Zastosowanie układu sprzężonego CE ICP-MS do badania oddziaływań kompleksów metali, potencjalnych preparatów przeciwnowotworowych, z albuminą i transferyną

Jan Abramski

Abstract

The aim of the presented study was to develop a novel analytical methodology allowing characterization of potential metallodrug-protein interactions. Classical spectrophotometric UV-Vis detection along with rare hyphenation of capillary electrophoresis with element specific mass detection (ICP-MS) was used to accomplish the goal. The UV-Vis detector was supposed to provide easy, fast and cost-effective method to study pharmacokinetical parameters of ruthenium(III) compounds. It was used to calculate reaction rates of ruthenium(III) complex with plasma proteins as well as to compare reactions of two ruthenium(III) complexes with proteins. Due to low sensitivity and lack of specifity the UV-Vis detector failed to provide essential information about ruthenium complexes although allowed to estimate similarity of two ruthenium(III) complexes in adduct formation. Differentiation of ruthenium(III) adducts was not possible with the UV-Vis detection. The hyphenated techniques were used to calculate reaction rates of ongoing ruthenium(III) complex reaction with plasma proteins, albumin and transferrin. The selectivity of the developed method allowed to study competitive interaction of ruthenium(III) complex with the mixture of proteins indicating the major role of albumin. It also provided information about the influence of reducing agent (ascorbic acid) on ruthenium(III) complex stability showing no effect of reduction. Gallium(III) complex studies with the hyphenated techniques gave the opportunity to gather information on its interactions with plasma proteins. Model in vitro experiments proved the high affinity of gallium(III) complex toward transferrin and low toward albumin. The two forms of three acquired for transferrin-gallium(III) adduct were also recorded for serum sample analysis. The results are in agreement with in vivo studies of gallium interactions with proteins indicating the main role of transferrin in the therapeutic agent transport.
Diploma typeDoctor of Philosophy
Author Jan Abramski (FC)
Jan Abramski,,
- Faculty of Chemistry
Title in PolishZastosowanie układu sprzężonego CE ICP-MS do badania oddziaływań kompleksów metali, potencjalnych preparatów przeciwnowotworowych, z albuminą i transferyną
Languagepl polski
Certifying UnitFaculty of Chemistry (FC)
Disciplinechemistry / (chemical sciences domain) / (physical sciences)
Defense Date25-10-2010
Supervisor Maciej Jarosz (FC / CAC)
Maciej Jarosz,,
- Chair Of Analytical Chemistry

Internal reviewers Maria Balcerzak (FC / CAC)
Maria Balcerzak,,
- Chair Of Analytical Chemistry
External reviewers Andrzej Janiszewski
Andrzej Janiszewski,,
-

Bogusław Buszewski - [Uniwersytet Mikołaja Kopernika w Toruniu]
Bogusław Buszewski,,
-
- Uniwersytet Mikołaja Kopernika w Toruniu
Pages79
Keywords in Englishxxx
Abstract in EnglishThe aim of the presented study was to develop a novel analytical methodology allowing characterization of potential metallodrug-protein interactions. Classical spectrophotometric UV-Vis detection along with rare hyphenation of capillary electrophoresis with element specific mass detection (ICP-MS) was used to accomplish the goal. The UV-Vis detector was supposed to provide easy, fast and cost-effective method to study pharmacokinetical parameters of ruthenium(III) compounds. It was used to calculate reaction rates of ruthenium(III) complex with plasma proteins as well as to compare reactions of two ruthenium(III) complexes with proteins. Due to low sensitivity and lack of specifity the UV-Vis detector failed to provide essential information about ruthenium complexes although allowed to estimate similarity of two ruthenium(III) complexes in adduct formation. Differentiation of ruthenium(III) adducts was not possible with the UV-Vis detection. The hyphenated techniques were used to calculate reaction rates of ongoing ruthenium(III) complex reaction with plasma proteins, albumin and transferrin. The selectivity of the developed method allowed to study competitive interaction of ruthenium(III) complex with the mixture of proteins indicating the major role of albumin. It also provided information about the influence of reducing agent (ascorbic acid) on ruthenium(III) complex stability showing no effect of reduction. Gallium(III) complex studies with the hyphenated techniques gave the opportunity to gather information on its interactions with plasma proteins. Model in vitro experiments proved the high affinity of gallium(III) complex toward transferrin and low toward albumin. The two forms of three acquired for transferrin-gallium(III) adduct were also recorded for serum sample analysis. The results are in agreement with in vivo studies of gallium interactions with proteins indicating the main role of transferrin in the therapeutic agent transport.
Thesis file
Abramski.pdf 1.22 MB
Citation count*5 (2020-09-18)

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