Author's personal copy Bioactive hepta-and penta-coordinated supramolecular diorganotin(IV) Schiff...

This article appeared in a journal published by Elsevier. The attachedcopy is furnished to the author for internal non-commercial researchand education use, including for instruction at the authors institution

and sharing with colleagues.

Other uses, including reproduction and distribution, or selling orlicensing copies, or posting to personal, institutional or third party

websites are prohibited.

In most cases authors are permitted to post their version of thearticle (e.g. in Word or Tex form) to their personal website orinstitutional repository. Authors requiring further information

regarding Elsevier’s archiving and manuscript policies areencouraged to visit:

http://www.elsevier.com/authorsrights

http://www.elsevier.com/authorsrights

Author's personal copy

Bioactive hepta- and penta-coordinated supramoleculardiorganotin(IV) Schiff bases

Shaukat Shujah a,b,**, Zia-ur-Rehman a,*, Niaz Muhammad c, Afzal Shah a, Saqib Ali a,*,Nasir Khalid d, Auke Meetsma e

aDepartment of Chemistry, Quaid-i-Azam University, Islamabad 45320, PakistanbDepartment of Chemistry, Kohat University of Science & Technology, Kohat, PakistancDepartment of Chemistry, Abdul Wali Khan University Mardan, PakistandChemistry Division, Pakistan Institute of Nuclear Science and Technology, PO Nilore, Islamabad, PakistaneCrystal Structure Center, Chemical Physics, Zernike Institute for Advanced Materials, University of Groningen, Nijenborgh 4, NL-9747 AG Groningen, TheNetherlands

a r t i c l e i n f o

Article history:Received 14 March 2013Received in revised form6 May 2013Accepted 14 May 2013

Keywords:SupramolecularHepta-coordinated organtinAntileishmanialAntiureaseAntibacterialAntifungal

a b s t r a c t

This article describes the synthesis, characterization and bioactivity of dimethyl (1), diethyl (2), diphenyl(3), di-n-octyl (4), di-tert-butyl (5), n-butylchlorotin(IV) (6) derivatives of N0-(2-hydroxy-3-methoxybenzylidene)formohydrazide ligand. On the basis of presence or absence of steric factor, thesecompounds are either mononuclear in which Sn atom is in distorted trigonal bipyramidal geometry (3)or homobimetallic with each Sn atom in pentagonal bipyramidal environment (1). Packing diagramssuggest that the H/N, H/p and p/p interactions play a seminal role in generating fascinating su-pramolecular structures. These complexes show good antileishmanial, antiurease, antibacterial andantifungal activities. Moreover, the antileishmanial activity of 3 and 5 is comparable with standardantileishmanial drug Amphotericin B.

� 2013 Elsevier B.V. All rights reserved.

1. Introduction

Supramolecular organometallic compounds generated throughnon-covalent interactions such as coordinative bonds, hydrogenbonds, or p/p interactions are of particular interest due to theirinteresting structural architectures and applications in variousfields [1,2]. Although considerable advancement has been made inthe field of supramolecular chemistry yet little is known aboutassemblies derived from organometallic building blocks. Moreover,in comparison to transition metals and lanthanides, few supra-molecular aggregates containing main group elements are knownbecause of their less kinetic and thermal stability, and because ofthe inappropriate size of the metal center to coordinate withchelating-ligand functions [3] Among the main group elements tin-directed self-assembly has received the most attention because it

meets well with the above two mentioned criteria. In addition tothis, fine-tuning of chemical, physical, and structural properties ofthe supramolecular system can be made by modulating the organicgroups attached to the tin atom.

In recent years, organotin Schiff bases have been paid equitableattention due to their stimulating structural features and because oftheir versatile applications in various fields like catalysis, biotech-nology, analytical and medicinal chemistry [4e6]. In ONO tri-dentate ligands based derivatives of organotins, the tin atom istypically penta-coordinate with a trigonal bipyramidal or square-pyramidal geometry [7]. In addition to this, supramolecular archi-tectures can be achieved through self-organization of molecules bynon-covalent forces including hydrogen bonding, hydrophobic,hydrophilic effects, electrostatic and p/p interactions etc. [8].

In view of all these considerations, we aimed to synthesis andcharacterize monometallic (trigonal bipyramidal) and bimetallic(pentagonal bipyramidal) organotin(IV) derivatives of N0-(2-hydroxy-3-methoxybenzylidene)formohydrazide ligand and sub-sequently screened them for antimicrobial and antiurease activ-ities. Some of these compounds have promising antileishmanialactivity, and after further investigations may emerge as new tin-based antileishmanial agents.

* Corresponding authors. Tel.: þ92 5190642208; fax: þ92 512873869.** Corresponding author. Department of Chemistry, Quaid-i-Azam University,Islamabad 45320, Pakistan.

E-mail addresses: [email protected] (S. Shujah), [email protected]( Zia-ur-Rehman), [email protected] (S. Ali).

Contents lists available at SciVerse ScienceDirect

Journal of Organometallic Chemistry

journal homepage: www.elsevier .com/locate/ jorganchem

0022-328X/$ e see front matter � 2013 Elsevier B.V. All rights reserved.http://dx.doi.org/10.1016/j.jorganchem.2013.05.019

Journal of Organometallic Chemistry 741-742 (2013) 59e66


2. Experimental

2.1. Chemicals and instrumentation

Organotin(IV) dichlorides, dioctyltin(IV) oxide, n-butyl-chlorotin(IV) dihydroxide, formic hydrazide and 2-hydroxy-3-methoxybenzaldehyde were procured from Aldrich. The organicsolvents used were of Merck, Germany. These solvents were freshlydried using standard procedures [9].

The melting points were recorded on an electrothermalmelting point apparatus, model MP-D Mitamura Rieken Kogyo(Japan) by using capillary tubes and are uncorrected. The infrared(IR) spectra were recorded using NaCl cells or KBr pellets on a Bio-Rad Excaliber FT-IR, model FTS 300 MX spectrophotometer (USA)in the frequency range of 4000e400 cm�1. Multinuclear NMR (1H,13C, and 119Sn) spectra were recorded on a Bruker ARX 300 MHz-FT-NMR and a Bruker 400 MHz-FT-NMR spectrometersSwitzerland using CDCl3 as an internal reference. Chemical shifts(d) and coupling constants (J) are given in ppm and Hz, respec-tively. The multiplicities of signals in 1H NMR are given withchemical shifts; (s ¼ singlet, d ¼ doublet, t ¼ triplet, q ¼ quartet,m ¼ multiplet).

The mass spectra were recorded on a MAT-311A Finnigan(Germany). The m/z values were evaluated assuming that H ¼ 1,C ¼ 12, N ¼ 14, O ¼ 16, Cl ¼ 35 and Sn ¼ 120.

The X-ray diffraction data were collected on a Bruker SMARTAPEX CCD diffractometer, equipped with a 4 K CCD detector. Dataintegration and global cell refinement was performed with theprogram SAINT. The program suite SAINTPLUS was used for spacegroup determination (XPREP). The structure was solved by Patter-son method; extension of the model was accomplished by directmethod and applied to different structure factors using the pro-gram DIRDIF. All refinement calculations and graphics were per-formed with the program PLUTO and PLATON package [10].

2.2. Synthesis

2.2.1. Synthesis of N0-(2-hydroxy-3-methoxybenzylidene)formohydrazide (H2L)

An ethanolic solution of 2-hydroxy-3-methoxybenzaldehyde2.53 g (16.65 mmol) was added slowly to the solution of formichydrazide 1.0 g (16.65 mmol), in ethanol with constant stirring atroom temperature. The mixture was refluxed for 1 h and on coolingyellow crystalline solid was obtained (Scheme 1a and b).

amido form iminol form

R/Cl

Scheme 1. Synthesis of N0-(2-hydoxy-3-methoxybenxylidene)formohydrazide (H2L) (a,b) diorganotin(IV) and butylchloridetin(IV) derivatives (cee).

S. Shujah et al. / Journal of Organometallic Chemistry 741-742 (2013) 59e6660


Yield 83%, m.p. 176e177 �C. Anal. Calc. for C9H10N2O3 (M¼ 194):C, 55.67; H, 5.19; N, 14.43 Found: C, 55.70; H, 5.21; N, 14.39%. EI-MS,m/z (%): [C9H10N2O3]þ 194 (100.0), [C8H9N2O2]þ 165 (3.9),[C8H7NO2]þ 149 (81.3), [C8H6NO]þ 132 (9.9), [C7H7O2]þ 123 (7.2),[C7H5NO]þ 119 (19.2), [C6H5]þ 77 (11.7) FT-IR (cm�1): 3173m, nNeH;3385m, nOeH; 1691s, nC]O; 1625 nC]N; 1055 nNeN. 1H NMR (ppm):H-3: 6.97 (dd, 1H, phenyl, 3JHeH ¼ 8.1), H-4: 6.79 (t, 1H, phenyl, 3JHeH ¼ 8.1), H-5: 7.22 (dd, 1H, phenyl, 3JHeH ¼ 7.8), H-7: 8.36 (s, 1H,CH]N), H-8: 11.66 (s,1H, CHO), H-9: 3.83 (s, 3H, OCH3), NH: 8.66 (s,1H, NH), OH: 10.10 (s, 1H, OH), 13C NMR (ppm): C-7: 143.3 (HC]N);C-8: 165.2 (CHONH); 146.4, 148.4, 120.7, 119.6, 118.4, 113.4 (PheC):C-9: 56.3 (OCH3).

2.2.2. Synthesis of dimethyltin(IV) [N0-(3-methoxy-2-oxidobenzyli-dene)-N-(oxidomethylene)hydrazine] (1)

A 250 mL two-necked flask containing 100 mL toluene, equip-ped with a reflux condenser was charged with N0-(2-hydroxy-3-methoxybenzylidene)formohydrazide 0.58 g (3.0 mmol), and trie-thylamine 0.84 mL (6.0 mmol) along with a magnetic bar. To thesolution of triethylammonium salt of the ligand, dimethytin(IV)dichloride (0.66 g, 3.0 mmol) in dry toluene was added drop wisewith stirring at room temperature. When the solution turned yel-low, then it was stirred for 5 h at room temperature. The whiteprecipitates of Et3NHCl formed during the reaction were filtered.The filtrate was concentrated by rotary evaporator to obtain yellowsolid. The product was recrystallized from CHCl3/n-hexane (4:1)mixture (Scheme 1c and d).

Yield 84%, m.p. 140e141 �C. Anal. Calc. for C11H14N2O3Sn(M ¼ 342): C, 38.75; H, 4.14; N, 8.22, Found: C, 38.78; H, 4.12; N,8.19%. EI-MS, m/z (%): [(C9H8N2O3)Sn(CH3)2]þ 342 (100.0);[(C9H8N2O3) Sn(CH3)]þ 327 (43.7); [(C9H8N2O3)Sn]þ 312 (96.0);[(C8H6NO2Sn)]þ 268 (8.2); [Sn(CH3)2]þ 150 (5.6); [SnCH3]þ 135(28.3); [Sn]þ 120 (12.8). FT-IR (cm�1): 1623s, nC]N; 1072m, nNeN;586m, nSneO; 478w, nSneN. 1H NMR (ppm): H-3: 6.82 (d, 1H, phenyl,3JHeH ¼ 7.8), H-4: 6.70 (t, 1H, phenyl, 3JHeH ¼ 7.8), H-5: 6.94 (d, 1H,phenyl, 3JHeH ¼ 7.8), H-7: 8.62 [(s, 1H, CH]N, 3J(119Sne1H)¼ 46 Hz)], H-8: 7.63 (s, 1H, N]OCH), H-9: 3.87 (s, 3H, OCH3), H-a: 0.88 (s, 6H, 2CH3), 2J(119/117Sne1H) ¼ 80, 76 Hz. 13C NMR (ppm):C-7: 156.9 (HC]N); C-8: 163.7 (CHONH); 163.1, 151.2, 126.0, 116.6,115.9, 115.7 (PheC): C-9: 56.1 (OCH3), Ca: 2.61 1J[119/117Sne13C] ¼ 657, 627 Hz, 119Sn NMR: d (ppm) ¼ �164.

2.2.3. Diethyltin(IV) [N0-(3-methoxy-2-oxidobenzylidene)-N-(oxido-methylene)hydrazine] (2)

Compound 2was prepared in the sameway as 1, using followingprecursors quantities: N0-(2-hydroxy-3-methoxybenzylidene)for-mohydrazide 0.58 g (3.0 mmol), diethyltin(IV) dichloride 0.74 g(3.0mmol), triethylamine 0.84mL (6.0mmol) were reacted in 1:1:2ratio. Solid product was recrystallized from chloroform and n-hexane (4:1) mixture.

Yield 88%, m.p. 182e183 �C. Anal. Calc. for C13H18N2O3Sn(M ¼ 370): C, 42.31; H, 4.92; N, 7.59 Found: C, 42.28; H, 4.90; N,7.56%. EI-MS, m/z (%): [(C9H8N2O3)Sn(C2H5)2]þ 370 (83.0);[(C9H8N2O3) Sn(C2H5)]þ 341 (61.8); [(C9H8N2O3)Sn]þ 312 (100.0);[(C8H6NO2Sn)]þ 268 (6.8); [Sn]þ 120 (5.2). FT-IR (cm�1): 1618s,nC]N; 1068m, nNeN; 582m, nSneO, 472w, nSneN. 1H NMR (ppm): H-3: 6.79 (dd, 1H, phenyl, 3JHeH ¼ 7.8), H-4: 6.66 (t, 1H, phenyl, 3JHeH ¼ 7.8), H-5: 6.93 (dd, 1H, phenyl, 3JHeH ¼ 7.8), H-7: 8.64 [(s, 1H,CH]N, 3J(119Sne1H) ¼ 42 Hz)], H-8: 7.68 (s, 1H, N]OCH), H-9:3.87 (s, 3H, OCH3), H-a: 1.54 (q, 2H, 2CH2), 2J(119Sne1H) ¼ 72 Hz,H-b: 1.28 (t, 3H, CH3, 3JHeH ¼ 7.8). 13C NMR (ppm): C-7: 157.8(HC]N); C-8: 164.1 (CHONH); 162.9, 151.2, 126.1, 116.2, 115.9,115.8 (PheC): C-9: 56.2 (OCH3), Ca: 15.7, 1J[119/117Sne13C] ¼ 621,593 Hz, Cb: 9.2 2J[119Sne13C] ¼ 46 Hz, 119Sn NMR:d (ppm) ¼ �199.7.

2.2.4. Diphenyltin(IV) [N0-(3-methoxy-2-oxidobenzylidene)-N-(oxidomethylene)hydrazine] (3)

Compound 3was prepared in the sameway as 1, using followingprecursors quantities: N0-(2-hydroxy-3-methoxybenzylidene)for-mohydrazide 0.58 g (3.0 mmol), diphenyltin(IV) dichloride 1.03 g(3.0mmol), triethylamine 0.84mL (6.0mmol) were reacted in 1:1:2ratio. Solid product was recrystallized from chloroform and n-hexane (4:1) mixture.

Yield 82%, m.p. 120e121 �C. Anal. Calc. for C21H18N2O3Sn(M ¼ 466): C, 54.23; H, 3.90; N, 6.02. Found: C, 54.21; H, 3.91; N,6.05%. EI-MS, m/z (%): [(C9H8N2O3)Sn(C6H5)2]þ 466 (100.0);[(C9H8N2O3) Sn(C6H5)]þ 389 (13.1); [(C9H8N2O3)Sn]þ 312 (11.4);[(C8H6NO2Sn)]þ 268 (3.1); [Sn(C6H5)2]þ 274 (4.1); [SnC6H5]þ 197(39.8); [Sn]þ 120(15.8). FT-IR (cm�1): 1604s, nC]N; 1074m, nNeN;589m, nSneO; 450w, nSneN. 1H NMR (ppm): H-3: 6.84 (dd, 1H,phenyl, 3JHeH ¼ 7.8), H-4: 6.74 (t, 1H, phenyl, 3JHeH ¼ 7.8), H-5: 7.06(dd, 1H, phenyl, 3JHeH ¼ 7.8), H-7: 8.64 [(s, 1H, CH]N, 3J(119Sne1H)¼ 51 Hz)], H-8: 7.66 (s, 1H, N]OCH), H-9: 3.88 (s, 3H, OCH3), H-b: 7.87e7.90 (m, 4H, phenyl), H-g, H-d: 7.40e7.49 (m, 6H, phenyl)13C NMR (ppm): C-7: 158.0 (HC]N); C-8: 163.7 (CHONH); 163.1,151.8, 126.1, 117.0, 116.7, 116.2 (PheC): C-9: 56.5 (OCH3), Ca: 138.5,Cb: 136.2 2J[119Sne13C]¼ 57 Hz, Cg: 129.0, 3J[119Sne13C]¼ 98 Hz, Cd:130.7 4J[119Sne13C] ¼ 18 Hz, 119Sn NMR: d(ppm) ¼ �338.

2.2.5. Di-n-octyltin(IV) [N0-(3-methoxy-2-oxidobenzylidene)-N-(oxi-domethylene)hydrazine] (4)

Compound 4 was prepared by refluxing N0-(2-hydroxy-3-methoxybenzylidene)formohydrazide 0.58 g (3.0 mmol) with dio-ctyltin(IV) oxide 1.09 g (3.0 mmol) in 100 mL dry toluene in 1:1ratio. Thewater formed during the reactionwas removed by DeaneStark apparatus. The yellow solution obtained was rotary evapo-rated under reduced pressure and the solid formed was recrystal-lized from chloroform and n-hexane (4:1) mixture (Scheme 1e).

Yield 75%, m.p. 70e72 �C. Anal. Calc. for C25H42N2O3Sn(M ¼ 538): C, 55.88; H, 7.88; N, 5.21 Found: C, 55.91; H, 7.86; N,5.23%. EI-MS, m/z (%): [(C9H8N2O3)Sn (C8H17)2]þ 538 (39.0);[(C9H8N2O3)Sn(C8H17)]þ 425 (15.9); [(C9H8N2O3)Sn]þ 312 (100.0);[(C8H6NO2Sn)]þ 268 (5.9); [Sn]þ 120 (4.3); [C4H9]þ 57 (36.8). FT-IR(cm�1): 1618s, nC]N; 1082m, nNeN; 590m, nSneO; 480w, nSneN. 1HNMR (ppm): H-3: 6.79 (dd, 1H, phenyl), H-4: 6.67 (t, 1H, phenyl,3JHeH¼ 7.8), H-5: 6.93 (dd,1H, phenyl, 3JHeH¼ 7.8), H-7: 8.61 [(s,1H,CH]N, 3J(119Sne1H)¼ 41 Hz)], H-8: 7.66 (s, 1H, N]OCH), H-9: 3.86(s, 3H, OCH3), H-a, H-b: 1.50e1.57 (m, 8H, 2CH2), H-g, H-g0 1.21e1.27 (br, 16H, 2CH2 CH2CH2 CH2), H-d0 0.86 (t, 6H, CH3, 3JHeH ¼ 7.8 ¼ 6.8 Hz), 13C NMR (ppm): C-7: 157.7 (HC]N); C-8: 164.0(CHONH); 162.8, 151.3, 126.0, 116.2, 116.0, 115.8 (PheC): C-9: 56.2(OCH3), Ca: 23.3, 1J[119/117Sne13C] ¼ 595, 571 Hz, Cb: 24.7 2J[119Sne13C] ¼ 38 Hz, Cg: 33.4, 3J[119Sne13C] ¼ 86 Hz, Cd: 29.2, C-a0: 29.1, C-b0: 31.8, C-g0: 22.7, C-d0: 14.1, 119Sn NMR: d(ppm) ¼ �200.

2.2.6. Di-tert-butyltin(IV) [N0-(3-methoxy-2-oxidobenzylidene)-N-(oxidomethylene)hydrazine] (5)

Compound 5was prepared in the sameway as 1, using followingprecursors quantities: N0-(2-hydroxy-3-methoxybenzylidene)for-mohydrazide 0.58 g (3.0 mmol), di-tert-butyltin(IV) dichloride0.91 g (3.0 mmol), triethylamine 0.84 mL (6.0 mmol) were reactedin 1:1:2 ratio. Solid product was recrystallized from chloroform andn-hexane (4:1) mixture.

Yield 80%, m.p. 120e121 �C. Anal. Calc. for C17H26N2O3Sn(M ¼ 426): C, 48.03; H, 6.16; N, 6.59 Found: C, 48.06; H, 6.20; N,6.61%. EI-MS, m/z (%): [(C9H8N2O3)Sn(C(CH3)3)2]þ 426 (11.6);[(C9H8N2O3)Sn]þ 312 (100.0); [(C8H6NO2Sn)]þ 268 (7.3); [Sn]þ 120(5.7); [C4H9]þ 57 (36.7). FT-IR (cm�1): 1616s, nC]N; 1078m, nNeN;582m, nSneO; 468w nSneN. 1H NMR (ppm): H-3: 6.80 (dd,1H, phenyl,3JHeH ¼ 8.1), H-4: 6.63 (t, 1H, phenyl, 3JHeH ¼ 7.8), H-5: 6.95 (dd, 1H,

S. Shujah et al. / Journal of Organometallic Chemistry 741-742 (2013) 59e66 61


phenyl, 3JHeH ¼ 7.8), H-7: 8.63 [(s, 1H, CH]N, 3J(119Sne1H)¼ 38 Hz)], H-8: 7.72 (s, 1H, N]OCH), H-9: 3.86 (s, 3H, OCH3), H-b: 1.34 (s, 18H, 2CH3), 3J(119/117Sne1H) ¼ 111, 106 Hz, 13C NMR(ppm): C-7: 159.5 (HC]N); C-8: 163.9 (CHONH); 162.5, 151.6, 126.3,

117.8, 116.4, 115.9 (PheC): C-9: 57.1 (OCH3), Ca: 40.9, 1J[119/117Sne13C] ¼ 581, 556 Hz, Cb: 29.6, 119Sn NMR: d(ppm) ¼ �289.

2.2.7. n-Butylchlorotin(IV) [N0-(3-methoxy-2-oxidobenzylidene)-N-(oxidomethylene) hydrazine] (6)

Compound 6was prepared in the sameway as 4, using followingprecursors quantities: N0-(2-hydroxy-3-methoxybenzylidene)for-mohydrazide 0.58 g (3.0 mmol), n-butylchlorotin(IV) dihydroxide0.74 g (3.0 mmol) were reacted in 1:1 ratio. Solid product wasrecrystallized from chloroform and n-hexane (4:1).

Yield 77%, m.p. 210e212 �C. Anal. Calc. for C13H17ClN2O3Sn(M ¼ 194): C, 38.70; H, 4.25; N, 6.94 Found: C, 38.68; H, 4.21; N,6.91%. EI-MS, m/z (%): [(C9H8N2O3) Sn(C4H9)Cl]þ 404 (43.2);[(C9H8N2O3)Sn(C4H9)]þ 369 (15.2); [(C9H8N2O3)SnCl]þ 347 (4.7);[(C9H8N2O3)Sn]þ 312 (100.0); [(C8H6NO2Sn)]þ 268 (9.1); [SnCl]þ

155 (29.7); [Sn]þ 120 (7.9); [C4H9]þ 57 (100.0). FT-IR (cm�1): 1620s,nC]N; 1082m, nNeN; 578m, nSneO; 470w, nSneN. 1H NMR (ppm): H-3:6.80 (dd, 1H, phenyl, 3JHeH ¼ 7.8), H-4: 6.66 (t, 1H, phenyl, 3JHeH ¼ 7.8), H-5: 6.94 (dd, 1H, phenyl, 3JHeH ¼ 7.8), H-7: 8.61 [(s, 1H,CH]N, 3J(119Sne1H)¼ 42 Hz)], H-8: 7.66 (s, 1H, N]OCH), H-9: 3.86(s, 3H, OCH3), H-a: 1.51e1.67 (m, 2H, 2CH2), H-b: 1.51e1.67 (m 2H,CH2), H-g: 1.34 (q, 4H, 2CH2, 3JHeH¼ 7.2), H-d: 0.87 (t, 6H, 2CH3, 3JHeH ¼ 7.2), 13C NMR (ppm): C-7: 1567.6 (HC]N); C-8: 162.2 (CHONH);159.5, 151.5, 126.5, 117.4, 117.2, 116.7 (PheC): C-9: 56.4 (OCH3), Ca:25.6, Cb: 28.5, Cg: 27.4, Cd: 14.2, 119Sn NMR: d(ppm) ¼ �201.

3. Results and discussion

3.1. Spectroscopic studies

In the IR spectrum of ligand (H2L) absorption bands wereobserved at 3175, 3385, 1691 and 1612 cm�1 due to the stretchingvibrations of the NeH, OeH, C]O and C]N groups, respectively.The significant differences in the IR spectra of ligand and complexes(1e6) were the disappearance of n(NeH), n(OeH) and n(C]O)

Table 1(CeSneC) angles (�) based on NMR parameters of organotin(IV) complexes 1e6.

Comp. No. Compound 1J(119Sn,13C) (Hz) 2J(119Sn,1H) (Hz) Angle (�)

1 Me2SnL 657 80 134.4 130.82 Et2SnL 621 72 131.2 121.83 Ph2SnL e e e e

4 Oct2SnL 595 e 134.4 e

5 t-Bu2SnL 581 e 133.1 e

6 BuClSnL e e e e

Fig. 1. Molecular structure of compound 1 (molecule a).

Table 2Crystal data and structure refinement parameters for compounds 1 and 3.

Complex No. 1 3

Empirical formula C22H28N4O6Sn2 C21H18N2O3SnFormula mass 681.91 465.10Crystal system triclinic monoclinicSpace group P-1 P21/na (�A) 6.688(5) 11.628(5)b (�A) 9.979(8) 11.156(5)c (�A) 18.66(15) 15.388(7)a (�) 99.06(14) 90.00b (�) 96.82(13) 108.70(6)g (�) 99.61(13) 90.00V (�A3) 1198.8(16) 1890.59(15)Z 2 4Crystal habit Block Blocksize (mm) 0.49 � 0.36 � 0.11 0.21 � 0.19 � 0.14T (K) 100 (1) 100 (1)r (g cm�3) 1.889 1.634m (Mo Ka) (mm�1) 21.29 13.75F(000) 672 928Total reflections 10,689 16,898Independent reflections 5645 4693For (Fo � 4.0 s (Fo)) 5042 3929R(F) ¼ (jjFoj � jFcjj)/jFojFor Fo > 4.0 s (Fo)

0.0300 0.0295

wR(F2) ¼ [[w(Fo2 � Fc2)2]/[w(Fo2)2]]1/2 0.1011 0.0700

Goodness-of-fit 1.183 1.048q range (�) 2.56e29.51 2.60e29.12Data/restrictions/params 5645/0/419 4693/0/316

Table 3Selected bond lengths (�A) and bond angles (�) of dimer di-nuclear molecule a and bof compound 1.

Molecule (1) (x ¼ 1) Molecule (2) (x ¼ 2)

Bond lengthsSnxeOx1 2.231(3) 2.233(2)SnxeOx2 2.186(3) 2.209(2)SnxeNx1 2.246(3) 2.246(3)SnxeOx3 2.585(4) 2.617(2)SnxeCx10 2.105(4) 2.113(4)SnxeCx11 2.108(3) 2.117(4)SnxeOx1 2.555(3) 2.557(3)Bond anglesOx1eSnxeOx2 152.72(10) 151.89(10)Ox1eSnxeNx1 81.16(10) 80.59(10)Ox1eSnxeCx10 92.85(13) 90.94(12)Ox1eSnxeOx3 135.97(9) 136.18(9)Ox2eSnxeNx1 71.63(10) 71.80(11)Ox2eSnxeCx10 92.65(13) 89.29(12)Ox2eSnxeOx3 71.32(9) 71.83(9)Nx1eSnxeCx11 97.81(12) 93.55(12)Nx1eSnxeOx3 142.75(10) 142.97(9)Cx10eSnxeOx1 83.02(12) 83.07(12)Cx11eSnxeOx1 84.01(12) 83.98(12)Ox1eSnxeOx3 62.29(9) 62.71(8)Ox1eSnxeCx11 91.65(13) 93.71(12)Ox2eSnxeCx11 90.11(13) 90.11(13)Nx1eSnxeCx10 97.55(13) 97.55(13)Nx1eSnxeOx1 154.87(10) 154.87(10)Cx10eSnxeCx11 164.48(14) 164.48(14)Cx10eSnxeOx3 80.44(12) 80.44(12)Ox1eSnxeOx1 73.73(9) 73.48(9)Cx11eSnxeOx3 86.01(11) 86.08(11)



bands due to deprotonation and enolization of the ligand, thussuggest the coordination of phenolic and enolic oxygens to thediorganotin(IV) moiety [11]. The n(C]N) band is shifted to lowerfrequency indicating the coordination of azomethine nitrogen to tincenter [12]. The band at 1055 cm�1 due to n(NeN) is shifted tohigher frequencies at 1068e1082 cm�1 in the spectra of organo-tin(IV) complexes (1e6). The increase in the frequency of this bandis attributed to an increase in bond length and decrease in repulsionof the lone pairs of electrons on the nitrogen atoms [13,14]. The IRbands observed in the regions of 578e590 cm�1 and 450e

480 cm�1 indicate the presence of SneO and SneN bonds,respectively [15].

The 1H NMR signals at 10.10, 11.66 and 8.66 ppm in the ligandare due to eOH, CHO and eNHN] protons. In the diorgnaotin(IV)complexes (1e6), all these signals were disappeared due to theconversion of amido form of the ligand to imine form (Scheme 1b)and subsequent deprotonation. The down field shift in the eCH]Nproton resonance to 8.61e8.64 ppm with 3J (119Sn, 1H) couplingconstant of 38e51 Hz confirmed the shift of electron density fromazomethine nitrogen to Sn atom. This coordination was furtherconfirmed by the single crystal X-ray structures of compounds 1and 3. No significant shift in the signal of methoxy protons wasobserved because of the monomeric nature of all complexes (1e6)in solution. This observation is in marked contrast to the solid statestructure in which the methoxy oxygen is coordinated to the tinatom (single crystal structure of complex 1). All the other protons ofthe ligand and the R groups bonded to Sn atom were appeared intheir expected regions. The 2J(119Sn, 1H) coupling constant ofcomplex 1 (80 Hz) and complex 2 (72 Hz) correspond to CeSneCangel of 130.8� and 121.8�, calculated using Lockhart’s equation(Table 1), q ¼ 0.0161 [2J]2 e 1.32 [2J] þ 133.4, support the pentacoordinated Sn atom in non-coordinating solvents [16].

The characteristic resonance peaks in the 13C NMR spectra ofcomplexes were recorded in CDCl3. In the 13C NMR spectrum of theligand, C-7 (HC]N) and C-8 (CHONH) were appeared at 143.3 and165.2 ppm, respectively. The complexes showed a down field shiftof phenyl carbon resonances, especially C-1 due to the formation ofSneO bond [17]. The 1J [119Sne13C] coupling constants were used toestablish the coordination around tin in solution [18]. The calcu-lated coupling constants (556e657 Hz) further support the idea ofpenta coordinated Sn atom in solutions for complexes 1e6 [19]. Thesignals for rest of the carbons were observed as expected.

The 119Sn NMR resonances for dimethyl, diethyl, di-tert-butyland di-octyl complexes were observed at �164, �200, �289and �200 ppm, respectively. For diphenyl complex the anisotropicshielding effects and pi interactions caused the signal to appearat �338 ppm. The 119Sn NMR chemical shifts for all the complexes(1e6) demonstrated the presence of five coordinate tin(IV) cores[12,20e22].

3.2. X-ray crystal structure of complexes (1and 3)

The asymmetric unit of centrosymmetric dinuclear complex (1)consists of half of the dimer. The molecular structure and atomicnumbering scheme for one of the di-nuclear molecule is given inFig.1. The crystallographic data, selected bond lengths and angles ofthe dinuclearmolecules ‘a’ and ‘b’ of complex 1 are listed in Tables 2and 3. Each molecule possesses a dinuclear centrosymmetric

Fig. 2. (a) Supramolecular single wavy layer of compound 1 mediated by H13/N22(2.643 �A), O22/H17 (2.448 �A), p/H17 (2.777 �A) and H28/N12 (2.594 �A) intermo-lecular non-covalent interactions. (b) Two wavy layers are connected through p/p(3.282 �A) interactions (blue dotted lines). (For interpretation of the references to colorin this figure legend, the reader is referred to the web version of this article.)

Fig. 3. Molecular structure of compound 3.

Table 4Selected bond lengths (�A) and bond angles (�) of complex 3.

Bond lengthsSneO(1) 2.067(17) SneC(16) 2.119(2)SneO(2) 2.124(18) N(1)eN(2) 1.410(3)SneN(1) 2.158(2) N(1)eC(7) 1.291(3)SneC(10) 2.120(2) N(2)eC(8) 1.290(4)Bond anglesO(1)eSneO(2) 157.84(8) C(10)eSneC(16) 124.93(9)O(1)eSneN(1) 84.04(7) SneO(1)eC(1) 132.92(15)O(1)eSneC(10) 96.99(8) SneO(2)eC(8) 112.53(18)O(1)eSneC(16) 94.38(8) SneN(1)eN(2) 115.64(16)O(2)eSneN(1) 74.18(8) SneN(1)eC(7) 128.39(16)O(2)eSneC(10) 95.03(8) SneC(10)eC(11) 120.20(2)O(2)eSneC(16) 93.90(8) SneC(10)eC(15) 120.00(2)N(1)eSneC(10) 112.28(9) SneC(16)eC(17) 120.52(18)N(1)eSneC(16) 122.43(9) SneC(16)eC(21) 120.53(18)



dimeric structurewith a fourmembered planar Sn2O2 ring. The SneO bond distances are 2.231(3) and 2.555(3) �A for molecule a and2.233(2) and 2.557(3) �A for molecule b. Each dinuclear moleculecontains two formula unit bridged together through phenolic andmethoxy oxygen atoms. The Sn(x) atom and O(x1), C(x1), C(x6),C(x7), N(x1) atoms forma sixmembered ring,while Sn, O(x2), C(x8),N(x1), N(x2) and Sn(x), O(x1), C(x1), C(x2), O(x3) atoms form fivemembered rings. Each (CH3)2Sn(IV)moiety is bonded to four oxygenatoms and a nitrogen forming O4NC2 core around the tin atom. Theligand is non-planar probably due to the steric requirements of thefive- and six-membered rings. The geometry around the Sn atomcan be characterized as a distorted pentagonal bipyramidal with themethyl groups in apical positions with C(x10)eSnxeC(x11) angle of164.48(14)�. The smallest angle within the plane formed by the

O4NC2 core in molecule a and b is O(x1)eSnxeO(x3) 62.29(9)� and62.71(8)�, respectively, whereas the other angles are N(x1)eSnxeO(x2) {71.63(10)� and 71.80(11)�], O(x2)eSnxeO(x3) {71.32(9)� and71.83(9)�}, O(x1)eSnxeO(x1) {73.73(9)� and 73.48(9)o} andO(x1)eSnxeN(x1) {81.16(10)� and 85.59(10)�}. The SnxeO(x1) {2.231(3)and 2.233(2)�A} and SnxeO(2) {2.186(3) and 2.209(2)} bond lengthsare less than the sum of van derWaals radii of the Sn and O (3.68�A).The SnxeN(x1) interaction is strong enough to be called as bondbecause the bond distance (2.246(3)�A) is well below the sum of thevan derWaals radii of the Sn and N (3.75�A). Packing diagram offer awavy supramolecular structure to compound 1 mediated byH13/N22 (2.643 �A), O22/H17 (2.448 �A), p/H17 (2.777 �A) andH28/N12 (2.594 �A) intermolecular non-covalent interactions(Fig. 2a). The adjacent wavy layers are connected to one another viap/p (3.282 �A) interactions (Fig. 2b). These interactions are com-parable with the literature values [23e29].

The single-crystal X-ray diffraction (XRD) study of complex 3shows its mononuclear nature which is in marked contrast to thecomplex 1 (Fig. 3). This may be due to the bulky phenyl groups that

Fig. 4. Two Y-shaped chains connected together via H9�/p (2.813 �A) and H19/p (2.864 �A) interactions. Hydrogens of phenyl rings not involve in non-covalent interactions areomitted for clarity.

Fig. 5. (a) Showing point of contact (p/p 3.385 �A) between two differently orientedY-shaped cleft units. (b) Overall view of two Y-shaped cleft units.

Table 5Antileishmanial activityaed of ligand and its organotin(IV)complexes.

Compound IC50 (mg/mL) � S.D

H2L 21.8 � 0.01(1) 3.06 � 0.02(2) 6.41 � 0.06(3) 2.03 � 0.03(4) 8.25 � 0.11(5) 1.26 � 0.02(6) 3.91 � 0.03

a Test organism: Leishmania major (DESTO).b Standard drug: Amphotericin B (mg/mL) � S.D ¼ 0.50 � 0.02.c Incubation period: 72 h.d Incubation temperature: 22 � 1 �C.

Table 6Antiurease activity of ligand and its organotin(IV) complexes.aed

Compound No. H2L (1) (2) (3) (4) (5) (6)

% Inhibition 48.8 62.6 18.1 35.5 42.6 36.1 30.5IC50 � S.D [mM] e 101.0 � 2.16 e e e e e

a Sample Concentration [mM] 0.5.b Standard: thiourea, IC50 � SEM [mM], 21.0 � 0.11.c Proposed implications of inhibitor: acute ulcer.d IC50 reported for those compounds whose % inhibition is more than 55%.



hinder the coordination of methoxy oxygen to the Sn atom. Here,the tin center is coordinated by five donor atoms, two oxygens anda nitrogen from the ligand, and two carbon of the phenyl groups.The calculated s of 0.5 suggests that geometry is a midway betweensquare-pyramidal and trigonal bipyramidal geometry. The distor-tion is mainly due to the rigidity of the chelating rings together

with the large covalent radius of tin(IV). The nitrogen (SneN1:2.158(2) E) and the carbon atoms (SneC10: 2.120(17) and SneC16:2.119(18) E) occupy the equatorial plane, whereas the oxygen atoms(SneO1: 2.067(2) and SneO2: 2.124(2) E) are in axial positions,with O1eSneO2 bond angle of 157.84(8)�. The Sn(1)eN(1) distance(2.158(2) E) is close to the sum of the non-polar covalent radii(2.15 E), but is considerably less than the sum of the van der Waalsradii (3.75 E) indicating a strong tinenitrogen interaction (Table 4).1D Y-shaped chain (Fig. 4) is formed by the interactions of H9�with p electronic cloud of N2CHO moiety [H9�/p (2.813�A)]. Twoneighboring Y-shaped chains are cleft together via edge-to-faceCH/p interactions (2.864 �A). These two cleft chains are heldtogether with next similar unit by p/p (3.385 �A) contacts asshown in Fig. 5a and b, thus generating 1D microporous channelswhen viewed along b-axis (Fig. 6). Such material may find appli-cations in separation, storage, transport, and catalysis [3].

4. Biological activities

4.1. Antileishmanial activity

The ligand and complexes (1e6) were screened against thepathogenic Leishmania major using Amphotericin B (0.50 mg/mL)as standard drug (Table 5). All the studied organotin(IV) derivativeswere found more active than corresponding free ligand whichimply the vital role of Sn atom in the antileishmanial activity. The

Fig. 7. Antibacterial activity of H2L and its organotin(IV) derivatives against various bacteria.

Fig. 6. Microporous channels in the structure of compound 3 when viewed along b-axis.

Fig. 8. Antifungal activity of H2L and its organotin(IV) derivatives against various fungi.



tert-dibutyltin(IV) and diphenyltin(IV) derivatives (5 and 3) showedcomparable activity to the standard drug. This can be attributed totheir high lipophilic character. Two factors, planarity and low mo-lecular weight, which facilitate smooth diffusion are presumablyturn into high activity of the diphenyltin(IV) complex (3). The samefactor seems responsible for the lowest activity of the dioctyltin(IV)complex (4).

4.2. Antiurease activity

In vitro antiurease activity at 0.5 mM concentration against jackbean urease was undertaken for free ligand and its complexes ac-cording to the literature protocol [30], using thiourea as the stan-dard inhibitor having an IC50� S.D [mM] value of 21�0.01 (Table 6).As evident from the results, the parent ligand and its organotin(IV)derivatives are moderate urease inhibitors except compound 1which shows promising activity with IC50 � S.D [mM] value of101 � 2.16. This is probably due to its ability to establish secondaryinteractions with the active site of enzyme.

4.3. Antibacterial activity

The parent ligand and complexes (1e6) also show their inhibi-tory effect against two gram-positive (Bacillus subtilis, Staphylo-coccus aureus) and four gram-negative bacteria (Escherichia coli,Shigella flexenari, Pseudomonas aeruginosa, Salmonella typhi), usingImipenem (C12H17N3O4S) as a standard drug for comparison (Fig. 7).In general, the diorganotin(IV) derivatives were found more activeagainst gram-positive bacteria than gram negative bacteria. Thisfact can be attributed to ease of permeation of the complexes in theformers owing to the simplicity of the cell membrane structure.

The most probable reason for high antibacterial activity oforganotin derivatives than the parent ligand is due to the reductionin the polarity of the Sn(IV) atom upon complexation with theligand. This reduction in polarity is because of the partial sharing ofpositive charge of Sn(IV) with donor groups and also due to p-electrons delocalization within the whole chelating ring. As aconsequence the lipophilic nature of the central Sn atom increases,which in turn enhances the permeation of the complexes throughthe lipid layer of the cell membrane.

4.4. Antifungal activity

The % inhibition of the synthesized compounds was studiedin vitro against six human pathogenic fungal strains includingyeasts (Candida albicans ATCC 2192, Candida glabrata ATCC 90030),dermatophytes (Microsporum canis ATCC 9865, Trichphyton long-ifusus ATCC 22397), opportunistic molds (Aspergillus flavus ATCC1030 and Fusarium solani ATCC 11712) using the agar tube dilutiontest (Fig. 8). The ligand was found active only against Aspergillusflavis with inhibitory action almost equal to the standard drugAmphotericin B. Compound 3 was highly active against Candidaglaberata, and fairly active against C. albicans. Trichophyton long-ifusus was the only strain resistive to all complexes.

5. Conclusion

In summing up, six new diorganotin(IV) derivatives of N0-(2-hydroxy-3-methoxybenzylidene)formohydrazide ligand were syn-thesized and characterized. Based on X-ray single crystal analysis,these compounds were either mononuclear in which Sn atom is indistorted trigonal bipyramidal geometry (3) or homobimetallicwith

each Sn atom in pentagonal bipyramidal environment (1). This dualnature can be attributed to the steric factor in the former. Packingdiagram offered a wavy supramolecular layer structure to com-pound 1 mediated by H13/N22 (2.643 �A), O22/H17 (2.448 �A),p/H17 (2.777 �A) and H28/N12 (2.594 �A) intermolecular non-covalent interactions. For compound 3, 1D Y-shaped chain wereformed by H9�/p interactions. Two neighboring Y-shaped chainswere cleft together via edge-to-face CH/p interactions (2.864 �A).The combination of various such cleft units via p/p (3.385 �A)contacts generated 1Dmicroporous channels when viewed along b-axis. Such material may find applications in separation, storage,transport, and catalysis. These complexes presented good anti-leishmanial, antiurease, antibacterial and antifungal activities andthe significance of Snwas clearly visible. Compound3 and5have thepotential to be used as antileishmanial agents due to their compa-rable activity with standard antileishmanial drug Amphotericin B.

Appendix A. Supplementary material

CCDC 688811 and 698810 contain the supplementary crystal-lographic data for this paper. These data can be obtained free ofcharge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.

References

[1] C.N.R. Rao, S. Natarajan, R. Vaidhyanathan, Angew. Chem. Int. Ed. 43 (2004)1466e1496.

[2] S.A. Bourne, J. Lu, A. Mondal, B. Moulton, M.J. Zaworotko, Angew. Chem. Int.Ed. 40 (2001) 2111e2113.

[3] R. Garcia-Zarracino, H. Höpfl, J. Am. Chem. Soc. 127 (2005) 3120e3130.[4] H.L. Singh, A.K. Varshney, Appl. Organomet. Chem. 15 (9) (2001) 762e768.[5] K. Srinivasan, P. Michaud, J.K. Kochi, J. Am. Chem. Soc. 108 (1986) 2309e2320.[6] M. Nath, P.K. Saini, Dalton Trans. 40 (2011) 7077e7121.[7] S. Shuja, Zia-ur-Rehman, N. Muhammad, S. Ali, N. Khalid, M.N. Tahir,

J. Organomet. Chem. 696 (2011) 2772e2781.[8] C. Ma, Y. Han, R. Zhang, J. Inorg. Organomet. Polym. Mater. 17 (2007) 541e546.[9] W.F.L. Armarego, C. Chai, Purification of Laboratory Chemicals, fifth ed., But-

terworth, Oxford, 2003.[10] A.L. Spek, PLATON (Version of October 2007), Program for the Automated

Analysis of Molecular Geometry (A Multipurpose Crystallographic Tool),University of Utrecht, The Netherlands, J. Appl. Crystallogr. 36 (2003) 7.

[11] D.K. Deya, B. Samantaa, A. Lyckab, L. Dahlenburg, Z. Naturforsch. 58b (2003)336e344.

[12] C. Pettinari, F. Marchetti, R. Pettinari, D. Martini, A. Drozdov, S. Troyanov,Inorg. Chim. Acta 325 (2001) 103e114.

[13] H. Yin, J. Cui, Y. Qiao, Polyhedron 27 (2008) 2157e2166.[14] M.A. Ali, A.H. Mirza, A.L. Tan, L.K. Wei, P.V. Bernhardt, Polyhedron 23 (2004)

2037e2043.[15] H.D. Yin, M. Hong, G. Li, D.Q. Wang, J. Organomet. Chem. 690 (2005) 3714e

3719.[16] T.P. Lockhart, W.F. Manders, Inorg. Chem. 25 (1986) 892e895.[17] V. Barba, E. Vega, R. Luna, H. Höpfl, H.I. Beltrán, L.S. Zamudio-Rivera,

J. Organomet. Chem. 692 (2007) 731e739.[18] T.P. Lockhart, W.F. Manders, E.M. Holt, J. Am. Chem. Soc. 108 (1986) 6611e

6616.[19] T.P. Lockhart, F. Davidson, Organometallics 6 (1987) 2471e2478.[20] J.M. Rivera, H. Reyes, A. Cortés, R. Santillan, P.G. Lacroix, C. Lepetit, K. Nakatani,

N. Farfán, Chem. Mater. 18 (2006) 1174e1183.[21] N. Farfán, T. Mancilla, R. Santillan, A. Gutiérrez, L.S. Zamudio-Rivera,

H.I. Beltrán, J. Organomet. Chem. 689 (2004) 3481e3491.[22] H. Reyes, C. Garcıa, N. Farfán, R. Santillan, P.G. Lacroix, C. Lepetit, K. Nakatani,

J. Organomet. Chem. 689 (2004) 2303e2310.[23] R. Caspar, C. Cordier, J.B. Waern, C. Guyard-Duhayon, M. Gruselle, P. Le Floch,

H. Amouri, Inorg. Chem. 45 (2006) 4071e4078.[24] G.R. Desiraju, Acc. Chem. Res. 35 (2002) 565e573.[25] J. Moussa, H. Amouri, Angew. Chem. Int. Ed. 47 (2008) 1372e1380.[26] M. Mascal, Chem. Commun. (1998) 303e304.[27] C. Janiak, J. Chem. Soc. Dalton Trans. (2000) 3885e3896.[28] S.M. Draper, D.J. Gregg, E.R. Schofield, W.R. Browne, M. Duati, J.G. Vos,

P. Passaniti, J. Am. Chem. Soc. 126 (2004) 8695e8701.[29] C. Janiak, T.G. Scharmann, Polyhedron 22 (2003) 1123e1133.[30] M. Serwar, T. Akhtar, S. Hameed, K.M. Khan, ARKIVOC vii (2009) 210e221.


Author's personal copy Bioactive hepta-and penta-coordinated supramolecular diorganotin(IV) Schiff...

Documents

Transcript of Author's personal copy Bioactive hepta-and penta-coordinated supramolecular diorganotin(IV) Schiff...