Synthesis, structural characterization and antimicrobial activity of mixed aryl-alkyl diorganotin(IV) compounds with quinoline-2-carboxylate (L -): {RR'SnLCl}n and RR'SnL2

Article abstract of DOI:10.1002/aoc.2890

A series of unsymmetrical diorganotin derivatives of quinoline-2-carboxylic acid (LH), namely polymeric {MePhSnClL}_n (1) and {EtPhSnClL} _n (2), and mononuclear MePhSnL₂ (3) and EtPhSnL ₂ (4), was synthesized by the reaction of LH with the MePhSnCl ₂, EtPhSnCl₂, MePhSnO, and EtPhSnO precursors, respectively. The compounds were characterized by elemental analysis and infrared spectroscopy, as well as by ¹ H, ¹³ C and ¹¹⁹Sn NMR. The molecular structures of representative compounds 2 and 4 were determined by single-crystal X-ray crystallography. This study showed that polymeric 2 adopts a distorted octahedral geometry as the carboxylate ligand N,O chelates an Sn atom and at the same time bridges a neighbouring Sn atom via the second O atom, with the remaining sites being occupied by the Cl and two C atoms; the O atoms are trans to each other. The result of the μ₂-bridging mode of L^- is the formation of a supramolecular helical chain. Compound 4 adopts a skew-trapezoidal bipyramidal geometry with the organo groups lying over the plane of the two N,O-chelating carboxylate ligands and being directed over the weaker Sn-N bonds. The in vitro antimicrobial activities of 1-4 against a Gram-positive bacteria strain (Bacillus subtilis), a Gram-negative bacteria strain (Escherichia coli) and against Candida albicans were studied and compared with the antimicrobial activities of Ph₂SnL₂ and Me₂SnL₂, and with the antimicrobial standards gentamicin, tetracycline, ampicillin and penicillin. All organotin compounds displayed remarkable antibacterial activities that were comparable to those of the standard drugs, in particular against B. subtilis, where the activity was correlated with the number of Cl substituents.

Full text of DOI:10.1002/aoc.2890

Full Paper
Received: 22 January 2012
Revised: 1 May 2012
Accepted: 2 May 2012
Published online in Wiley Online Library
(wileyonlinelibrary.com) DOI 10.1002/aoc.2890
Synthesis, structural characterization and
antimicrobial activity of mixed aryl–alkyl
diorganotin(IV) compounds with quinoline-2-
carboxylate (Lꢀ): {RR0SnLCl}n and RR0SnL2
Marzieh Vafaeea, Mostafa M. Aminia*, Hamid Reza Khavasia,
Seik Weng Ngb,c and Edward R. T. Tiekinkb**
A series of unsymmetrical diorganotin derivatives of quinoline-2-carboxylic acid (LH), namely polymeric {MePhSnClL}n (1) and
{EtPhSnClL}n (2), and mononuclear MePhSnL2 (3) and EtPhSnL2 (4), was synthesized by the reaction of LH with the MePhSnCl2,
EtPhSnCl2, MePhSnO, and EtPhSnO precursors, respectively. The compounds were characterized by elemental analysis and
infrared spectroscopy, as well as by 1 H, 13 C and 119Sn NMR. The molecular structures of representative compounds 2 and 4
were determined by single-crystal X-ray crystallography. This study showed that polymeric 2 adopts a distorted octahedral
geometry as the carboxylate ligand N,O chelates an Sn atom and at the same time bridges a neighbouring Sn atom via the
second O atom, with the remaining sites being occupied by the Cl and two C atoms; the O atoms are trans to each other. The
result of the m2-bridging mode of Lꢀ is the formation of a supramolecular helical chain. Compound 4 adopts a skew-trapezoidal
bipyramidal geometry with the organo groups lying over the plane of the two N,O-chelating carboxylate ligands and being
directed over the weaker Sn-N bonds. The in vitro antimicrobial activities of 1–4 against a Gram-positive bacteria strain (Bacillus
subtilis), a Gram-negative bacteria strain (Escherichia coli) and against Candida albicans were studied and compared with the
antimicrobial activities of Ph2SnL2 and Me2SnL2, and with the antimicrobial standards gentamicin, tetracycline, ampicillin
and penicillin. All organotin compounds displayed remarkable antibacterial activities that were comparable to those of the
standard drugs, in particular against B. subtilis, where the activity was correlated with the number of Cl substituents. Copyright
© 2012 John Wiley & Sons, Ltd.
Keywords: organotin(IV); quinoline-2-carboxylic acid; crystal structure; NMR structure; antimicrobial activity
quinoline-2-carboxylic acid (HL) is particularly interesting due
to its inherent steric bulk, which is capable of controlling the
Introduction
Diorganotin carboxylates have been subject of extensive investi-
gations owing to their biological activity, including their potential
antineoplastic and anti-tuberculosis activities.[1–6] In the context
of anti-cancer activity, a particular motivation for their study
stems from the known side effects exhibited by the widely used
anti-tumour drugs cisplatin and carboplatin, which has stimu-
lated the search for organometallic compounds as alternative
drugs for combating human cancer.[7–10] The significant biologi-
cal activities of organotin compounds in general and organotin
carboxylates in particular, i.e. in vitro antifungal, antibacterial,
antiviral, pesticidal and antitumour activities, have been attrib-
uted to the number and nature of the organic groups attached
to the central tin atoms.[4,5] However, the role of carboxylate
ligand should not be discounted.[11] For instance, a number of
biological activities such as anti-inflammatory, anti-allergic,[12]
antibacterial,[13] antimalarial,[14] anti-parasitic,[15] anti-proliferative,[16]
and anti-cancer[17] have been observed for quinoline-containing
compounds. Recent studies on organotin(IV) derivatives containing
carboxylate ligands with additional donor atoms such as nitrogen
and sulphur have revealed new structural motifs which can lead
to compounds with enhanced biological activities;[18] accordingly,
coordination geometry of tin regardless of the nature of the R
groups bonded to tin.[18–21] To investigate the role of tin-bound
organic groups upon biological activity of organotin compounds,
in this work a series of unsymmetric diorganotin derivatives of
Lꢀ have been prepared. As the accumulated evidence shows
that the activities of mixed organotin systems are significantly
different from those of the symmetrical systems,[22] the investiga-
tion of organotin compounds with an asymmetric tin centre
will reveal valuable insight into the biological activity of organotin
(IV) compounds. Herein, the synthesis, characterization and
*
Correspondence to: M. M. Amini, Department of Chemistry, Shahid Beheshti
University, Tehran 1983963113, Iran. E-mail: m-pouramini@sbu.ac.ir
**Correspondence to: Edward R. T. Tiekink, Department of Chemistry, University
of Malaya, 50603 Kuala Lumpur, Malaysia. E-mail: Edward.Tiekink@gmail.com
a Department of Chemistry, Shahid Beheshti University, Tehran 1983963113, Iran
b Department of Chemistry, University of Malaya, 50603, Kuala Lumpur, Malaysia
a
number of such organotin(IV) carboxylates have been
c
Chemistry Department, Faculty of Science, King Abdulaziz University, PO
Box 80203, Jeddah, Saudi Arabia
reported.[19–21] Among the many carboxylic acids available,
Appl. Organometal. Chem. (2012)
Copyright © 2012 John Wiley & Sons, Ltd.

M. Vafaee et al.
molecular structures of four new unsymmetrical diorganotin(IV)
compounds derived from quinoline-2-carboxylic acid, some
known symmetric derivatives, and their in vitro antimicrobial
activity against a Gram-positive bacteria strain (Bacillus subtilis),
a Gram-negative bacteria strain (Escherichia coli) and Candida
albicans are reported. Dialkyltin(IV), diaryltin(IV) and alkylaryltin
(IV) compounds of quinoline-2-carboxylic acid were prepared
employing methods reported in previous studies by reaction of
diorganotin(IV) dichloride with sodium quinoline-2-carboxylate
or condensation of diorganotin(IV) oxide with HL.[18–21] The
specific motivation of the study was to evaluate the influence
of the tin-bound organic groups and also role of mixed tin-
bound alkyl/aryl groups on their antibacterial activity.
Table 1. Crystal data and refinement details for 2 and 4
Crystal data
2
4
Empirical formula
Formula weight
Crystal colour
Crystal dimensions (mm)
Crystal system
Space group
a (Å)
C
18H16ClNO2Sn
C28H22N2O4Sn
569.17
432.46
Colourless
Colourless
0.20 ꢂ 0.25 ꢂ 0.30 0.25 ꢂ 0.30 ꢂ 0.35
Monoclinic
P21/n
Monoclinic
P21/n
11.0263(3)
12.4110(3)
12.4432(4)
91.448(3)
1702.28(8)
4
9.9932(3)
16.2070(4)
15.0750(5)
105.410(3)
2353.77(12)
4
b (Å)
c (Å)
b (deg.)
V Å3
Z
Dx (g cmꢀ3
)
1.687
1.606
Experimental
F (000)
m(Mo Ka) (mmꢀ1
856
1144
Materials
)
1.666
1.124
Reflections collected
Rint
12244
24877
Triphenyltin(IV) chloride, methyl bromide, ethyl bromide, sodium,
quinoline-2-carboxylic acid (HL) and magnesium were purchased
from Merck and used without further purification. All solvents
were dried and distilled under a nitrogen atmosphere prior to
use. Methyltriphenyltin(IV) was prepared using a conventional
Grignard synthesis with triphenyltin(IV) chloride and methyl
magnesium bromide, and purified by recrystallization from meth-
anol (m.p. 47 ꢁC; yield 75%).[23] Ethyltriphenyltin(IV) was prepared
similarly from triphenyltin(IV) chloride and ethyl magnesium
bromide, and purified by recrystallization form ethanol at room
temperature (m.p: 55 ꢁC, yield 72%).[24]
0.032
0.045
Unique reflections
3919
5442
Obs. reflections [I > 2s(I)] 3405
R [obs. reflns] 0.025
a, b, in weighting scheme 0.025, 1.251
4563
0.029
0.041, 1.663
0.079
wR (all data)
0.032
CCDC deposit no.
856935
856936
Methylphenyltin(IV) dichloride and ethylphenyltin(IV) dichloride
were prepared by hydrochlorination of methyltriphenyltin(IV)
and ethyltriphenyltin(IV), respectively, according to the literature
synthesis[31] of mixed organotin compounds of the type (C6H5)
RSnCl2. For the preparation of 1, a solution of MePhSnCl2
(0.28 g, 1 mmol) in methanol (5 ml) was added to a solution of
sodium quinoline-2-carboxylate (0.20 g, 1 mmol) also in methanol
(5 ml) at room temperature with vigorous stirring. After 2 h,
sodium chloride was removed by filtration and the solid was
crystallized (yield 75%; m.p. 185–186 ꢁC). Anal. Calcd for
C17H14ClNO2Sn: C, 48.80; H, 3.37; N, 3.35%. Found C, 48.12;
H, 3.78; N, 3.23%. IR (KBr, cmꢀ1): nas(OCO), 1674; ns(OCO), 1322;
n(Sn-C), 550; n(Sn-N), 482; n(Sn-O), 445. 1 H NMR (CDCl3, ppm;
the atom numbering for the 1 H and 13 C NMR spectra for
quinoline-2-carboxylato ligand in 1–4 is shown in Scheme 1):
1.29 (3 H, s, Sn-CH3, 2 J117/119Sn-H = 78 Hz), 7.33–7.37 (3 H, m,
Physical Measurements
Melting points were obtained with an Electrothermal 9200 melt-
ing point apparatus and are not corrected. Infrared spectra in the
range 4000–400 cmꢀ1 were recorded on a Shimadzu 470 FT-IR
spectrophotometer using KBr pellets. 1 H, 13 C and 119Sn NMR
spectra were recorded at room temperature in CDCl3 solution
on a Bruker AVANCE 300-MHz instrument operating at 300.3,
75.4 and 111.9 MHz, respectively. The NMR spectra are referenced
to Me4Si (1 H and 13 C) or Me4Sn (119Sn) as internal standards.
X-Ray Crystallography
Intensity data were measured at 100 K on an Agilent Technolo-
gies SuperNova Dual CCD with an Atlas detector fitted with Mo
Ka radiation so that θmax = 27.6ꢁ. Data processing and absorption
correction were accomplished with CrysAlis PRO.[25] The
structures were solved by direct methods with SHELXS-97[26]
and refinement (anisotropic displacement parameters, hydrogen
atoms in the riding model approximation and a weighting
scheme of the form w = 1/[s2(Fo2) + (aP)2 + bP] for P = (Fo2 + 2F2c)/3)
was on F2 by means of SHELXL-97.[26] Crystallographic data and
final refinement details are given in Table 1. Figures 1(a) and 2
were drawn with ORTEP-3[27] at the 50% probability level and
the remaining crystallographic figures were drawn with DIA-
MOND using arbitrary spheres.[28] Data manipulation and inter-
pretation were with WinGX[29] and PLATON.[30]
H
m,p-C6H5), 7.58 (2 H, d, Ho-C6H5, 3 J H-H = 6.0 Hz), 7.81–7.87
(3 H, m, H5–7), 8.12 (1 H, d, H8, 3 J H-H = 7.0 Hz), 8.61 (1 H, d, H3,
3 J H-H = 7.0 Hz), 8.67 (1 H, d, H2, 3 J H-H = 7.0 Hz). 13 C NMR
(DMSO-d6, ppm): 165.0 (COO), 147.9 (C6H5, Cipso,
1 J117/119Sn-13
C = 622 Hz), 135.2 (C H5, Co, 2 J117/119Sn-13 C = 48 Hz), 128.7
(C6H5, Cp), 125.4 (C6H5, Cm, 3 J117/119Sn-13 C = 65 Hz), 142.6 (C1),
142.2 (C9), 132.8 (C2), 130.8 (C8), 130.4, 130.0 (C4), 129.2 (C6),
125.3, 121.3, 9.6 (Sn-CH3, 1 J117/119Sn-13 C = 632 Hz). 119Sn NMR
(DMSO-d6, ppm): ꢀ312.4.
6
EtPhSnClL (2) was prepared similarly from EtPhSnCl2 and
sodium quinoline-2-carboxylate, and was recrystallized from
methanol (yield 71%; m.p. 190–191 ꢁC). Anal. Calcd for
C18H16ClNO2Sn: C, 49.99; H, 3.73; N, 3.24%. Found C, 50.22; H,
3.28; N, 3.48%. IR (KBr, cmꢀ1): nas(OCO) 1642; ns(OCO) 1334;
n(Sn-C) 595; n(Sn-N) 523; n(Sn-O) 456. 1 H NMR (CDCl3, ppm):
1.00 (3 H, t, SnCH2CH3, 3 J H-H = 7.8 Hz, 3 J117/119Sn-H = 195 Hz),
1.59 (2 H, q, SnCH2, 3 J H-H = 7.8 Hz, 2 J117/119Sn-H = 98 Hz), 7.30–
7.34 (3 H, m, Hm,p-C6H5), 7.58 (2 H, d, Ho-C6H5, 3 J H-H = 6.0 Hz),
Synthesis of Compounds
Synthesis of catena-poly[[chlorido(methyl)phenyltin(IV)]-m-quinoline-2-
carboxylato-k3 N,O:O0], {MePhSnLCl}n (1) and catena-poly[[chlorido(ethyl)
phenyltin(IV)]-m-quinoline-2-carboxylato-k3 N,O:O0], {EtPhSnLCl}n (2)
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Appl. Organometal. Chem. (2012)

Antimicrobial activity of asymmetric diorganotin carboxylates
Figure 1. (a) The asymmetric unit in polymeric {PhEtSnLCl}n (2) showing the atom labelling scheme and displacement ellipsoids drawn at 50% probability
level, and (b) helical supramolecular chain along [010] mediated by intermolecular Sn–O2 interactions. Selected geometric parameters: Sn–Cl1 2.4387(6),
Sn–O1 2.1136(16), Sn–N1 2.4311(19), Sn–O2i 2.6255(16) Å; O1–Sn–O2i 177.40(6), C1–Sn–C7 152.59(9)ꢁ. Symmetry operation i: 3/2 ꢀ x, ꢀ1/2 + y, 3/2 ꢀ z
Synthesis of methyl(phenyl)bis(quinoline-2-carboxylato-k2 N,O)tin(IV) (MePhSnL2)
(3) and ethyl(phenyl)bis(quinoline-2-carboxylato-k2 N,O)tin(IV) (EtPhSnL2) (4)
Methylphenytinoxide(IV) (MePhSnO) and ethylphenytinoxide(IV)
(EtPhSnO) were prepared by reacting methylphenyltin(IV)
dichloride and ethylphenyltin(IV) dichloride with sodium hydrox-
ide, respectively. The resulting white precipitate was removed by
filtration and washed copiously with water and dried at room
temperature. For the preparation of 3, a mixture of methylphe-
nyltin oxide (0.21 g, 1 mmol) and quinoline-2-carboxylic acid
(0.40 g, 2 mmol) in toluene (25 ml) was refluxed and the water
that was produced during the reaction was removed azeotropi-
cally by a Dean–Stark trap. After 8 h, toluene was removed under
reduced pressure and the white solid was recrystallized from
methanol (yield 82%; m.p. 140 ꢁC dec.). Anal. Calcd for
C27H20N2O4Sn: C, 58.42; H, 3.63; N, 5.05%. Found: C, 57.84; H,
4.32; N, 4.98%. IR (KBr, cmꢀ1): nas(OCO) 1674; ns(OCO) 1329;
n(Sn-C) 545; n(Sn-N) 501; n(Sn-O) 455. 1 H NMR (DMSO-d6, ppm):
Figure 2. Molecular structure of PhEtSnL2 (4) showing the atom
labelling scheme and displacement ellipsoids drawn at 50% probability
level. Selected geometric parameters: Sn–O1 2.1023(16), Sn–N1 2.532(2),
d 1.01 (3 H, s, SnCH3, 2 J117/119Sn-H = 87 Hz), 7.18–7.23 (3 H, m,
H
m,p-C6H5), 7.58 (2 H, d, Ho-C6H5, 3 J H-H = 6.0 Hz), 7.78–7.83 (6 H,
m, H5–7), 8.01 (2 H, d, H8, 3 J H–H = 7.0 Hz), 8.68 (2 H, d, H3, 3 J
H-H = 7.0 Hz), 8.74 (2 H, d, H2, 3 J H-H = 7.0 Hz), 119Sn NMR
(DMSO-d6, ppm): ꢀ362.3.
Sn–O3 2.0929(17), Sn–N2 2.473(2) Å; O1–Sn–O3 80.61(7), N1–Sn–N2
137.21(7), C1–Sn–C7 152.33(10)ꢁ
EtPhSnL2 (4) was prepared similarly but from ethylphenyltin(IV)
oxide and quinoline-2-carboxylic acid, and crystallized from etha-
nol (yield 75%; m.p. 245–246 ꢁC). Anal. Calcd for C28H22N2O4Sn: C,
59.09; H, 3.90; N, 4.92%. Found; C, 59.22; H, 3.55; N, 5.15%. IR (KBr,
cmꢀ1): nas(OCO) 1678; ns(OCO) 1324; n(Sn-C) 522; n(Sn-N) 498;
n(Sn-O) 452. 1 H NMR (DMSO, ppm): 1.16 (3 H, t, SnCH2CH3, 3 J H-
H = 7.8 Hz, 3 J117/119Sn-H = 171 Hz), 1.85 (2 H, q, CH2, 3 J H-
H = 7.8 Hz, 2 J117/119Sn-H = 108 Hz), 7.13–7.17 (3 H, m, Hm,p-C6H5),
7.66 (2 H, d, Ho-C6H5, 3 J H-H = 6.0 Hz), 7.22–7.83 (6 H, m, H5–7),
8.00 (2 H, d, H8, 3 J H-H = 7.0 Hz), 8.46 (2 H, d, H3, 3 J H-H = 7.0 Hz),
8.52 (2 H, d, H2, 3 J H-H = 7.0 Hz). 13 C NMR (DMSO, ppm): 165.0
Scheme 1. The atom numbering for quinoline-2-carboxylic acid
7.78–7.83 (3 H, m, H5–7), 8.10 (1 H, d, H8, 3 J H-H = 7.0 Hz), 8.64
(1 H, d, H3, 3 J H-H = 7.0 Hz), 8.69 (1 H, d, H2, 3 J H-H = 7.0 Hz). 13 C
(COO), 146.7 (C6H5, Cipso,
1 J117/119Sn-13 C = 785 Hz), 137.9 (C6H5,
NMR (CDCl3, ppm): 164.5 (COO), 148.2 (C6H5, Cipso,
1 J117/119Sn-13
Co, 2 J117/119Sn-13 C = 48 Hz), 129.6 (C6H5, Cp), 124.6 (C6H5, Cm,
3 J117/119Sn-13 C = 68 Hz), 141.8 (C1), 141.7 (C9), 132.1 (C2), 131.8
(C8), 131.6, 127.5 (C5), 126.7, 124.4, 119.4, 21.0 (CH2, 1 J117/119Sn-13
C = 775 Hz), 135.4 (C H5, Co, 2 J117/119Sn-13 C = 46 Hz), 128.6 (C6H5,
Cp), 125.5 (C6H5, Cm, 3 J117/119Sn-13 C = 65 Hz), 142.9 (C1), 142.2
(C9), 132.7 (C2), 130.7 (C8), 130.3, 129.9 (C4), 129.2 (C6), 125.1,
121.5, 22.1 (CH2), 9.6 (CH3). 119Sn NMR (CDCl3, ppm): ꢀ158.4
and 119Sn NMR (DMSO-d6, ppm): ꢀ319.8.
6
C = 768 Hz), 7.3 (CH ). 119Sn NMR (CDCl3, ppm): ꢀ309.7 and 119Sn
3
NMR (DMSO-d6, ppm): ꢀ367.1.
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M. Vafaee et al.
Synthesis of dimethyl-bis(quinoline-2-carboxylato-k2 N,O)tin(IV) Me2SnL2 (5)
and diphenyl-bis(quinoline-2-carboxylato-k2 N,O)tin(IV) Ph2SnL2 (6)
Dimethyltin(IV) and diphenyltin(IV) compounds of quinoline-2-
carboxylate, 5 and 6, known materials (m.p. 268–269 ꢁC cf. lit.[21]
268–270 ꢁC and 218–219 ꢁC cf. lit.[18] 217–219 ꢁC, respectively),
were prepared similarly from the reaction of freshly prepared
Me2SnO and Ph2SnO with quinoline-2-carboxylic acid in toluene
and their purity confirmed by 1 H NMR analysis.
Scheme 3. Reaction of RPhSnO with quinoline-2-carboxylic acid
Antimicrobial Activity
The anti-microbial activity of the synthesized diorganotin(IV)
compounds was evaluated by the disc diffusion method against
Bacillus subtilis (ATCC 9372, Gram-positive), Escherichia coli (ATCC
9763, Gram-negative) and Candida albicans (ATCC 1023) with the
determination of inhibition zones.[32]
Infrared Spectroscopy
In each of the IR spectra of polymeric {MePhSnLCl}n (1) and
{EtPhSnClCl}n (2), and monomeric MePhSnL2 (3) and EtPhSnL2
(4), the absence of a broad band in the range 2500–3400 cmꢀ1
and the presence of Sn-O vibrations in the range 450–500 cmꢀ1
clearly indicate that deprotonation of the quinoline-2-carboxylic
acid has taken place, resulting in coordination to tin. The infrared
spectra of 1–4 exhibit υasym(OCO) and υsym(OCO) stretching
vibrations in the ranges 1642–1678 and 1322–1334 cmꢀ1, respec-
tively. The red shifts of these bands with respect to the free acid
also serve to confirm the formation of 1–4. The magnitude of Δυ
(= υasym ꢀ υsym) has been previously employed to determine
the specific type of carboxylate binding present.[33] For all four
compounds, the Δυ values indicate monodentate coordination
modes for the carboxylate ligands. In comparison with the free
ligand, the new bands in the 482–524 cmꢀ1 region were assigned
to Sn-N vibrations, which prove coordination of nitrogen to tin.
The presence of a single Sn-C stretching vibration at 550, 595,
545 and 522 cmꢀ1 in the infrared spectra of 1–4, respectively,
indicates that the C–Sn–C bond angles approach linearity,
conclusions confirmed by single-crystal structure determinations
on 2 and 4.
A stock solution of each synthesized compound (1 mg mlꢀ1) in
DMSO was prepared and used in all evaluations. In a typical test,
a 10 ml solution of each trial organotin compound was poured
into a disc prior to placement in bacterial lawns. The control
antibiotic discs were gentamicin (10 mg), tetracycline (30 mg),
ampicillin (10 mg) and penicillin (10 mg). The plates were incu-
bated at 37 ꢁC for 24 h, after which the diameters of inhibition
zones (mm) were measured. The tests were performed in
triplicate and the results were averaged.
Results and Discussion
The reaction of each of MePhSnCl2 and EtPhSnCl2 with sodium
quinoline-2-carboxylate in a 1:1 molar ratio led to the formation
of compounds 1 and 2, respectively (Scheme 2).
The reaction of each of MePhSnO and EtPhSnO with quinoline-
2-carboxylic acid in a 1:2 molar ratio in boiling toluene with re-
moval of formed water in a Dean–Stark trap afforded compounds
3 and 4, respectively (Scheme 3).
The compounds were characterized by elemental analysis, IR
spectroscopy, as well as 1 H, 13 C and 119Sn NMR. The molecular
structures of representative compounds 2 and 4 were also veri-
fied by single-crystal X-ray analyses.
NMR Spectroscopy
For the determination of structural features of the prepared com-
pounds in solution, attempts were made to record 1 H, 13 C and
119Sn NMR spectra of 1–4. However, the poor solubility of 3, even
in DMSO-d6 solution, precluded the recording of 13 C and 119Sn
NMR spectra. In the 1 H NMR spectrum of 1, recorded in the
non-coordinating solvent CDCl3, the 2 J117/119Sn-C-1 H coupling
constant of 78 Hz is consistent with trigonal bipyramidal geome-
try about the tin atom and indicates that the observed polymeric
solid-state structure (see below) is not maintained in solution.
Based on the magnitude[34] of 2 J119/117Sn-C-1 H for 1 in CDCl3
solution, the C_Sn_C angle is estimated to be 128.4ꢁ. The 13 C
NMR spectra of 1, 2 and 4 showed the expected aliphatic and/
or aromatic signals. Similar behaviour was reported for 5 in an
earlier report.[21] The slight downfield shifts of all carbon reso-
nances compared with the free acid in their 13 C NMR spectra is
attributed to the coordination of quinoline-2-carboxylate ligand
to tin and formation of Sn-N bonds.
Table 2 summarizes the 119Sn NMR data, when obtained, for
1–4 along with those for 5 and 6, two known derivatives,[18,21]
in coordinating (DMSO-d6) and non-coordinating (CDCl3)
solvents. As mentioned earlier, insufficient solubility of 1 and 3
precluded the measurement of chemical shifts in CDCl3, but for
2 and 4 119Sn data were accessible in both solvents. The signifi-
cant up-field shift in the 119Sn resonance of 2 in DMSO-d6
Scheme 2. Reaction of MePhSnCl2 and EtPhSnCl2 with sodium quinoline-
2-carboxylate
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Antimicrobial activity of asymmetric diorganotin carboxylates
Table 2. 119Sn NMR data (d, ppm) for 1–6, recorded in CDCl3 and
DMSO-d6 solution
layers in the ab-plane are of the type C-H. . .Cl and C-H. . .
p
[C5–H5. . .Cl1i = 2.79 Å, C5. . .Cl1i = 3.655(3) Å, and angle at
H5 = 151ꢁ for symmetry operation i: 2-x, 1-y, 1-z. C4–H4. . .Cg
(C13-C18)ii = 2.77 Å, C41. . .Cg(C53-C58)ii = 3.643(3) Å, and angle
at H4 = 153ꢁ for symmetry operation ii: 1-x, 1-y, 1-z] (see Fig. 3).
In 4, supramolecular layers mediated by C-H. . .O interactions
formed in the ab-plane [C21–H21. . .O2i = 2.56 Å, C21. . .O2i =
3.274(4) Å, and angle at H21= 132ꢁ. C22–H22. . .O1i = 2.45 Å,
C22. . .O1i = 3.363(3) Å, and angle at H22 = 161ꢁ. C24–H24. . .O4i =
2.43 Å, C24. . .O4i = 3.226(3) Å, and angle at H24 = 141ꢁ. Symmetry
operation i: 3/2-x, -1/2 + y, 3/2-z] (Fig. 4a), and these stack along
the c-axis with no specific intermolecular interactions between
the layers (see Fig. 4b). A comparison of Figs 3 and 4(b) reveals a
remarkable similarity in the global crystal packing despite the
different chemical compositions and modes of supramolecular
association operating in their crystal structures.
Compound
CDCl3
DMSO-d6
a
{MePhSnLCl}n (1)
{EtPhSnLCl}n (2)
MePhSnL2 (3)
EtPhSnL2 (4)
—
ꢀ312.4
ꢀ319.8
ꢀ362.3
ꢀ367.1
ꢀ260.8[21]
ꢀ158.4
a
—
ꢀ309.7
Me2SnL2 (5)
a[21]
b
Ph2SnL2 (6)
ꢀ312.0[18]
—
aNot measured due to poor solubility.
bNot determined.
solution in comparison with that in CDCl3 solution is consistent
with dissociation of the six-coordinate solid-state structure (see
below) in CDCl3 solution, leading to a low coordination number
(five), and coordination of DMSO in DMSO-d6 solution, leading
to a higher (six) coordination number. Interestingly, no significant
solvent dependence was found in the chemical shifts observed for
4, an observation that indicates that the six-coordinate solid-state
structure (see below) remains intact in solution. Further, the values
of 119Sn chemical shifts for 1 and 2 in DMSO-d6 solution, when
compared to the value observed for six-coordinate 4, lends support
to the notion of coordination by DMSO and formation of six-
coordinate coordination geometries for 1 and 2 in DMSO-d6
solution. While the molecular structures of 3 and 4 are similar to
that of 5,[21] the 119Sn chemical shift of the latter is shifted about
100 ppm down-field when measured in the same solvent (Table 2).
This large shift is attributed to the presence of tin-bound phenyl
groups in 3 and 4, which are absent in 5.
Antimicrobial Activity
The organotin(IV) derivatives of N,O donor ligands are of consid-
erable interest as they have been suggested to possess mild to
good biological activities.[6] The antimicrobial activities of 1–6, to-
gether with those of MePhSnCl2 and EtPhSnCl2 and several stan-
dard antibiotics were evaluated against B. subtilis (Gram-positive),
E. coli (Gram-negative) and C, albicans using the disc diffusion
technique; results are listed in Table 3. The first key observation
is that the diorganotin compounds displayed remarkable activity
against all three bacteria. In particular, 1–6 as well as the chloride
precursor molecules, MePhSnCl2 and EtPhSnCl2, proved as effec-
tive as the known antibiotics against B. subtilis. Of the organotin
compounds, the chloride species were the most active, followed
by the monochlorides 1 and 2, with hexa-coordinated 3 and 4
the least potent. The greater antibacterial activities against
B. subtilis can be attributed to the presence of chloride atom
and enhanced Lewis acidity this imparts to the tin centres. It is
notable that there is no measurable difference in antibacterial
activity between pairs of related compounds (Table 3). It is also
of interest that the organotin compounds with the same tin-bound
substituents, i.e. Me2SnL2 (5) and Ph2SnL2 (6), have slightly reduced
antibacterial activity compared to their unsymmetrical analogues.
Such behaviour has been reported earlier in antibacterial trials
of mixed aryl–alkyl organotin compounds.[38] Additional work is
required for deeper understanding of this phenomenon.
Crystal Structures
Molecular structure of {EtPhSnLCl}n (2)
The asymmetric unit of 2 is shown in Fig. 1(a) and salient bond
lengths and angles are listed in the figure caption. The tin atom
in 2 is N,O-chelated by the quinoline-2-carboxylate anion, with
the second O atom bridging a neighbouring Sn, resulting in a
supramolecular chain with a helical topology (see Fig. 1b). The co-
ordination geometry is distorted octahedral based on a C2ClNO2
donor set with the O atoms trans to each other, subtending an an-
gle of 177.40(6)ꢁ at the tin atom. A similar coordination geometry
and polymeric structure were observed previously in the crystal
structure of the dimethyltin analogue, {Me2SnLCl}n.[35]
Molecular structure of EtPhSnL2 (4)
The molecular structure of 4 is illustrated in Fig. 2 and selected
bond lengths and angles are given in the figure caption. The tin
atom in 4 is N,O-chelated by two quinoline-2-carboxylate ligands
and the six-coordinate coordination geometry is completed by
the two C atoms derived from the tin-bound substituents. The
resultant C2N2O2 donor set defines a skewed trapezoidal bipyra-
midal geometry, with the Sn-C bonds lying over the weaker
Sn-N bonds; the C1–Sn–C7 bond angle is 152.33(10)ꢁ. The
structural motif is consistent with literature precedents.[18,21,36]
Crystal packing patterns in {EtPhSnLCl}n (2) and EtPhSnL2 (4)
In 2, the supramolecular chains aligned along the b-axis assemble
along the a-axis by weak C14-H14. . .Cl1 interactions of 3.10 Å
[symmetry operation 1 + x, y, z]. The connections between the
Figure 3. A view of the crystal packing in {PhEtSnLCl}n (2) shown in pro-
jection down the a-axis. The C-H. . .Cl and C-H. . .p interactions are shown
as orange and purple dashed lines, respectively
Appl. Organometal. Chem. (2012)
Copyright © 2012 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/aoc

M. Vafaee et al.
Figure 4. Crystal packing in PhEtSnL2 (4): (a) a view of the supramolecular layer in the ab-plane mediated by C-H. . .O interactions (orange dashed lines),
and (b) a view of the unit cell contents shown in projection down the a-axis
Conclusions
Table 3. Antibacterial activity of the diorganotin (IV) compounds
and standard anti-microbial agents
This work described the synthesis of unsymmetric diorganotin(IV)
compounds with quinoline-2-carboxylate and their full character-
ization, including by X-ray crystallography. The {RR0SnLCl}n
Compound (10 ml) Bacillus subtilis Escherichia coli Candida albicans
{MePhSnLCl}n (1)
{EtPhSnLCl}2 (2)
MePhSnL2 (3)
EtPhSnL2 (4)
Me2SnL2 (5)
Ph2SnL2 (6)
MePhSnCl2
EtPhSnCl2
22
22
19
19
18
16
25
25
23
20
20
20
19
25
10
24
0
16
22
14
18
12
10
—
—
32
—
24
32
compounds adopt polymeric structures as the quinoline-2-
carboxylate ligand is tridentate and bridging. Monomeric,
six-coordinate structures are found in the RR0SnL2 compounds.
Antibacterial assays prove the remarkable activity of the organo-
tin compounds against the Gram-positive bacterium B. subtilis,
with enhanced potency correlated with the number of chloride
substituents/Lewis acidity of the tin centre. In trials against
Gram-negative E. coli and C. albicans, evidence was provided to
10
17
17
27
22
25
30
Ampicillin
indicate
a
benefit of having unsymmetric diorganotin
Penicillin
compounds and, especially, those with tin-bound ethyl groups.
Gentamicin
Tetracycline
Acknowledgements
The authors thank the Vice-President’s Office for Research Affairs
of Shahid Beheshti University for supporting this work. We also
thank Dr Maryam Yousefi for help in antimicrobial tests. The
Ministry of Higher Education (Malaysia) is thanked for funding
studies in Metal-Based Drugs through the High-Impact Research
Scheme (UM.C/HIR/MOHE/SC/12).
The antibacterial activities against E. coli and C. albicans exhib-
ited by the organotin compounds are quite different from that
against B. subtilis. As indicated in Table 3, the activities of com-
pounds 2 and 4, with tin-bound ethyl groups, against E. coli are
higher than their methyl counterparts, 1 and 3. This difference
is associated with the organic group attached to the tin and
may be due to the difference in the structure of the cell
walls,[11,38] where the more hydrophobic nature of ethyl group
allows favourable interaction with the lipopolysaccharides of
the outer lipid membrane.
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