|
| |
|
|
MRI contrast agents based on saturation transfer
Krchová, Tereza ; Kotek, Jan (advisor) ; Štěpnička, Petr (referee)
Title: MRI Contrast Agents Based on Saturation Transfer Author: Bc. Tereza Krchová Department: Department of Inorganic Chemistry, Faculty of Science, Charles University in Prague Supervisor: doc. RNDr. Jan Kotek, Ph.D. Supervisor's email: modrej@natur.cuni.cz Abstract: The aim of this thesis was to synthesize macrocyclic ligands (based on the DO3A and DO2A framework) with exchangeable protons on the aminic coordinating groups that could be (after the complexation with suitable paramagnetic metal ions) potential contrast agents based on saturation transfer, so called CEST contrast agents (Chemical Exchange Saturation Transfer). Two ligands H3L1 and H2L2 with one and two aminoethyl groups have been synthesized. The structurally similar ligands H3L1 Me and H3L1 2Me with one exchangeable proton and without it have been also prepared. The protonation constants of the ligands H3L1 and H2L2 have been determined by pH 1 H NMR and potentiometric titrations. The stability constants of metal ion complexes with H3L1 and H2L2 have been also determined by potentiometry. The CEST effect of Eu3+ and Yb3+ complexes with H3L1 , H3L1 Me and H3L1 2Me in solution have been studied. The residence lifetime of the inner-sphere water molecule has been determined for Gd-L1 complex. Keywords: CEST, MRI, aminoethyl, DO3A, DO2A, 17 O...
|
|
|
Coordination behaviour of substituted cyclen derivatives
Bárta, Jiří ; Kotek, Jan (advisor) ; Vargová, Zuzana (referee) ; Lubal, Přemysl (referee)
Magnetic resonance imaging (MRI) is one of the none-invasive techniques of human body examination. The only disadvantage of MRI is a low resolution and specificity, therefore, MRI contrast agents (CAs) are widely used in clinical practice (approximately in 40 % of all examinations). They increase not only resolution and specificity but also efficiency of the examination. The CAs consist of paramagnetic ion (Gd3+ or Mn2+ ) and strong chelator such as H4DOTA. Macrocycle cyclen (1,4,7,10-tetraazacyclododecane) is basis of many derivatives which are being used, including mentioned the H4DOTA ligand. 1,4-phosphonic or 1,4-phosphinic acid cyclen derivatives could be a better alternative to commercially available ones. In this thesis, a synthetic pathway to 5 of these novel derivatives is introduced. The protonation constants and stability constants with metals used in CAs (Mn2+ , Gd3+ ) and other selected ones using the potentiometric titrations are determined for 1,4-H4DO2P, 1,4-H2DO2POEt and 1,4-H2DO2Bn2PH . All three ligands have higher stability constant with Mn2+ - log KLM around 12, than with Ca2+ - log KLM around 8, which is the closest rival for transmetallation under physiological conditions. Strong Gd3+ -complex is formed by hexadentate ligand 1,4-H4DO2P - log KLM = 19.15, which is comparable...
|
|
|
Nanodiamonds coated with thermoresponsive paramagnetic polymers
Čopák, Jakub ; Kotek, Jan (advisor) ; Kubíček, Vojtěch (referee)
Temperature is a fundamental physical quantity referring to processes occurring in living systems. Therefore, it is important to design a thermometer which can measure the temperature in a real time and in nano-resolution. Fluorescent nanodiamonds, showing fluorescence thanks to nitrogen-vacancy pairs (NV centres) present as common crystal lattice defects, seem to be promising candidates. The NV centres are highly sensitive to magnetic field changes (magnetic noise). Paramagnetic metal ions reduce T1 relaxation time of nanodiamonds NV centres and this effect strongly depends on the distance between the metal ion and the NV centrum. Among all paramagnetic ions, Gd3+ is most suitable due to its high spin (7/2) and thus causes a great change in reduce T1 relaxation time. Thermoresponsive polymers can be used to achieve a distance change of the Gd3+ ion from nanodiamons NV centres. The aim of this thesis is the preparation of nanodiamonds coated with thermoresponsive paramagnetic polymer layer which can be further utilized as nanothermometer. The nanodiamonds were covered with a thermoresponsive polymeric layer containing a Gd3+ -containing monomer. This architecture responds to temperature changes in a geometric manner, altering the distance of Gd3+ ions from the NV centres. Keywords: nanodiamonds, NV...
|
|
|
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.
|
|
|
Macrobicyclic ligands for use in MRI
Pniok, Miroslav ; Kotek, Jan (advisor) ; Veselý, Jan (referee)
4 Title: Macrobicyclic ligands for use in MRI Author: Bc. Miroslav Pniok Department: Department of Inorganic Chemistry, Faculty of Science Supervisor: doc. RNDr. Jan Kotek, Ph.D. Supervisor's e-mail address: modrej@natur.cuni.cz Abstract: The aim of this project is to synthesize new kind of macrobicyclic ligands for Ln3+ ions, especially Gd3+ ion. Gadolinium(III) complexes are widely used in the clinical practice as contrast agents for MR imaging and an improvement of their properties is in the center of interest of many scientific teams. The macrobicyclic ligands have been designed to make possible coordination of two water molecules in the first coordination sphere with fast water exchange. The macrocyclic core (cyclen) is combined with a linking phosphinate chain in N1 ,N4 - and N1 ,N7 -positions forming a cryptand-like structure. The N1 ,N7 -isomer Et2L1 was synthesized in a small amount so only the N1 ,N4 -isomer H2L3 has been studied. The protonation constants have been determined by pH 31 P NMR titration. Keywords: cyclen, chelating agent, cryptand, MRI, phosphinate
|
|
|
Chelating Polymers for the Haemochromatosis Treatment
Groborz, Ondřej ; Hrubý, Martin (advisor) ; Kotek, Jan (referee)
5 Chelating Polymers for the Haemochromatosis Treatment Author: Ondřej Groborz Tutor: Mgr. Martin Hrubý, Ph.D., DSc. Advisors: Ing. Kristýna Kolouchová Ing. Pavel Švec Institute of Macromolecular Chemistry, Czech Academy of Sciences Abstract Haemochromatosis is a group of hereditary diseases which are characterised by toxic accumulation of iron in parenchymal organs, leading to organ toxicity and irreversible damage. Currently, there are only a few approved medications for this disease, yet all of them possess severe side effects. Herein, we have proposed a new paradigm for treatment: insoluble polymers with negligible systemic biological availability would form stable complexes with iron ions in the gastrointestinal tract, hence decreasing biological availability of iron. The insolubility of polymers prevents them from being absorbed into the organism in the first place while having no systemic side effects or toxicity. We have prepared polymers with several covalently bound iron-chelating ligands and based on the biological data we selected the most successful chelators for possible future applications. These polymers exhibited negligible resorbability and toxicity, superior in vitro iron chelating activity and their efficacy was proven in an in vivo model. Therefore they could be used as a...
|
|
|
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.
|
|
| |
|
|
Design and synthesis of selective gallium(III) chelators
Krchová, Tereza ; Kotek, Jan (advisor) ; Lorenc, Miroslav (referee)
This bachelor thesis is focused on the preparation of two new ligands (based on the 1-oxa-4,7-diazacyclononane skeleton), which would be potentially suitable for fast and selective complexation of Ga(III). Complexes of these ligands could find applications in radiodiagnostics (PET, SPECT), or as a new class of contrast agents for MRI based on proton chemical exchange saturation transfer (CEST). This thesis also describes the preparation of 1-oxa-4,7-diazacyclononane and attempts of preparation of N-benzyloxycarbonylaziridine. Thesis also includes a description of radiodiagnostic and radiotherapeutic methods of nuclear medicine. It also discusses the method of magnetic resonance tomography (MRI), especially the method using CEST contrast agents. Thesis contains an overview of the use of Ga(III) radioisotopes in radiomedicine.
|
guest ::
RSS feed.