Synthesis and Characterization of Transition Metal Complexes of Some Thiosemicarbazide ligands by Aml Mahmoud Madyan Mansour By Aml Mahomud Madyan Mansour Outlines 1- Introduction a) Structure of the thiosemicarbazides and their metal complexes. b) Applications of the thiosemicarbazide. 2- Experimental a) Materials. b) Synthesis of the ligands. c) Synthesis of the metal complexes. d) Characterization of the ligands and their metal complexes using different analytical and spectroscopic techniques. e) Biological studies 3 - Results and Discussion a) General b) Identification of the ligands c) Identification of the metal complexes i) Infrared spectra ii) Electronic spectra and magnetic measurements iii) Conductivity measurements v) TGA analysis iv) ESR spectra 4- Biological studies 5- Conclusions a) Structure of the thiosemicarbazides and their metal complexes Thiosemicarbazides and their metal complexes have attracted a special attention due to their : 1- carcinostatic properties against a spectrum of transplaced neoplasm. 2- activity against certain types of tumors. 3- anti-tuberclostatic activity and medicinal properties. 4- analytical reagents in micro-determination of some metal ions. 5- separation of some pollutants and precious ions. 6- antifungal, antimicrobial and antitiumor, biological activities. 7- radiopharmaceuticals applications. 8- semiconductors applications. Experimental a) Materials Ethyl benzoate ester Methylchloro formate ester Diethyl-3,5-pyridine dicarboxylate ester Hydrazine monohydrate Ammonium thiocyanate Solvents 1- Organic: 2- Msetal salts Co(II), Ni(II), Cu(II), Zn(II), Fe(III),Cr(III), and Cd(II) ions were used as nitrate salts. VOSO 4.H 2 O and UO 2 (OAc) 2.2H 2 O. b) Synthesis of the ligands H4L3H4L3 HL 1 HL 2 Ligands 1-) Synthesis of theN-thiosemicarbazide, HL 1, and HL 2 ligands 2-) Synthesis of Bis-thiosemicarbazide, H4L3 C) SYNTHESIS OF THIOSMICARBAZIDE METAL COMPLEXES + Reflux Methanol h Complexes M2+ or M3+ HL 1 HL 2 H 4 L 3 M 2+ = Ni(II), Co(II), Cu(II), Zn(II), Cd(II), VO(IV) or UO 2 (VI) M 3+ = Fe(III) or Cr(III) Biological studies Using agar cup method in DMF of 2 mg/mL and 1 mg/mL samples against: Gram-positive bacteria: S. aureus and S. pyogenes Gram-negative bacteria: P. fluorescens and P. phaseolicola. Fungi : F. oxysporum and A. fumigatus e) Biological studies D) Characterization of the ligands and their metal complexes using different analytical and spectroscopic techniques. Elemental (C, H, N and S) analyses. Elemental (C, H, N and S) analyses. Determination of the metal ions using EDTA Determination of the metal ions using EDTA 1 H-NMR spectra 1 H-NMR spectra Mass spectra Mass spectra Infrared spectra Infrared spectra Electronic spectra Electronic spectra ESR spectra ESR spectra Magnetic measurements Magnetic measurements Molar conductance measurements Molar conductance measurements Thermal gravimetric analysis (TGA) Thermal gravimetric analysis (TGA) Melting points Melting points 1- Three series of metal complexes were synthesized and characterized. 2- The chelating sites are: (NS) or (NO) for HL 1, HL 2 and (NO) or (SNNS) for H 4 L 3 ligand. 3- Different geometrical arrangements viz. octahedral; tetrahedral; square planar and square pyramid geometries. 4- Application of the metal complexes against bacteria and fungi. a) General Figure 1. Infrared spectra of the HL 1 ligand and its precursors. Figure 2. Mass spectrum of the N-benzoylthiosemicarbazide, HL 1, ligand. Scheme 1. Mass fragmentation pattern of the Bis- thiosemicarbazide, H 4 L 3, ligand. Figure 3. 1H-NMR spectra for HL 1. 1 / 2 HCl ligand, and its [Zn(L) 2 ].2H 2 O (5) complex Chemical Shifts ( ) HL 1 HL 2 H4L3H4L3H4L3H4L3Assignments ___ [s, 1H, SH] 7.4, 7.5 and , 7.59 [m, 5H, Ar-H] (HL), [m, 10H, Ar-H] 9.33* 9.10 *, 9.40* 8.66*, 8.97* and 9.50* [s, 1H, NH] 10.5* [s, 2H, NH 2 ] (HL), [s, 4H, NH 2 ] Table 1. 1 H-NMR Elemental Analyses Calcd. (found) Calcd. (found) C H N S M C H N S MColor Yield (%) M.PC Molecular formula formula(M.Wt) Ligand / Complex __13.7(11.8)19.68(19.63)4.49(4.58)45.0 (44.8 ) White(75.3)182 C 8 H 9.5 N 3 OSCl 0.5 (213.47) (HL 1. 1 / 2 HCl) 13.3(13.5)7.29(7.36)16.1(16.2)4.66(4.55)37.0(36.8) Olive green (43.4)>260 C 16 H 24 N 6 O 6 S 2 Co (519.46) [Co(L 1 ) 2 (H 2 O) 2 ].2H 2 O 11.6(13.5)7.61(7.68)15.3(15.5)5.16(4.93)39.5(39.7) Dark green (58.2)>260 C 18 H 28 N 6 O 6 S 2 Ni (547.27) [Ni(L 1 ) 2 (H 2 O) 2 ].2CH 3 OH 14.6(15.7)7.86(8.81)17.0(16.9)3.19(3.28)26.3(26.4)Darkblue(59.1)>260 C 8 H 13 N 5 O 8 SCu (410.23) [Cu(HL 1 )(NO 3 ) 2 ].CH 3 OH 13.9(13.7)6.38(6.79)11.1(11.2)4.82(4.97)28.7(28.7) Brown orange (43.4)>260 C 12 H 24 N 5 O 11 SFe (502.26) [Fe(L 1 )(NO 3 ) 2 (H 2 O) 2 ].2C 2 H 5 OH 10.8 (11.6) 13.0(13.1)17.1(17.0)4.12(4.16)39.2(39.2)White(63.3)>260 C 16 H 20 N 6 O 4 S 2 Zn (484.88) [Zn(L 1 ) 2 ].2H 2 O 21.2(21.2)12.1(12.0)15.91(15.91)3.72(3.60)36.3(36.3)White(48.6)>260 C 16 H 19.5 N 6 O 3.5 S 2 Cd (528.40) [Cd(L 1 ) 2 ].1 1 / 2 H 2 O __14.6(14.2)9.56(9.69)4.13(4.30)27.3(27.2) Dark blue (45.4)>260 C 10 H 18 N 3 O 9 S 2 V (439.33) [VO(HL 1 )(SO4)(H 2 O)].2CH 3 OH __8.78(8.69)11.5(11.6)3.31(3.22)26.3(26.4)Brown(38.3)>260 C 16 H 24 N 6 O 8 S 2 U (730.56) [UO 2 (L 1 ) 2 (H 2 O) 2 ].2H 2 O Table 2. Physical and analytical data for N-benzoylthiosemicarbazide, ligand and its metal complexes c) Identification of the metal complexes i) Elemental (C, H, N and S) an alyses. Elemental Analyses Calcd. (found) Calcd. (found) C H N S M C H N S MColor Yield (%) M.PC Molecular formula formula(M.Wt) Ligand / Complex __19.1(19.3)25.1(25.6)4.48(4.36)21.5(21.4)White(74.05)145 C 3 H 7.5 N 3 SCl 0.5 O (167.63) (HL 2. 1 / 2 HCl) 11.3(11.6)12.3(12.4)21.6(21.5)3.48(3.32)13.9(13.8)Black(54.06)>260 C 6 H 18 N 8 S 2 O 12 Co (516.93) [Co(HL 2 ) 2 (NO 3 ) 2 ].2H 2 O 10.8(10.9)11.7(11.8)20.5(20.7)3.86(3.81)13.2(13.3) Dark olive green(42.21)>260 C 6 H 21 N 8 S 2 O 13.5 N i (543.86) [Ni(HL 2 ) 2 (NO 3 ) 2 ].3 1 / 2 H 2 O 15.8(15.6)7.99(8.11)17.4(17.5)3.74(3.69)14.9(14.8) Bluish gray (48.40)>260 C 5 H 15 N5SO 10 Cu (400.5) [Cu(HL 2 )(NO 3 ) 2 ].2CH 3 OH 17.5(17.3)8.35(8.61)18.6(18.4)2.93(3.11)12.8(12.6)White(60.93)>260 C 4 H 11 N 5 SO 9 Zn (374.73) [Zn(HL 2 )(NO 3 ) 2 ].CH 3 OH 29.1(29.5)8.30(8.42)18.1(18.2)1.81(1.83)9.3(9.2)White(46.55)>260 C 3 H 7 N 5 SO 8 Cd (385.4) [Cd(HL 2 )(NO 3 ) 2 ] [Cd(HL 2 )(NO 3 ) 2 ] __14.7(14.8)19.3(19.4)4.61(4.52)16.5(16.4)Black(55.92)>260 C 6 H 20 N 6 S 2 O 9 V (433.80) [(VO)(L 2 ) 2 ].4H 2 O Table 3. Physical and analytical data for N- methylformylthiosemicarbazide, and its metal complexes Elemental Analyses Calcd. (found) Calcd. (found) C H N S M C H N S MColor Yield (%) M.PC Molecular formula formula(M.Wt) Ligand / Complex __13.7(13.4)21.0(21.2)4.08(4.01) 54.1 (54. 4) 54.1 (54. 4)White(74.05)229 C 21 H 19 N 7 S 2 O 2 (465.01) H4L3H4L3H4L3H4L3 13.3(13.9)7.29(7.55)14.3(14.6)4.21(4.13)31.47(31.15) Dark green (49.55)>300 C 23 H 37 N 9 S 2 O 16 Co 2 (876.86) [Co 2 (H 2 L 3 )(NO 3 ) 2 (H 2 O) 4 ]. 2H 2 O.2CH 3 OH 11.6(11.8)7.61(7.68)14.9(14.6)3.92(3.75)32.48(32.67)Palebrown(50.45)>300 C 23 H 33 N 9 S 2 O 14 Ni 2 (840.42) [Ni 2 (H 2 L 3 )(NO 3 )2(H 2 O) 4 ].2CH 3 OH 14.6(14.9)7.86(8.81)15.4(15.9)3.56(3.44)33.91(33.45) Dark blue (51.15)>300 C 23 H 29 N 9 S 2 O 12 Cu 2 (814.08) [Cu 2 (H 2 L 3 )(NO 3 ) 2 (CH 3 OH) 2 (H 2 O) 2 ] 9.32(10.3)6.38(6.79)18.7(18.4)3.17(3.27) (42.35) Brown orange (56.15)>300 C 21 H 19 N 8 S 2 O 6 Fe (598.81) [Fe(H 2 L 3 )(NO 3 )( H 2 O )] 10.8 (10.4) 13.0(13.1) 16.1 (16.75) 4.49(4.37) (41.55) White(49.15)>300 C 21 H 27 N 7 S 2 O 6 Zn (600.37) [Zn(H 2 L 3 )].4H 2 O 17.3(17.7)12.1(12.0)15.1(15.6)4.17(4.42) (38.65) White(46.55)>300 C 21 H 27 N 7 S 2 O 6 Cd (647.4) [Cd(H 2 L 3 )].4H 2 O __14.6(14.2)17.8(17.6)5.10(5.6)45.90(45.87) Dark blue (63.20)>300 C 21 H 28 N 7 S 2 O 7.5 V (548.94) [(VO)(H 2 L 3 )].H 2 O __8.78(8.69)8.53(8.12)2.26(2.18)26.11(26.44)Brown(51.20)>300 C 28 H 26 N 7 S 2 O 11.5 U 2 ( ) [(UO 2 ) 2 (H 2 L 3 )(CH 3 COO) 2 ].1 1 / 2 H 2 O Table 4. Physical and analytical data for of Bis-thiosemicarbazide, H 4 L 3, and its metal complexes Other bands Other bands (M-N) (C-S)(C=O)(N-C=S)(NH)Ligand/complexes 1261 vs, (C=S). ________ 1701 s 2053 m 3300 s, 3145 s 3145 s HL 1. 1 / 2 HCl ____ 444 w 699 m 1661 w ____ 3297 m, 3182 m [Co(L 1 ) 2 (H 2 O) 2 ].2H 2 O (1) ____ 455 w 697 m ________ 3332 m, 3283 m [Ni(L 1 ) 2 (H 2 O) 2 ].2CH 3 OH (2) 1431 s,1351 vs, 831 m; Unidentate NO w 706 m 1667 m ____ 3293 s, 3188 s [Cu(HL 1 )(NO 3 ) 2 ].CH 3 OH (3) 1434 s, 1354 vs, 837 m; Unidentate NO 3 -. Unidentate NO 3 -.____ 688 m ________ 3297 m, 3194 m [Fe(L 1 )(NO 3 ) 2 (H 2 O) 2 ].2C 2 H 5 OH (4) ____ 467 w 698 m 1586 m ____ 3294 m, 3183 m [Zn(L 1 ) 2 ].2H 2 O (5) ____ 448 w 711 m ________ 3313 m, 3279 m [Cd(L 1 ) 2 ].1 1 / 2 H 2 O (6) 930 m, (V=O); 1270 s, 1075 m, 625 m, 449 w, bidentate SO 4 - group. 432 w 708 m 1675 s ____ 3282 s, 3182 s [VO(HL 1 )(SO 4 )(H 2 O)].2CH 3 OH (7) 901vs, (UO 2 ). 444 w 704 m 1609 m ____ 3240 m, 3113 s [UO 2 (L 1 ) 2 (H 2 O) 2 ].2H 2 O (8) Table 5. Characteristic vibrational frequencies of the HL 1 ligand and its metal complexes and their assignments. ii) Infrared spectra Other bands (M-O)(M-N)(C=S)(C=O)(N-C=S)(NH) (NH 2 ) Ligand/complexes 3298s, (NH 3 ). ________ 828 m 1718 vs 2065 m 3172 m ___ HL 2. 1 / 2 HCl HL 2. 1 / 2 HCl 1494 vs, 1306 m, 1144 m; Unidentate NO w 459 w 756 m 1598 vs 2082 m 3172m 3402 s, 3298 s [Co(HL 2 ) 2 (NO 3 ) 2 ].2H 2 O (9)(9)(9)(9) 1483 m, 1313 vs, 1104 m; Unidentate NO w 444 w 760 m 1596 vs 2092 w 3157m 3424 s 3307 s [Ni(HL 2 ) 2 (NO 3 ) 2 ].3 1 / 2 H 2 O (10) 1464 m, 1252m, 1138 m; Unidentate NO w 450w 764 m 1608 s 2157 m 3168 s 3371,s 3264 s [Cu(HL 2 ) (NO 3 ) 2 ].2CH 3 OH (11) 1489 vs,1292 vs, 1117 m; Unidentate NO m; Unidentate NO w 457 w 743 s 1600 vs 2060 w 3177 m 3413 s, 3313 s [Zn(HL 2 )(NO 3 ) 2 ].CH 3 OH (12) 1495 vs,, 1327 vs, 1100m; Unidentate NO w 476 w 723 m 1597 s 2030 w 3163 s 3434 vs, 3306 vs [Cd(HL 2 )(NO 3 ) 2 ] (13) 1098 s (V=O) 419 w 456 w 752 m ____ 2089 m 3172 s 3403 m 3260 s [(VO)(L 2 ) 2 ].4H 2 O (14) Table 6. Characteristic vibrational frequencies of the HL 2 ligand and its metal complexes and their assignments. iii) Electronic spectra and magnetic measurements c c c c eff. eff. (B.M.) (B.M.) d-d transition assignments Electronic absorption bands (nm) and their assignments Ligand/complexes d-d transition n * and CT - * (C=N) (phenyl ring) (phenyl ring) HL 1. 1 / 2 HCl A 2 g (F) 4 T 1 g (F) 4 T 1 g (P) 4 T 1 g (F) 615 sh, [Co(L 1 ) 2 (H 2 O) 2 ].2H 2 O (1) T 1 g(F) 3 A 2 g(F) 732, 690 sh [Ni(L 1 ) 2 (H 2 O) 2 ].2CH 3 OH (2) T 2 g(G) E 2 (G) [Cu(HL 1 )(NO 3 ) 2 ].CH 3 OH (3) Charge transfer tailing from UV to visible region. 740,605, [Fe(HL 1 )(NO 3 ) 2 (H 2 O) 2 ].2C 2 H 5 OH (4) 16 [Zn(L 1 ) 2 ].2H 2 O (5) 18 [Cd(L 1 ) 2 ].1 1 / 2 H 2 O (6) b 1 b 2 565, [VO(HL 1 )(SO 4 )(H 2 O)].2CH 3 OH (7) 18 Charge transfer [UO 2 (L 1 ) 2 (H 2 O) 2 ].2H 2 O (8) Table 7. Electronic transition bands, magnetic moments and molar conductance of the HL 1, ligand and its metal complexes. eff. eff.(B.M.) d-d transition assignments Electronic absorption bands (nm) and their assignments Ligand/complexes d-d transition n * and CT and CT - * (C=N) HL 2. 1 / 2 HCl HL 2. 1 / 2 HCl A 2 g (F) 4 T 1 g (F) 4 T 1 g (P) 4 T 1 g (F) 662 sh, [Co(HL 2 ) 2 (NO 3 ) 2 ].2H 2 O (9) T 1g (P) 3 A 2g (F) 3T1g(F) 3A2g(F) [Ni(H 2 L 2 ) 2 (NO 3 ) 2 ].3 1 / 2 H 2 O (10) T 2 g(G) E 2 (G) [Cu(HL 2 ) (NO 3 ) 2 ].2CH 3 OH (11) 150 [Zn(HL 2 )(NO 3 ) 2 ].CH 3 OH (12) 142 [Cd(HL 2 )(NO 3 ) 2 ] (13) b 1 b [(VO)(L 2 ) 2 ].4H 2 O (14) Table 8. Electronic transition bands, magnetic moments and molar conductance of the HL 2, ligand and its metal complexes. eff. B.M. eff. B.M. comp. B.M. d-d transition assignments Electronic absorption bands (nm) and their assignments Ligand/complexes d-dtransitin n * and CT and CT -*-*-*-* (phenyl ring) (phenyl ring) H 4 L 3 H 4 L T 1 g (P) 4 T 1 g (F) 4 A 2 g (F) 4 T 1 g (F) 470 sh, [Co 2 (H 2 L 3 )(NO 3 ) 2 (H 2 O) 4 ]. 2H 2 O.2CH 3 OH (15) T 1g (P) 3 A 2g (F) 3T1g(F) 3A2g(F) [Ni 2 (H 2 L 3 )(NO 3 ) 2 (H 2 O) 4 ].2CH 3 OH ( T 2 g(G) E 2 (G) [Cu 2 (H 2 L 3 )(NO 3 ) 2 (CH 3 OH) 2 (H 2 O) 2 ] (17) Charge transfer tailing from UV to visible region 502, 480, [Fe( H 2 L 3 )(NO 3 )(H 2 O)] (18) 24.2 [Zn(H 2 L 3 )]4.H 2 O (19) 18.7 [Cd(H 2 L 3 )].4H 2 O (20) b 1 b [(VO)(H 2 L 3 )].H 2 O (21) Charge transfer [(UO 2 ) 2 (H 2 L 3 )(CH 3 COO) 2 ].1 1 / 2 H 2 O (22) Table 9. Electronic transition bands, magnetic moments and molar conductance of the H 4 L 3, ligand and its metal complexes. iv) ESR spectra Figure 4. X-Band of the ESR spectra of: (A) [Cu(HL1)(NO 3 ) 2 ].CH 3 OH (B) [VO(HL 1 )(SO 4 )(H 2 O)].2CH 3 OH complexes Figure 5. Thermal gravimetric analysis (TGA) (DrTGA) and differential thermal analysis (DTA) of: (A) [Ni(L 1 ) 2 (H 2 O) 2 ].2CH 3 OH and (B) [Cu(HL 1 )(NO 3 ) 2 ].CH 3 OH v) TGA analysis Scheme 2. Thermal degradation of [Co 2 (H 2 L 3 (NO 3 ) 2 (H 2 O) 4 ]. 2H 2 O.2CH 3 OH complex Complexes of The Thiosemicarbazid ligands Figure 6. Representative structures of the metal complexes of the N-benzoylthiosemicarbazide ligand Figure 7. Representative structures of the metal complexes of the N-methylformyllthiosemicarbazide ligand Figure 8. Representative structures of the metal complexes of the Bis-thiosemicarbazide ligand Mean of zone diameter a, (mm) Fungi c Gram-negative bacteria b Gram-positive bacteria b AspergillusfumigatusFusariumoxysporumPseudomonas fluorescens fluorescens (S 97) (S 97) Pseudomonas phaseolicola (GSPB 2828) Streptococcus pyogenes pyogenes (ATCC 19615) (ATCC 19615)Staphylocu aureus aureus(ATCC23)Organisms BABABABABABA 3 L 5 L 8 L 2L 2 L 4L 5 L ____________ HL 2. 1 / 2 HCl HL 2. 1 / 2 HCl 22 H 31 H 20 H 29 H 24H32H22H30H13I18I13I19I [Co(HL 2 ) 2 (NO 3 ) 2 ].2H 2 O (9) 20 H 29 H 20 H 27 H 19I28H18H26H26H34H20H30H [Ni(HL 2 ) 2 (NO 3 ) 2 ].3 1 / 2 H 2 O (10) 8 L 17I7L16I13I22I15I22I8I16I10I18I [Cu(HL 2 ) (NO 3 ) 2 ].2CH 3 OH (11) 21 H 25 H 20 H 30 H 22H31H24H28H23H25H20H24H [Zn(HL 2 )(NO 3 ) 2 ].CH 3 OH (12) 18 H 24 H 19 H 26 H 24H32H29H35H20H26H19H24H [Cd(HL 2 )(NO 3 ) 2 ] (13) ____________ 3 L 6 L 5 L 9 L 3 L 7 L 5 L 8L [(VO)(L 2 ) 2 ].4H 2 O (14) Control # Control # Table 9. Biological activity of the N-methylformylthiosemicarbazide, HL 2, ligand and its metal complexes Mean of zone diameter a, (mm) Fungi c Gram-negative bacteria b Gram-positive bacteria b Organisms Aspergillus fumigatus fumigatusFusariumoxysporum Pseudomons fluorescens (S 97) (S 97) Pseudomonas phaseolicola (GSPB 2828) Streptococcus pyogenes (ATCC19615) Staphylos aureus aureus(ATCC23) BABABABABABA ________________________________10I17I10I15I H4L3H4L3H4L3H4L3 9 L 3 L 8L10L21H26H18H26H24H30H22H26H [Co 2 (H 2 L 3 )(NO 3 ) 2 (H 2 O) 4 ]. 2H 2 O.2CH 3 OH (15) 18I23I13I21I14I20I12I20I21H29H20H30H [Ni 2 (H 2 L 3 )(NO 3 ) 2 (H 2 O) 4 ].2CH 3 OH (16) 15I22I17I22I20H25H 18 H 25H15I22I13I19I [Cu 2 (H 2 L 3 )(NO 3 ) 2 (CH 3 OH) 2 (H 2 O) 2 ] (17) 23 H 31H20H28H17I23I14I20I 4 L 8L 8L [Fe( H 2 L 3 )(NO 3 )(H 2 O)] (18) ________________10I17I12I18I20H24H19H25H [Zn(H 2 L 3 )]4.H 2 O (19) ________________18I20I12I19I18I19I15I20I [Cd(H 2 L 3 )].4H 2 O (20) ________________3L5L2L6L2L5L 3 L 5 L [(VO)(H 2 L 3 )(H 2 O)].H 2 O (21) ________________10I17I10I16I12I18I10I17I [(UO 2 ) 2 (H 2 L 3 )(CH 3 COO) 2 ].1 1 / 2 H 2 O (22) Control # Control # Table 10. Biological activity of the N-methylformylthiosemicarbazide, H 4 L 3, ligand and its metal complexes The HL1 and HL2 ligands were reacted with metal ions in 1:1. The HL 1, HL 2 and H 4 L 3 ligands act as either neutral, monobasic bidentate, or dibasic bidentate ligands which coordinates through NS or NO sites. The H 4 L 3 ligand was reacted with metal ions in 1:1 and 1:2 (H 4 L 3 : metal ion). The H4L3 ligand acts as dibasic with two sets of bidentate of either NO or NS sites. Different varieties of geometries of the metal complexes were obtained (octahedral, square planer, tetrahedral and square pyramid). The ligands and their metal complexes were screened towards antimicrobial activity. my sincerest appreciation to: Dr. Adel A. A. Emara Dr. Hussein Sakr Seleem