Abstract
M.Sc. (Chemistry)
Secondary cancer tumour formation, often called metastasis, remains one of the great scientific challenges in public health. Patients with skeletal metastases have a low survival rate, with great discomforts experienced by the sufferers. Pain, decreased mobility, pathologic bone fractures are some of the effects that these patients have to live with. Significant inroads have been made in using radio pharmaceuticals as a pain palliation treatment for bone metastases. They comprise of a bone seeking phosphonate ligand and a radionuclide. The structural variation of the phosphonate affects to a great extend the effectiveness of the radiopharmaceutical with the greatest shortfall being myelosuppression at high doses. In this study an attempt is made at synthesizing novel bisphosphonates, APDDAM and APDDPE. After several synthetic steps from the protected β-alanine tert butyl ester, the free acid precursor was achieved (as shown in the NMR and elemental analysis) in good yields. Unfortunately the final reaction step to form the bisphosphonate ligand was unsuccessful, with the free acid precursor dissociating in the acidic conditions to form salts. A polymer ligand poly-HEDP was synthesized from its free acid form in relatively low yields. The ligand was used in potentiometric studies with the metal ions Ca(II), Mg(II), Cu(II), Zn(II), Sn(II) and Sn(IV) to evaluate its potential as radiopharmaceutical candidate. The ESTA model formation constants obtained were used in the ECCLES blood plasma model to evaluate the competitive stability of the complexes against biological metal ions and ligands. The Sn(IV)-poly-HEDP complex was shown to be unstable, with a 100 % dissociation. On the other hand the Sn(II)-poly-HEDP showed much improved stability with 100 % of the metal ion remaining bound to the ligand.