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Synthesis of rhenium(I) carbonyl complexes of functionalized phosphines for potential applications in nuclear medicine
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Type
Thesis
Author
Zeng, Yun
Supervisor
Yan, Yaw Kai
Abstract
In this project, the chemistry of a series of new bifunctional phosphine ligands and their rhenium(I) tricarbonyl complexes have been studied.
Phosphine-derivatized amine and amino carboxylic acid ligands 2.1, 2.2, 3.1-3.10 were synthesized in good yields through the modified Mannich reaction using bis(hydroxymethyl)diphenylphosphonium chloride [Ph2P(CH2OH)2]+Cl- as the key starting material.
The phosphine-derivatized amine and amino carboxylic acid ligands synthesized have high coordination ability with Re(I) tricarbonyl core. Three different rhenium precursors [Re(CO)3Br3] [NEt4]2, [Re(CO)5Br] and [Re(CO)3Br2MeOH][NEt4] were used for the complexation to form the corresponding rhenium(I) tricarbonyl complexes. These complexes can serve as model compounds for further functionalization for potential radiopharmaceutical applications. Complexes 3.11 and 3.17 were coupled with gly-gly and gly-gly-gly, which served as model small peptides, via TFP esters to form compounds 3.26-3.29. In order to investigate the poor yields in the synthesis of compounds 3.19 and 3.20 from [Re(CO)3Br3]2-, phosphine-derivatized diamine ligands 4.1-4.5 were synthesized as well, the results suggest that the poor yields were due to the interference from the carboxyl groups of 3.19 and 3.20.
The structures of all the compounds were characterized by 1H and 31P NMR spectroscopy; all the rhenium complexes were characterized by IR spectroscopy; compounds 2.1, 2.3, 2.4, 2.5, 3.8, 3.11, 3.15 and 3.25 were characterized by X-ray crystallography.
The kinetics of the reactions 3.1 -> 3.11 and 3.5 3.15 were studied by means of time-dependent 31P NMR and a mechanism involving four elementary steps was proposed.
The stability of the rhenium complexes of phosphine-derivatized carboxylic acids were studied by Electrospray mass spectrometric in neutral and aged mildly basic solutions. The results suggested these complexes to possess significant stability.
Cytotoxicity testing of compounds 3.21, 3.15, 3.11, 3.13, 2.3, 2.4, 2.5 and 4.7 showed that these complexes are active against human leukemic MOLT-4 cell line.
Phosphine-derivatized amine and amino carboxylic acid ligands 2.1, 2.2, 3.1-3.10 were synthesized in good yields through the modified Mannich reaction using bis(hydroxymethyl)diphenylphosphonium chloride [Ph2P(CH2OH)2]+Cl- as the key starting material.
The phosphine-derivatized amine and amino carboxylic acid ligands synthesized have high coordination ability with Re(I) tricarbonyl core. Three different rhenium precursors [Re(CO)3Br3] [NEt4]2, [Re(CO)5Br] and [Re(CO)3Br2MeOH][NEt4] were used for the complexation to form the corresponding rhenium(I) tricarbonyl complexes. These complexes can serve as model compounds for further functionalization for potential radiopharmaceutical applications. Complexes 3.11 and 3.17 were coupled with gly-gly and gly-gly-gly, which served as model small peptides, via TFP esters to form compounds 3.26-3.29. In order to investigate the poor yields in the synthesis of compounds 3.19 and 3.20 from [Re(CO)3Br3]2-, phosphine-derivatized diamine ligands 4.1-4.5 were synthesized as well, the results suggest that the poor yields were due to the interference from the carboxyl groups of 3.19 and 3.20.
The structures of all the compounds were characterized by 1H and 31P NMR spectroscopy; all the rhenium complexes were characterized by IR spectroscopy; compounds 2.1, 2.3, 2.4, 2.5, 3.8, 3.11, 3.15 and 3.25 were characterized by X-ray crystallography.
The kinetics of the reactions 3.1 -> 3.11 and 3.5 3.15 were studied by means of time-dependent 31P NMR and a mechanism involving four elementary steps was proposed.
The stability of the rhenium complexes of phosphine-derivatized carboxylic acids were studied by Electrospray mass spectrometric in neutral and aged mildly basic solutions. The results suggested these complexes to possess significant stability.
Cytotoxicity testing of compounds 3.21, 3.15, 3.11, 3.13, 2.3, 2.4, 2.5 and 4.7 showed that these complexes are active against human leukemic MOLT-4 cell line.
Date Issued
2005
Call Number
QD181.R4 Zen
Date Submitted
2005