Synthesis and in vitro fungicidal study of organotin(IV) complexes of monomethyl glutarate

Article abstract of DOI:10.1007/s11173-005-0181-4

The synthesis and study of new coordination compounds of some organotin(IV) chlorides with monomethyl glutarate are reported. The ligand molecule appears to be bound to the tin atom through the carboxylic oxygen. The results obtained from ¹H, <

Full text of DOI:10.1007/s11173-005-0181-4

Russian Journal of Coordination Chemistry, Vol. 31, No. 12, 2005, pp. 856–860. From Koordinatsionnaya Khimiya, Vol. 31, No. 12, 2005, pp. 902–906.
Original English Text Copyright © 2005 by Rehman, Baloch, Badshah, Ali.
Synthesis and in vitro Fungicidal Study of Organotin(IV)
Complexes of Monomethyl Glutarate1
W. Rehman*, M. K. Baloch*, A. Badshah**, and S. Ali**
* Department of Chemistry, Gomal University, Dera Ismail Khan, Pakistan
** Department of Chemistry, Quaid-e-Azam University, Islamabad, Pakistan
e-mail: sono_waj@yahoo.com
Received December 3, 2004
Abstract—The synthesis and study of new coordination compounds of some organotin(IV) chlorides with
monomethyl glutarate are reported. The ligand molecule appears to be bound to the tin atom through the car-
boxylic oxygen. The results obtained from 1H, 13C, and 119Sn NMR, FT-IR and 119Sn Mössbauer spectra show
that the complexes are pentacoordinated with the trigonal bipyramidal structure. Biological screening of orga-
notin(IV) derivatives shows promising activity, especially for the triphenyltin complex exhibiting higher anti-
fungal activity. In addition, the rest of the compounds also prove to be active against various fungi used.
1
INTRODUCTION
determined using an inductively coupled plasma atomic
emission spectrometry (ICP-AES) method on an ARL
The chemistry of organotin(IV) complexes has wit-
nessed quantum leap during the past few decades. They
have wide applications as catalysts, stabilizers, bio-
cides, antifouling agents, and wood preservers [1–5].
Investigations have also been carried out to find their
1
13
3410 instrument. The H, C, and 119Sn NMR spectra
were recorded on a multinuclear FT NMR (200 MHz)
JEOL instrument using TMS as an internal standard.
Some of the 13C spectra were measured on a BrukerAM
application as antitumour agents. It has been noted that, 270 instrument at 50 MHz with a 13C probe. Mössbauer
indeed, several di- and triorganotin(IV) species, partic-
ularly, organotin(IV) carboxylates, are found to be
active against various types of cancer [5–7].
spectra were recorded at 80 K on a Cryophysics instru-
ment equipped with a 15 mCi Ca 119SnO3 source.
In the past few years, a number of biologically
important organotin(IV) complexes have been prepared
by our research group [8–12]. As a continuation of our
interest in organotin(IV) carboxylates we are now
reporting the synthesis, spectroscopic characterization,
Synthesis of Monomethyl Glutarate (HL)
Glutaric anhydride (50 mmol) was refluxed in
excess dry methanol for 10 h under anhydrous condi-
tions; excess solvent was removed under reduced pres-
and in vitro fungicidal activity of a series of triorgano- sure, resulting a yellow oil. The yield was 85%.
tin(IV) complexes of monomethyl glutarate.
For C6H10O4Sn (M = 146)
anal. calcd (%):
Found (%):
C 49.27,
C 49.29,
H 6.80.
H 6.82.
EXPERIMENTAL
All triorganotin(IV) compounds, except tribenzyltin
chloride, were purchased from Fluka and used as
received. Tribenzyltin chloride was synthesized by a
described method [13]. All the reactions were carried
out under anhydrous and oxygen-free nitrogen atmo-
sphere. The solvents were dried before use according to
the literature method [14]. The melting points were
measured on a Reichert thermometer (F.G. Bode Co.
Austria). IR spectra were obtained in KBr using a Per-
kin-Elmer FT IR-1605 spectrophotometer in a range of
400–4000 cm–1. Elemental analyses were carried out on
a Yanaco MT-3 high-speed CHN analyzer with an anti-
pyrene as a reference compound. The amount of tin was
1H NMR (CDCl3, δ, pmm): 3.5 (s., H-1), 2.5 (t., H-3),
2.3 (q., H-4) 2.0 (t., H-5), 12.6 (s., H-6).
13C NMR (CDCl3, δ, pmm): 52.1 (C-1), 173.8 (C-2),
30.2 (C-3), 29.5 (C-4), 31.5 (C-5), 174.5 (C-6).
IR (KBr, cm–1): 1720 – ν(C=O), 2065 – ν(OH).
Synthesis of Trimethyl, Tributyl, Triphenyl,
and Tribenzyltin Complexes
of Monomethyl Glutarate (I–IV)
The monomethyl glutarate (5 mmol) was dissolved
in a minimum amount of methanol (25 ml). To this tri-
ethyl amine (5 mmol) was added, and the reaction mix-
1
The text was submitted by the authors in English.
1070-3284/05/3112-0856 © 2005 Pleiades Publishing, Inc.

SYNTHESIS AND in vitro FUNGICIDAL STUDY OF ORGANOTIN(IV) COMPLEXES
857
IR (KBr, cm–1): 1642s—νas(OCO); 1440br—
νs(OCO); ∆ν = 194; 1730—ν(C=O), 547w—ν(Sn–C),
572sh—ν(Sn–O).
ture was refluxed for 10–30 min, a hot methanolic solu-
tion of trimethyl-, tributyl-, triphenyl-, or tribenzyltin
chloride (5 mmol) was added to the above reaction mix-
ture, and this mixture was refluxed for 8–9 h under
nitrogen. The reaction mixture was centrifuged and fil-
tered to remove triethylaminechloride, and excess sol-
vent was removed under reduced pressure. Liquid com-
plexes were formed for trimethyl- and tributyltin chlo-
ride, while solid complexes were obtained for
triphenyl- and tribenzyltin, which were recrystallized
from a 1 : 2 (vol/vol) mixture of methanol and petro-
leum ether (b.p. 40–60°C).
119Sn NMR (CDCl3, δ, pmm): –171.
119Sn Mössbauer (CDCl3, mm/s): QS: 3.90 0.05;
IS: 1.43 0.01; Γ1: 0.96; Γ2: 0.98.
III. The yield was 78%, solid, m.p. = 107°C; Λ,
Ω−1 cm2 mol–1 (10–3 M methanol): 2.8.
For C24H24O4Sn (M = 496)
anal. calcd (%):
Found (%):
C 57.90, H 4.82, Sn 24.50.
C 58.06, H 4.84, Sn 24.19.
I: The yield was 75%, colorless liquid; Λ, Ω–1 cm2 mol–1
(10–3 M methanol): 2.1.
1H NMR (CDCl3, δ, pmm): 3.3 (s., H-1), 2.7 (t., H-3),
2.6 (q., H-4) 2.1 (t., H-5), 7.8 (m., H-α), 7.6 (m., H-β),
7.75 (m., H-γ), 7.80 (m., H-δ).
For C9H18O4Sn (M = 310)
anal. calcd (%):
Found (%):
C 34.82, H 5.80, Sn 38.69.
C 34.84 H 5.81, Sn 38.71.
13C NMR (CDCl3, δ, pmm): 52.3 (C-1), 174.5 (C-2),
31.1 (C-3), 30.2 (C-4), 31.6 (C-5), 178.8 (C-6);
1
126.3 (C-α, J(119Sn–13C) = 690 Hz), 130.7 (C-α,
1H NMR (CDCl3, δ, pmm): 3.2 (s., H-1), 2.4 (t., H-3),
2.6 (q., H-4) 2.0 (t., H-5), 0.5 (s., H-α).
3
2J(119Sn–13C) = 22 Hz), 129.2 (C-α, J(119Sn–13C) =
62 Hz), 128.5 (C-δ).
13C NMR (CDCl3, δ, pmm): 51.9 (C-1), 173.8 (C-2),
30.3 (C-3), 29.6 (C-4), 29.1 (C-5), 176.8 (C-6); –2.5
(C-α, 1J(119Sn–13C) = 555 Hz).
IR (KBr, cm–1): 1630s—νas(OCO); 1454br—
νs(OCO); ∆ν = 176; 1722s—ν(C=O), 520br—ν(Sn–C),
566sh—ν(Sn–O).
IR (KBr, cm–1): 1638s—νas(OCO), 1454br—
νs(OCO), ∆ν = 184, 1720s—ν(C=O), 540w—ν(Sn–C),
563sh—ν(Sn–O).
119Sn NMR (CDCl3, δ, pmm): –98.5.
119Sn Mössbauer (CDCl3, mm/s): QS: 3.15 0.05;
IS: 1.22 0.01; Γ1: 1.36; Γ2: 1.41.
IV. The yield was 80%, solid, m.p. = 121°C; Λ,
119Sn NMR (CDCl3, δ, pmm): –240.
Ω−1 cm2 mol–1 (10–3 M methanol): 2.5.
119Sn Mössbauer (CDCl3, mm/s): quadrupole split-
ting (QS): 3.78 0.05; isomeric shift (IS): 1.28 0.01;
Γ1: 1.10; Γ2: 1.12.
For C27H30O4Sn (M = 538)
anal. calcd (%):
Found (%):
C 60.20, H 5.55, Sn 22.27.
C 60.22, H 5.57, Sn 22.30.
II: The yield was 70%, colorless liquid; Λ, Ω–1 cm2 mol–1
(10–3 M methanol): 2.3.
1H NMR (CDCl3, δ, pmm): 3.5 (s., H-1), 2.5 (t., H-3),
2.4 (q., H-4) 2.0 (t., H-5), 2.1 (s., H-α), 7.75 (m., H-β),
7.70 (m., H-γ), 7.72 (m., H-δ), 7.80 (H-ω).
For C18H36O4Sn (M = 436)
anal. calcd (%):
Found (%):
C 49.52, H 8.25, Sn 27.50.
C 49.54, H 8.26, Sn 27.52.
13C NMR (CDCl3, δ, pmm): 51.8 (C-1), 174.7 (C-2);
30.9 (C-3), 30.4 (C-4), 32.2 (C-5), 175.8 (C-6);
1
29.6 (C-α, J(119Sn–13C) = 570 Hz), 134.3 (C-β,
3
2J(119Sn–13C) = 20 Hz), 128.5 (C–γ, J(119Sn–13C) =
1H NMR (CDCl3, δ, pmm): 3.3 (s., H-1), 2.5 (t., H-3),
2.5 (q., H-4) 1.9 (t., H-5), 0.5 (s., H-α), 1.32 (m., H-β
and H-γ).
57 Hz), 125.5 (C-δ), 123.5 (C-ω).
IR (KBr, cm–1): 1632—νas(OCO), 1460—νs(OCO),
∆ν = 172, 1722s—ν(C=O), 522br—ν(Sn–C), 560sh—
ν(Sn–O).
13C NMR (CDCl3, δ, pmm): 52.1 (C-1), 174.1 (C-2),
30.7 (C-3), 29.8 (C-4), 31.2 (C-5), 177.2 (C-6);
26.7 (C-α, 1J(119Sn–13C) = 560 Hz), 25.3 (C-β,
119Sn NMR (CDCl3, δ, pmm): –150.
119Sn Mössbauer (CDCl3, mm/s): QS: 3.89 0.01;
IS: 1.41 0.01; Γ1: 0.88; Γ2: 0.86.
3
2J(119Sn–13C) = 18 Hz), 24.9 (C-γ, J(119Sn–13C) =
59.5 Hz), 13.3 (C-δ).
RUSSIAN JOURNAL OF COORDINATION CHEMISTRY Vol. 31 No. 12 2005

858
REHMAN et al.
Biological Studies
H. graminium by the hanging drop method developed
by Brian [15].
Different concentrations (50, 100, 250, and 500 ppm)
of the ligand and test compounds (I–IV) were used to
study the effect of germination of C. glocosporiodes,
The germination of spores was observed under a
microscope after 8 h of incubation. The percentage inhi-
A. brassicicola, A. brassicae, C. capsici, and bition of spore germination was calculated as follows.
Total number of ungerminated spores
-----------------------------------------------------------------------------------------
Inhibition of spore germination (%) =
× 100.
Total number of spores
RESULTS AND DISCUSSION
practically bidentate. Compounds where 200 <
∆ν(COO) < 350 are considered as an intermediate state
between monodentate and bidentate, which is called
anisobidentate. On the basis of ∆ν(COO), the carboxy-
late group in the synthesized compounds is monoden-
tate, because the ∆ν(COO) value obtained in all the
complexes is greater than 350. The C=O stretching fre-
quencies were also observed at 1720–1735cm–1.
Compounds I–IV were prepared by adding trime-
thyl- (5 mmol), tributyl- (5 mmol), triphenyl- (5 mmol),
and tribenzyltin chloride (5 mmol) to monomethyl glu-
tarate (5 mmol) together with Et3N according to equa-
tion:
R3SnCl + HL + Et3N
R3SnL + Et3N · HCl, (1)
The 1H NMR data of the synthesized compounds are
completely resolved. All the protons in the spectra are
in good agreement with the expected structure (A)
HL = monomethyl glutarate (proposed structure
MeO
OH
); R = methyl, butyl, phenyl,
O
O
and benzyl.
R
R
MeO
O
The mixture was refluxed for 8–9 h under nitrogen,
which resulted in a good yield of complexes. The com-
plexes of trimethyl- and tributyltin chlorides with
monomethyl glutarate were colorless liquids, while
those obtained with triphenyl- and tribenzyltin chlo-
rides were colorless solids. The solid complexes were
soluble in chloroform, acetone, DMF, and DMSO. The
elemental analysis obtained for all the synthesized
compounds is in good agreement with the proposed 1 : 1
stoichometry between the organotin moiety and
monomethyl glutarate. Structural proposals are based
Sn
O
α
O
γ
R
α
β
δ
R = CH3, CH3CH2CH2CH2,
γ
δ
β
α
α
β
ω
,
δ
α
CH2
(A)
1
on FT-IR, H NMR, 13C NMR, 119Sn and Mössbauer
The spectra of the ligand contain a peak at 12.6 ppm
for the hydroxylic proton. This peak is absent in the
spectra of all the complexes, which suggests complex-
ation through the carboxylic oxygen. The proton NMR
data for methylic, butylic, phenylic, and benzylic pro-
tons are consistent with the earlier reported works [17–
19]. All the protons in the spectra were identified, and
total number of calculated protons is in good agreement
with the proposed structure.
studies.
Spectroscopy
The complexes of tin(IV) with the monomethyl glu-
tarate (HL) are identified by the presence of Sn–O and
Sn–C bands in ranges of 560–573 and 520–547 cm–1,
respectively [16–18]. Coordination of the complexes
was based on the difference (∆ν) between νs(COO) and
νas(COO). According to [19], the values of ∆ν = (νas –
The characteristic resonance peaks in the 13C NMR
νs) can be divided into three groups. For ∆ν(COO) > spectra of the complexes were recorded in CDCl3. The
350, these compounds contain, with high probability, carboxylic carbon in the ligand resonates at 174.5 ppm.
the monodentate carboxylate group. However, other This peak shifts to higher range (175.8–178.8 ppm)
very weak intra- and intermolecular interactions cannot after complexation. This shift indicates complexation
be excluded. When ∆ν(COO) < 200, the carboxylate through the carboxylic oxygen [15]. Further the alkyl
groups of these compounds can be considered to be groups attached to the tin(IV) atom resonate at their
RUSSIAN JOURNAL OF COORDINATION CHEMISTRY Vol. 31 No. 12 2005

SYNTHESIS AND in vitro FUNGICIDAL STUDY OF ORGANOTIN(IV) COMPLEXES
859
Table 1. Antifungal activity of monomethyl glutarate
(HL)*
proper positions [15–19], which once again confirms
complexation.
% Inhibition (dose ppm)
Name of Fungi
The 119Sn chemical shifts of organotin(IV) com-
pounds cover a range of 600 ppm. The data obtained
depict the clear picture about the synthesized com-
plexes. The resonance peaks obtained for the synthe-
sized compounds are in a range of –210…–216.5 ppm,
which is quite similar with the previously reported
works [18–20]. These results are in agreement with the
500
250
100
50
C. capsici
na
+
+
+
C. gloeosporioides
A. brassicicola
A. brassicae
+
na
+
Na
+
na
+
+
+
na
+
Na
Na
na
na
hypothesis that the increase in the coordination number H. graminium
+
of the tin atom in the complexes is due to tin nuclear
shielding screening [21].
* (+)—low activity; na—no activity.
The 119Sn Mössbauer method is a powerful tool for
the determination of coordination of the synthesized
compounds [22]. The results obtained show quadrupole
splitting and the isomeric shift in the ranges 3.15–3.90
and 1.28–1.43 mm–1, respectively, suggesting that all
the synthesized compounds exhibit coordination num-
Table 2. Antifungal activity of compound I*
% Inhibition (dose ppm)
250 100
Name of Fungi
500
50
C. capsici
+
+
+
+
+
+
+
+
ber 5 with trigonal bipyramidal geometry (A). The C. gloeosporioides +
na
+
na
+
results obtained are in full agreement with the hypoth-
esis of the Sn–O interaction, leading to penta-coordi-
nated complexes as reported for the analogous com-
pounds [22].
A. brassicicola
A. brassicae
+
++
+
+
na
na
H. graminium
na
* (+)—low activity; (++)—medium activity; (+++)—high activity;
na—no activity.
Antifungal Activity
Table 3. Antifungal activity of compound II*
The results summarized in Tables 1–5 show that
among the synthesized compounds, compound III
(triphenyltin complex) was found to be the most effi-
cient against all the species of test fungi at all concen-
trations used. The inhibition of spore germination was
higher at 500 ppm. The complete inhibition was
recorded even at 250 ppm in C. gloeosporioides and
A. brassicae. The toxicity of organotin(IV) enhanced
up to large extent may be due to the coordination of the
tin(IV) atom with oxygen of the ligand. The presence of
phenyl groups bonded with the tin(IV) atom is also con-
sidered responsible for the rise of toxicity, which may
be get free in solution and play a key role to increase the
toxic effect of the phenyl complex (III).
% Inhibition (dose ppm)
Name of Fungi
500
++
C. gloeosporioides ++
250
100
50
C. capsici
+
+
Na
+
+
+
+
+
+
A. brassicicola
A. brassicae
+
++
+
na
+
+
H. graminium
++
++
na
* (+)—low activity; (++)—medium activity; (+++)—high activity;
na—no activity.
Table 4. Antifungal activity of compound III*
All the complexes show promising activity
against plant pathogens. In general, the fungicidal
activity of the alkyltin complexes were based on the
R group attached to the tin atom. On the basis of the
R group, the activity of the tin(IV) complexes
decreases in the following order: phenyl > benzyl >
butyl > methyl > ethyl. The overall results reveal that
the triphenyl complex shows more fungicidal activ-
ity than others, which is due to the presence of the R
group, because phenyl is more active than the other
alkyl groups.
% Inhibition (dose ppm)
Name of Fungi
500
+++
C. gloeosporioides +++
250
100
50
C. capsici
+++
++
+
+++
++
+
+
+
+
na
+
A. brassicicola
A. brassicae
++
+++
+++
+++
++
na
+
H. graminium
* (+)—low activity; (++)—medium activity; (+++)—high activity;
na—no activity.
RUSSIAN JOURNAL OF COORDINATION CHEMISTRY Vol. 31 No. 12 2005

860
REHMAN et al.
Table 5. Antifungal activity of compound IV*
5. Ahmed, S., Ali, S., Ahmed, F., et al., Synth. React.
Inorg.-Org. Chem., 2002, vol. 32, p. 1521.
% Inhibition (dose ppm)
500 250 100
++ na
6. Gielen, M., Dalil, H., Ghys, L., et al., Organometallics,
Name of Fungi
C. capsici
1998, vol. 17, no. 19, p. 4259.
50
7. De Vos, D., Willem, R., Gielen, M., et al., Metal-Based
Drugs, 1998, vol. 5, p. 179.
8. Ali, S., Khokhar, M.N., Mazhar, M., et al., Synth. React.
Inorg.-Org. Chem., 2002, vol. 32, p. 1373.
9. Ali, S., Ahmed, F., Mazhar, M., et al., Synth. React.
Inorg.-Org. Chem., 2001, vol. 32, p. 357.
10. Rehman, W., Badshah, A., Baloch, M.K., et al., J. Chin.
Chem. Soc., 2004, vol. 51, p. 929.
+
+
+
+
+
+
C. gloeosporioides
A. brassicicola
A. brassicae
++
+
na
+
na
+
++
++
+
na
na
H. graminium
na
* (+)—low activity; (++)—medium activity; (+++)—high activity;
na—no activity.
11. Ashfaq, M., Khan, M.I., Baloch, M.K., and Malik, A.,
J. Organomet. Chem., 2004, vol. 689, p. 238.
12. Rehman, W., Baloch, M.K., Muhammad, B., et al., Chin.
Sci. Bull., 2004, vol. 49, p. 119.
13. Sisido, K., Takeda, Y., and Kingawa, Z., J. Am. Chem.
Soc., 1961, vol. 83, no. 3, p. 538.
The fungi toxic activity for other synthesized com-
plexes is significant at maximum concentration.
ACKNOWLEDGMENTS
14. Perrin, D.D. and Armengo, W.L.F., Purification of Lab-
oratory Chemicals, Oxford: Pergamon, 1988.
15. Brian, P.W., Trans. Brit. Mycol. Soc., 1960, vol. 1, p. 43.
16. Rahman, A., Choudhary, M.I., and Thomsen, W.J., Bio-
assay Techniques for Drug Development, The Nether-
lands: Harwood Acad., 2001, vol. 16.
17. Winter, C.A., Fisley, E.A., and Nuss, G.W., Proc. Soc.
Exp. Biol., 1962, vol. 111, p. 544.
18. Smith, Q.E., Pharmacological-Screening Test Progress
in Medicinal Chemistry, London: Butter Worth, 1960,
vol. 1.
19. Vornefeld, M., Huber, F., Preut, H., et al., Appl. Orga-
nomet. Chem., 1992, vol. 6, p. 75.
One of the authors, Dr. Amin Badshah, is highly
thankful to Professor B. Wrackmeyer (University of
Bayreuth Germany) for spectral studies. HEJ Institute
of Chemistry and University of Karachi (Pakistan) are
highly acknowledged for the determination of some of
the bioactivities. Associate Professor A. Christofides
(University of Thessalonki, Greece) is highly obliged
for providing useful research material.
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