Utilization of mass spectrometry and other analytical techniques for analysis of rhenium complexes

Rheniové komplexy s vybranými organickými ligandy jsou perspektivními radiodiagnostiky používanými v nukleární medicině. Pro jejich lékařské využití je nutná detailní znalost jejich chemických a farmakologických vlastností a musí být k dispozici vhodné analytické metody pro hodnocení čistoty aplikovaných preparátů. V této práci byly připraveny vybrané komplexy rhenia s pyrogalolem, 1,2-dihydroxynaftalenem a katecholem jako silně vázanými organickými ligandy. Pro určení struktury vznikajících komplexů a jejich následných degradačních produktů přímo v reakční směsi byla využita hmotnostní spektrometrie s elektrosprejovou ionizací a dalšími měkkými ionizačními technikami. Pro detailní monitorování průběhu chemických reakcí během vzniku a následných rozkladů komplexů byla využita UV-VIS absorpční spektrometrie a kontinuální ESI-MS analýza. Byly vyvinuty metodiky HPLC a CZE analýz umožňující hodnotit složení reakčních směsí během přípravy komplexů a hodnocení čistoty izolovaných konečných produktů. Preparativní HPLC byla úspěšně využita pro izolaci čistého Re(VII) katecholového komplexu z reakční směsi. Klíčová slova Rheniové komplexy, pyrogalol, 2,3-dihydroxynaftalen, katechol, hmotnostní spektrometrie, ESI/MS, strukturní analýza, UV-VIS absorpční spektrometrie, Reakční kinetika, HPLC, CZE.Rhenium complexes coordinated with suitable organic ligand gain increased interest in radiopharmaceutical medicine. Besides suitable radiological properties given by a metal ion itself, detailed knowledge of overall chemical properties of formed complexes, namely their exact structures, chemical stabilities and possible degradation pathways are essential pre-requisites for their clinical application. Selected rhenium complexes with pyrogallol 2,3-dihydroxynaphthalene and catechol as strongly bound ligands were prepared by a reaction of tetrabutylammonium tetrachlorooxorhenate with twofold molar excess of ligand in presence of various amount of triethylamine. The structures of formed complexes and their consequent reaction products were estimated by means of mass spectrometry with electrospray ionization. The kinetics of reactions in course of complex formation and consequent decomposition were primarily followed by UV- Vis absorption spectra measurement, complemented by single or continuous electrospray mass spectrometry analyses. Optimized HPLC and CZE procedures were utilized for monitoring of the composition of reaction mixtures in course of Re complex formation and for purity check of prepared complexes. Semi-preparative HPLC mode was succesfully utilized for isolation and final purification of...Katedra analytické chemieDepartment of Analytical ChemistryPřírodovědecká fakultaFaculty of Scienc

Utilization of mass spectrometry and other analytical techniques for analysis of rhenium complexes

Rhenium complexes coordinated with suitable organic ligand gain increased interest in radiopharmaceutical medicine. Besides suitable radiological properties given by a metal ion itself, detailed knowledge of overall chemical properties of formed complexes, namely their exact structures, chemical stabilities and possible degradation pathways are essential pre-requisites for their clinical application. Selected rhenium complexes with pyrogallol 2,3-dihydroxynaphthalene and catechol as strongly bound ligands were prepared by a reaction of tetrabutylammonium tetrachlorooxorhenate with twofold molar excess of ligand in presence of various amount of triethylamine. The structures of formed complexes and their consequent reaction products were estimated by means of mass spectrometry with electrospray ionization. The kinetics of reactions in course of complex formation and consequent decomposition were primarily followed by UV- Vis absorption spectra measurement, complemented by single or continuous electrospray mass spectrometry analyses. Optimized HPLC and CZE procedures were utilized for monitoring of the composition of reaction mixtures in course of Re complex formation and for purity check of prepared complexes. Semi-preparative HPLC mode was succesfully utilized for isolation and final purification of..

Role of benzo[a]pyrene in cancer development

4 ABSTRACT Cancer is nowadays one of the most serious diseases. Tumor development is a multistage process in which the effect of internal and external factors lead to failure of regulatory and defense mechanisms of the organism and to the accumulation of mutations which are generated by these organisms. Chemical carcinogens and also biological and physical factors can be regarded as the main external factors. Polycyclic aromatic hydrocarbons are large group of chemical carcinogens. One of them, benzo[a]pyren is the most studied polycyclic aromatic hydrocarbon. Carcinogenic, mutagenic and teratogenic effects of benzo[a]pyrene had been shown on laboratory animals. Benzo[a]pyrene is considered as the main carcinogen in tobacco smoke and is connected with lung cancer development among smokers. Benzo[a]pyrene is metabolized in activation or detoxication pathways by enzymes of mixed function monooxygenase systeme of cytochromes P450. The most important enzymes involved in the activation of these compounds are CYP1A1 and CYP1B1 with cooperation of epoxide hydrolase. The reactive species generated in its activation pathway are able to form covalent adducts with DNA. The most important carcinogenic product of benzo[a]pyrene is benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide, which can caused irreversible ganges in..