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

Quim. Nova, Vol. 39, No. 1, 19-25, 2016 http://dx.doi.org/10.5935/0100-4042.20150171 Muhammad Ashfaqa,#, Muhammad Mahboob Ahmedb, Salama Shaheena, Rukhsana Tabussama and Gildardo Riverac,* a Department of Chemistry, The Islamia University of Bahawalpur, Bahawalpur, Pakistan b Institute of Chemical Sciences, Bahauddin Zakariya University, Multan, Pakistan c Centro de Biotecnología Genómica, Instituto Politécnico Nacional, Reynosa, 88710, México Artigo SYNTHESIS AND BIOLOGICAL ACTIVITY OF NEW SERIES OF ORGANOTIN(IV) ESTERS WITH N,N‑DIACETYLGLYCINE Recebido em 27/05/2015; aceito em 14/09/2015; publicado na web em 11/11/2015 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 OTCs 1 and 3 was <200 cm-1 exhibiting trans-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 and 7 (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 and 7) is clearly due to their tetrahedral. The OTCs 4 and 5 exhibited excellent activity against M. minimum and good activity against T. castaneum. LD50 of all the compounds were determined and OTCs 4, 5 and 7 were found to be active. Keywords: N,N-diethylglycine; organotin(IV); complexes; antibacterial; insecticide. INTRODUCTION EXPERIMENTAL 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 and tribolium castaneum pests insects, respectively.18 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 record 1H, 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 3 O *e-mail: # alternative e-mail: O 4 N O 2 1 OH Scheme 1. Structure of N, N-diacetylglycine (NNDAG) 20 Ashfaq et al. 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, 1610sym msp; C_O (ether linkage): 1080 sp. 1 H 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%). Quim. Nova [ ( C 4H 9) 2S n { C H 2N ( C H 3C O ) 2} ] .+ 3 4 6 ( 3 7 % ) ; [ S n { O 2C 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%). 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 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-stannoxane-di-N-acetylglycine (dimer) (2): [{(C4H9)2SnO2- CCH2N(COCH3)2}2O]2: N,N-diacetylglycine1 g (6.29 mmol) w (...truncated)