Using Linear Combination of Atomic Orbital Calculations to Develop a Novel Fluorine-Labeled Pharmaceutical Compound

This dissertation, "Using Linear Combination of Atomic Orbital Calculations to Develop a Novel Fluorine-labeled Pharmaceutical Compound" by Chui-shan, Chu, 朱翠珊, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Abstract of the thesis entitled Using Linear Combination of Atomic Orbital Calculations to Develop a Novel Fluorine-labeled Pharmaceutical Compound Submitted by CHU ChuiShan for the degree of Master of Medical Sciences at the University of Hong Kong In August 2014 Radiopharmaceuticals are radioactive compounds used in radiotherapy and 99m diagnosis. Tc glucarate is a diagnostic radiopharmaceutical for the localization of 99m tumor necrosis and myocardial infarction. Tc releases low-energy photons to Positron emission tomography (PET) scanner. However, the PET images are 18 unqualified for disease diagnosis. Our ultimate goal is to develop F glucarate for detecting tumor necrosis in the future. In this research, linear combination of atomic 19 orbital (LCAO) calculations determined where F atom attacks on glucarate, and the 19 chemical synthesis was conducted to obtain fluorine-labeled glucarate molecule. LCAO calculated wave functions for glucarate qualitatively. A secular determinant was set up to formulate a polynomial equation. By using Mathematica 9, it solved the equation and showed roots of x that represented different energy levels for glucarate. Each value for the roots was substituted into ratios c /c of other polynomials to find n 1 coefficients for atoms. These polynomials arose from the original secular determinant, but they were subject to which atom was focused. All these ratios c /c were squared n 1 2 2 and summed together to obtain ∑(c /c ) . Therefore, a square root of ∑(c /c ) divided n 1 n 1 the ratios to calculate coefficients for each atom. Our results suggested that electrophiles react with carbonyl OH and nucleophiles attack α-carbon of glucarate. For chemical synthesis, d-saccharic acid (d-glucaric acid) potassium salt mixed with crystalline xenon difluoride. Synthesized reaction product was obtained after the colorless solution changed to pale yellow. Thin-layer chromatography suggested the reaction between the precurors probably occurred. Our selected column for high-performance liquefied chromatography (HPLC) was unfit to purify the product. 1 19 13 H, F and C NMR and Mass Spectrometry were employed for identification. The noisy data could not identify synthesized reaction product. To conclude, further studies are crucial to the confirmation of the molecular structure. Our future plan is to secure research fundings for acquiring a separation HPLC column. The sufficient support can improve the accuracy of NMR and MS data. The successful isolation may 18 open a new avenue for developing F glucarate to detect necrotic tumor cells. (Word count: 329) DOI: 10.5353/th_b5319993 Subjects: Radiopharmaceuticals