Synthesis and Characterization of some Novel Organometallic Compounds of Expected Biological and Anticancer Activity

Abstract

Due to the importance of Sulfa drugs, for example sulfaguanidine (SG), because of their cost-effectiveness, low-toxicity coupled with their assorted pharmacological effects. And motivated by the wide-spectrum antimicrobial properties of the natural biopolymer chitosan (CS) against a number of organisms, including bacteria, fungi and algae. We aim in our thesis to synthesize new Schiff bases bearing sulfaguanidine (SG) or chitosan (CS) and ionic-liquids (ILs) terminals followed by metallation in order to obtain novel metallated Schiff bases. Moreover, study there in vitro antimicrobial/ anticancer assessment of the new compounds, which may allow us to develop a new promising therapeutic strategy to combat antibiotic and anticancer resistance against breast and human colon carcinoma. The work in my thesis was divided into 4 chapters: Chapter 1 (Introduction) Gave short account about the Sulfa drug, sulfaguanidine (SG), chitosan (CS), ionic-liquids (ILs), Schiff bases and Pd(II) complexes and their pharmacological importance. Chapter 2 (Results and Discussions) Involve the essential work and divided into 4 parts 1. Part 1: Synthesis of salicaldehyde ionic liquids (Sal-ILs). Protocol to synthesize these compounds involves four main reactions: i. o-Formylation of 2-isopropylphenol to create 3-isopropysalicylaldehyde; ii. Chloromethylation of salicylaldehydes and 3-isopropysalicylaldehyde to yield 5-Chloromethylsalicylaldehydes; iii. Quaternizationof-methylpyridine (α-picoline, Pic), 1,2-dimethylimidazole ((Me)2Im), 1-nbutylimidazole (nBuIm) or qunioline (Qn)1-methyl imidazole,4 methoxy pyridinium with 5-Chloromethylsalicylaldehydes to generate the Sal-IL chlorides (96-104) Introduction 20 iv. Anion metathesis of Sal-IL chlorides with hexafluorophosphoric acid (HPF6(aq)) and sodium tetrafluoroborate afford the corresponding hexafluorophosphate (103) and tetrafluoroborate salts (104). (Scheme 1). Scheme 2 Schematic diagram for the synthesis of salicylaldehydes ionic liquids (Sal-ILs) Introduction 21 The structures of compounds (96-104) were elucidated based on spectral analyses FTIR, NMR (1H,13C, 31P and 19F) 2. Part 2: Synthesis of ionic Sulfaguanidine-salicyladimine Schiff bases and their metallation by Pd (II )ion A series of novel N-(salicylidene)-sulfaguanidines (Sal-SG) bearing ionic liquid (IL) terminals (ILSSGH, 105-111) have been synthesized by Schiff base condensation of IL-functionalized salicylaldehydes (ILSal, 96-104) with sulfaguanidine (SG). Unfortunately all trials to metallate ionic sulfaguanidine Schiff bases ILSSGH ligands with palladium(II) chloride were unsuccessful. Instead, Pd(II) complexes, [Pd(II)(SGSIL)Cl(H2O)] (112-118) were obtained: (Scheme 2). Scheme 2 Synthesis of ionic sulfaguanidine-salicylaldimine Schiff base architectures (ILSSGH, 105-111) and their metalation by Pd(II) ion The structures of ILSSGH ligands and their Pd(II) complexes were proposed based upon elemental and spectral analysis (FTIR, NMR (1H, 13C, 19F, 31P, 11B), ESI-MS) as well as conductivity measurements. Introduction 22 3. Part 3: Synthesis of chitosan salicyladimine schiff base and their metallation by Co+2, Ag+ and Pd+2 salts A series of biopolymeric chitosan Schiff bases bearing salicylidene ionic liquid (IL-Sal) brushes (ILCSB1-3, poly-(GlcNHAc-GlcNH2-(GlcNSal- IL)) (119-121) were successfully synthesized by Schiff base condensation of ionic salicylaldehydes salts (2a-c) with a natural biopolymer, chitosan (Scheme 3). Unfortunately, metalation trials of these biopolymeric Schiff bases afford the corresponding Ag(I)/ M(II) complexes (122-130) (where M = Co, Pd). Scheme 2 Schematic diagram for the synthesis of ionic liquids-based salicylaldehydes (ILs-Sal), surface-functionalized chitosan and their complexes. Introduction 23 These chitosan architectures (119-130) were isolated in high to excellent yields and structurally characterized by elemental analysis, FTIR and NMR (1H, 13C). Part 4: