الفهرس 
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Abstract
The present thesis comprises two chapters:
- The first chapter includes an introduction to thiosemicarbazone ligands and their metal chelates, their chemical structures and their biological activities. This is in addition to a description of the thiosemicarbazone ligands and complexes in this study.
- The second chapter consists of three published papers describing thiosemicarbazones with iron, cobalt and antimony:
The first article extracted from this thesis was published in Heliyon (Impact Factor 3.776). The 2- formylpyridine TSCs reacted with ferric iron to produce new chelates [FeL2] Cl. 2H2O {L = L1 (C1) [HL1 = 4-(4-nitrophenyl)-1-((pyridin-2- yl) methylene) thiosemicar-bazide] and L = L2 (C2) [HL2 = 4-(2, 5- dimethoxyphenyl)-1-((pyridin-2-yl) methylene) thiosemicarbazide]}.
The two ligand anions in each complex, being with tridentate NNS ligation system, Resulted in saturation of the iron coordination number and consequently the existence of these complexes as 1:1 electrolytes. As well, the iron in the complexes exhibited low-spin electronic configuration being the thiosemicarbazones strong ligands able to couple the metal electrons. X-ray crystallography of complex C1 indicated its crystal system and space group {triclinic and P-1} and proved the ligation via thiol sulfur and two nitrogen atoms of pyridine and azomethine groups in addition to the presence of two water molecules of crystallization in its structure. The ligand HL1 was selected for anti-proliferative activity screening against human MCF-7, A-549, HEPG-2 and HCT-116 cancer cells and the most enhanced activities were against the breast cancer cells. All free ligands and coordination compounds were examined as anticancer agents against MCF-7 cells that the coordination compounds gave the most enhanced activities based on their IC50 in μM. The activities against MCF-7 cells are less significant compared with the measured value for doxorubicin. But this standard is more toxic to normal cells than the thiosemicarbazones (IC50 (doxorubicin) = 9.66 μM against MCF-7 cells and 36.42 μM against BHK cells).
The second article extracted from this thesis was published in Inorganics (Impact Factor 3.149). This article describes preparation of TSC complexes of trivalent cobalt with HL1 = 4-(4-nitrophenyl)-1-((pyridin-2- yl) methylene) thiosemicarbazide and HL2 = 4-(2, 5-dimethoxyphenyl)-1- ((pyridin-2-yl) methylene) thiosemicarbazide}.
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The complexes were synthesized Via the in situ oxidation of divalent cobalt chloride accompanying its addition to the ligands. The complexes C3 and C4 were characterized via elemental (CHNS) analysis and 1H NMR, FT-IR and UV-Vis. spectroscopic data. Further, conductometric studies on the DMF solutions of the complexes indicated their 1:1 nature, and their diamagnetism revealed the low-spin trivalent oxidation state of the cobalt in the complexes. X-ray diffraction analysis of complex C3 indicated its crystallization in the triclinic space group P-1. The metal exhibits an octahedral environment built by two anionic ligands bound via pyridine nitrogen, imine nitrogen and thiol sulfur atoms. The complex ion is counterbalanced by a chloride ion and two lattice water molecules were detected in the asymmetric unit of the unit cell. The ligand HL2 (20 mg/mL in DMSO) displayed inhibition zones of 10 mm against S. aureus and E. coli, and the same concentration of the respective complex raised this activity to 15 and 12 mm against these bacterial strains, respectively. As a comparison, ampicillin inhibited these bacterial strains by 21 and 25 mm, respectively. Screening assay by HL1 on four human cancer cells revealed the most enhanced activity against the MCF-7 cells. The induced growth inhibitions in the MCF-7 cells by all compounds (0–100 μg/mL) have been detected. The ligands {HL1 and HL2} and complex C4 gave inhibitions with IC50 values of 52.4, 145.4 and 49.9 μM, respectively. These results are more meaningful in comparison with similar cobalt complexes, but less efficient compared with the inhibition with IC50 of 9.66μM afforded by doxorubicin. In addition, doxorubicin, HL1 and HL2 induced cytotoxicity towards healthy BHK cells with IC50 values of 36.42, 54.8 and 110.6 μM, but surviving fractions of 66.1% and 62.7% of these cells were detected corresponding to a concentration of 100 μg/mL of the complexes (136.8 μM of C3 and 131.4 μM of C4).
The third article extracted from this thesis was published in Inorganics (Impact Factor 3.149). This article showed the preparation of two Sb(III) – TSC complexes {[Sb(L3)Cl2] C5 and [Sb(L2)Cl2] C6} with the ligands {HL3 = 4- (2,4-dimethylphenyl)-1-((pyridin-2-yl)methylene)thiosemicarbazide and HL2 = 4-(2,5-dimethoxyphenyl)-1-((pyridin-2-l)methylene)thiosemicarbazide}. The structures were elucidated on the basis of CHNS analysis, spectroscopic techniques (UV-Vis and FT-IR), and DMF solution electrical conductivities. Single crystal X-ray diffraction analysis of complex C5 assigned the complex pseudo-octahedral geometry and triclinic P-1 space group. Only the ligand HL3 and its derived complex displayed antifungal activities against C. albicans and this activity was enhanced from 10 mm to 21 mm for the respective complex, which is the same activity given by the amphotericin B drug. The ligands HL3 and HL2 gave inhibitions,
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respectively, of 14 and 10 mm against S. aureus and 15 and 10 mm against E. coli; however, complexes C5 and C6 increased these inhibitions to 36 and 32 mm against S. aureus and 35 and 31 mm against E. coli exceeding the activities given by the ampicillin standard (i.e., 21 mm against S. aureus and 25 mm against E. coli). Against MCF-7 cancer cells, the IC50 values of HL3 (68.9 μM) and HL2 (145.4 μM) were notably enhanced to the values of 34.7 And 37.4 μM for both complexes, respectively. Further, the complexes induced less toxicity in normal BHK cells (HL3 (126.6 μM), HL2 (110.6 μM), C5 (>210.1 μM), and C6 (160.6 μM)). As a comparison, doxorubicin gave an IC50 value of 9.66 μM against MCF-7 cells and 36.42 μM against BHK cells.