New mononuclear organotin(IV) 4-benzhydrylpiperazine-1-carbodithioates: Synthesis, spectroscopic...

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New mononuclear organotin(IV) 4-benzhydrylpiperazine-1-carbodithioates:Synthesis, spectroscopic characterization, X-ray structures and in vitroantimicrobial activities

Zia-ur-Rehman a,b, Niaz Muhammad a, Saqib Ali a, Ian S. Butler b,⇑, Auke Meetsma c

a Department of Chemistry, Quaid-i-Azam University, Islamabad 45320, Pakistanb Department of Chemistry, McGill University, 801 Sherbrooke St. West, Montreal, Quebec, Canada H3A2K6c Crystal Structure Center, Chemical Physics, Zernike, Institute for Advanced Materials, University of Groningen, Nijenborgh 4, NL-9747 AG Groningen, The Netherlands

a r t i c l e i n f o

Article history:Received 26 May 2009Received in revised form 6 April 2011Accepted 9 April 2011Available online 16 April 2011

Keywords:4-Benzhydrylpiperazine-1-carbodithioateOrganotin(IV) complexesTrigonal bipyramidal and square-pyramidalgeometriesMolecular spectroscopyAntimicrobial activity

a b s t r a c t

A new series of organotin(IV) complexes with 4-benzhydrylpiperazine-1-carbodithioate (L) were syn-thesised by the metathesis reactions of the ligand-salt with triorganotin(IV) chlorides and diorganotin(IV)dichlorides in the appropriate molar ratio. All the complexes were characterized by elemental analysis,Raman, IR, and multinuclear NMR (1H, 13C and 119Sn) spectroscopy. Solid-state studies (Raman, IR andX-ray analysis) confirmed the bidentate coordination of the ligand in all cases. Multinuclear NMR spec-troscopy suggested that some tri- and diorganotin complexes reduce their geometry by one unit in solu-tion. The s values, 0.6 and 0.24 for chlorodibutyl- and chlorodiethyltin(IV) derivatives, respectively,authenticated the trigonal bipyramidal geometry for the first complex and distorted square-pyramidalgeometry for the latter. The low s value for the chlorodiethyltin(IV) complex is attributed to the addi-tional Sn��Cl and Sn��S intermolecular interactions. The antimicrobial results indicated the compoundsare active biologically.

� 2011 Elsevier B.V. All rights reserved.

1. Introduction

Organotin(IV) compounds are amongst the most widely usedorganometallic compounds owing to a variety of industrial andagricultural applications, including their use as pesticides, fungi-cides and anti-fouling agents [1]. For several decades since theirinitial discovery, organotins, especially the triorganotins, areremarkably persistent in the environment and the study of theirtoxicology is a matter of some exigency [2]. It has been established,however, that successive dealkylations of organotins yield ‘‘non-toxic’’ Sn(II) species. Although the mechanism of organotin degra-dation is not yet fully explored, it is generally acknowledged thatin vivo deactivation of R3Sn and R2Sn systems involves enzymeswith two sulfur donor sites [3]. Dithiocarboxylates merit specialattention because of their antitumor, antiviral and pesticidal activ-ities. In addition, diethyldithiocarboxylate salts have applicationsin chronic alcoholic therapy and the treatment of HIV-patients[4]. The chemistry of organotin dithiocarboxylates has been a mat-ter of interest because of their antimicrobial action. Menezes et al.recently evaluated a series of organotin dithiocarboxylates for theirantifungal activity and discovered that the fungicidal action ofthese compounds is due to the inhibition of the biosynthesis of

ergosterol. Moreover, the significance of the presence of tin wasillustrated by the fact that all the organotin compounds investi-gated had activities greater than those exhibited by the uncoordi-nated dithiocarboxylate ligand [5]. With respect to theantibacterial activity of this class of compound, several attemptshave been made to replace the commercially available drugs but,thus far, none of them has proven successful [6,7]. Nevertheless,investigations are continuing in an effort to develop more potentderivatives so as to overcome to the current and projected prob-lems of organisms developing drug resistance. To be an active par-ticipant in this field and as a continuation of our interest [8], aseries of new organotin(IV) 4-benzhydrylpiperazine-1-carbodi-thioates has been synthesized (Scheme 1b) and the compoundshave been characterized and evaluated for their antibacterial andantifungal activity. Some of these complexes revealed greater anti-bacterial activity than the standard drug. This work is reported inthis paper.

2. Experimental

2.1. Materials and methods

The reagents, organotin(IV) chlorides and 4-benzhydrylpiper-azine, were obtained from Aldrich, while CS2 was purchased fromRiedal-de Haën; methanol was dried before use by the literature

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⇑ Corresponding author. Tel.: +1 514 398 6910; fax: +1 514 398 3797.E-mail address: [email protected] (I.S. Butler).

Inorganica Chimica Acta 373 (2011) 187–194

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procedure [9]. Microanalyses were done using a Leco CHNS 932apparatus. Infrared spectra were recorded as KBr pellets in therange from 4000–400 cm�1 using a Bio-Rad Excaliber FT-IR, modelFTS 300 MX spectrometer (USA). Raman spectra (±1 cm�1) weremeasured with an InVia Renishaw spectrometer, using argon-ion(514.5 nm) and near-infrared diode (785 nm) lasers. WiRE 2.0 soft-ware was used for the data acquisition and spectra manipulations.NMR spectra (DMSO-d6) were obtained with Varian Mercury300 MHz spectrometer (1H and 13C) and a Varian Unity 500-MHzinstrument [119Sn; SnMe4 (ext) ref].

2.2. Syntheses

The syntheses and Raman, IR and mass spectral data of the li-gand-salt and the new organotin(IV) complexes, together withthe 1H and 13C NMR data of ligand-salt are presented in this sec-tion. For the complexes, 1H NMR are given in Table 1, whereas13C and 119Sn NMR are listed in Table 2. The assignments of the1H and 13C NMR spectra of the ligand and the organic groups at-tached to Sn were made according to Scheme 1a.

2.2.1. 4-Benzhydrylpiperazinium 4-benzhydrylpiperazine-1-carbodithioate (L-salt)

Dropwise addition of CS2 (in excess) in methanol (50 mL) to 4-benzhydrylpiperazine (6 g, 23.79 mmol) in methanol (50 mL) fol-lowed by stirring for 6 h at 0 �C gave a white precipitate. The prod-uct was filtered off and washed with diethyl ether (Yield: 11.03 g,80%). M.p. 191–193 �C. Anal. Calc. for C35H40N4S2: C, 72.37; H, 6.94;N, 9.65; S, 11.04. Found: C, 72.11; H, 6.69; N, 9.45; S, 10.87%. Ra-man (cm�1): 650 m(C–S), 1045 m(C@S), 1460 m(C–N). IR (cm�1):1035 m(C–S), 1450 m(C–N). 1H NMR (ppm): 2.62, 2.46 (bs, 8H,H2,20 ,2a,20a), 4.40, 3.32 (bs, 8H, H3,30 ,3a,30a), 4.28 (s, 2H, H4,40), 7.48–7.17 (m, 10H, Ar-H), 8.1 (s, 2H, NH2). 13C NMR (ppm): 209.6 (C-1), 49.6, 44.8 (C-2, 20, 2a, 20a), 52.4, 50.8 (C-3, 30, 3a, 30a), 69.8 (C-4), 142.5, 142.0, 128.9, 128.8, 128.1, 127.9, 127.6, 127.4 (Ar-C).

2.2.2. General procedure for synthesis of complexesTriorganotin(IV) chloride or diorganotin(IV) dichloride in meth-

anol (30 mL) was added dropwise to the ligand-salt in methanol(50 mL) in the appropriate molar ratio and the mixture was re-fluxed for 6–8 h with constant stirring. The solvent was rotary

a

N NS

S

NH2N1

2

2'

3

3'4

2a

2a'

3a

3a'4a

H2CCH3α

β γδ

,

αβ γ

δ ,

αδ

γβ

, CH2 CH3

βα

, CH3

α

b

+ CS2a) MeOHb) 4 h stirringc) 0 oC

N NS

S

NH2N

N NH NNrA ArSH

S

N NS

SSn

R

RR

N NH2Cl

R = n-C4H9, C6H11, C6H5

Dry MeOH6 h refluxR3SnCl

Dry MeOH6 h reflux1/2R2SnCl2

R = n-C4H9, C2H5, CH3

S

SSn

R

R

S

SN NAr NN Ar

Salt =

-Salt

-Salt

N NS

SSn

R

R

Ar Cl

Dry MeOH6 h refluxR2SnCl2

-Salt

N NHAr ..

Ar

R = n-C4H9, C2H5, CH3

ArAr

Ar

Ar =,

Scheme 1. (a) Numbering scheme of ligand-salt and organic moiety of tin; (b) Synthesis of ligand-salt and complexes 1-9.

188 Zia-ur-Rehman et al. / Inorganica Chimica Acta 373 (2011) 187–194


evaporated off and the product obtained was recrystallized fromchloroform–ethanol mixture (Scheme 1b).

2.2.3. Tributyltin(IV) 4-benzhydrylpiperazine-1-carbodithioate (1)Yield: 0.73 g, 69%. M.p. 77–79 �C. Anal. Cacl. for C30H46N2S2Sn: C,

58.35; H, 7.51; N, 4.54; S, 10.38. Found: C, 58.23; H, 7.43; N, 4.50; S,10.31%. Raman (cm�1): 644 m(C–S), 1026 m(C@S), 1462 m(C–N), 590m(Sn–C), 371 m(Sn–S). IR (cm�1): 955 m(C–S), 1460 m(C–N).

2.2.4. Tricyclohexyltin(IV) 4-benzhydrylpiperazine-1-carbodithioate(2)

Yield: 0.78 g, 65%. M.p. 164–166 �C. Anal. Calc. for C36H52

N2S2Sn: C, 62.16; H, 7.53; N, 4.03; S, 9.22. Found: C, 62.01; H,7.45; N, 4.01; S, 9.17%. Raman (cm�1): 635 m(C–S), 1024 m(C@S),1437 m(C–N), 646 m(Sn–C), 376 m(Sn–S). IR (cm�1): 960 m(C–S),1460 m(C–N).

2.2.5. Triphenyltin(IV) 4-benzhydrylpiperazine-1-carbodithioate (3)Yield: 0.87 g, 75%. M.p. 140–142 �C. Anal. Calc. for C36H34

N2S2Sn: C, 63.82; H, 5.06; N, 4.13; S, 9.47. Found: C, 63.71; H,5.01; N, 4.11; S, 9.41%. Raman (cm�1): 652 m(C–S), 1022 m(C@S),

1480 m(C–N), 268 m(Sn–C), 392 m(Sn–S). IR (cm�1): 985 m(C–S),1469 m(C–N).

2.2.6. Chlorodibutyltin(IV) 4-benzhydrylpiperazine-1-carbodithioate(4)


N2S2SnCl: C, 52.41; H, 6.26; N, 4.70; S, 10.76. Found: C, 52.30; H,6.18; N, 4.66; S, 10.70%. Raman (cm�1): 617 m(C–S), 1029 m(C@S),1443 m(C–N), 588 m(Sn–C), 382 m(Sn–S), 272 m(Sn–Cl). IR (cm�1):935 m(C–S), 1470 m(C–N).

2.2.7. Dibutyltin(IV) bis[4-benzhydrylpiperazine-1-carbodithioate] (5)Yield: 0.65 g, 85%. M.p. 207–209 �C. Anal. Calc. for C44H56

N4S4Sn: C, 59.52; H, 6.36; N, 6.31; S, 14.45. Found: C, 59.44; H,6.29; N, 6.27; S, 14.38%. Raman (cm�1): 617 m(C–S), 1025 m(C@S),1443 m(C–N), 587 m(Sn–C), 384 m(Sn–S). IR (cm�1): 937 m(C–S),1456 m(C–N).

2.2.8. Chlorodiethyltin(IV) 4-benzhydrylpiperazine-1-carbodithioate(6)


N4S4Sn: C, 48.95; H, 5.42; N, 5.19; S, 11.88. Found: C, 48.84; H,

Table 11H NMR dataa, b of complexes 1–9.

1H (1) (2) (3) (4) (5) (6) (7) (8) (9)

2,20

2.65(bs)

2.48–2.45(m)

2.57(bs)

3.22(bs)

3.22(bs)

2.63(bs)

2.63(bs)

2.54–2.51(m)

2.49–2.46(m)

3,30

3.15(bs)

4.20–4.17(m)

3.07(bs)

3.97(bs)

3.97(bs)

3.15–3.12(m)

3.15–3.12(m)

3.96–3.93(m)

4.10–4.05(m)

Ar-H 7.40–7.15(m)

7.42–7.17(m)

7.37–7.18(m)

7.41–7.16(m)

7.41–7.16(m)

7.40–7.14(m)

7.40–7.14(m)

7.42–7.18(m)

7.42–7.17(m)

4 4.23(s)

4.26(s)

4.27(s)

4.29(s)

4.29(s)

4.29(s)

4.29(s)

4.29(s)

4.26(s)

a 1.62–1.26(m)

2.00–1.28(m)

– 1.85–1.35(m)

1.85–1.35(m)

1.81(q), (7.5)

1.81(q), (7.5)

1.28(s)[75,73]

1.48(s)[85, 82]

b 1.62–1.26(m)

2.00–1.28(m)

7.70–7.66(m)

1.85–1.35(m)

1.85–1.35(m)

1.46(t),(7.5)

1.46(t),(7.5)

– –

c 1.62–1.26(m)

2.00–1.28(m)

7.44–7.36(m)

1.85–1.35(m)

1.85–1.35(m)

– – – –

d 0.89(t), (7)

2.00–1.28(m)

7.44–7.36(m)

0.94(t), (7.5)

0.94(t), (7.5)

– – – –

aChemical shifts (d) in ppm. 2J[119Sn, 1H], 3J(1H, 1H) in Hz are listed in square brackets and parenthesis, respectively. Multiplicity is given as s = singlet, d = doublet,m = muliplet, bs = broad signal.bNumbering in accordance with Scheme 1a.

Table 213C and 119Sn NMR dataa,b of complexes 1–9.

13C (1) (2) (3) (4) (5) (6) (7) (8) (9)

1 198.4 199.3 196.9 196.6 198.1 196.5 202.4 195.9 199.12,2

052.0 52.0 52.7 52.0 52.0 52.1 51.9 52.1 51.4

3,30

51.6 51.6 51.4 51.2 51.2 51.2 51.2 51.1 44.4Ar-C (i, o,

m, p)141.7, 127.8,129.0, 127.6

141.7, 127.8,129.0, 127.6

142.0, 127.9,128.9, 127.5

141.7, 127.8,129.0, 127.7

141.7, 127.8,129.0, 127.7

141.7, 127.9,129.0, 127.7

141.8, 127.9,129.0, 127.6

141.7, 128.0,129.0, 127.7

142.1, 128.0,128.9, 127.5

4 75.8 75.8 75.7 75.7 75.6 75.6 75.6 75.8a 17.9

[340, 321]35.5[335,318]

142.6[791]

26.5[595]

26.6[605]

21.4[532,509]

21.4[620,595]

10.3[570,545]

15.1[675, 660]

b 29.1[16]

32.1[17]

136.4[48]

28[18]

34.1[19]

10.5[38]

10.5[48.5,44.7]

– –

c 27.3[67]

29.6[68]

129.3[62]

27.3[65]

28.8[65]

– – – –

d 13.9 27.4 130.5[12.8]

13.8 13.9 – – – –

119Sn 27.6 �26.9 �185.4 �195.1 �194.9 �188.5 �188.1 �194.3 �331.1

a Chemical shifts (d) in ppm. nJ[119Sn, 13C] in Hz are listed in square brackets.b Number in accordance with Scheme 1a.

Zia-ur-Rehman et al. / Inorganica Chimica Acta 373 (2011) 187–194 189


5.38; N, 5.16; S, 11.81%. Raman (cm�1): 592 m(C–S), 1024 m(C@S),1484 m(C–N), 490 m(Sn–C), 387 m(Sn–S), 259 m(Sn–Cl). IR (cm�1):945 m(C–S), 1470 m(C–N).

2.2.9. Diethyltin(IV) bis[4-benzhydrylpiperazine-1-carbodithioate] (7)Yield: 0.51 g, 71%. M.p. 153–154 �C. Anal. Calc. for

C44H56N4S4Sn: C, 57.76; H, 5.82; N, 6.74; S, 15.42. Found: C,57.66; H, 5.73; N, 6.71; S, 15.36%. Raman (cm�1): 621 m(C–S),1031 m(C@S), 1464 m(C–N), 492 m(Sn–C), 385 m(Sn–S). IR (cm�1):955 m(C–S), 1460 m(C–N).

2.2.10. Chlorodimethyltin(IV) 4-benzhydrylpiperazine-1-carbodithioate (8)

Yield: 0.71 g, 81%. M.p. 166–167 �C. Anal. Calc. forC44H56N4S4Sn: C, 46.94; H, 4.92; N, 5.47; S, 12.53. Found: C,46.85; H, 4.86; N, 5.44; S, 12.48%. Raman (cm�1): 561 m(C–S),1026 m(C@S), 1462 m(C–N), 518 m(Sn–C), 389 m(Sn–S), 261 m(Sn–Cl). IR (cm�1): 995 m(C–S), 1466 m(C–N).

2.2.11. Dimethyltin(IV) bis[4-benzhydrylpiperazine-1-carbodithioate](9)

Yield: 0.51 g, 74%. M.p. 216–218 �C. Anal. Calc. forC44H56N4S4Sn: C, 56.78; H, 5.52; N, 6.97; S, 15.96. Found: C,56.69; H, 5.46; N, 6.93; S, 15.90%. Raman (cm�1): 558 m(C–S),1026 m(C@S), 1475 m(C–N), 509 m(Sn–C), 376 m(Sn–S). IR (cm�1):991 m(C–S), 1457 m(C–N).

3. Results and discussion

3.1. Vibrational spectra

The appearance of a new Sn–S stretching vibration in the Ra-man spectra indicated the formation of complexes. A band in the490–646 cm�1 region, which can be assigned to a Sn–C stretch,was identified in all the organotin(IV) derivatives except for the tri-phenyltin(IV) compound (a weak vibration at 267 cm�1). In thechlorodiorganotin(IV) derivatives, the peak associated with m(Sn–Cl) was also observed, which pointed to substitution of one chlo-ride by a ligand moiety.

In the IR spectra, the m(C–S) mode, which appears in the region�1000 cm�1, is of prime importance in deciding the mode of coor-dination of the dithiocarboxylate ligand. The presence of singlepeak in this region indicates bidentate coordination, while splittinginto a doublet signifies monodentate coordination [10]. A singlesharp band at 1035 cm�1 was observed in the ligand-salt, whichwas shifted to lower energy in the complexes, thus suggestingbidentate coordination of the ligand via the CSS moiety. The m(N–CSS) mode was observed between the ranges reported for a C–Nsingle bond (1250–1360 cm�1) and a C@N double bond (1640–1690 cm�1), indicative of the partial double bond character in theC–N bond [11]. On passing from the ligand-salt to the complexes,the m(N–CSS) mode is shifted to higher energies, showing an in-crease in C–N double bond character. The m(N–CSS) band appearedat higher energy in the chlorodiorganotin(IV) derivatives than inthe counterparts without a chloride substituent, because the elec-tron-withdrawing capacity of the chloride leads to a higher posi-tive charge on the nitrogen atom.

3.2. Multinuclear NMR spectra

The 1H NMR spectra were recorded for compounds 1–10 inDMSO-d6. The characteristic chemical shifts were recognized bytheir intensity and multiplicity patterns. The total numbers of pro-tons, calculated from the integration curves, were in agreementwith the proposed molecular structure of the compounds. The

geometry of the methyltin derivatives was predicted from the val-ues of the 2J [119Sn, 1H] coupling constants. The CSnC angles, calcu-lated from Lockhart’s equation (h = 0.0105 [2J]2 � 0.799 [2J] +122.4) shown in Table 3, are in agreement with trigonal bipyrami-dal and octahedral geometry for compounds 8 and 9, respectively.Owing to the complex peak patterns observed for the organicgroups attached to Sn, in the case of the butyl-, cyclohexyl, phenyland ethyltin derivatives, no tin-proton satellites were observedand hence assignment of the geometry is not possible. The geom-etry of the triphenyltin compound was confirmed by the differenceof the ortho protons compared to those of the meta- and para pro-tons and corresponded to a five-coordinate Sn atom [12].

The 13C NMR data exhibited explicitly the resonances of all thedistinct carbon atoms present in the compounds. The assignmentof the carbon resonances associated with the organotin moietieswas made on the basis of the nJ [119Sn, 13C] coupling constant(s)and signal intensities, as illustrated earlier [13]. The resonancesin CS2 for the complexes were shifted slightly upfield thus suggest-ing coordination of the metal to the ligand. The 1J [119Sn, 13C] cou-pling constants observed in some compounds were exploited toobtain geometry information. For compounds 1 and 2, the 1J[119Sn, 13C] coupling constants correspond to tetrahedral geometry,while for compounds 6 and 8, the values obtained match well witha pentacoordinated environment about the Sn centre [14a,b]. Acharacteristic feature for triphenyltin derivatives is the observationof the 13C chemical shift of the ipso-carbon at about 142.6 ppm,which is attributed to a five-coordinated Sn atom [15].

The appearance of a single peak in the 119Sn NMR spectra of allthe complexes signified the formation of single species. The 119Snchemical shifts for compounds 1 and 2 are in accord with tetrahe-dral geometry. Complex 9 exhibited a 119Sn peak corresponding toan octahedral environment about the Sn atom. The 119Sn values ob-served for compounds 3–8 were indicative of a five-coordinated Snatom [16]. These results indicate that in solution the diorganotinderivatives change their solid-state octahedral geometry to a trigo-

Table 3(C–Sn–C) angles (�) based on NMR parameters of selected of complexes 1–9.

Compounds number 1J(119Sn, 13C) (Hz) 2J(119Sn, 1H) (Hz) Angle (�)

1J 2J

1 340 – 106.6 –2 335 – 106.1 –3 – 791 125.44 – 595 – 1285 – 605 – 129.86 532 – 123.4 –7 620 131.18 570 75 126.7 121.59 675 85 135.9 130.3

R

S

SSn R

S

S

R

R

RS

SSn R

S

S

R

R

RS

SSnR

S

S

R

R

a b

c

Scheme 2. (a) Solid-state structure; (b and c) solution structures.



nal bipyramidal one, most probably by the mechanism shown inScheme 2.

3.3. Crystal structures of compounds 4 and 6

The asymmetric unit for compound 4 contains two different mol-ecules, each having a slightly different geometry. Fig. 1 shows ORTEPdiagrams for both molecules together with the atom numberingScheme. Crystal data and selected interatomic parameters are

Fig. 1. ORTEP drawing of molecule 1 (top) and molecule 2 (lower) of the 4 with atomic numbering scheme.

Table 4Crystal data and structure refinement parameters for compounds 4 and 6.

4 6

Empirical formula C26H37N2S2SnCl C22H29N2S2SnClFormula mass 595.89 539.77Crystal system triclinic monoclinicSpace group P�1 C2/ca (Å) 9.9510(10) 29.612(15)b (Å) 13.3727(14) 9.609(5)c (Å) 21.113(2) 18.082(10)a (�) 100.6968(14) –b (�) 91.2796(14) 117.844(10)c (�) 92.3442(14) –V (Å3) 2757.1(5) 4549(4)Z 4 (2) 8 (1)Crystal size (mm) 0.49 � 0.23 � 0.14 0.32 � 0.28 � 0.16Temperature (K) 100(1) 100(1)Total reflections 20874 3682Independent reflections

All10225 3682

For Fo P 4.0 r(Fo) 7585 2448R(F) =

P(||Fo| � |Fc||)/

P|Fo|

For Fo > 4.0 r(Fo)0.0528 0.0716

wR(F2) = [P

[w(F2o � F2

c )2]/P

[w(F2o )2]]1/2

0.1302 0.2084

R indices (all data) 0.0528 0.0716Final R indices [I > 2r(I)] 0.1302 0.2084Goodness-of-fit (GOF) 1.034 1.138h Range for data collections (�) 2.51–25.68 2.77–25.03Data/restraints/parameters 10225/0/581 3682/0/256

Table 5Selected bond lengths (Å) and bond angles (�) for compound 4.

x = 1 x = 2

Snx–Clx 2.446(2) 2.4721(13)Snx–Sx2 2.754(2) 2.7849(13)Snx–Cx23 2.125(11) 2.145(6)Sx2–Cx18 1.716(6) 1.705(4)

Clx–Snx–Sx1 88.07(6) 85.52(4)Clx–Snx–Cx19 95.4(2) 99.27(16)Sx1–Snx–Sx2 68.55(5) 68.31(4)Sx1–Snx–Cx23 119.7(4) 114.57(16)Sx2–Snx–Cx23 96.8(3) 91.83(14)Snx–Sx1–Cx18 90.9(2) 91.58(14)Sx1–Cx18–Sx2 117.3(3) 117.7(2)Snx–Cx23–Cx24 138.5(11) 115.8(4)

Snx–Sx1 2.4705(15) 2.4688(13)Snx–Cx19 2.208(8) 2.137(6)Sx1–Cx18 1.740(6) 1.756(4)

Clx–Snx–Sx2 156.57(7) 153.84(4)Clx–Snx–Cx23 96.2(4) 99.55(14)Sx1–Snx–Cx19 115.3(2) 116.18(17)Sx2–Snx–Cx19 93.4(2) 92.43(16)Cx19–Snx–Cx23 124.0(5) 126.8(2)Snx–Sx2–Cx18 82.3(2) 82.45(14)Snx–Cx19–Cx20 115.9(6) 113.3(4)



collected in Tables 4 and 5, respectively. The configuration about thetin atom is five-coordinate with a distorted trigonal–bipyramidalgeometry at the central Sn atom. The sums of the equatorial anglesinvolving the two a-carbons of the butyl groups and an S atom,(x1): 359�: 357.5�, show little deviation from the ideal angle of360�. The s values, 0.6 and 0.62, for both molecules agree well withthe distorted trigonal bipyramidal structure. For each molecule, theCl atom occupies one of the apical positions of the trigonal-bipyra-mid with Cl1–Sn1–S11 and Cl2–Sn2–S21 angles of 88.07(6)� and85.52(4)�, respectively. The quasi-axial S11 and S12 atoms cannot

occupy exactly the position trans to Cl and the Cl1–Sn1–S12 andCl2–Sn2–S22 angles are 156.57(7)� and 153.84 (4)�. Thus, the dithio-carboxylate groups in both molecules are asymmetrically coordi-nated, as shown by Snx–Sx2(ax) [2.754 (2) Å and 2.7849 (13) Å]and Sn–Sx2(eq), [2.4705(15) Å and 2.4688(13) Å] bond lengths.The S–C bond lengths [(Sx1–Cx18 = 1.740(6) Å and 1.756 (4) Å)and (Sx2–Cx18 = 1.716(6) Å and 1.705 (4) Å)] also show the asym-metric nature of the dithiocarboxylate group in each molecule. Thepacking of molecules to form a supramolecular chain is shown inFig. 2, which indicates no intermolecular Sn��S and Sn��Cl interac-tions, however, the molecules are linked together via p��Hinteractions.

For compound 6, the pertinent crystallographic parameters, se-lected bond lengths and bond angles are given in Tables 4 and 6,respectively. An ORTEP view of compound 7, together with atomicnumbering Scheme, is presented in Fig. 3. The asymmetric unitcontains a single SnEt2 moiety connected to a chloride and to adithiocarboxylate ligand via two Sn–S bonds. The Sn–S2 [2.784(4) Å] distance for the bond approximately trans- to the chlorideis longer than is the other Sn–S1 [2.457(4) Å] distance. The coordi-nation geometry is almost intermediate between square-pyrami-dal and trigonal bipyramidal with a slight bias towards theformer, based on the s value (0.24), and is consistent with 0.29 va-lue for (MeO(O@)CCH2CH2)2Sn (S2CNMe2)Cl [17]. More tangibleexplanations are available for the deviation of the coordinationgeometries towards square pyramidal. In complex 7, there are

Fig. 2. Supramolecular chain structure of compound 4.

Table 6Selected bond lengths (Å) and bond angles (�) for compound 6.

Sn–Cl 2.462(4) Sn–S1 2.457(4)Sn–S2 2.784(4) Sn–C19 2.120(14)Sn–C21 2.113(15) S1–C18 1.724(15)S2–C18 1.707(17)

Cl–Sn–S1 85.43(12) Cl–Sn–S2 153.29(12)Cl–Sn–C19 97.1(4) Cl–Sn–C21 97.6(4)S1–Sn–S2 67.87(12) S1–Sn–C19 108.9(4)S1–Sn–C21 110.5(4) S2–Sn–C19 91.1(4)S2–Sn–C21 92.6(4) C19–Sn–C21 138.9(6)Sn–S1–C18 92.3(5) Sn–S2–C18 82.0(5)S1–C18–S2 117.8(8)

Fig. 3. ORTEP drawing of 6 with atomic numbering scheme.

Fig. 4. Supramolecular chain in the structure of 6 mediated by Sn��Cl andsecondary Sn��S interactions.



two intermolecular interactions responsible for lowering the s va-lue, a Sn��Cl and a secondary Sn��S interaction, which lead to theformation of a supramolecular chain structure (Fig. 4). The Cl atomoccupies one of the apical positions of the highly distorted trigo-nal-bipyramid with a Cl–Sn–S1 angle of 85.43(12)�. The quasi-axialS2 atom again cannot occupy exactly the position trans to Cl andCl–Sn–S2 is 153.29(12)�. Thus, the 4-benzhydrylpiperazine-1-car-bodithioate ligand chelates the Sn atom via its two sulfur atomsin anisobidentate fashion, forming a four-membered ring withS1–Sn–S2 bond angle of 67.87(12)�. The S–C bond lengths [S1–C18 = 1.724(15) Å and S2–C18 = 1.707(17) Å] also demonstratethe asymmetric nature of the ligand.

3.4. Antibacterial activity

The antibacterial activities of DMSO solutions of the new com-pounds were tested against five bacterial strains by the agar welldiffusion method. The activities were compared with that of thereference antibiotic, streptomycin, and the results are given in Ta-ble 7. The complexes have activities comparable to that of the ref-erence drug in some cases. The higher activities observed for thechlorodiorganotin(IV) complexes are most probably due to thepresence of the more labile chloride group the presence of whichmake these complexes easily hydrolysable [18]. Among the chlo-rodiorganotin compounds, the low activity of complex 9, confirmsthe notion that activity increases with increasing alkyl chainlength. This situation arises because increasing chain length en-hances the lipophilicity of the molecules, so that they can pene-trate faster to produce a cytotoxic effect. The higher activity ofthe chlorodiethyltin complex compared to that of the chlorodibu-tyltin species indicates that lipophilicity is not the sole factorresponsible for cytotoxic action. The ease of detachment of the la-bile group must also play a significant role. The crystal structural

data for both complexes indicate that the Sn–Cl bond is compara-tively longer in chlorodiethyltin complex than in the chlorodibu-tyltin derivative and hence it is more easily hydrolysed. Thepossible inhibitory action of the complexes may be attributableto their inhibition of DNA replication by interacting with the en-zyme prosthetic group. These compounds are quite active due totheir membrane penetrating ability. The reduced activities in somecases can, however, be attributed to the inability of hydrogen bondformation with the cell constituents [19].

3.5. Antifungal activity

The agar tube dilution protocol method was employed to testthe antifungal activities of the synthesized compounds against fivedifferent strains of fungi, namely Aspergillus nigar, Aspergillus flavus,Helminthosporium solani, Alternia solani, Fusarium sp. The resultsare shown in Table 8. The inhibition of fungal growth, expressedin percentage terms, was determined using the Vincent equation[20]:

Inhibition % ¼ 100ðC � TÞ=C ð1Þ

where C is the diameter of fungal growth for a control and T is thediameter of fungal growth for the sample.

The complexes inhibit the fungal growth to a medium extent;however, the zone of inhibition of complexes 5 and 7 is comparablewith those of a standard fungicide, especially against the A. nigarand A. solani fungi.

4. Conclusion

Nine new organotin(IV) 4-benzhydrylpiperazine-1-carbodithio-ates have been synthesised and characterized by various spectros-copy techniques. X-ray single crystal study proved supramolecular

Table 7Antibacterial activity data a,b of ligand-salt and organotin(IV) derivatives 1–9.

Bacterium Clinical implication Zone of Inhibition (mm) Reference drug

L-salt (1) (2) (3) (4) (5) (6) (7) (8) (9)

Escherichia coli Infection of wounds, urinary tract and dysentery 20 25 13 21 22 18 26 19 0 0 34Salmonella typhi Typhoid fever, localized infection 21 0 0 25 35 22 32 0 17 11 31Pseudomonas aeruginosa Infection of wounds, eyes, septicemia 0 13 0 0 12 0 13 12 0 0 24Staphlococcus aureus Food poisoning, scaled skin syndrome, endocarditic 0 0 0 0 14 13 18 13 12 0 38Streptococcus Strep throat 12 0 13 0 13 0 20 20 12 13 38

a In vitro, agar well diffusion method, conc. 1 mg/mL of DMSO.b Reference drug, streptomycin.

Table 8Antifungal activitya of ligand-salt and organotin(IV) derivatives 1–9.

Sample Tested fungi

Aspergillus nigar Aspergillus flavus Helminthosporium solani Alternia solani Fusarium sp.

Lineargrowth

%Inhibition

Lineargrowth

%Inhibition

Lineargrowth

%Inhibition

Lineargrowth

%Inhibition

Lineargrowth

%Inhibition

Control 85 86 87 90 70

L-salt 68 20.0 70.0 18.6 74.0 14.9 68.0 24.4 62 11.4

(1) 80 5.9 81.0 5.8 78.0 10.3 74.0 17.8 70 0(2) 78 8.2 78.0 9.3 74.0 14.9 80.0 11.1 70 0(3) 74 12.9 78.0 9.3 72.0 17.2 80.0 11.1 70 0(4) 66 22.4 78.0 9.3 76.0 12.6 70.0 22.2 68 2.8(5) 78 8.2 78.0 9.3 73.0 16.1 74.0 17.8 68 2.8(6) 66 22.4 72.0 16.3 73.0 16.1 66.0 26.7 60 14.2(7) 83 2.4 82.0 4.7 76.0 12.6 73.0 18.9 70 0(8) 80 5.9 83.0 3.5 80.0 8.0 78.0 13.3 68 2.8(9) 80 5.9 78.0 9.3 68.0 21.8 64.0 28.9 61 12.8Clotrimazole 60 29.4 52 39.5 51 41.4 48 46.7 44 37.1

a Concentration: 200 lg/mL of DMSO.



molecular structure for complexes 4 and 9 with a distorted trigonalbipyramidal and a distorted square-pyramidal geometry, respec-tively. The square-pyramidal geometry is of particular interest be-cause geometry of such kind is scantly available in the literaturefor organotins. The different geometry of 9 than 4 can be attributedto the intermolecular Sn��Cl interactions in the former. The antimi-crobial activities of the complexes are, in broad terms, excellentand far exceed the level for the free ligand. The influence of the me-tal is clearly visible in the antibacterial activity. The antibacterialactivity maximizes for complexes 4 and 6, although the activityof all the organotin complexes is reasonable.

Acknowledgements

We thank the Higher Education Commission of Pakistan and theNSERC (Canada) for financial support.

Appendix A. Supplementary material

CCDC 733924 and 733923 contain the supplementary crystallo-graphic data for complexes 4 and 6, respectively. These data can beobtained free of charge from The Cambridge Crystallographic DataCentre via www.ccdc.cam.ac.uk/data_request/cif. Supplementarydata associated with this article can be found, in the online version,at doi:10.1016/j.ica.2011.04.016.

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New mononuclear organotin(IV) 4-benzhydrylpiperazine-1-carbodithioates: Synthesis, spectroscopic...

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