TOPIC: EVALUATING THE INTERACTION OF NOTA CHELATOR WITH ALKALI METALS AND RADIOMETALS: A THEORETICAL STUDY.
Fatima.Y. Adeowo1, Bahareh. Honarpavar1, Adam.A Skelton1
1 School of Health Sciences, Discipline of Pharmacy, University of KwaZulu-Natal, Durban 4001, South Africa.
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Abstract:
The movement of drugs in vivo can be monitored by incorporating radioisotopes into molecules designed specifically for a target. This is beneficial in pharmacology because, it provides precise dosing information and important safety. An excellent delivery of radioactivity to a selective tumour target can be achieved when antibodies are attached to a bifunctional chelator (BFC) radiolabelled with a suitable metallic radioisotope. This calls for the need to select the appropriate radioisotope for a particular chelator, whether for imaging or therapy purpose, because this affects the efficacy of the imaging and therapeutic agent. An in-depth understanding of the structures and the features of a ligand and the aqueous coordination chemistry of a metal however help in an accurate matching of a ligand with the appropriate radiometal.
The purpose of this study is to provide insight into the structures and properties of NOTA complex with alkali metals (Li+, Na+, K+ and Rb+). The focus of this present work is on the complexation of alkali metal, the conformation of the NOTA and electronic structure of the complexes. The major goal of this work is to gain an elementary knowledge of the interaction between NOTA and alkali metals.
All calculations were performed within the Gaussian 09 program suite using the Density Functional Theory (DFT). The geometry optimization of all complexes was performed at B3LYP level of theory. NBO analysis was performed through the natural population charges and the second order perturbation analysis, for the full understanding of charge transfer. Global scalar properties such as HOMO/LUMO energies, HOMO–LUMO energy gap, chemical hardness, chemical potential, electronegativity, global hardness, global softness and electrophilicity index were determined for complexes.
The results of the study indicate that stability of alkali metals with NOTA decreases down the group in the periodic table. Attractive interactions exist between alkali metals and some of the atoms in NOTA molecule. Natural bond orbital (NBO) analysis gives an insight into charge-transfer between NOTA and alkali metals indicating that, there exist charges transfer between alkali metal and atoms in the NOTA molecule. This interaction may be important in evaluating the impact of these competing ions to the radiolabelling yield of NOTA.
Keywords: NOTA, alkali metals, DFT.
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