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Química Nova

versão impressa ISSN 0100-4042versão On-line ISSN 1678-7064

Quím. Nova vol.39 no.1 São Paulo jan. 2016

http://dx.doi.org/10.5935/0100-4042.20150171 

Artigo

SYNTHESIS AND BIOLOGICAL ACTIVITY OF NEW SERIES OF ORGANOTIN(IV) ESTERS WITH N,N-DIACETYLGLYCINE

Muhammad Ashfaqa  # 

Muhammad Mahboob Ahmedb 

Salama Shaheena 

Rukhsana Tabussama 

Gildardo Riverac  * 

aDepartment of Chemistry, The Islamia University of Bahawalpur, Bahawalpur, Pakistan

bInstitute of Chemical Sciences, Bahauddin Zakariya University, Multan, Pakistan

cCentro de Biotecnología Genómica, Instituto Politécnico Nacional, Reynosa, 88710, México

ABSTRACT

A bioactive N,N-diacetylglycine (NNDAG) and new organotin(IV) complexes (OTCs) (1-7) were synthesized. Spectroscopic techniques were employed to characterize NNDAG and OTCs. FTIR was employed to verify N,N protection of glycine by acetyl groups. The disappearance of υ(OH) at 3000-2600 cm-1 showed de-protonation of free ligand. The Δυ 150<200 cm-1 of OTCs 4-7 verified bidentate coordination with tetrahedral geometry. The Δυ of OTCs1 and 3 was <200 cm-1 exhibitingtrans -octahedral geometry while OTC 2 dimer was assigned a unique sinusoidal view. The 1H NMR spectra of OTCs verified their synthesis by de-protonation of NNDAG and no chemical shift was found downfield for carboxylic acid proton. The 13C, 119Sn NMR and Mass spectrometric data also supported FTIR and 1H NMR descriptions. The OTCs 4, 5, 6 and7 (500 ppm) proved twice as active against Escherichia coli as the standard antibiotic enoxacin (1000 ppm). The promising property of the OTCs (4, 5, 6 and7) is clearly due to their tetrahedral. The OTCs 4and 5 exhibited excellent activity against M. minimum and good activity against T. castaneum.LD50 of all the compounds were determined and OTCs4, 5 and 7 were found to be active.

Keywords: N,N-diethylglycine; organotin(IV); complexes; antibacterial; insecticide

INTRODUCTION

Organotin(IV) complexes (OTCs) have been investigated on account of broad spectrum of their uses in daily field of life. Particularly, organotin(IV) esters have been given importance on account of their applications in the fields of pesticide, antibacterial, and antitumor agents, wood preservatives, among others.1-4

On the other hand, amino acids and their derivatives show antioxidant activity and enhanced hormonal immunity which inhibits lactic acid level. Interestingly, glycine acts as antioxidant as well as improves hormonal immune system. Therefore, ligand N,N-diacetylglycine has been synthesized on the basis of potential of glycine described in the literature.3-5

The organotin(IV) esters have been given special attention in the recent years due to their excellent pharmacological importance.5,6 Moreover, organotin esters of amino acids and N-protected amino acids have been reported as biocides for example, tricyclohexyltin(IV) alaninate is used as fungicide and bactericide and trialkyltin(IV) derivatives of both amino acids and N-acetylamino acids play as intermediate role for the synthesis of peptides.7-9 In the last two decades very little literature is found on the organotin(IV) esters of N-protected amino acids.10-14 On account of broad spectrum of applications of organotin(IV) carboxylates as well N-protected amino acids and interesting finding of our earlier research work here we report the spectroscopic characterization, and preliminary biological investigation of OTCs of N,N-diacetylglycine.15-17 The toxicity bioassays were also studied in addition to antibacterial and insecticidal bioassays of all 1-7 OTCs against Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumonia and Salmonella typhi strains with clinical interest and Monomorium minimum, mealybug andtribolium castaneum pests insects, respectively.18

EXPERIMENTAL

Materials and instruments

Glycine, di-n-butyltin(IV) oxide, triphenyltin(IV) chloride, tricyclohexyltin(IV) chloride and triethylamine of Merck Chemicals were used as such. The di- and tri-benzyltin(IV) chloride were prepared according to reported procedure.19 All organic solvents were dried as per reported procedures.20 The FTIR spectra were carried out on a JASCO 302-ghgA spectrometer by KBr sampling technique from 4000-400 cm-1. Finnigan MAT 12 spectrometer was used to record EI-MS spectra for the determination of % m/z. Bruker AM 400 NMR was used to record1H, 13C and 119Sn spectra at HEJ Institute of Chemical Sciences, University of Karachi. The chemical shifts were reported relative to (CH3)4Si and (CH3)4Sn signal used as internal standards. Enoxacin as reference drug was used to determine antibacterial activity using disc diffusion method. Half maximal lethal dose (LD50) of compounds was determined by Brine Shrimp hatching method as reported.21

Synthesis of N,N-diacetylglycine (NNDAG)

Glycine 5 g (66.7 mmol) and acetyl chloride 10.0 mL (133.4 mmol) were added in 100.0 mL dioxane and refluxed for 6 hours of reaction time. The solvent was removed under vacuum and the product was obtained in n -hexane (Scheme 1).22

Scheme 1 Structure of N, N-diacetylglycine (NNDAG) 

Yield: 60%, m.p. : 220 ºC, Solubility: H2O, CH3OH, CH3CH2OH, and CHCl3. CHN analysis (%) antipyrene: C, 45.2 (45.2); H, 5.7 (5.7) and N, 8.7 (8.8), theoretical values are given in the parenthesis. FTIR (KBr) cm-1: OH: 3000-2600 b; CO (acetyl): 1770 mw; CO (carbonyl): 1730asym,sp, 1610symmsp; C-O (ether linkage): 1080 sp.1H NMR (CDCl3) δ: OH: 9.7 s; H-2: 3.90 s; H-3: 2.35 s.13C NMR (CDCl3) δ: C-1: 169.22; C-2: 42.45; C-3: 171.90; C-4: 21.68. MS m/z: [HO2CCH2N(COCH3)2]+M+ 159 (10%); [OCCH2N(COCH3)2]+ 142 (15%); [CH2N(COCH3)2].+ 114 (100%); [CH2N- (COCH3)]+ 71 (27%); [CH2NCH3)]+ 56 (38%); [CH2N]+28 (45%).

Synthesis of organotin(IV) complexes

Diorganotin(IV) complexes (1 and 2) have been synthesized by taking dibutyltin(1V) oxide and N,N-diacetylglycine in 2:1 (monomer) and 1:l (dimer) molar ratios in ethanol and toluene (3:1, v/v) with the azeotropical removal of water. The appropriate molar ratio (2:1/1:1) of silver salt of NNDAG and the corresponding organotin(IV) chloride were refluxed for 6 h in chloroform to synthesized compounds 3-7. The solvent were removed under vacuum. The synthesized compounds were recrystallized in different solvents. OTCs have been synthesized by adopting the procedures as cited in literature and given in Scheme 2.2,15-17,23

Scheme 2 Synthesis of organotin(IV) complexes 

The compounds are soluble in organic solvents and stable on room temperature. The analytical data is accordance to the proposed stoichiometric ratio of complexes.

Dibutyltin(IV)-di-N,N-diacetylglycine(monomer) (1): [(C4H9)2Sn{O2CCH2N(COCH3)2}: N,N-diacetylglycine 1 g (6.29 mmol) was reacted with dibutyltin(IV) oxide 0.47 g (3.14 mmol) in 2:1 ratio in 66.0 mL ethanol and 33.0 mL toluene. Recrystallized in chloroform and ethanol in 1:2 ratio. Yield: 78%. m.p.: 202-204 ºC. Solubility: CH3OH, CH3CH2OH, CHCl3and CCl4. CHN analysis (%) antipyrene: C, 43.7 (43.7); H, 6.2 (6.2) and N, 5.8 (5.10), theoretical values are given in the parenthesis. FTIR (KBr) υ(cm-1): CO(acetyl): 1765 mw; CO (carbonyl): 1620asym,sp, 1470sym msp; Δυ:150; C-O(ether linkage): 1025 sp; Sn-C: 517 w; Sn-O: 498 sp.1H NMR (CDCl3) δ: H-2: 3.82 s; H-4: 2.35 s; H-a: 1.04 t (7); H-b: 1.59 m; H-c: 1.26 m; H-d: 0.90 t (7).13C NMR (CDCl3) δ: C-1: 172.73; C-2: 40.10; C-3: 168.50; C-4: 21.78; C-a: 23.50; C-b: 27.13; C-c: 26.48; C-d: 13.55.119Sn NMR (CH3)4Sn:-190.35. MS m/z: [(C4H9)2Sn{O2CCH2N(CH3CO)2}2].+M+ 548 (4%); [(C4H9)Sn{O2CCH2N(CH3CO)2}2]+491 (53%); [(C4H9)2Sn{O2CCH2N(CH3CO)2}]+390 (100%); [(C4H9)2Sn{CH2N(CH3CO)2}].+346 (37%); [Sn{O2C-CH2N(CH3CO)2}2].+400 (21%); [Sn{CH2N(CH3CO)2}2]+312 (27%); [(C4H9)2Sn]+232 (15%); [(C4H9)Sn]+ 175 (30%); [Sn/SnH]+119/120 (5%); [CH3CH2- CH2]+ 43 (55%); [CH3CH2]+ 29 (33%); [CH3]+ 15 (14%).

Dibutyltin(IV)-di-stannoxane-di-N-acetylglycine (dimer) (2): [{(C4H9)2SnO2-CCH2N(COCH3)2}2O]2: N,N-diacetylglycine1 g (6.29 mmol) was reacted with dibutyltin(IV) oxide 0.94 g (6.29 mmol) in 2:1 ratio in 66.0 mL ethanol and 33.0 mL toluene. Recrystallized in chloroform and n-hexane in 1:2 ratio. Yield: 72%. m.p. : 220 ºC. Solubility: CH3OH, CH3CH2OH, CHCl3 and CCl4. CHN analysis (%) antipyrene: C, 41.3 (41.3); H, 6.4 (6.4) and N, 3.4 (3.4). FTIR (KBr) υ(cm-1): CO (acetyl): 1755 w; CO (carbonyl): 1608asym,sp, 1455sym msp; υΔ: 143; C-O(ether linkage): 1018 sp; Sn-C: 522 m; Sn-O: 490 sp.1H NMR (CDCl3) δ: H-2: 4.00 s; H-4: 2.36 s; H-a: 1.91 t (7); H-b: 1.61 m; H-c: 1.27 m; H-d: 0.94 t (7).13C NMR (CDCl3) δ: C-1: 173.73; C-2: 41.19; C-3: 170.44; C-4: 22.51; C-a: 29.50; C-b: 27.59; C-c: 26.63; C-d: 14.10.119Sn NMR (CH3)4Sn: -210.4, -216.2. MS m/z: [{(C4H9)2SnO2CCH2N(CH3CO)2}2O]2+ M+; [(C4H9)2SnO2CCH2N(CH3CO)2]+390 (58%); [(C4H9)2SnCH2N(CH3CO)2].+346 (38%); [(C4H9)SnO2CCH2N(CH3CO)2]+333(16%); [SnO2CCH2N(CH3CO)2].+276 (34%); [SnCH2N(CH3CO)2]+ 232 (45%); [(C4H9)2Sn]+ 229 (100%); [Sn/SnH]+ 119/120 (13%); [CH3CH2CH2]+ 43 (70%); [CH3CH2]+ 29(27%); [CH3]+ 15 (42%).

Dibenzyltin(IV)-di-N,N-diacetylglycine (3): [(C6H5CH2)2Sn{O2CCH2N(COCH3)2}2]: N,N-diacetylglycine 1 g (6.29 mmol) and AgNO3 1.06 g (6.29 mmol) were reacted with dibenzyltin(IV) chloride 1.16 g (3.14 mmol) in 2:1 ratio in 100.0 mL chloroform. Recrystallized in chloroform and benzene in 1:2 ratio. Yield: 79%. m.p. : 166 ºC. Solubility: DMSO, CH3OH, CH3CH2OH, CHCl3 and CCl4. CHN analysis (%) antipyrene: C, 50.5 (50.5); H, 4.9 (4.9) and N, 4.5 (4.5). FTIR (KBr) υ(cm-1): CO (acetyl): 1760 m sp; CO (carbonyl): 1635asym,sp, 1462sym msp; Δυ: 173; C-O (ether linkage): 1032 m;Sn-C: 515 m; Sn-O: 505 w.1H NMR (CDCl3) δ: H-2: 3.80 s; H-4: 2.10 s; H-a: 2.87 s; H-c: 7.05 t (7); H-d: 7.37 m; H-e: 7.80 t (7).13C NMR (CDCl3) δ: C-1: 171.34; C-2: 39.23; C-3: 169.89; C-4: 21.62; C-a: 20.14; C-b: 136.19; C-c: 127.60; C-d: 130.34; C-e: 125.53.119Sn NMR (CH3)4Sn: -127.5. MS m/z (%): [(C6H5CH2)2Sn{(O2CCH2N(CH3CO)2}2]+M+ 616 (7%); [(C6H5CH2)Sn{O2CCH2N(CH3CO)2}2]+525 (77%); [(C6H5CH2)2Sn{O2CCH2N(CH3-CO)2}].+458 (100%); [Sn{O2CCH2N(CH3CO)2}2]+434 (10%); [(C6H5CH2)2Sn- {CH2N(CH3CO)2}]+ 414 (57%); [Sn{CH2N(CH3CO)2}2]+346 (41%); [(C6H5CH2)2Sn].+ 300 (15%); [(C6H5CH2)Sn]+ 209 (55%); [Sn/SnH]+ 119/120 (10%); [C6H5CH2]+ 91 (48%); [C6H5]+ 77 (18%).

Tribenzyltin(IV)-N,N-diacetylglycine (4): [(C6H5CH2)3-SnO2CCH2N(COCH3)2]: N,N-diacetylglycine 1 g (6.29 mmol) and AgNO3 1.06 g (6.29 mmol) were reacted with tribenzyltin(IV) chloride 2.64 g (6.29 mmol) in 1:1 ratio in 100.0 mL chloroform. Recrystallized in chloroform and ethanol in 1:2 ratio. Yield: 82%. m.p. : 191 ºC. Solubility: (C2H5)2O, CH3CH2OH and CHCl3. CHN analysis (%) antipyrene: C, 58.9 (58.9); H, 5.3 (5.3) and N, 2.5 (2.5) the calculated values are in the parenthesis. FTIR (KBr) υ(cm-1): CO (acetyl): 1753 m w; CO (carbonyl): 1660 asym,sp, 1488sym msp; Δυ: 188; C-O (ether linkage): 1050 m; Sn-C: 510 m; Sn-O: 498 w.1H NMR (CDCl3) δ: H-2: 3.92 s; H-4: 2.25 s; H-a: 2.64 s; H-c: 7.73 t (7); H-d: 7.29 m; H-e: 7.91 t.13C NMR (CDCl3) δ: C-1: 168.66; C-2: 40.25; C-3: 170.35; C-4: 21.57; C-a: 19.87; C-b: 138.10; C-c: 129.18; C-d: 128.43; C-e: 124.93.119Sn NMR (CH3)4Sn: -142.71. MS m/z: [(C6H5-CH2)3SnO2CCH2N(COCH3)2]+M+ 549 (7%); [(C6H5CH2)2SnO2-CCH2N(COCH3)2]+458 (100%); [(C6H5CH2)3Sn]+ 391 (72%); [(C6H5- CH2)SnO2-CCH2N(COCH3)2].+ 367 (50%); [SnO2CCH2N(COCH3)2].+276 (40%); [(C6H5CH2)2-Sn]+300 (57 %); [SnCH2N- (COCH3)2]+ 232 (45%); [(C6H5CH2)- Sn]+ 209 (52%); [Sn/SnH]+ 119/120 (8%), [CH2N(COCH3)2]+ 114 (38%); [C6H5CH2]+ 91 (34%); [C6H5]+ 77 (12%); [CH2N- (COCH3)]+71 (30%).

Tributyltin(IV)-N,N-diacetylglycine (5): [(C4H9)3SnO2CCH2N-(COCH3)2]: N,N-diacetylglycine 1 g (6.29 mmol) and AgNO3 1.06 g (6.29 mmol) were reacted with tributyltin(IV) chloride 2.04 g (6.29 mmol) in 1:1 ratio in 100.0 mL chloroform. Recrystallized in chloroform. Yield: 85%. m.p. : 105 ºC. Solubility: CH3OH, CH3CH2OH, CHCl3and THF. CHN analysis (%) antipyrene: C, 48.2 (48.2); H, 7.8 (7.8) and N, 3.1 (3.1). FTIR (KBr) υ(cm-1): CO (acetyl): 1765 m w; CO (carbonyl): 1674asym,sp, 1515sym msp; Δυ: 159; C-O (ether linkage): 1043 m; Sn-C: 517 m; Sn-O: 505 w.1H NMR (CDCl3) δ: H-2: 3.77 s; H-4: 2.55 s; H-a: 0.76 t; H-b: 1.39 m; H-c: 1.25 m; H-d: 0.88 t (7).13C NMR (CDCl3) δ: C-1: 172.95; C-2: 40.11; C-3: 170.61; C-4: 21.71; C-a: 16.50; C-b: 27.12; C-c: 26.30; C-d: 13.56.119Sn NMR (CH3)4Sn: 123.7. MS m/z: [(C4H9)3SnO2CCH2N(COCH3)2]+M+ 447 (4%); [C4H9)2SnO2CCH2N(COCH3)2]+390 (100%); [C4H9)SnO2CCH2N(COCH3)2]+333 (35%); [C4H9)3Sn]+ 289 (85%); [SnO2-CCH2N(COCH3)2].+276 (39%); [(C4H9)2Sn]+ 233 (22%); [SnCH2N(COCH3)2].+232 (49%); [(C4H9)Sn]+ 175 (45%); [CH2N(COCH3)2]+114 (37%); [Sn/SnH]+ 119/120 (5%); [CH2N(COCH3)]+71 (17%); [CH3CH2]+ 29 (25%); [CH3]+ 15 (8%).

Triphenyltin(IV)-N,N-diacetylglycine (6): [(C6H5)3SnO2CCH2N(COCH3)2]: N,N-diacetylglycine 1 g (6.29 mmol) and AgNO3 1.06 g (6.29 mmol) were reacted with triphenyltin(IV) chloride 2.42 g (6.29 mmol) in 1:1 ratio in 100.0 mL chloroform. Recrystallized in chloroform and ether in 1:2 ratio. Yield: 78%. m.p. : 126 ºC. Solubility: (C2H5)2O, CH3CH2OH, CHCl3 and THF. CHN analysis (%) antipyrene: C, 56.7 (56.7); H, 4.5 (4.5) and N, 2.7 (2.7), the calculated values are in the parenthesis. FTIR (KBr) υ(cm-1): CO (acetyl): 1745 m w; CO (carbonyl): 1656asym,sp, 1471sym msp; Δυ: 185; C-O (ether linkage): 1027 m; Sn-C: 547 m; Sn-O: 512 w.1H NMR (CDCl3) δ: H-2: 3.80 s;H-4: 2.78 s; H-b: 7.64. t (7); H-c: 7.28 m; H-d: 7.15 t (7).13C NMR (CDCl3) δ: C-1: 172.26; C-2: 40.73; C-3: 170.45; C-4: 21.37; C-a: 135.61; C-b: 133.54; C-c: 131.18; C-d: 130.39.119Sn NMR (CH3)4Sn: -99.29. MS m/z: [(C6H5)3SnO2CCH2N(COCH3)2]+M+ 507 (5%); [(C6H5)2SnO2CCH2-N(COCH3)2]+430 (100%); [(C6H5)SnO2CCH2N(COCH3)2]+353 (21%); [(C6H5)3Sn]+ 349 (25%); [SnO2CCH2N(COCH3)2]+276 (32%); [(C6H5)2Sn]+ 272 (30%); [SnCH2N(COCH3)2].+ 232 (38%); [CH2N(COCH3)2]+ 114 (43%); [(C6H5)Sn]+ 195 (36%); [Sn/SnH]+119/120 (17%); [(C6H5)]+ 77 (24%). [CH2N-(COCH3)]+71 (17%).

Tricyclohexyltin(IV)-N,N-diacetylglycine (7): [(C6H11)3-SnO2CCH2N(CH3CO)2]: N,N-diacetylglycine 1 g (6.29 mmol) and AgNO3 1.06 g (6.29 mmol) were reacted with tricylohexyltin(IV) chloride 2.64 g (6.29 mmol) in 1:1 ratio in 100.0 mL chloroform. Recrystallized in chloroform. Yield: 76%. m.p. : 112 ºC. Solubility: (C2H5)2O, CH3OH, CH3CH2OH and CHCl3. CHN analysis (%) antipyrene: C, 54.7 (54.7); H, 7.8 (7.8) and N, 2.6 (2.6). FTIR (KBr) υ(cm-1): CO (acetyl): 1747 mw; CO (carbonyl): 1645asymsp, 1490sym msp; Δυ: 155; C-O (ether linkage): 1035 m; Sn-C: 540 m; Sn-O: 518 w.1H NMR (CDCl3) δ: H-2: 3.76 s; H-4: 2.81 s; H-a: 1.14. t (7); H-b: 1.35 m; H-c: 1.55 m; H-d: 1.81m.13C NMR (CDCl3) δ: C-1: 172.17; C-2: 39.35; C-3: 168.71.; C-4: 21.57; C-a: 22.69; C-b: 28.89; C-c: 26.44; C-d: 25.50.119Sn NMR (CH3)4Sn: 9.1. MS m/z: [(C6H11)3SnO2CCH2N(COCH3)2]+M+ 525 (3%); [(C6H11)2SnO2CCH2N- (COCH3)2]+ 442 (100%); [(C6H11)3Sn]+ 367 (75%); [(C6H11)SnO2CCH2N(COCH3)2]+340 (44%); [(C6H11)2Sn]+ 284 (52%); [SnO2CCH2N(COCH3)2]+276 (30%); [SnCH2N- (COCH3)2].+ 232 (22%); [CH2N(COCH3)2]+ 114 (27%); [C6H11Sn]+ 201 (42%); [Sn/SnH]+119/120 (15%); [C6H11]+ 83 (30%); [CH2N(COCH3)]+ 71 (11%).

Bioactivity studies

Antibacterial bioassay

For the purpose antibacterial activity, glassware was sterilized at 150 °C for 20 minutes before use. The microbial specimens were accumulated as swabs of pus, blood, urine, sputum, siemen etc. from the Bahawal Victoria Hospital (BVH) of Bahawalpur. E. coli, P. aeruginosa, K. pneumoniaand S. typhi were isolated and used for the purpose of antibacterial activity. MacConkey agar (10.0 g) and C.L.E.D mediums (10.0 g) in 250.0 mL distilled water and autoclaved which is used for preparation of Petri plates. The strains were inoculated and incubated at 37 °C. The ligand and OTCs methanolic solutions of 200 and 500 ppm were prepared. The pregnant discs were soaked in test solutions and dried and autoclaved as well. All the prepared petri plates were, incubated at 37 °C for 24 h.

Insecticidal bioassay

Monomorium minimum, mealybug andtribolium castaneum insects were selected to determine % toxicity rate as per reported method.15 While in vitro LD50 values were analyzed by Probit statistical method.21

Brine shrimp bioassay

The lethality assays on the OTCs were carried out. LD50 was determined according to the literature.24

RESULTS AND DISCUSSIONS

FTIR study

FTIR successfully employed to verify 2:1 molar ratio of acetyl chloride and glycine respectively. The 3500-3100 cm-1 region was remained transparent for N-H moiety that is the indication of N,N-protection of glycine by acetyl groups whereas the OH broad band appeared at 3000-2600 cm-1and C-H stretching of CH3 of acetyl group occurred at 2961 cm-1. The important υ(CO)sym.υ(CO)asym. υ(Sn-C), and υ(Sn-O) were observed in the region as reported in the literature.24 The reaction among {R2Sn- (IV)}2+/{R3Sn(IV)}+ and ligand was confirmed by the absence of the broad band of υ(OH) at 3000-2600 cm-1 showing the de-protonation of free ligand and presence of υ(Sn-O) in the range of 520-400 cm-1 given the indication of ligand metal complexation.25-29 The involvement of the COO group in the coordination can be concluded by the shifting of υ(COO) band of the complexes to lower wave number as compared to that of the free ligand.30 The difference between the υ(COO)asym and υ(COO)sym bands, Δυ(COO) of bidentate carboxylate group is below 200 cm-1 while unidentate carboxylate is above 200 cm-1.31 The characteristic υ(COO)asym and υ(COO)symvibrations of the carboxylic group appeared at 1655 ± 20 and 1490 ± 20 cm-1, respectively, for tri-organotin(IV) complexes4-7. The Δυ(COO) vibrations values are about 170 ± 15 cm-1 indicating the covalent bonding of the metal-oxygen bond.32 The increasing of asymmetric and decreasing of symmetric stretching values of compounds than ligand while Δυ in the complexes was also larger than the Δυ of ligand, suggested that SnR3 groups are bidentate coordinated to the oxygen of COO group of NNDAG which is also similar to the reported general pattern of coordination: υasym(OTCs) < υasym(ligand)υsym(OTCs) < υsym (ligand)Δυ(OTCs) > Δυ (ligand).16,33,34 The Sn-C stretching frequency at 510, 517, 547, and 540 cm-1 for benzyl, butyl, phenyl and cyclohexyl groups suggested the presence of all three organic groups in the equatorial positions of the polymeric trigonal bipyramidal structure in Figure 1.34,35

Figure 1 Polymeric trigonal bipyramidal structure of tri-organotin(IV) complexes (4-7

The characteristic υ(CO)asym. and υ(CO)sym.vibration of monomeric compounds 1 and 3 appeared at 1620±15 and 1462±8 cm-1, respectively,33-35 while Δυ value of CO was < 200 cm-1 exhibit bidentate bonding to NNDAG withtrans -octahedral geometry (Figure 2).16,36 Very sharp band at 634 cm-1of compound 2 recommend Sn-O-Sn-O ring dimeric networking with endo and exo Sn(IV) atoms that proposed the hexa coordination geometry given in Figure 3 and the general observed pattern for υCO in accordance with literature is as follow: υasym(comp.)asym(lig.), <υsym(comp.)sym(lig.), Δυ(comp.)>Δυ (lig.).15,16,36

Figure 2 Octahedral geometry of monomer 1, and3 

Figure 3 Sinusoidal view of compound 2 exhibiting weakly bonded two dimer units 

1H NMR study

The CH3CO protons of NNDAG resonated at 2.30-1.5 ppm and O-H proton shifted at downfield region 11.3 ppm indicating the N,N-protected of glycine. Interestingly no N-H chemical shift was observed in the 1H NMR spectra of ligand. It is facile and more convenient route that can be used to protect glycine at NN site is not found in the literature. The 1H NMR study of OTCs (1-7) successfully verified their synthesis by de-protonation of NNDAG ligand and no chemical shift was found at downfield for carboxylic acid proton. All data is given in experimental part. The -CH2 chemical shifting is found at 3.71-4.00 ppm while CH2 of benzyl at 2.64-2.87 ppm is seen as reported.16,36-39 The proton signal of phenyl, cyclohexyl and aromatic proton of benzyl were found at range 7.32-8.23 ppm. Two molar stoichiometric ratio of NNDAG was used to synthesize OTCs 1, and 3 are confirmed by1H NMR data and the literature evidences supported octahedral geometry (Figure 2).31,40

In case of compounds 2 the endo- and exocyclic Sn(IV) centers were difficult to identify as reported in literature because there is no distinct signals of butyl group attached to endo- and exocyclic tin(IV) centers giving the equal status to endo and exo tin(IV) centers.16,17,41,42 It is obviously due to six coordination sites of each endo and exotin(IV) atom with chemically equivalent nature. Hence it might be purposed that dimer have a ladder topology with sinusoidal view from one unit to other that linked with each other through oxygen atom of carboxylate of one unit to Sn(IV) atom of other unit as we reported previously and shown in Figure 3.15,31

For triorganotin(IV) compounds (TOTCs) 4-7, the 1H NMR spectra (data can be seen in experimental part) show the chemical shift that verifying the tetrahedral structure in CDCl3 solvent and established the coordination of oxygen of carboxylic group to tin(IV) centers (Figure 4) with support of literature as well.41,42

Figure 4 Tetrahedral geometry of triorganotin(IV) complexes (4-7

13C NMR study

The 13C NMR spectra of NNDAG data can be seen in experimental part. According to Scheme 1, all the carbon atoms 1, 2, 3, 4 were resonated at the specified chemical shifts as reported in the literature.16,17,31 The C-1of COOH gave 13C signal at 169.22 ppm and whereas the C-4 of CH3 at 21.68 ppm is confirming the synthesis of NNDAG. All the OTCs have COO values at down field up to 173.73 ppm as well confirmed carboxylate carbon (C-1) bonding to tin(IV) atom. The 13C chemical shift of butyl, phenyl, benzyl and cyclohexyl (C-a, C-b, C-c, C-d, C-e) were observed at range 13.55-27.13, 130-140 and 22-30 ppm, respectively.16,17,41

119Sn NMR study

The 119Sn chemical shifts of the tribenzyl-, tributyl-, triphenyl-, and tricyclohexyl-tin(IV) carboxylates were at -142.71, 123.7, -99.29, and 71.21 ppm indicating a tetrahedral environment.43,44 While dibutyl- and dibenzyl-tin(IV) complexes exhibited 119Sn chemical shift at -190.35 and -238.32 ppm respectively confirming thetrans octahedral arrangement (Figure 2).45 While pair of119Sn resonance peaks of equal intensities at -210.4 and -216.2 were confirming the endo- and exo-cylic status of tin(IV) respectively that substantiated the sinusoidal view of compound 2 given in Figure 3.15,23

Mass spectral study

Molecular ion peak at m/z 159 is the actual mass of ligand NNDAG is true evidence of existence of two moles of acetyl groups at N terminal of glycine is the most important step toward synthesis of NNDAG through this new and facile route to protect N terminal. In the organotin(IV) derivatives major fragmentation was observed due to the loss of the ligand moiety from the tin(IV) derivatives. Successive loss of R groups (Bu, Bz, Ph) during fragmentation was happened until the Sn4+ ion was resulted. In an alternative route, R groups were eliminated first and next one molecule of CO2 removed as per revealed in literature.23,46 Further, the remaining substituents were defragmented on same pattern as given in Schemes 3 and 4.

Scheme 3 Fragmentation pattern of triorganotin(IV) complexes 

Scheme 4 Fragmentation pattern of diorganotin(IV) complexes 

Antibacterial activity

The results related to antibacterial activity is given in Table 1. The OTCs 4, 5,6 and 7 (500 ppm) is promising more than two fold activity than the standard antibiotic enoxacin (1000 ppm). The compounds1, 2 and 3 reflected good activity at 500 ppm dose whereas the NNDAG is too less promise as given in selected petri plate of E. coli (Figure 5) and the comparative zone of inhibition of OTCs 1-7 versus bacterial strains is given in Figure 6. It is obvious that promising property of OTCs (4, 5,6 and 7) is due to tetrahedral geometry of tin(IV) atom that bears CO oxygen free for coordinate with corresponding metal ions of enzymatic system of strains as well the tin(IV) metal ions has more vacant coordination site to block the metabolites to protein synthesis along with ribosomal sub units of bacterial strains.47-50 From this study following trend of OTCs may be concluded for the antibacterial inhibition: TOTCs (alkyl) > TOTCs (aryl) > dimer > monomer > ligand.

Table 1 Antibacterial bioassay 

Compounds (500 ppm) E. coli P. aeruginosa K. pneumoniae S. typhi
Inhibition (mm) Results Inhibition (mm) Results Inhibition (mm) Results Inhibition (mm) Results
NNDAG 10 + 8 + 7 + 9 +
1 18 ++ 15 ++ 13 ++ 14 ++
2 22 +++ 18 ++ 16 ++ 15 ++
3 15 ++ 13 ++ 12 ++ 14 ++
4 25 +++ 22 +++ 20 ++ 19 ++
5 39 ++++ 33 +++ 29 +++ 28 +++
6 35 ++++ 30 +++ 27 +++ 30 +++
7 32 ++++ 31 ++++ 23 ++ 25 ++
*Standard 28 +++ 29 +++ 30 +++ 34 ++++

where - = no result, + = insignificant, ++ = significant, +++ = more significant, ++++ = most significant.

*enoxacin = 1000 ppm doze

Figure 5 Selected experimental petri plates against E. coli 

Figure 6 Comparison of antibacterial activity 

Insecticide activity

The OTCs 4 and 5 have excellent activity againstM. minimum and T. castaneum but remained insignificant against Mealy bug . The LD50 value and the results are given in Table 2.

Table 2 Insecticidal bioassay 

*Compounds Type of insects (% Death) μg/mg
Monomorium minimum Tribolium castaneum Mealy bug
1000 700 400 100 10 LD50 Result 1000 700 400 100 10 LD50 Result Result
NNDAG 10 10 10 - - - - 10 10 - - - - - -
1 80 70 60 40 30 140.48 + 80 60 60 40 20 100.00 + -
2 100 100 80 70 20 28.18 ++ 60 60 40 40 30 350.80 ++ -
3 80 80 80 80 40 35.48 ++ 90 90 60 60 10 79.43 ++ -
4 100 100 90 80 60 6.60 ++ 90 80 70 70 40 35.48 ++ -
5 100 100 90 70 50 1.00 +++ 100 100 80 60 30 28.18 +++ -
6 90 90 60 30 30 39.81 ++ 70 70 50 50 20 141.48 ++ -
7 90 80 80 80 30 39.81 ++ 80 70 50 40 20 100.00 ++ -

*compounds and flour are in w/w % ratio; where: - = no result, + = insignificant, ++ = significant, +++ = more significant, ++++ = most significant

Cytotoxicity study

Cytotoxicity was evaluated using brine shrimp lethality assay (Table 3). LD50 of all compounds were carried out against brine shrimp larvae using standard statistical procedure Probit analysis. OTCs 4, 5 and7 were found to be active.

Table 3 Brine shrimp LD50 bioassay 

Compounds % Death at dose (μg/mg) LD50 Results
1000 700 400 100 10
NNDAG 20 20 10 - - - +
1 40 30 20 20 20 - ++
2 90 80 70 70 60 7.94 ++++
3 30 30 10 10 10 - ++
4 90 80 80 80 60 3.16 ++++
5 100 100 100 90 70 3..98 ++++
6 100 100 70 70 50 10.00 ++
7 90 90 90 90 60 3.16 +++

where: ++++ = more significant, +++ = significant – = no activity

CONCLUSIONS

A new series of monomeric organotin(IV) esters 1, 3 dimeric organotin(IV) esters 2 and triorganotin(IV) esters 4-7, were synthesized with N,N-diacetylglycine. All the complexes were more active than the ligand and some were even more active than standard used. The following trend may be concluded for the antibacterial inhibition; OTCs (alkyl) > OTCs (aryl) > monomeric organotin(IV) esters > monomer organotin(IV) esters > ligands, the bacterial strains were inhibited as: E. coli > P. aeruginosa > K. pneumonia > S. typhi. While the rate of toxicity and LD50 values have following order: T. castaneum > M. minimium >Mealybug in cotton plant. LD50 against Brine Shrimp larvae were found to be active for dimer and inactive for monomer while OTCs esters have very narrow range of LD50 values of 3-10 µg/mg.

ACKNOWLEDGEMENTS

The authors are thankful to Department of Chemistry (Inorganic Ph. D. Lab) The Islamia University of Bahawalpur-Pakistan for providing all research facilities. HEJ Research Institute, University of Karachi for spectroscopic analysis and Quaid-e-Azam Medical College Bahawalpur for antibacterial activities are gratefully acknowledged. Gildardo Rivera Sánchez wish to thank the financial support received from the Comisión de Operación y Fomento de Actividades Académicas (COFAA-Instituto Politécnico Nacional), and the Programa de Estímulos al Desempeño de los Investigadores (EDI-Instituto Politécnico Nacional).

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Received: May 27, 2015; Accepted: September 14, 2015

*e-mail: gildardors@hotmail.com

#alternative e-mail:chashfaqiub@yahoo.com

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