Skelton, Adam Arnold.Adeowo, Fatima Yetunde.2020-04-012020-04-0120162016https://researchspace.ukzn.ac.za/handle/10413/17428Master degree. University of KwaZulu-Natal, Westville. 2016The application of chelators is an ongoing interest in diagnostic and therapeutic radiopharmaceuticals. Bifunctional chelators labelled with radiometal ions are covalently bonded with a lead compound to form complexes with targeted biomolecules. The binding affinity of a ligand is thus an exclusively essential feature of an ideal radiopharmaceutical ligand. 1,4,7 triazacyclononane-1,4,7 triacetic acid (NOTA) a key radiolabelling chelator in radiopharmaceuticals, which is studied in this project, has been identified as one of the popularly investigated chelators. NOTA is known with the ability to form a stable complex with radiometal ions. A number of experimental investigations have been performed to study the structure and the radiolabelling efficiency of NOTA chelator while little attention has been paid to exploiting the structure and the binding features of the ligand at the molecular level. In this project, an investigation was made of the structure of NOTA and it complexation with alkali metal and radiometal ions, using density functional theory. In the first step, efforts were made to evaluate the complexation of NOTA with alkali metal ions (Na+ , Li+ , K+ and Rb+ ) with the intention of assessing the level of competition of alkali metal ions, found in the body. The complexation of NOTA with radiometal ions (Cu2+, Ga3+, In3+, Sc3+) was also investigated. This study reveals that nitrogen and oxygen atoms in the NOTA molecule are important for complexation processes. Interaction and relaxation energies, Gibbs free energies and entropies show that the stability of NOTA― alkali metal ion complexes decreases down the group of the periodic table. In the case of NOTA―radiometal ions complexes, NOTA― Ga3+ is identified to be more stable than the remaining radiometal complexes, which is in good agreement with experimentally reported binding constants. For both alkali metal and radiometal ion complexes, implicit water solvation affects the NOTA―ion complexation, causing a decrease in the stability of the system. NBO analysis performed through the natural population charges and second order perturbation theory reveals the charge transfer between NOTA and both alkali metal and radiometal ions. The theoretical 1H NMR chemical shifts of NOTA complexes, in vacuum and water, are in good agreement with experiment; these values are influenced by the presence of the ions, which have a deshielding effect on the protons of NOTA. A noteworthy conclusion from the investigation is that the interaction of NOTA with radiometal ions is stronger than the interaction of NOTA with alkali metal ions. Thus, confirming that the presence of alkali metal in human body may not interfere with the binding of radiometal to NOTA chelator. This study serves as a guide to researchers in the field of organometallic chelators, particularly, radio-pharmaceuticals in finding the efficient optimal match between chelators and different metal ions.enTriacetic acid.Density functional theory.Natural bond orbital.Thesis