Izolacija i strukturna karakterizacija komponenata reakcijske smjese 9a-(2-feniletil) makrozona primjenom sustava LC-SPE/NMR

master's thesis

• Title (english): Isolation and structural characterization of ethyl-phenyl macrozone reaction mixure components using the LC-SPE/NMR
• Author: Noelle Benčić
• Mentor: Predrag Novak (mentor)
• Committee member: Predrag Novak (predsjednik povjerenstva)
• Committee member: Vesna Petrović Peroković (član povjerenstva)
• Committee member: Željka Soldin (član povjerenstva)
• Committee member: Branimir Bertoša (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Chemistry); Zagreb
• Defense date and country: 2019-12-20, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry

Abstract

Makrozoni su novi konjugati azitromicina i derivata tiosemikarbazida koji pokazuju zadovoljavajuće antibakterijsko djelovanje in vitro na odabrane Gram-pozitivne i Gram-negativne bakterije. Zbog sve učestalije pojave bakterija rezistentnih na makrolide, nastavljaju se istraživanja s ciljem razvoja novih oblika makrolidnih antibiotika koji će biti djelotvorni na otporne bakterijske sojeve. Izolacija i određivanje strukture komponenata reakcijske smjese 9a-(2-feniletil)makrozona u ovome radu postignuta je primjenom vezanog sustava LC-SPE/NMR. Istraženi su uvjeti za uspješnu izolaciju i zadržavanje analita na SPE-nosačima. Makrozon je pokazao dobro zadržavanje na nepolarnoj nepokretnoj fazi SPE-nosača baziranoj na silika-materijalu, dok se veći broj polarnih onečišćenja zadržao bolje na divinilbenzenskim polimernim SPE-nosačima. Uz to, većina polarnih onečišćenja uspješno je ekstrahirana koristeći pritom veći dodatni protok vodene pokretne faze. Na temelju snimljenih jedno- i dvodimenzijskih spektara NMR, te analizom spektara MS, predložene su strukture izoliranih komponenata.

Abstract (english)

Macrozones are new conjugates of azithromycin analogues, 9a-(γ-aminopropyl) derivatives, and thiosemicarbazides which show good in vitro activity against selected Gram-positive and Gram-negative bacterial strains. Due to the increasing number of macrolide-resistant bacteria, a search for new antibiotics continues, aimed at discovery of more effective antimicrobial agents. In this work, isolation and determination of the 9a-(2-phenylethyl)macrozone reaction mixture components was achieved using the LC-SPE/NMR system. Several parameters for successful separation and extraction of analytes were optimised. It was found that silica-bonded phase gave satisfactory results for the main compound, macrozone, however, for more polar compounds divinylbenzene polymer phase was better. Additionally, extraction efficiency for more polar impurities was obtained by using higher make-up flow. Structures of the isolated components were proposed on the basis of the recorded one- and two-dimensional NMR spectra and the MS spectra, respectively.

• Keywords: azitromicin; LC-SPE/NMR; makrolidni antibiotici; makrozoni; profil onečišćenja; tiosemikarbazoni; vezani sustavi
• Keywords (english): azithromycin; hyphenated systems; impurity profiling; LC-SPE/NMR; macrolide antibiotics; macrozones; thiosemicarbazone
• Language: croatian
• URN:NBN: urn:nbn:hr:217:265560
• Study programme: Title: Graduate university studies in chemistry; specializations in: Research programme; Course: Research programme; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra kemije (magistar/magistra kemije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access; Embargo expiration date: 2021-12-20
• Created on: 2020-01-13 09:41:57