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Bifunctional chelators for selective copper(II) binding
Paúrová, Monika ; Kotek, Jan (advisor) ; Vojtíšek, Pavel (referee)
Title: Bifunctional chelators for selective copper(II) binding Autor: Bc. Monika Paúrová Department: Department of Inorganic Chemistry, Faculty of Science Supervisor: doc. RNDr. Jan Kotek, Ph.D. Supervisor's e-mail: modrej@natur.cuni.cz Abstract: In this Master thesis, cyclam bifunctional derivatives bearing pendant phosphinate groups (4-methyl-11-p-aminobenzyl-1,4,8,11-tetraazacyclotetradecane-1,8- bis(methylenephosphinic acid)) and phosphonate groups (4-methyl-11-p-aminobenzyl- 1,4,8,11-tetraazacyclotetradecane-1,8-bis(methylenephosphonic acid)), were prepared and studied as potential ligands for complexation of divalent copper. These ligands are suitable for binding to a macromolecular carrier. Keywords: radiomedicine, copper, cyclam, chelating agent, phosphinate, phosphonate, kinetic inertness, kinetic lability, thermodynamic stability
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Bifunctional ligands for copper(II) complexation
Blahut, Jan ; Kotek, Jan (advisor) ; Svoboda, Jan (referee)
Because of an indisputable pharmacological advatages of radiometal-labeled compounds, a purpose of this work it to design and synthesize a new chelatation system for copper(II) complexation. The solution properties of the ligand and copper complex are also studied, as well as its ability for binding a targeting molecule.
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Bifunctional ligands for copper(II) complexation
Benešová, Martina ; Kotek, Jan (advisor) ; Kozempel, Ján (referee)
Title: Bifunctional ligands for copper(II) complexation Author: Bc. Martina Benešová Supervisor: doc. RNDr. Jan Kotek, Ph.D. Institution: Department of Inorganic Chemistry, Faculty of Science, CU in Prague Author's e-mail: EvaGlaser@seznam.cz ABSTRACT The main aim of this thesis was preparation of macrocyclic ligands based on 1,4,8,11- tetraazacyclotetradecane skeleton, which is suitable for selective complexation of divalent copper, and study of their properties. These ligands are suggested for potential utilization in nuclear medicine. Cyclam macrocycle was modified to bear one coordinating aminobenzylphospinate pendant arm (compound L1) or monophosphinate-bis(phosphonate) pendant arm (compound L2). During the synthesis, the skeleton was protected in positions 1, 4 and 8. In the frame of this work the synthesis of both targeted products was developed. Furthermore, a study of the thermodynamic, kinetic and coordination properties of ligand L2 was investigated by UV/VIS spectrophotometry and potentiometric titrations. A model bioconjugation of ligand L1 with primary amine was also studied. KEYWORDS Cyclam, phosphinates, phosphonates, nuclear medicine, copper(II) complexes, kinetic inertness, thermodynamic stability.
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Ligand design for medicinal applications
Paúrová, Monika ; Kotek, Jan (advisor) ; Trávníček, Zdeněk (referee) ; Řezanka, Pavel (referee)
In recent years, copper radioisotopes have been extensively studied for their suitable coordination and physical properties. Nuclides 61 Cu, 64 Cu and 67 Cu are used in nuclear medicine - in diagnostic as well as in therapeutic applications. The aim of the Thesis is a study of the coordination properties of divalent copper as a stepping stone for the next potential applications. The presented Thesis consists of two thematic parts. The first part deals with the synthesis of cyclam derivatives. Sixteen new macrocyclic ligands with different phosphorus acid coordinating pendant arms (phosphinate, phosphonate, germinal P-C-P) were prepared; an analogous ligand endowed by carboxylic acid pendant arm as well as tetramethylcyclam without coordinating arm were prepared for comparison. The influence of the nature of coordinating acid pendant arms on selectivity and on the rate of copper(II) complexation was studied in detail. The protonation constants of the free ligands and the stability constants of the complexes with selected transition metal ions were determined by potentiometric titrations and by 1 H and 31 P NMR spectroscopy. Kinetic properties - i.e. studies of the formation rate and kinetic inertness of the copper(II) complexes - were performed by UV-Vis spectroscopy. The formation kinetics of the selected...
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Ligand design for medicinal applications
Paúrová, Monika ; Kotek, Jan (advisor) ; Trávníček, Zdeněk (referee) ; Řezanka, Pavel (referee)
In recent years, copper radioisotopes have been extensively studied for their suitable coordination and physical properties. Nuclides 61 Cu, 64 Cu and 67 Cu are used in nuclear medicine - in diagnostic as well as in therapeutic applications. The aim of the Thesis is a study of the coordination properties of divalent copper as a stepping stone for the next potential applications. The presented Thesis consists of two thematic parts. The first part deals with the synthesis of cyclam derivatives. Sixteen new macrocyclic ligands with different phosphorus acid coordinating pendant arms (phosphinate, phosphonate, germinal P-C-P) were prepared; an analogous ligand endowed by carboxylic acid pendant arm as well as tetramethylcyclam without coordinating arm were prepared for comparison. The influence of the nature of coordinating acid pendant arms on selectivity and on the rate of copper(II) complexation was studied in detail. The protonation constants of the free ligands and the stability constants of the complexes with selected transition metal ions were determined by potentiometric titrations and by 1 H and 31 P NMR spectroscopy. Kinetic properties - i.e. studies of the formation rate and kinetic inertness of the copper(II) complexes - were performed by UV-Vis spectroscopy. The formation kinetics of the selected...
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Bifunctional ligands for copper(II) complexation
Benešová, Martina ; Kotek, Jan (advisor) ; Kozempel, Ján (referee)
Title: Bifunctional ligands for copper(II) complexation Author: Bc. Martina Benešová Supervisor: doc. RNDr. Jan Kotek, Ph.D. Institution: Department of Inorganic Chemistry, Faculty of Science, CU in Prague Author's e-mail: EvaGlaser@seznam.cz ABSTRACT The main aim of this thesis was preparation of macrocyclic ligands based on 1,4,8,11- tetraazacyclotetradecane skeleton, which is suitable for selective complexation of divalent copper, and study of their properties. These ligands are suggested for potential utilization in nuclear medicine. Cyclam macrocycle was modified to bear one coordinating aminobenzylphospinate pendant arm (compound L1) or monophosphinate-bis(phosphonate) pendant arm (compound L2). During the synthesis, the skeleton was protected in positions 1, 4 and 8. In the frame of this work the synthesis of both targeted products was developed. Furthermore, a study of the thermodynamic, kinetic and coordination properties of ligand L2 was investigated by UV/VIS spectrophotometry and potentiometric titrations. A model bioconjugation of ligand L1 with primary amine was also studied. KEYWORDS Cyclam, phosphinates, phosphonates, nuclear medicine, copper(II) complexes, kinetic inertness, thermodynamic stability.
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Bifunctional chelators for selective copper(II) binding
Paúrová, Monika ; Kotek, Jan (advisor) ; Vojtíšek, Pavel (referee)
Title: Bifunctional chelators for selective copper(II) binding Autor: Bc. Monika Paúrová Department: Department of Inorganic Chemistry, Faculty of Science Supervisor: doc. RNDr. Jan Kotek, Ph.D. Supervisor's e-mail: modrej@natur.cuni.cz Abstract: In this Master thesis, cyclam bifunctional derivatives bearing pendant phosphinate groups (4-methyl-11-p-aminobenzyl-1,4,8,11-tetraazacyclotetradecane-1,8- bis(methylenephosphinic acid)) and phosphonate groups (4-methyl-11-p-aminobenzyl- 1,4,8,11-tetraazacyclotetradecane-1,8-bis(methylenephosphonic acid)), were prepared and studied as potential ligands for complexation of divalent copper. These ligands are suitable for binding to a macromolecular carrier. Keywords: radiomedicine, copper, cyclam, chelating agent, phosphinate, phosphonate, kinetic inertness, kinetic lability, thermodynamic stability
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Bifunctional ligands for copper(II) complexation
Blahut, Jan ; Kotek, Jan (advisor) ; Svoboda, Jan (referee)
Because of an indisputable pharmacological advatages of radiometal-labeled compounds, a purpose of this work it to design and synthesize a new chelatation system for copper(II) complexation. The solution properties of the ligand and copper complex are also studied, as well as its ability for binding a targeting molecule.
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