Transformacijski put modela lijekova u klorirajućim uvjetima. Kvantno-kemijska studija

master's thesis

• Title (english): Transformation pathway of drug models in chlorinating conditions. Quantum-chemical study
• Author: Ratko Preradović
• Mentor: Davor Šakić (mentor)
• Committee member: Davor Šakić (predsjednik povjerenstva)
• Committee member: Marijan Marijan (član povjerenstva); MBZ: 335524
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of analytical chemistry); Zagreb
• Defense date and country: 2022-07-01, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry; Theoretical Chemistry

Abstract

Lijekovi nakon uporabe bivaju eliminirani iz organizma i kao takvi dospijevaju u otpadne vode i
dezinfekcijske bazene. Prilikom obrade takvih voda najkorištenija metoda je kloriranje raznim
klorirajućim specijama među kojima je najučestalija hipokloritna kiselina i plinoviti klor. U
reakcijama s klorirajućim specijama metaboliti lijekova, među kojima su nama najzanimljiviji oni
koji sadrže amino skupinu, nastaju N-kloramini koji su reaktivniji, toksičniji i perzistentniji oblici.
Sudbine N-kloraminskih specija smo proučavali putem Hoffman-Löffler-Freytag (HLF) reakcije.
Računato je koji su produkti vjerojatniji s obzirom na energetske barijere reakcija te stabilnost
produkata.
Mehanizmi ovih reakcija proučavani su kvantno-kemijskim modelima kojima su se računale
energije produkata, reaktanata i prijelaznih stanja te se putem IQmol programa vizualizirale
strukture. Kvantno kemijski izračuni izvedeni su korištenjem programskog paketa Orca. Orca nudi
najsuvremenije metode u područjima funkcionala gustoće (DFT – Density Functional Theory) kao
i metode temeljene na valnim funkcijama.
Rezultati dobiveni u ovom radu pokazuju da se N-klorirani derivati pregrađuju u N-radikale koji se
putem intramolekulskog prijenosa vodika pregrađuju u stabilnije C-radikale koji se kloriraju i pod
utjecajem baze cikliziraju u piperidinske i pirolidinske sustave dajući spojeve novih karakteristika.
Na kraju reakcije ostajemo s pirolidinskim (ili piperidinskim) prstenom i trimetilamin
hidrokloridnom soli.

Abstract (english)

After use, drugs are eliminated from the body and as such end up in wastewater and disinfection
pools. When treating such waters, the most used method is chlorination with chlorinating spices,
among which hypochlorous acid and chlorine gas are most common. In reactions with chlorinating
species, drug metabolites, among which the most interesting are those containing an amino group,
N-chloramines are formed which are more reactive, toxic and persistent forms.
The fate of N-chloramine species was studied by Hoffman-Löffler-Freytag (HLF) reactions. It was
calculated which products are more likely given the barrier energy response and the stability of
products.
The mechanisms of these reactions have been studied by quantum chemical models that calculate
the energy of products, reactants and transition states, and structures are visualized through the
IQmol program. Quantum chemical calculations were performed using the Orca software package.
Orca offers state-of-the-art methods in the field of functional density theory (DFT - Density
Functional Theory) as well as methods based on wave functions.
The results obtained in this paper show that N-chlorinated derivatives are converted into Nradicals
which are converted into more stable C-radicals by intramolecular hydrogen transfer
which are then chlorinated and cyclized under the influence of base into piperidine and pyrrolidine
systems giving compounds of new characteristics. At the end of the reaction we are left with a
pyrrolidine (or piperidine) ring and trimethylamine hydrochloride salt.

• Keywords: kloriranje; otpadne vode; Hoffman-Löffler-Freytag (HLF) reakcija; 2-aminoheptan; računalna studija
• Keywords (english): chlorination; waste water; Hoffman-Löffler-Freytag (HLF) reaction; 2-aminoheptan; computer study
• Language: croatian
• URN:NBN: urn:nbn:hr:163:670348
• Study programme: Title: Pharmacy; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: magistar/magistra farmacije (magistar/magistra farmacije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2022-07-05 08:15:28