Biokatalitička sinteza (R)-3-hidroksi-4,4-dimetilpentan nitrila

master's thesis

• Title (english): Biocatalytic synthesis of (R)-3-hydroxy-4,4-dimethylpentane nitrile
• Author: Jelena Jelačić
• Mentor: Zvjezdana Findrik Blažević (mentor)
• Committee member: Zvjezdana Findrik Blažević (predsjednik povjerenstva)
• Committee member: Martina Sudar (član povjerenstva)
• Committee member: Marija Vuković Domanovac (član povjerenstva)
• Granter: University of Zagreb; Faculty of Chemical Engineering and Technology; Zagreb
• Defense date and country: 2020-07-14, Croatia
• Scientific / art field, discipline and subdiscipline: TECHNICAL SCIENCES; Chemical Engineering

Abstract

U ovom radu obrađena je tematika biokatalitičke sinteze kiralnih molekula, odnosno (R)-3-hidroksi-4,4-dimetilpentan nitrila iz 3,3-dimetil-1,2-epoksibutana pomoću enzima halogenhidrin-dehalogenaze. Sinteza optički čistih tvari izuzetno je važan dio farmaceutske industrije s obzirom da dva enantiomera mogu imati potpuno različita svojstva, a nerijetko jedan od njih može pokazivati štetno i toksično biološko djelovanje. Epoksidi su visoko vrijedni spojevi u organskoj sintezi zbog toga što se epoksidni prsten može kemijski transformirati u brojne sintetski korisne intermedijere. Reakcije u kojima su uključeni enzimi potrebno je dobro istražiti i okarakterizirati kako bi se mogle provoditi u industrijskom mjerilu. Obzirom na različitu aktivnost enzima u različitim reakcijskim uvjetima (temperatura, koncentracije supstrata, pH, zasićenost kisikom, prisutnost kofaktora) izuzetno je važno poznavati njihovu strukturu i reakcijski mehanizam kako bi se mogli odrediti najpogodniji reakcijski uvjeti koji će omogućiti dobivanje maksimalnih prinosa željenog produkta. Matematičko modeliranje izvrstan je alat za provođenje istraživanja ove vrste. Sastoji se od kinetičkog modela i bilanci tvari u reaktoru. Za potrebe razvoja matematičkog modela određena je stabilnost 3,3-dimetil-1,2-epoksibutana u puferu te se došlo do spoznaje da je 3,3-dimetil-1,2-epoksibutan podložan kemijskoj hidrolizi. Provedbom simulacija u programskom paketu Scientist utvrđeno je da kemijska hidroliza epoksida ima znatan utjecaj na enzimsku reakciju. Najpogodniji reaktor za biokatalitičku sintezu (R)-3-hidroksi-4,4-dimetilpentan nitrila je kotlasti reaktor uz dotok supstrata jer je u njemu odabirom odgovarajućih radnih uvjeta moguće smanjiti utjecaj inhibicije enzima supstratom i raditi u uvjetima maksimalne aktivnosti enzima.

Abstract (english)

This paper deals with the topic of biocatalytic synthesis of chiral molecules, i.e. (R)-3- hydroxy-4,4-dimethylpentane nitrile from 3,3-dimethyl-1,2-epoxybutane using the enzyme halohydrin dehalogenase. The synthesis of optically pure substances is an extremely important part of the pharmaceutical industry considering that two enantiomers can have completely different properties, and often one of them can have harmful and toxic biological effects. Epoxides are highly valuable compounds in organic synthesis because the epoxy ring can be chemically transformed into plenty of synthetically useful intermediates. Reactions involving enzymes need to be well investigated and characterized to be carried out on an industrial scale. Given the different activity of enzymes in different reaction conditions (temperature, substrate concentrations, pH, oxygen saturation, presence of cofactor), it is extremely important to know their structure and reaction mechanism in order to determine the most suitable reaction conditions that will allow obtaining maximum yields of the desired product. Mathematical modelling is an excellent tool for conducting research of this kind. It consists of a kinetic model and a mass balance in the reactor. For the development of a mathematical model, the stability of 3,3-dimethyl-1,2-epoxybutane in buffer was determined and it was found that 3,3-dimethyl-1,2-epoxybutane is subject to chemical hydrolysis. Simulations in the package programme Scientist showed that chemical hydrolysis of epoxy have a significant impact on the enzymatic reaction. The most suitable reactor for biocatalytic synthesis of (R)-3-hydroxy-4,4-dimethylpentane nitrile is a fed-batch reactor with a continuous supply of substrate because it enables the selection of working conditions that minimize the effect of substrate inhibition, and working at the substrate concentration that provides the maximum reaction rate.

• Keywords: biokatalitička sinteza; epoksid; halogenhidrin-dehalogenaza; kemijska hidroliza; kinetika enzimske reakcije; matematičko modeliranje
• Keywords (english): biocatalytic synthesis; epoxy; halohydrin dehalogenase; chemical hydrolysis; enzyme reaction kinetics; mathematical modelling
• Language: croatian
• URN:NBN: urn:nbn:hr:149:075512
• Study programme: Title: 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 resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2022-03-05 08:22:05