Chelating carbene ligands and their metal complexes

This thesis describes the synthesis of a number of functionalised imidazolium salts as precursors to N- heterocyclic carbenes and their subsequent coordination to Ag and Pd. Further a number of the Pd complexes were tested in the Heck reaction and their activities compared to complexes with similar structural features currently within the literature. A range of imidazolium salts have been synthesised which include quinoline and octahydroacridine moieties and have been characterised by a number of methods including X-ray crystallography. A bis imidazolium salt has also been prepared as a DIOP analogue. The imidazolium salts were successfully reacted with Ag20 to form the NHCAg(I) complexes. The quinoline and octahydroacridine based NHCs were transmetallated to Pd as chelating ligands, the quinoline based systems appearing as planar, strained complexes in the X-ray structure. The activities of the quinoline and octahydroacridine based NHCPd(II) complexes in the Heck coupling of 4-bromoacetophenone and 4-chlorobenzaldehyde with n-butyl acrylate were assessed and found to be comparable to similar systems with low to satisfactory conversions.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Chelating carbene ligands and their metal complexes

This thesis describes the synthesis of a number of functionalised imidazolium salts as precursors to N- heterocyclic carbenes and their subsequent coordination to Ag and Pd. Further a number of the Pd complexes were tested in the Heck reaction and their activities compared to complexes with similar structural features currently within the literature. A range of imidazolium salts have been synthesised which include quinoline and octahydroacridine moieties and have been characterised by a number of methods including X-ray crystallography. A bis imidazolium salt has also been prepared as a DIOP analogue. The imidazolium salts were successfully reacted with Ag20 to form the NHCAg(I) complexes. The quinoline and octahydroacridine based NHCs were transmetallated to Pd as chelating ligands, the quinoline based systems appearing as planar, strained complexes in the X-ray structure. The activities of the quinoline and octahydroacridine based NHCPd(II) complexes in the Heck coupling of 4-bromoacetophenone and 4-chlorobenzaldehyde with n-butyl acrylate were assessed and found to be comparable to similar systems with low to satisfactory conversions.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Chelating carbene ligands and their metal complexes

This thesis describes the synthesis of a number of functionalised imidazolium salts as precursors to N- heterocyclic carbenes and their subsequent coordination to Ag and Pd. Further a number of the Pd complexes were tested in the Heck reaction and their activities compared to complexes with similar structural features currently within the literature. A range of imidazolium salts have been synthesised which include quinoline and octahydroacridine moieties and have been characterised by a number of methods including X-ray crystallography. A bis imidazolium salt has also been prepared as a DIOP analogue. The imidazolium salts were successfully reacted with Ag20 to form the NHCAg(I) complexes. The quinoline and octahydroacridine based NHCs were transmetallated to Pd as chelating ligands, the quinoline based systems appearing as planar, strained complexes in the X-ray structure. The activities of the quinoline and octahydroacridine based NHCPd(II) complexes in the Heck coupling of 4-bromoacetophenone and 4-chlorobenzaldehyde with n-butyl acrylate were assessed and found to be comparable to similar systems with low to satisfactory conversions

Employing pancreatic tumour;-glutamyl transferase for therapeutic delivery

γ-glutamyltransferase (γGT) is a cell surface enzyme that catalyses hydrolysis of the bond linking the glutamate and cysteine residues of glutathione and glutathione-S-conjugates. I have observed that human pancreatic tumour cells and tumour-associated stellate cells express high levels of this enzyme when compared to normal pancreatic epithelial and stellate cells. Detection of the protein in tumour sections correlated with γGT activity on the surface of the cultured tumour and stellate cells. I tested whether the tumour γGT could be employed to deliver a therapeutic to the tumour endothelial cells. GSAO is a glutathione-S-conjugate of a trivalent arsenical that is activated to enter endothelial cells by γGT cleavage of the γ-glutamyl residue. The arsenical moiety triggers proliferation arrest and death of the endothelial cells by targeting the mitochondria. Human pancreatic tumour and stellate cell γGT activated GSAO in culture and γGT activity positively correlated with GSAO-mediated proliferation arrest of endothelial cells in transwell and co-culture systems. A soluble form of γGT is found in blood and I measured the rate of activation of GSAO by this enzyme. I calculated that systemically administered GSAO would circulate through the pancreatic blood supply several times before appreciable activation by normal blood levels of γGT. In support of this finding, tumour γGT activity positively correlated with GSAO-mediated inhibition of pancreatic tumour angiogenesis and tumour growth in mice. My findings indicate that pancreatic tumour γGT can be used to deliver a therapeutic to the tumour

Investigations on the use of amidic ligands in copper-catalysed arylation reactions

This thesis reports investigations on the use of amidic ligands, in particular picolinamide ligands, in copper-catalysed arylation of nucleophiles with aryl halides. An introduction to the field of copper-catalysed arylations of nucleophiles, mostly focusing on the mechanistic aspects of these processes, from the early investigations to the most recent developments, is reported in Chapter 1. Following this introduction, the results of this research are presented in three chapters, each dealing with a different topic. Chapter 2 reports on the synthesis of a range of differently substituted picolinamide ligands and their use in the copper-catalysed arylation of phenols and amides. The catalytic screenings reported in this chapter are the basis for the mechanistic investigations reported in Chapter 4. A range of phenols, amides and aryl halides were tested under optimised conditions to assess the validity of the method. All the coupling products were isolated and characterised. Chapter 3 describes the synthesis of copper complexes with picolinamide ligands, to be used for mechanistic investigations. Five different types of complexes, with differently substituted ligands, were obtained, and their structural features in the solid state are summarised in this chapter. Discussion on the mechanism of formation of these complexes, and on the role of the base in the process is also included. Investigations on the mechanism of the coupling reaction between phenols and aryl halides, facilitated by picolinamide ligands, are reported in Chapter 4. The complexes synthesised in Chapter 3, used as pre-catalysts for the coupling process, and electrochemical measurements on these complexes, are employed to investigate the role of the electronic properties of the ligands in the reaction, and its influence on the metal centre. Other miscellaneous experiments, such as radical clock experiments, are also reported. The final two chapters of this thesis, Chapters 5 and 6, contain general conclusions and suggestions for further investigation topics (Chapter 5), and detailed experimental procedures and characterisation data for all of the compounds prepared in Chapters 2-4 (Chapter 6)

Online antioxidant activity and ultra-performance LC-electrospray ionisation-quadrupole time-of-fight mass spectrometry for chemical fingerprinting of Indian polyherbal formulations

<div><p>A HPLC–DAD–DPPH method was developed for evaluating the 1, 1-diphenyl-2-picryl hydrazyl free radical scavenging activity of ethylacetate extracts of different polyherbal formulations (draksarista, draksava, lohasava and arvindasava) by using RP-18e column. The ethylacetate extract from polyherbal, ‘draksarista’ exhibited maximum free radical scavenging activity (99.9 ± 0.38%) followed by draksava (99.8 ± 0.34%), lohasava (98.5 ± 0.30%) and arvindasava (42.3 ± 0.34%) at 100 μg mL^− 1. Simultaneously, ultra-performance liquid chromatography coupled with electrospray ionisation-quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOF-MS) was used to study chemical composition of the ethylacetate extracts of formulations. The characteristic electrospray mass ionisation reveals the dominance of polyphenols and their glycosides in the four polyherbal formulations.</p></div