prikaz prve stranice dokumenta Priprava novih heterocikličkih oksima i njihova učinkovitost pri reaktivaciji fosforiliranih kolinesteraza
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doctoral thesis
Priprava novih heterocikličkih oksima i njihova učinkovitost pri reaktivaciji fosforiliranih kolinesteraza
Zagreb: University of Zagreb, Faculty of Science, 2014. urn:nbn:hr:217:131355
Baumann, Krešimir
University of Zagreb
Faculty of Science
Department of Chemistry

Institutional repository: Repository of the Faculty of Science

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Baumann, K. (2014). Priprava novih heterocikličkih oksima i njihova učinkovitost pri reaktivaciji fosforiliranih kolinesteraza (Doctoral thesis). Zagreb: University of Zagreb, Faculty of Science. Retrieved from https://urn.nsk.hr/urn:nbn:hr:217:131355

Baumann, Krešimir. "Priprava novih heterocikličkih oksima i njihova učinkovitost pri reaktivaciji fosforiliranih kolinesteraza." Doctoral thesis, University of Zagreb, Faculty of Science, 2014. https://urn.nsk.hr/urn:nbn:hr:217:131355

Baumann, Krešimir. "Priprava novih heterocikličkih oksima i njihova učinkovitost pri reaktivaciji fosforiliranih kolinesteraza." Doctoral thesis, University of Zagreb, Faculty of Science, 2014. https://urn.nsk.hr/urn:nbn:hr:217:131355

Baumann, K. (2014). 'Priprava novih heterocikličkih oksima i njihova učinkovitost pri reaktivaciji fosforiliranih kolinesteraza', Doctoral thesis, University of Zagreb, Faculty of Science, accessed 25 November 2024, https://urn.nsk.hr/urn:nbn:hr:217:131355

Baumann K. Priprava novih heterocikličkih oksima i njihova učinkovitost pri reaktivaciji fosforiliranih kolinesteraza [Doctoral thesis]. Zagreb: University of Zagreb, Faculty of Science; 2014 [cited 2024 November 25] Available at: https://urn.nsk.hr/urn:nbn:hr:217:131355

K. Baumann, "Priprava novih heterocikličkih oksima i njihova učinkovitost pri reaktivaciji fosforiliranih kolinesteraza", Doctoral thesis, University of Zagreb, Faculty of Science, Zagreb, 2014. Available at: https://urn.nsk.hr/urn:nbn:hr:217:131355

Metadata
TitlePriprava novih heterocikličkih oksima i njihova učinkovitost pri reaktivaciji fosforiliranih kolinesteraza
Title (english)Synthesis of novel heterocyclic oximes and their efficiency in reactivation of phosphorylated cholinesterases
AuthorKrešimir Baumann
MentorSrđanka Tomić-Pisarović (mentor)
MentorInes Primožič (komentor)
Committee memberSnežana Miljanić (predsjednik povjerenstva)
Committee memberSrđanka Tomić-Pisarović (član povjerenstva)
Committee memberRuža Frkanec (član povjerenstva)
GranterUniversity of Zagreb
Faculty of Science
(Department of Chemistry)
Zagreb
Defense date and country2014-06-10, Croatia
Scientific / art field,
discipline and subdiscipline		NATURAL SCIENCES
Chemistry
Universal decimal classification
(UDC)		54 - Chemistry. Crystallography. Mineralogy
Abstract
U okviru ove disertacije opisana je priprava devet N-alkilnih derivata te po jedanaest 2- karbaldehida i 2-aldoksima imidazola i benzimidazola od kojih devet do sada nisu opisani u literaturi. Ispitana je i mogućnost mehanokemijske sinteze oksima karbaldehida imidazola, benzimidazola i piridina bez dodatka ili uz katalitičku količinu otapala s hidroksilaminom bez dodatka baze. Nadalje, pripravljena su 34 različito supstituirana, kvaterna imidazolijeva i benzimidazolijeva 2-aldoksima (32 nova spoja) da bi se ispitala njihova učinkovitost u reaktivaciji butirilkolinesteraze iz ljudskog seruma inhibirane O,O-dietil-O-(4-nitrofenil)fosfatom (paraoksonom). Kvaternizacija je provedena s metil-, etil- i alil-jodidom i različito para i meta supstituiranim benzil-bromidima. Svi pripravljeni spojevi dobiveni su u zadovoljavajućem iskorištenju te im je struktura dokazana standardnim analitičkim spektroskopskim metodama (1D i 2D NMR, IR, MS). Oksimskim skupinama četiriju kvaternih derivata određene su pKa vrijednosti. Stupanj disociranosti oksimske skupine derivata imidazola (pKa = 8,0–8,4) je približno jednak ili manji od onoga PAM-2 (8,1), dok je pri fiziološkom pH prisutno najviše disociranog derivata benzimidazola (pKa = 7,8). Svi kvaterni spojevi testirani su kao reverzibilni inhibitori (IC50 0,12–390 μmol dm–3) te reaktivatori (8–88 %) paraoksonom inhibirane butirilkolinesteraze.
Abstract (english)
In this thesis syntheses of nine novel N-alkyl derivatives as well as eleven 2-carbaldehydes and 2- aldoximes of imidazole and benzimidazole are described. The possibility of mechanochemical synthesis of imidazole, benzimidazole and pyridine oximes from appropriate carbonyl compounds and hydroxylamine hydrochloride, without any base and with or without catalytic amount of solvent was also tested. Further more, 34 differently substituted, quaternary imidazole and benzimidazole 2- aldoxime derivatives were prepared (32 new compounds) in order to evaluate their efficiency in reactivation of O,O-diethyl-O-(4-nitrophenyl)phosphate (Paraoxon) inhibited human serum butyrylcholinesterase. Quaternization was carried out with methyl, ethyl, allyl iodide and differently substituted meta and para benzyl bromides. All compounds were prepared in good yields and were characterized by standard analytical spectroscopy methods (1D and 2D NMR, IR, MS). pKa values were measured and compared to that of the antidote PAM-2 (8.1). Values for the oxime group of three quaternary imidazoles were in the range of 8.0–8.4 and benzimidazole derivative 7.8. All tested quaternary derivatives were shown to be reversible inhibitors of butyrylcholinesterase (IC50 0.12–390 μmol dm–3) and reactivators of Paraoxon inhibited enzyme in the range of 8–88 %.
Keywords
Keywords (english)
Languagecroatian
URN:NBNurn:nbn:hr:217:131355
Study programmeTitle: Doctoral study in chemistry
Study programme type: university
Study level: postgraduate
Academic / professional title: doktor/doktorica znanosti, područje prirodnih znanosti, polje kemija (doktor/doktorica znanosti, područje prirodnih znanosti, polje kemija)
Type of resourceText
Extent141 str. ; 30 cm
File originBorn digital
Access conditionsClosed access
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Created on2019-03-21 13:46:35