Synthesis and Characterization of Thiosemicarbazones: Biological Screening Solid State Assembly and Potential as Chemosensor for Biologically Important Ions

Abstract

The aim of this thesis is to synthesize thiosemicarbazone derivatives and to investigate their biological and chemosensing properties. Five series of thiosemicarbazones have been synthesized with different scaffolds like coumarin, 2-naphthyl, dihydrobenzofuranyl, 2-acetyl5-bromothiophene, 2-acetyl-3-methylpyrazine, 5,6-dimethoxy-1-indanone, 4- nitrobenzaldehyde, 2-nitrocinnamaldehyde and 4-fluorocinnamaldehyde scaffolds. After complete characterization with spectroscopic techniques like (IR, 1H-NMR, 13CNMR and MS), they have been screened out for urease inhibition and colorimetric chemosensing for anions. In last chapter, thiourea derivatives of N-ally aniline have been synthesized and then these thiourea derivatives were further cyclized using flow electrochemical approach. The first chapter of this thesis elucidates chemosensing properties, biological activities, crystal packing of thiosemicarbazones and their significance in biological and environmental fields as mentioned in literature. The second chapter describes synthesis and investigations of receptor-spacer-fluorophore based coumarin thiosemicarbazones as chemosensor against different anions. The anion interaction with thiosemicarbazone based receptors (ligands) was observed and investigated with naked-eye and by using UV-Visible, fluorescence and 1H NMR spectroscopic techniques. The deprotonation of NH protons upon binding with Fˉ was confirmed via 1H NMR spectroscopic data. Binding constants and limit of detection was also calculated. The third chapter contains three parts (3A, 3B and 3C). In first part (3A), a series of Nsubstituted thiosemicarbazones (3a-u) bearing 2-naphthyl, dihydrobenzofuranyl and 2-Acetyl5-bromothiophene while in second part (3B) another series of N-substituted thiosemicarbazones (4a-w) bearing 2-acetyl-3-methylpyrazine, 5,6-Dimethoxy-1-indanone and 4-nitrobenzaldehyde scaffolds were synthesized in good to excellent yields. The synthesized compounds were characterized by advanced spectroscopic techniques, such as FTIR, 1HNMR, 13CNMR and ESI-MS and evaluated as urease inhibitors. The structure of compound 3m was unambiguously confirmed by single crystal X-ray analysis. (3r & 4g) were investigated for crystal packing. All compounds showed remarkable activities against urease enzyme with IC50 values in range of 1.4-36.1 µM in (3a-u) while 2.7-109.2 in (4a-w) µM. The majority of the synthesized compounds showed higher activity than the standard compound thiourea. In the third part (3C), eight compounds of above two series (3b, 3s, 3q, 3r, 4b,4g, 4v, 4l) were selected for chemo sensing studies and were found good colorimetric chemosensors especially for fluorides and cyanides. Detection limits and binding constants were also calculated from UV Visible colorimetric experiments. The fourth chapter reveals synthesis and characterization two series of thiosemicarbazone compounds (5a-r) and (6a-s) in good yield. Characterization of all compounds is done with spectroscopic techniques, such as FTIR, 1HNMR, 13CNMR and ESI-MS. Six compounds (5a, 5b, 5c, 6a, 6b, 6c) were screened for chemo sensing experiments for colorimetric detection of fluoride and cyanide ions that are very important for sensor chemistry. Florescence studies were also carried out for (6a, 6b and 6c) and found these molecules as good turn on fluorescent chemosensors. Detection limits and binding constants were also calculated from UV Visible colorimetric experiments. The chapter V of this thesis relates to synthesis, characterization and electrochemical cyclization of N-allyl thiourea derivatives. Characterization was done with FTIR, 1HNMR, 13CNMR and ESI-MS. Cyclization of thiourea derivatives to get thiazole-2-imine derivatives have gained significant biological attention due to their interesting pharmacological activities. Many of their synthesis suffer from the drawbacks such as the handling of toxic reagents, harsh reaction conditions, longer reaction times and tedious separation procedures. To their easy access, we applied first time flow electrochemical approach under free supporting electrolytes conditions and without the use of expensive catalysts and reagents. This is not only the first electrochemical cyclization to access thiazolidin-2-imines also represents the first intramolecular sulfurization of unfuctionalized terminal alkenes. Muhammad Islam PhD Thesis.