Synthesis of thiacrown and azacrown ethers based on the spiroacetal framework

This thesis describes the synthesis of novel thiacrown and azacrown ethers based on the 1.7-dioxaspiro[5.5] undecane ring system. Each chapter discusses the research in some detail. Chapter five describes the attempted kinetic resolution of the spiroacetal moiety, to provide enantiopure starting material for the synthesis of non-racemic spiroacetal crown ethers. Three different approaches were investigated. Chapter six summarises the results achieved and discusses possible strategies emanating from these results

Synthesis of thiacrown and azacrown ethers based on a spiroacetal framework

A novel class of thiacrown and azacrown ethers incorporating the 1,7-dioxaspiro[5.5]undecane spiroacetal ring system was prepared by reaction of ditosylate 5 with the appropriate dithiols 9a–c or protected diamine 12a. Spiroacetal ditosylate 5 in turn, was prepared from diol 3 via ozonolysis of bisallyl ether 7 followed by tosylation of the derived diol 8

Metal binding studies using spiroacetal thiacrown ethers

The binding ability of a series of spiroacetal thiacrown ethers with Li+, Na+, K+, Cs+, Co2+, Cd2+, Ag+ and Pb2+ is reported. The thiacrown ethers showed an affinity for the heavy metals. The interaction of the three thiacrown ethers 1–3 and [Al(acac)3] 5, [Co(NH3)5NO2](BPh4)2 6 and [Co(en)3](BPh4)3 7 complexes is also investigated

The effect of ancillary ligand chirality and phenanthroline functional group substitution on the cytotoxicity of platinum(II)-based metallointercalators

Fifteen platinum(II)-based metallointercalators have been synthesised that utilise substituted 1,10-phenanthroline (phen) ligands, including 5-chloro-1,10-phenanthroline (5-Cl-phen), 5-methyl-1,10-phenanthroline (5-CH3-phen), 5-amino-1,10-phenanthroline (5-NH2-phen), 5-nitro-1,10-phenanthroline (5-NO2-phen) and dipyrido[3,2-d:2′,3′-f]quinoxaline (dpq), and achiral ethylenediamine (en) and the chiral ancillary ligands 1S,2S-diaminocyclohexane (S,S-dach) and 1R,2R-diaminocyclohexane (R,R-dach). Their cytotoxicity in the L1210 murine leukaemia cell line was determined using growth inhibition assays. The most cytotoxic metal complexes are those that contain S,S-dach ancillary ligands and 5-CH3-phen intercalating ligands. One metallointercalator [Pt(5-CH3-phen)(S,S-dach)]Cl2 (5MESS), displays a 5-10-fold increase in cytotoxicity compared to the clinical agent cisplatin. From DNA binding experiments there appears to be no significant difference between any of the metal complexes, indicating that neither DNA binding affinity nor the mode of binding/DNA adduct formed is the sole determinant of the cytotoxicity of this family of platinum(II)-based metallointercalators