995)
51.
[
22] A.R. Amundsen, E.W. Stern, Patent, US 4457926 A 19840703
[44] T.K. Sham, G.M. Bancroft, Inorg. Chem. 14 (1975) 2281.
[45] R.V. Parish, C.E. Johnson, J. Chem. Soc. (A) (1971) 1906.
[46] T.K. Sham, J.S. Tse, V. Wellington, G.M. Bancroft, Can. J. Chem.
55 (1977) 3487.
[47] A.G. Davies, P.J. Smith, in: G. Wilkinson, F.G.A. Stone, E.W. Ebel
(Eds.), Comprehensive Organometallic Chemistry, Pergamon, New
York, 1982, pp. 519, 525.
[48] B.Y.K. Ho, J.J. Zuckerman, Inorg. Chem. 12 (1973) 1552.
[49] L.E. Khoo, J.P. Charland, E.J. Gabe, F.E. Smith, Inorg. Chim. Acta
128 (1987) 139.
(1984).
[
[
23] A.R. Amundsen, E.W. Stern, Patent, DE 3022957 19810122 (1981).
24] Y.D. Fridman, S.V. Alikeeva, N.V. Dolgashova, M.T. Nanaeva, T.S.
Sabirova, L.I. Atarskaya, Khimiko-Farmatsevticheskii Zhurnal 22
(1988) 425.
[
[
25] Y. Yu, L. Ming, W. Deng, Patent, CN 85107690 A 19874029 (1987).
26] W. Jabs, H. Fuellbier, W. Gaube, Patent, DD 221178 A1 19850417
(1985).
[27] E.L. Weaver, R.N. Bose, J. Inorg. Biochem. 95 (2003) 231.
[
28] L.S. Hallis, A.R. Amundsen, E.W. Stern, J. Am. Chem. Soc. 107
[50] G.M. Bancroft, B.W. Davies, N.C. Payne, T.K. Sham, J. Chem. Soc.,
Dalton Trans. (1975) 973.
(1985) 274.
[
[
29] C.J. Cardin, A. Roy, Inorg. Chim. Acta 107 (1985) L37.
30] J.S. Casas, M.V. Castaño, M.S. Garc ´ı a-Tasende, T. Pérez-Alvarez,
A. Sánchez, J. Sordo, J. Inorg. Biochem. 61 (1996) 97.
[51] M. Nath, R. Yadav, G. Eng, P. Musingarimi, Appl. Organometal.
Chem. 13 (1999) 29.
[52] A.J. Crowe, in: M. Gielen (Ed.), Metal-Based Antitumor Drugs, vol.
1, Freund, London, 1989, p. 103.
[31] M. Nath, S. Pokharia, X. Song, M. Gielen, M. Kemmer, M. Biese-
mans, R. Williams, D. deVos, Appl. Organometal. Chem. 17 (2003)
[53] G. Eng, Y.Z. Zhang, D. Whalen, R. Ramsammy, L.E. Khoo, M. De
Roso, Appl. Organometal. Chem. 8 (1994) 445.
[54] F. Caruso, M. Giomini, A.M. Giullani, E. Rivarola, J. Organometal.
Chem. 506 (1996) 67.
3
05.
32] A.C. Winter, E.A. Fisley, G.W. Nuss, Proc. Soc. Exp. Biol. 111
1962) 544.
[
[
(
33] I.G. Sayce, Talanta 15 (1968) 1397;
I.G. Sayce, Talanta 18 (1970) 653;
[55] N. Buzás, T. Gajda, L. Nagy, E. Kuzmann, A. Vértes, K. Burger,
Inorg. Chim. Acta 274 (1998) 167.