Sinteza statina imobiliziranim enzimom u različitim reaktorskim sustavima

master's thesis

• Title (english): Synthesis of statins by immobilized enzyme in different reactor systems
• Author: Marta Pinčić
• Mentor: Ana Vrsalović Presečki (mentor)
• Committee member: Ana Vrsalović Presečki (predsjednik povjerenstva)
• Committee member: Anita Šalić (član povjerenstva)
• Committee member: Ana Lončarić Božić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Chemical Engineering and Technology; Zagreb
• Defense date and country: 2024-09-27, Croatia
• Scientific / art field, discipline and subdiscipline: TECHNICAL SCIENCES; Chemical Engineering

Abstract

Statini su lijekovi s kojima se uspješno liječi hiperkolesterolemija i suzbija rizik razvoja kardiovaskularnih bolesti. Enzim 2-deoksiriboza-5-fosfat aldolaza (DERA) katalizira sintezu prekursora statina stereoselektivnom dvostrukom aldolnom adicijom. Produkti ove reakcije su 4-kloro-3-hidroksibutanal (4C-Cl) i (3R,5R)-6-kloro-3,5-dihidroksibutanal (6C-Cl) tj. laktol.
U ovom radu supstrati, acetaldehid (AA) i kloroacetaldehid (CAA), korišteni su za sintezu ovih prekursora statina, kataliziranu imobiliziranom DERA u različitim kontinuiranim reaktorima. DERA je kovalentno imobilizirana na mezoporoznu siliku i magnetske nanočestice. Cilj ovog istraživanja bio je usporediti nosioce za imobilizaciju, reaktorske sustave i varijacije procesnih parametara. Studija je također ispitala kako glutaraldehid i anhidrid jantarne kiseline djeluju kao aktivatori nosioca. Temeljito su analizirani ključni procesni pokazatelji, poput konverzije, produktivnosti i maksimalne koncentracije proizvoda. Rezultati su pokazali da je proces s enzimom imobiliziranim na mezoporoznu siliku pokazao bolje rezultate po ovim pokazateljima. Međutim, sustav koji koristi magnetske nanočestice pokazao je veću stabilnost enzima te je proces postigao stacionarne uvjete tijekom kontinuiranog rada.

Abstract (english)

Statins are highly effective drugs used to treat hypercholesterolemia and reduce the risk of cardiovascular disease. The enzyme 2-deoxy-d-ribose-5-phosphate aldolase (DERA) plays a key role in synthesizing statin precursors through stereoselective double aldol addition.
This reaction yields products such as 4-chloro-3-hydroxybutanal (4C-Cl) and
(3R,5R)-6-chloro-3,5-dihydroxybutanal (6C-Cl) i.e. lactol. In this work the substrates, acetaldehyde (AA) and chloroacetaldehyde (CAA), were used for the synthesis of these statin precursors, catalyzed by immobilized DERA in different flow reactors. DERA was covalently immobilized on mesoporous silica and magnetic nanoparticles. The aim of this study was to compare carriers for immobilisation, reactor systems, and process parameter variations. The study also examined how glutaraldehyde and succinic anhydride function as carrier activators. Key process indicators, such as conversion, productivity, and maximum product concentration, were thoroughly analyzed. Results demonstrated that process with enzyme immobilised on mesoporous silica led to better performance across these indicators. However, the system using magnetic nanoparticles showed greater enzyme stability and maintained a steady state during continuous operation.

• Keywords: statini; DERA; mezoporozna silika; magnetske nanočestice; kontinuirani proces; mikroreaktori
• Keywords (english): statins; DERA; mesoporous silica; magnetic nanoparticles; continuous process; microreactors
• Language: croatian
• URN:NBN: urn:nbn:hr:149:028900
• Study programme: Title: Environmental Engineering - Graduate study; Study programme type: university; Study level: graduate; Academic / professional title: sveučilišni/a magistar/magistra inženjer/inženjerka ekoinženjerstva (sveučilišni/a magistar/magistra inženjer/inženjerka ekoinženjerstva)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Embargoed access; Embargo expiration date: 2025-10-01
• Created on: 2024-11-07 11:56:21