Primjena analize osjetljivosti parametara na modelu kaskadne reakcije

master's thesis

• Title (english): The application of parameter sensitivity analysis on the cascade reaction model
• Author: Barbara Cvetić
• 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: 2020-09-30, Croatia
• Scientific / art field, discipline and subdiscipline: TECHNICAL SCIENCES; Chemical Engineering

Abstract

Napredak kiralne tehnologije i sposobnost proizvodnje enantiomerno čistih spojeva imaju važan utjecaj na dizajn, istraživanje i razvoj lijekova. U ovome radu provedena je analiza osjetljivosti parametara na modelu kaskadne reakcije. Ispitivana kaskadna rekacija sastoji se od tri reakcijska koraka: i. otvaranje (S)-epoksida i (R)-epoksida cijanatnim ionima, ii. otvaranje (S)-epoksida i (R)-epoksida bromidnim ionima, iii. zatvaranje prstena dibromoalkohola. Prva dva stupnja provedena su u prisustvu enzima halogenhidrin-dehalogenaze. Analiza osjetljivosti parametara provedena je za model kinetičke rezolucije i dinamičke kinetičke rezolucije, odnosno proveden je niz simulacija matematičkog modela. Budući da je kod kinetičke rezolucije maksimalni prinos samo 50 % te da je dosta teško odvajanje optički aktivnog supstrata i produkta, simulacije su provedene i za model dinamičke kinetičke rezolucije, odnosno uz dodatak bromidnih iona. Dobiveni su grafički prikazi ovisnosti odstupanja optičke čistoće (ee) od nulte ee vrijednosti o vrijednosti pojedinog parametra. Utjecaj vrijednosti pojedinog parametra na ee pri kinetičkoj rezoluciji promatran je pri 48 %-tnoj konverziji supstrata, dok je pri dinamičkoj kinetičkoj rezoluciji promatran pri 100 %-tnoj konverziji supstrata. Svi ispitani kinetički parametri imaju utjecaj na promjenu odstupanja ee od nulte vrijednosti, neki u cijelom ispitivanom području, a neki samo u djelu ispitivanog područja.

Abstract (english)

Advances in chiral technology and the ability to produce enantiomerically pure compounds have an important impact on drug design, research, and development. In this paper, the sensitivity analysis of the parameters on the cascade reaction model is performed. The investigated cascade reaction consists of three reaction steps: i. opening of (S)-epoxide and (R)-epoxide with cyanate ions, ii. opening of (S)-epoxide and (R)-epoxide with bromide ions, iii. closing the dibromoalcohol ring. The first two steps were performed in the presence of the enzyme halohydrin dehalogenase. The sensitivity analysis of the parameters was performed for the model of kinetic resolution and dynamic kinetic resolution, ie a series of simulations of the mathematical model were performed. Since the maximum yield at kinetic resolution is only 50 % and it is quite difficult to separate the optically active substrate and product, simulations were performed for the model of dynamic kinetic resolution, ie with the addition of bromide ions. Graphical representations of the dependence of the deviation of the optical purity (ee) from the zero ee value on the value of an individual parameter were obtained. The influence of the value of an individual parameter on ee at kinetic resolution was observed at 48 % substrate conversion, while at dynamic kinetic resolution it was observed at 100 % substrate conversion. All examined kinetic parameters have an influence on the change of the deviation ee from the zero value, some in the whole examined area, and some only in a part of the examined area.

• Keywords: kinetička rezolucija; dinamička kinetička rezolucija; matematičko modeliranje; halogenhidrin-dehalogenaza; epoksid; oksazolidinon; enzimska reakcijska kinetika; optička čistoća
• Keywords (english): kinetic resolution; dynamic kinetic resolution; mathematical modeling; halohydrin dehalogenase; epoxide; oxazolidinone; enzyme reaction kinetics; optical purity
• Language: croatian
• URN:NBN: urn:nbn:hr:149:282574
• 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; Embargo expiration date: 2022-10-01
• Created on: 2022-03-01 17:34:11