Thesis supervisor: Ferenc Krisztián Kálmán
Location of studies (in Hungarian): Departement of Physical Chemistry, Faculty of Science and Technology, University of Deberecen Abbreviation of location of studies: D622
Description of the research topic:
Description of the research topic:
In the late ’90s, the discovery of a new disease, the Nephrogenic Systemic Fibrosis (NSF), had shown that the in vivo application of the Gd(III)-based MRI (Magnetic Resonance Imaging) contrast agent believed to be safe, can cause serious side effects, even death, under specific circumstances. The NSF affects patients with severe kidney failure and it is triggered by the free Gd(III) ion liberated from certain Gd(III)-based CAs being administered intravenously (mostly from the the bis-amide derivatives of the [Gd(DTPA)] complex), and accumulated in different tissues and organs. A possible way to handle the problem of NSF, is the replacement of the paramagnetic Gd(III) ion with other one which is better tolerated in vivo. The Mn(II), Fe(II) or Fe(III) are good candidates to replace Gd(III), since these are essential elements and the humans have developed efficient routes to control their homeostasis. However, to avoid the occasional toxicity and the loss of the desired contrast enhancement effect those must be administered in the form of inert complexes. Of course, these complexes also have to meet with strict requirements for safe in vivo application. Such requirements are the high thermodynamic stability and inertness, good relaxivity and solubility, low toxicity etc.. Nevertheless, the replacement of Gd(III) with transition metal ion, is not an easy task since the ligands are suitable for Gd(III) are usually not good for them and vice versa. The lower coordination number and charge as well as the different “hard-soft” character of the ions requires substantial modification of the ligands originally designed for Gd(III) complexation.
In the first part of the PhD work, the synthesis of several ligands suitable for the chelation of Mn(II), Fe(II) and Fe(III) ions will be performed by techniques and methodes being used for long time in our group. After that, a very detailed coordination chemical investigation will be carried out in all cases by using pH-potentiometry, spectrophotometry, 1H relaxometry, multinuclear NMR, X-ray crystallography, DFT etc.. We will study the solution equilibria, the inertness, the relaxation properties, the red-ox behaviour, the structure of the complexes and so on. In the light of the in vitro experiments, the most promising candidates will be transfered to our partners for in vivo trial on animal models.
Required language skills: angol Number of students who can be accepted: 1
Deadline for application: 2023-01-16
2024. IV. 17. ODT ülés Az ODT következő ülésére 2024. június 14-én, pénteken 10.00 órakor kerül sor a Semmelweis Egyetem Szenátusi termében (Bp. Üllői út 26. I. emelet).
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