J. Serb. Chem. Soc. 71 (10) 1001–1013 (2006) UDC 546.811–039.7+546.681–039.7:543.4:57–188

JSCS–3494 Original scientific paper

Synthesis, spectroscopic and biological investigations of di-and

triorganotin(IV) derivatives containing germanium: X-ray study

of �Ph3GeCH(n-C3H7)CH2CO2�Sn�CH3�3

MUHAMMAD KALEEM KHOSA1, MUHAMMAD MAZHAR1*, SAQIB ALI1, SARIM

DASTGIR1, MASOOD PARVEZ2 and ABDUL MALIK3

1Department of Chemistry, Quaid-i-Azam University, Islamabad-45320, Pakistan, 2Department of

Chemistry, University of Calgary, 2500 University Drive NW, Calgary, Alberta, Canada T2N 1N4

and 3HEJ Research Institute of Chemistry, International Centre for Chemical Sciences, Univer-

sity of Karachi, Karachi 75270, Pakistan (e-mail: mazhar42pk@yahoo.com)

(Received 25 February, revised 25 April 2005)

Abstract: Bimetallic di- and triorganotin(IV) germanium carboxylates were synthe-sized and characterized by elemental analyses, as well as IR, multinuclear NMR(1H, 13C, 119Sn) spectroscopy and tested for bioactivity. The structure of the repre-

sentative compound, �Ph3GeCH(n-C3H7)CH2CO2�Sn�CH3�3, was determined byX-ray analysis and found to have a distorted trigonal bipyramidal geometry aroundthe tin atom. Some selected compounds were also screened against different micro-bes and showed promising antibacterial and antifungal activity.

Keywords: organotin(IV) carboxylates, organogermanium, spectroscopy, bioacti-vity, X-ray structure.

INTRODUCTION

In the past two decades, organotin carboxylates have received much attention be-

cause of their extensive application in different fields of life science, especially bioci-

dal applications utilizing the antitumour and anticancer activities of such compo-

unds.1–4 The biological importance of organotin compounds has been supported by

structure–activity correlation,5–7 dealing mainly with structural aspects and antitu-

mour activity and also linked with possible tumorigenic activity.8 Organogermanium

compounds form another kind of class that has received considerable attention beca-

use of their potential clinical applications.9 It has been reported that germanium-sub-

stituted organotin carboxylates possess potential activity against certain bacteria.10 In

order to extend the structural chemistry and biological applications of such compo-

unds, a new series of organotin carboxylates has been synthesized. Qualitative structu-

ral characterization of these compounds was based on the C–Sn–C angle. Further, the

1001

doi: 10.2298/JSC0610001K

* Corresponding author.

structure of �3-(triphenylgermyl)hexanoato�trimethyltin(IV) was also confirmed thro-

ugh X-ray crystallography.

EXPERIMENTAL

Chemicals

Substituted cinnamic acid, diorganotin(IV) oxide and triorganotin(IV) chlorides were pur-

chased from Aldrich Chemicals (USA) and were used as received, since their melting points agreed

with the literature values. Germanium dioxide (99.9 % purity) was purchased from the People's Re-

public of China and was used as received. Solvents were dried over sodium benzophenone before

use according to the standard method.11

Instrumentation

Elemental analyses were carried out at the Midwest Micro-Lab Indianapolis, USA. Melting

points were determined with a Mitamura Riken Kogyo (Japan) apparatus and are uncorrected. The

IR spectra were recorded on a Bio-Rad Excalibure FT-IR Model FTS 3000 MX spectrometer, using

the KBr disc technique. The 1H and 13C-NMR spectra were recorded on a Varian Mercury 300 spec-

trometer, operating at 300 and 75.5 MHz, respectively, using deuterated solvents and TMS as the

reference. 119Sn-NMR spectra were obtained on a Bruker 250 ARX spectrometer (Germany) with

TMS as the reference. The crystallogarphic data were collected at 173 K on a Nonius Kappa CCD

diffractometer. The crystals suitable for X-ray diffraction analysis were isolated from a solution in a

mixture of chloroform and acetone over a prolonged period at room temperature.

Synthesis

Germanium substituted diorganotin(IV) derivatives were synthesized by the condensation of

diorganotin oxide and triorganogermyl substituted hexanoic acid in a 1:2 mole ratio in a two-necked

flask fitted with a Dean and Stark apparatus, reflux condenser and magnetic stirrer. The reaction

mixture was refluxed for 10–12 h with continuous azeotropic removal of the formed water. The re-

action mixture was cooled to room temperature, then filtered and the toluene removed under re-

duced pressure. The thick residue was kept at low temperature for a few days and the resulting solid

was recrystallized from a suitable mixture of solvents to yield the product as a white solid.

Triorganotin(IV) derivatives(IV) containing germanium were synthesized by reaction of

triorganotin chloride and triorganogermyl substituted hexanoic acid in a 1:1 mole ratio in the pres-

ence of triethylamine and toluene in a two necked flask fitted with a reflux condenser and magnetic

stirrer. The reaction mixture was refluxed for 8–10 h and then cooled to room temperature. After

cooling, the triethylamine hydrochloride was filtered off. The solvent was evaporated under reduced

pressure and the thick residue kept at room temperature for a few days. The resulting solid was

recrystallized from a suitable mixture of solvents.

Recrystallization

Crystalls suitable for X-ray analysis were grown by dissolving 0.50 g of the compound in a

small quantity of chloroform to form a saturated solution. A few drops of acetone and petroleum

ether were added and the solution allowed to evaporate very slowly at room temperature to yield fine

crystals, which are subsequently washed with acetone.

X-ray crystallography

Intensity data for a colorless crystal (0.16 � 0.16 � 0.10 mm3) were measured at 173(2) K on a

Nonius Kappa CCD diffractometer with graphite monochromatized Mo–K� radiation using � and �

scans to a maximum � value of 27.5°. The data were corrected for Lorentz and polarization effects.

The details of the crystal data and structure refinement are listed in Table I. The structure was solved

by the direct method and refined by full-matrix least squares procedure using SHELXL-97.12 The

1002 KHOSA et al.

non-hydrogen atoms were refined anisotropically. The hydrogen atoms were included at geometri-

cally idealized postions.

TABLE I. Crystal data and structure refinement of compound 6

Empirical formula C27H34GeO2Sn

Formula weight 581.82

Crystal system Monoclinic

Space group P21/c

a/Å 14.148(3)

b/Å 9.235(2)

c/Å 19.684(4)

�/° 99.311(15)

Volume 2538.0(9) Å3

Z 4

Absorption coefficient 2.189 mm-1

�max/° 27.5

Reflections collected 10896

Independent reflections 5771 �R(int)=0.0269�

Max. and min. transmission 0.812 and 0.721

Goodness-of-fit on F2 1.04

Final R indices �I>2sigma(I)� R1 = 0.030, wR2 = 0.065

R indices (all data) R1 = 0.040, wR2 = 0.070

�max(e Å-3) 1.10

RESULTS AND DISCUSSION

3-(Triphenylgermyl)hexanoic acid was synthesized as reported earlier in the

literature.10 Di- and triorganotin(IV) carboxylates containing germanium were re-

spectively prepared in 70–80 % yield by the reaction of diorganotin(IV) oxides and

triorganotin chlorides with 3-(triphenylgermyl)hexanoic acid ligand in a 1:2 and

1:1 mole ratio, respectively,13–15 as given in Eqs. (1) and (2):

R2SnO+2Ph3GeCH(n-C3H7)CH2COOHToluene

� ����

�Ph3GeCH(n-C3H7)CH2CO2�Sn�R�2 + H2O

(1)

R = CH3, C2H5, n-C4H9, n-C8H17, C6H5

R3SnCl + Ph3GeCH(n-C3H7)CH2CO2HEt N3� ���

Ph3GeCH(n-C3H7)CH2CO2Sn[R]3+Et3N·HCl

(2)

R = CH3, n-C4H9, C6H5

Ge ORGANOTIN DERIVATIVES 1003

The compounds are soluble in common organic solvents, such as CHCl3,

CH2Cl2, and DMSO. The physical data are given in Table II.

TABLE II. Physical data of di- and triorganotin(IV) derivatives of the general formula

�(C6H5)3GeCH(n-C3H7)CH2CO2�xSn�R�4-x

Comp.No.

R Molecularformula

M.wt.

M.p.°C

Yield%

Elemental Analysis

C/% H/%

1 CH3 C50H56O4Ge2Sn 985 146–148 71 60.89 5.64

(60.91) (5.68)

2 C2H5 C52H60O4Ge2Sn 1013 145–147 65 61.54 5.90

(61.59) (5.92)

3 n-C4H9 C56H68O4Ge2Sn 1069 152–154 69 62.79 6.34

(62.86) (6.36)

4 n-C8H17 C64H84O4Ge2Sn 1181 138–140 73 64.99 7.12

(65.02) (7.11)

5 C6H5 C60H60O4Ge2Sn 1109 182–184 84 64.89 5.43

(64.92) (5.41)

6 CH3 C27H34O2GeSn 582 140–142 69 55.61 5.81

(55.67) (5.84)

7 C4H9 C36H52O2GeSn 708 188–190 64 60.92 7.33

(61.01) (7.34)

8 C6H5 C42H40O2GeSn 768 175–177 71 65.59 5.21

(65.62) (5.20)

x = 2 for compounds 1–5, 1 for 6–8.

TABLE III. Characteristic IR absorption frequencies in cm-1 of di- and triorganotin(IV) derivatives

with the general formula �(C6H5)3GeCH(n-C3H7)CH2COO�xSn�R�4-x

Comp. v(COO)asym v(COO)sym v v(Ge–C) v(Sn–C) v(Sn–O)

1 1604 1412 192 622 560 469

2 1599 1413 186 621 566 468

3 1606 1410 196 635 563 465

4 1603 1410 193 623 565 467

5 1610 1415 195 631 – 466

6 1601 1427 174 642 557 463

7 1594 1425 169 669 555 467

8 1580 1394 186 667 – 469

x = 2 for compounds 1–5, 1 for 6–8.

Infrared spectroscopy

The infrared spectra of these compounds were recorded in the range of 4000–400

cm–1. The main IR spectral data are listed in Table III. The assignment of Sn–C, Sn–O

1004 KHOSA et al.

and Ge–C are consistent with the values reported in the literature.16 The IR stretching

vibration frequencies of carbonyl groups in organotin(IV) carboxylates are helpful in

elucidating the structures and bonding behavior of the ligand. When the structure of

the complex changes from four to five or higher coordination symmetry, �(COO) asy

shifts to lower and �(COO)sym shift to higher values, which causes a decrease in �.13

The � values for the diorganotin(IV) compounds 1–5 and triorganotin(IV) com-

pounds 6–8 lie in the range of 186 to 196 cm–1 and 174 to 186 cm–1, respectively,

which indicates the bidentate nature of the COO group.17,18 Therefore, distorted octa-

hedral geometry and trigonal bipyramidal geometry are adopted by diorganotin(IV)

and triorganotin(IV) compounds around the tin atom, respectively.

NMR spectroscopy

1H-NMR. The 1H-NMR data of compounds 1–8 are presented in Table IV. All

protons in the compounds were identified by the intensity and multiplicity pattern and

the total number of protons calculated from the integration curve is in agreement with

the expected molecular composition. The proton resonance of the phenyl group of the

triphenyl tin(IV) compounds appeared as multiplets in the range of 6.8–7.2 ppm. The

methylene protons of the di- and tributyltin(IV) derivatives show multiplets in the re-

gion 1.21–2.14 ppm with a well defined triplet at 0.79 and 0.85 ppm, respectively, due

to presence of terminal methyl protons with a 1H–1H coupling constant of about 7.1

and 7.3 Hz.19 The dioctyltin(IV) derivatives exhibited a multiplet in the range of

1.18–1.32 ppm for the methylene protons, with a well defined triplet at 0.85 ppm hav-

ing a 1H–1H coupling constant of about 7.2 Hz. Similarly, for the di- and trimethyl-

tin(IV) derivatives, the methyl protons appeared as a sharp singlet at 0.84 ppm and

0.81 ppm with a well resolved 119Sn–1H coupling constant of 76 Hz and 57 Hz, re-

spectively. The Sn–C–Sn bond angles, 140.32° and 111.56°, calculated from the cou-

pling constant by application of the Lockhart equation, support a five-coordinated ge-

ometry for the diorganotin(IV) and a four-coordinated one for the triorganotin(IV) ger-

manium carboxylates in non-coordinating solvents.20

TABLE IV. 1H-NMR dataa-e for organotin derivatives of the general formula

�(C6H5)3GeCH(n-C3H7)CH2COO�xSn�R�4-x

Comp. CH CH2 n-C3H7 R C6H5Ge

1 3.05 (q, 2H) 2.44–2.58 0.79 (t, 6H, 7.5) 0.84 (s, 6H) 7.45–7.61

3J(6.8) (m, 4H) 1.21–1.75 (m, 8H) 2J�76� (m, 30H)

2 3.02 (q, 2H) 2.39–2.56 0.80 (t, 6H, 7.0) 0.80 (t, 6H, 7.0) 7.29–7.65

3J(7.1) (m, 4H) 1.32–1.72 (m, 8H) 1.16–2.4 (m, 4H) (m, 30H)

3 3.07 (q, 2H) 2.41–2.55 0.79 (t, 6H, 7.1) 0.79 (t, 6H, 7.1) 7.36–7.64

3J(7.1) (m, 4H) 1.29–1.65 (m, 8H) 1.25–2.14 (m, 12H) (m, 30H)

4 3.06 (q, 2H) 2.44–2.60 0.85 (t, 6H, 7.2) 0.85 (t, 6H, 7.2) 7.2–7.6

3J(6.9) (m, 4H) 1.38–1.74 (m, 8H) 1.18–1.32 (m, 28H) (m, 30H)

Ge ORGANOTIN DERIVATIVES 1005

Comp. CH CH2 n-C3H7 R C6H5Ge

5 3.15 (q, 2H) 2.37–2.51 0.89 (t, 6H, 6.9) 7.15–7.55 7.15–7.55

3J(7.6) (m, 4H) 1.36–1.61 (m, 8H) (m, 10H) (m, 30H)

6 2.55 (q, 1H) 2.30–2.45 0.58 (t, 3H, 7.1) 0.25 (s, 9H) 7.0–7.41

3J(7.8) (m, 2H) 1.0–1.5 (m, 4H) 2J�57� (m, 15H)

7 2.78 (q, 1H) 2.38–2.45 0.95 (t, 3H, 6.8) 0.85 (t, 9H, 7.3) 7.35–7.61

3J(7.51) (m, 2H) 1.45–1.85 (m, 4H) 1.21–1.45 (m, 18H) (m, 15H)

8 2.31–2.80 2.46–2.75 0.84 (t, 3H, 6.9) 6.85–7.65 6.85–7.65

(m, 1H) (m, 2H) 1.51–1.70 (m, 4H) (m, 15H) (m, 15H)

ax = 2 for compounds 1–5, 1 for 6–8; bIn CDCl3 at 295 K; cChemical shift in ppm, 3J(1H–1H),nJ�119Sn–1H� in Hz;

dMultiplicity is given as s = singlet, d = doublet, t = triplet, m = multiplet; eR =

CH3 for 1,6, C2H5 for 2, n-C4H9 (3,7), n-C8H17 (4), Ph for 5,8.

13C-NMR. The 13C data of compounds 1–8 are presented in Table V. The as-

signment of methyl, ethyl, n-butyl, n-octyl and aromatic moieties attached to tin

and other unique carbons are based on literature values.15,21 The aromatic carbon

resonances were assigned by comparision of the experimental chemical shifts with

those calculated by the incremental method and literature values.22,23

TABLE V. 13C and 119Sn-NMR dataa–c for organotin derivatives of the general formula

�(C6H5)3GeCH(n-C3H7)CH2COO�xSn�R�4-x

Signal no. 1 2 3 4 5 6 7 8

Ph–Ge a 134.51 133.98 135.26 135.29 135.87 136.61 136.70 136.15

b 133.49 133.89 133.96 133.99 134.25 135.35 135.38 135.22

c 128.53 128.90 128.92 128.96 128.74 128.15 128.17 128.19

d 131.49 131.36 131.07 131.10 131.51 128.77 128.79 128.95

n-C3H7 � 27.91 27.72 27.72 27.75 27.67 23.57 23.58 23.62

� 24.01 23.83 23.79 23.84 23.49 22.23 22.29 22.31

� 13.92 13.82 13.78 14.13 13.91 14.22 14.32 14.27

CH 33.44 33.44 33.43 33.46 33.44 34.56 34.65 34.51

CH2 38.53 38.53 38.52 38.55 38.49 37.14 37.22 37.34

COO 177.69 177.57 177.53 177.55 177.51 179.48 179.48 179.67

Sn–C 1 4.5 13.82 23.79 27.75 134.67 –2.54 16.39 135.30

1J�649� 1J�585� 1J�592� 1J�360� 1J�355�

2 – 8.65 27.72 29.71 133.14 – 27.90 134.51

2J�20� 2J�19� 2J�21�

3 – – 27.51 33.46 129.21 – 27.11 128.84

4 – – 13.78 31.9 131.47 – 13.72 128.79

5 – – – 31.8 – – – –

1006 KHOSA et al.

TABLE IV. Continued

Signal no. 1 2 3 4 5 6 7 8

6 – – – 23.84 – – – –

7 – – – 22.85 – – – –

8 – – – 13.82 – – – –

119Sn –125.9 –165.8 –168.7 –149.4 –179.6 129.1 120.5 107.2

ax = 2 for compounds 1–5, 1 for 6–8; b In CDCl 3 at 295 K; c Chemical shift in ppm.nJ�119Sn–1H� in Hz. n-C3H7 = �CH2– CH2–�CH3, Sn–CH3, Sn–1CH2–2CH3,

Sn–1CH2–2CH2–3CH2–4CH3, Sn–1CH2–2CH2–3CH2–4CH2–5CH2–6CH2–7CH2–8CH3

In the di- and trimethyltin(IV) compounds, the methyl carbon directly attached

to tin gave signals at 4.5 and –2.54 ppm with coupling constants 1J�119Sn–13C� of

649 and 360 Hz, respectively. In the di- and tributyltin(IV) compounds, the carbon

atom directly attached to tin was found at 23.79 and 16.79 ppm with coupling con-

stants 1J[119Sn–13C] of 585 and 355 Hz respectively. The position of the car-

boxylate carbon in all the synthesized compounds moved slightly to lower field as

compared with the substituted germyl hexanoic acid and lay in the range of

177–182 ppm indicating a weak participation of the carboxylic group in the coor-

dination of tin(IV).24,25 The values of nJ�119Sn–13C� fell in the range of 585 to 649

Hz for the diorganotin and 355 to 360 Hz for the triorganotin compounds, which

reflects a five to four-coordinated environment around the tin atom of the corre-

sponding compounds in non-coordinated solvents.26,27

119Sn-NMR. The 119Sn-NMR data for the synthesized compounds are listed in

Table V. 119Sn-NMR spectra give a sharp singlet, indicating the formation of a single

species. The 119Sn chemical shift moves to a lower frequency with increasing coordi-

nation number. The range was between + 200 to – 60 ppm for the four-coordinated

compounds and from –90 to –330 ppm for the five-coordinating system.10 Since

diorganotin(IV) compounds have � values between –125.9 to –179.6 ppm, this would

indicate that the compounds are five coordinated while in triorganotin(IV) com-

pounds, � values between 107.2 to 129.1 ppm show that the compounds are four-coor-

dinated. These results are consistent with the 1H and 13C-NMR results.

Mass spectrometry

The 80 eV monoisotopic mass spectral fragmentation patterns of the investigated

compounds 4,7 are cited in Table VI. The fragmentation pattern mainly depends on the

structure of the compounds and the properties of the carbonyl group.28 Diorganotin

compounds have a more complex fragmentation pattern as compared to triorganotin(IV)

carboxylates. The primary fragmentation of the diorganotin(IV) compounds is due to the

loss of the germyl acid unit, while in the triorganotin(IV) carboxylates, the primary frag-

mentation is due to loss of R. The rest of fragmentation follows the same pattern as re-

ported earlier.29 However, �R2Sn�, �RSn� and �R� group fragments are commonly ob-

served in both di- and triorganotin(IV) carboxylates.

Ge ORGANOTIN DERIVATIVES 1007

TABLE V. Continued

TA

BL

EV

I.F

rag

men

tio

ns

ob

serv

edfo

rco

mp

ou

nd

s4

and

7

m/z

Co

mp

ou

nd

4fr

agm

ents

Inte

nsi

tym

/zC

om

po

un

d7

frag

men

tsIn

ten

sity

11

84

�((C

6H

5) 3

GeC

H(n

-C3H

7)C

H2C

O2) 2

Sn

(n-C

8H

17) 2

�+n

.o7

10

�((C

6H

5) 3

GeC

H(n

-C

3H

7)C

H2C

O2)S

n(n

-C

4H

9) 3

�+1

.06

76

5��

(C

6H

5) 3

GeC

H(C

3H

7)C

H2C

OO

Sn

(C8H

17) 2

�+3

.21

65

3�(

(C

6H

5) 3

GeC

H(C

3H

7)C

H2C

OO

)Sn

(C4

H9) 2

�+6

5.4

8

45

9�C

H(C

3H

7)C

H2C

OO

Sn

(C8H

17)–

H�+

10

04

19

�(C

6H

5) 3

GeC

H(C

3H

7)C

H2C

OO

�+2

0.8

1

41

9�(

C6H

5) 3

GeC

H(C

H2C

H2C

H3)C

H2C

OO

�+3

0.2

14

05

�CH

3(C

H2) 3

CO

2S

n(C

4H

9)�

+1

6.4

37

6�(

C6H

5) 3

GeC

HC

H2C

O2�+

42

.80

34

9�C

H2C

O2S

n(C

4H

9) 3

�+2

5.6

34

6�S

n(C

8H

17) 2

�+1

8.3

23

48

[C

H3(C

H2) 3

CO

OS

n(C

4H

9)�

+1

0.9

2

30

5�(

C6H

5) 3

Ge�+

83

.20

30

5��

C6H

5) 3

Ge�+

10

0

29

9�(

C6H

5) 2

GeC

HC

H2C

O2�+

46

.74

29

2�C

H2C

O2S

n(C

4H

9) 2

�+6

.43

23

3�S

n(C

8H

17)�

+5

0.0

12

91

�Sn

(C

4H

9) 3

�+8

.76

22

8�(

C6H

5) 2

Ge�+

27

.52

23

4�S

n(C

4H

9) 2

�+2

0.5

4

15

1�(

C6H

5)G

e�+

28

.16

22

8�(

C6H

5) 2

Ge�+

25

.31

12

1�S

nH

�+9

.60

22

7�(

C6H

5) 2

Ge–

H�+

19

.26

11

3�n

-C8H

17�+

15

.36

17

7�S

n(C

4H

9)�

+4

1.0

1

74

�Ge�+

3.2

71

51

�(C

6H

5)G

e�+

16

.05

71

�CH

CH

2C

O2�+

80

.01

21

�Sn

H�+

14

.12

74

�Ge�+

8.7

6

Crystal Structure of [(C6H5)3GeCH(n-C3H7)CH2COO]Sn(CH3)3

The crystal structure of [(C6H5)3GeCH(n-C3H7)CH2COO]Sn(CH3)3 is depicted

in Fig. 1. Selected bond lengths and bond angles are listed in Table VII. The four-coor-

dinated germanium atom has a slightly distorted tetrahedral geometry with the mean of

the C–Ge–C bond angles being 108.31(11)°. The Ge–Csp3 bond is significantly longer,

1.988(3) Å, than the Ge–Caromatic distances, which are identical within experimental

error with a mean value of 1.956(3) Å. The tin atom has a distorted trans-R3SnO2

trigonal bipyramidal geometry with the methyl groups in the equatorial plane and the

oxygen from two asymmetric units of the carboxylate group occupying the axial posi-

tion, whereby a polymeric structure is developed. The tin atom is 0.098 Å out of plane

towards the more strongly bound oxygen atom. The Sn–C distances lie in the range of

2.117(3) to 2.122(3) Å and are in agreement with the corresponding literature values.30

The C–O bonds within the carboxyl group also have different lengths. The longer

C(4)–O(1) bond, 1.289(3) Å, and the shorter Sn(1)–O(1) bond, 2.136(18) Å, share the

same oxygen atom and vice versa. This could mean that one of the carboxyl oxygen at-

oms forms a covalent bond with the tin atom, while the other carboxyl oxygen atom

(double bonded) is coordinated to tin with a longer Sn–O distance because the C–O

bond retains some of its double bond character.

Biological studies

The in vitro biological activities of the selected compounds were determined

against various bacteria and fungi by the agar well diffusion and agar well dilution

protocols.31,32 The results are given in Tables VIII and IX.

The antibacterial activity was studied against six different types of bacteria, E.

coli, B. subtilis, S. flexinari, S. aureus, P. aeruginosa and S. typhi, relative to reference

drug, imipenum. The activities of the synthesized compounds were compared on the

basis of the substituent group R. The screening tests show that the n-butyltin(IV) and

Ge ORGANOTIN DERIVATIVES 1009

Fig. 1. X-ray structure of [(C6H5)3GeCH(n-C3H7)CH2COO)]Sn(CH3)3.

n-octyltin(IV) carboxylates are the most potent against the tested bacteria. However,

all the compounds show good activity against E. coli and S. typhi.

TABLE VII. Selected bond lengths/Å and bond angles/° for compound 6

Bond Lengths

Sn(1)–C(3) 2.117(3) O(1)–C(4) 1.289(3)

Sn(1)–C(1) 2.118(3) O(2)–C(4) 1.232(3)

Sn(1)–C(2) 2.122(3) C(4)–C(5) 1.524(4)

Sn(1)–O(1) 2.136(18) C(5)–C(6) 1.536(4)

Sn(1)–O(2)#1 2.645(2) C(6)–C(7) 1.538(4)

Ge(1)–C(22) 1.952(3) C(7)–C(8) 1.502(5)

Ge(1)–C(16) 1.955(3) C(8)–C(9) 1.551(5)

Ge(1)–C(10) 1.962(3) C(10)–C(15) 1.338(4)

Ge(1)–C(6) 1.988(3) C(10)–C(11) 1.390(4)

Bond Angles

C(3)–Sn(1)–C(1) 127.14(14) C(4)–O(1)–Sn(1) 116.32(17)

C(3)–Sn(1)–C(2) 114.25(14) O(1)–Sn(1)–O(2)#1 178.31(7)

C(1)–Sn(1)–C(2) 114.96(14) C(3)–Sn(1)–O(2)#1 80.63(11)

C(3)–Sn(1)–O(1) 98.05(11) C(1)–Sn(1)–O(2)#1 83.13(10)

C(1)–Sn(1)–O(1) 98.52(10) C(2)–Sn(1)–O(2)#1 87.79(10)

C(2)–Sn(1)–O(1) 91.82(10) O(2)–C(4)–C(5) 121.4(2)

C(22)–Ge(1)–C(16) 107.36(11) O(2)–C(4)–O(1) 123.0(2)

C(22)–Ge(1)–C(10) 110.42(11) O(1)–C(4)–C(5) 115.6(2)

C(16)–Ge(1)–C(10) 106.66(11) C(5)–C(6)–Ge(1) 112.82(18)

C(22)–Ge(1)–C(6) 107.83(11) C(7)–C(6)–Ge(1) 115.86(18)

C(16)–Ge(1)–C(6) 117.27(11) C(15)–C(10)–Ge(1) 121.61(2)

TABLE VIII. Antibacterial activity dataa-c of organotin derivatives (in vitro)

Name ofbacteria

Zone of inhibition of sample/mm Zone ofinhibition of

std. drug/mm1 2 3 4 5 6 7 8

Escherichia coli 14 18 25 29 12 14 28 19 30

Bacillus subtilis 10 16 30 28 10 27 29 15 31

Shigella flexenari – – – – – – – – 33

Staphylococcus

aureus

12 14 23 39 10 22 40 14 43

Pseudomonas

aeruginosa

10 15 14 23 5 12 24 17 25

Salmonella typhi 36 38 39 35 15 24 40 23 41

aConcentration of sample = 3 mg/mL; bConcentration of standard drug (imipenum) = 10 �g/disc;

c(–) = No activity

1010 KHOSA et al.

TABLE IX. Antifungal activity dataa-c of organotin derivatives (in vitro)

Name offungus

Inhibition of samples Std. drug

MIC �g/mL

% Inhibition ofstd. drug/mm

1 2 3 4 5 6 7 8

Trichophyton

longifusus

65 50 40 68 30 30 70 56 Miconazole 70

Candida albicans 40 40 55 101 60 60 108 78 " 110

Aspergillus flavus 20 – – – – – – 35 Amphotericin B 20

Microsporum

canis

35 20 45 87 30 30 90 55 Miconazole 98

Fusarium solani 60 60 30 65 30 30 63 49 " 73

Candida

glaberata

105 99 95 86 48 30 108 78 " 110

aConcentration of sample = 400 �g/mL of DMSO;bIncubation temperature (period) = 27 ± 1°C (7

days); c(–) = No activity

The agar tube dilution protocol was used to screen the activity of compounds

against different types of fungi, T. longifusus, C. albicans, A. flavus, M. canis, F.

solani and C. glaberata. Earlier reports show that tributyltin(IV) and triphenyl-

tin(IV) compounds show higher antifungal activity.33 The antifungal screening re-

sults of the synthesized compounds are in good agreement with the literature and

show good activity against the tested fungi.

The toxicity of these compounds, particularly dioctyltin(IV), was decreased

by the incorporation of germanium.15 The toxicity of the synthesized compounds

was measured by the brine shrimp (Artemia salina) method and their lethal doses

(LD50) are given in Table X. It can be seen that the toxicity of the organotin com-

pounds mainly depends on the nature of the organic group,34 the highest toxicity

being shown by those compounds having three tin carbon (Sn–C) bonds.

TABLE X. Cytotoxicity dataa-c of organotin(IV)

Comp. No. LD50/�g mL-1

1 502.09

2 501.18

3 508.01

4 305.38

5 499.01

6 25.64

7 59.98

8 12.15

bEtoposide 7.46

aOrganism = Artemia salina (brine shrimp); bReference drug; cLD50 = Lethal dose at which 50% of

the organism die

Ge ORGANOTIN DERIVATIVES 1011

Supplementary data

Crystallographic data for the compound 6 have been deposited with the Cam-

bridge Crystallographic Data Centre, as CCDC Number: 261767. Copies of the data

can be obtained on request to CCDC, 12 Union Road, Cambridge CB21, EZ, UK.

E-mail: deposited@ccdc.cam.ac.uk or http://www.ccdc.cam.ac.uk.

Acknowledgements: We thank the Higher Education Commission, Islamabad, Pakistan for fi-nancial support. (Grant No. 20-9/Acad-R/2003).

I Z V O D

SINTEZA, SPEKTROSKOPSKO I BIOLO[KO ISPITIVAWE DI- I

TRIORGANOKALAJNIH(IV) DERIVATA KOJI SADR@E GERMANIJUM:

KRISTALOGRAFSKO PROU^AVAWE �Ph3GeCH(n-C3H7)CH2CO2�Sn�CH3�3

MUHAMMAD KALEEM KHOSA1, MUHAMMAD MAZHAR1, SAQIB ALI1, SARIM DASTGIR1, MASOOD PARVEZ2

i ABDUL MALIK3

1Department of Chemistry, Quaid-i-Azam University, Islamabad-45320, Pakistan, 2

Department of Chemistry, University of

Calgary, 2500 University Drive, NW, Calgary, Alberta, Canada T2N 1N4 i3

HEJ Research Institute of Chemistry, Interna-

tional Centre for Chemical Sciences, University of Karachi, Karachi 75270, Pakistan

Sintetizovani su bimetalni di- i triorganokalajni(IV) germanijumski karbo-

ksilati, okarakterisani elementalnom analizom, IR i multinuklearnom NMR (1H,

13C, 119Sn) spektroskopijom i testirani na biolo{ku aktivnost. Struktura reprezen-

tativnog jediwewa, �Ph3GeCH(n-C3H7)CH2CO2�Sn�CH3��, odre|ena je difrakcijom X-zra-

ka. Utvr|ena je distorgovana trigonalna bipiramidalna geometrija oko atoma kalaja.

Neka odabrana jediwewa su ispitivana sa aspekta biolo{ke aktivnosti prema razli-

~itim mikrobima i pokazana je wihova antibakterijska i antigqivi~na aktivnost.

(Primqeno 25. februara, revidirano 25. aprila 2005)

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