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master's thesis
Provjera valjanosti kinetičkog modela biokatalitičke sinteze fluoriranog cijanoalkohola u različitim tipovima reaktora
Zagreb: University of Zagreb, Faculty of Chemical Engineering and Technology, 2022. urn:nbn:hr:149:638536
Marić, Ana-Katarina
University of Zagreb
Faculty of Chemical Engineering and Technology

Institutional repository: Repository of Faculty of Chemical Engineering and Technology University of Zagreb

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Marić, A. K. (2022). Provjera valjanosti kinetičkog modela biokatalitičke sinteze fluoriranog cijanoalkohola u različitim tipovima reaktora (Master's thesis). Zagreb: University of Zagreb, Faculty of Chemical Engineering and Technology. Retrieved from https://urn.nsk.hr/urn:nbn:hr:149:638536

Marić, Ana Katarina. "Provjera valjanosti kinetičkog modela biokatalitičke sinteze fluoriranog cijanoalkohola u različitim tipovima reaktora." Master's thesis, University of Zagreb, Faculty of Chemical Engineering and Technology, 2022. https://urn.nsk.hr/urn:nbn:hr:149:638536

Marić, Ana Katarina. "Provjera valjanosti kinetičkog modela biokatalitičke sinteze fluoriranog cijanoalkohola u različitim tipovima reaktora." Master's thesis, University of Zagreb, Faculty of Chemical Engineering and Technology, 2022. https://urn.nsk.hr/urn:nbn:hr:149:638536

Marić, A. K. (2022). 'Provjera valjanosti kinetičkog modela biokatalitičke sinteze fluoriranog cijanoalkohola u različitim tipovima reaktora', Master's thesis, University of Zagreb, Faculty of Chemical Engineering and Technology, accessed 20 December 2024, https://urn.nsk.hr/urn:nbn:hr:149:638536

Marić AK. Provjera valjanosti kinetičkog modela biokatalitičke sinteze fluoriranog cijanoalkohola u različitim tipovima reaktora [Master's thesis]. Zagreb: University of Zagreb, Faculty of Chemical Engineering and Technology; 2022 [cited 2024 December 20] Available at: https://urn.nsk.hr/urn:nbn:hr:149:638536

A. K. Marić, "Provjera valjanosti kinetičkog modela biokatalitičke sinteze fluoriranog cijanoalkohola u različitim tipovima reaktora", Master's thesis, University of Zagreb, Faculty of Chemical Engineering and Technology, Zagreb, 2022. Available at: https://urn.nsk.hr/urn:nbn:hr:149:638536

Metadata
TitleProvjera valjanosti kinetičkog modela biokatalitičke sinteze fluoriranog cijanoalkohola u različitim tipovima reaktora
Title (english)Validation of a kinetic model for the biocatalytic synthesis of fluorinated cyanoalcohol in different reactor modes
AuthorAna-Katarina Marić
MentorZvjezdana Findrik Blažević (mentor)
Committee memberZvjezdana Findrik Blažević (predsjednik povjerenstva)
Committee memberMarija Vuković Domanovac (član povjerenstva)
Committee memberDragana Vuk (član povjerenstva)
GranterUniversity of Zagreb
Faculty of Chemical Engineering and Technology
Zagreb
Defense date and country2022-09-14, Croatia
Scientific / art field,
discipline and subdiscipline		TECHNICAL SCIENCES
Chemical Engineering
Abstract
Optički čisti spojevi od velike su važnosti u farmaceutskoj indrustriji, uz sve veći interes za fluorirane spojeve. Za sintezu kiralnih gradivnih elemenata često se koriste enzimi halogenhidrin-dehalogenaze (HHDH), koje mogu primiti brojne anionske nukleofile, od cijanida, cijanata, tiocijanata do azida i nitrita. U njihovoj prisutnosti dolazi do reakcije otvaranja epoksidnog prstena, što dovodi do stvaranja β-substituiranog alkohola. Osnova ovog rada je biokatalitička reakcija, točnije HHDH-katalizirana reakcija otvaranja epoksidnog prstena rac-2-(4-fluorofenil)oksirana cijanidnim ionima. Uz željeni produkt (S)-3-(4-fluorofenil)-3-hidroksipropannitril, ovom reakcijom stvara se i neželjeni (R)-3-(4-fluorofenil)-3-hidroksipropannitril te rac-2-(4-fluorofenil)-1,2-etandiol. Prethodno je razvijen matematički model ove sinteze kombinacijom kinetičkih jednadžbi i reaktorskog modela. U svrhu validacije modela, provedena je serija eksperimenata u kotlastom reaktoru s različitim početnim koncentracijama epoksida, NaCN i HHDH. U eksperimentima inkubacije uočena je deaktivacija enzima ovisna o početnoj koncentraciji epoksida. Operacijska stabilnost matematički je opisana i uključena u model. Nadalje, porastom koncentracije epoksida, stabilnost enzima opada, dok cijanidni nukleofil nema značajan utjecaj na stabilnost enzima. Eksperimentalni podaci pokazuju zadovoljavajuće slaganje s ranije razvijenim matematičkim modelom. Također, matematičko modeliranje pokazalo je kako je sinteza u kotlastom reaktoru/kotlastom reaktoru s ponavljajućim dodatkom epoksida (repetitivnom šaržnom reaktoru) optimalan način proizvodnje danog spoja.
Abstract (english)
Optically pure compounds are of great significance in the pharmaceutical industry, with the increasing interest in fluorinated compounds. One important enzyme group often employed in synthesizing various chiral building blocks are halohydrin dehalogenases (HHDHs) that can accept numerous anionic nucleophiles from cyanide, cyanate, thiocyanate to azide and nitrite. In their presence the ring-opening reaction of epoxide occurs, leading to β-substituted alcohol formation. The foundation of this work lies in a biocatalytic reaction, precisely HHDH-catalysed rac-2-(4-fluorophenyl)oxirane ring-opening reaction mediated by cyanide ions. Besides the desired (S)-3-(4-fluorophenyl)-3-hydroxypropanenitrile, this reaction yields an undesired (R)-3-(4-fluorophenyl)-3-hydroxypropanenitrile and rac-2-(4-fluorophenyl)-1,2-ethanediol. Mathematical model was earlier developed by coupling kinetic equations with reactor model. A series of different batch experiments varying in initial concentrations of epoxide, NaCN and HHDH were conducted with aim of model validation. Enzyme deactivation influenced by the initial epoxide concentration was observed within incubation experiments. Operational stability decay was mathematically described and included in the model. Furthermore, with the increase in the epoxide concentration, enzyme stability decreased, while the cyanide nucleophile did not have a significant effect on the stability of the enzyme. Experimental data has shown a satisfactory match with an earlier developed mathematical model. Moreover, mathematical modeling has shown that synthesis in batch/repetitive batch reactor is the optimal pathway for production of this compound.
Keywords
Keywords (english)
Languagecroatian
URN:NBNurn:nbn:hr:149:638536
ProjectNumber: IP-2018-01-4493
Title: Enzimska sinteza fluoriranih kiralnih građevnih blokova
Acronym: EnzyFluor
Leader: Maja Majerić-Elenkov
Jurisdiction: Croatia
Funder: HRZZ
Funding stream: IP
Study programmeTitle: Applied Chemistry - Graduate study; specializations in: Environmental chemistry and green technologies, Advanced materials and technologies, Applied organic chemistry
Course: Advanced materials and technologies
Study programme type: university
Study level: graduate
Academic / professional title: magistar/magistra primijenjene kemije (magistar/magistra primijenjene kemije)
Type of resourceText
File originBorn digital
Access conditionsOpen access
Embargo expiration date: 2023-10-01
Terms of useLicence In copyright icon
Created on2023-03-19 18:06:09