Transacilacija u konjugatima ferocena i purinskih baza. Računalna studija mehanizma

master's thesis

• Title (english): Transacylation in ferrocene derivatives of purine nucleobases. Computational study of the mechanism
• Author: Lucija Božičević
• Mentor: Davor Šakić (mentor)
• Mentor: Valerije Vrček (komentor)
• Committee member: Davor Šakić (predsjednik povjerenstva)
• Committee member: Valerije Vrček (član povjerenstva)
• Committee member: Tin Weitner (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of analytical chemistry); Zagreb
• Defense date and country: 2019-09-25, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry; Organic Chemistry

Abstract

Purinske baze mogu biti supstituirane ferocenoilnom skupinom pri čemu se ista može vezati na N7- te N9-atom purinskog prstena. U polarnom organskom otapalu dimetilsulfoksidu (DMSO) dolazi do interkonverzije dvaju izomera. Reakciju je moguće pratiti NMR-spektroskopijom. Iz podataka dobivenih praćenjem reakcije do uspostave ravnoteže moguće je odrediti eksperimentalne konstante brzine reakcija kobs te konstante ravnoteže Keq te izračunati promjenu Gibbsove slobodne energije potrebnu za odvijanje procesa. Korištenjem računalno-kemijskih metoda modelirana su tri reakcijska mehanizma, ranije opisana u literaturi, koja bi potencijalno mogla odgovarati mehanizmu transacilacije u konjugatima ferocena i purinskih baza. Odgovarajućim procesima smatraju se oni čije su energetske barijere niže ili jednake eksperimentalno dobivenima. Reakcija koja uključuje dimetilsulfoksid kao nukleofilni reaktant jedina odgovara eksperimentalno dobivenim parametrima, zbog čega je ova SN2-like reakcija najvjerojatnije odgovorna za transacilaciju konjugata ferocena i purinskih baza. Supstituenti na C6-atomu pokazuju znatan utjecaj na brzinu reakcije transacilacije. Izomerizacija acilnih derivata purinskih baza u polarnim organskim otapalima, ukoliko njezin mehanizam nije poznat, predstavlja problem prilikom rukovanja sa spojevima. Transacilacija u polarnom otapalu poput DMSO-a nije ograničena samo na organometalne derivate purinskih baza, a poznavanje ovakvih reakcija moglo bi se pokazati ključnim i za derivate drugih nukleobaza, ali i brojnih heterocikličkih sustava.

Abstract (english)

In ferrocene-nucleobase conjugates ferrocenoyl group can be placed at N7- and N9-atoms of purine ring. There is an interconversion between the two when the compound is dissolved in polar organic solvents, such as dimethylsulfoxide (DMSO). Reaction was followed using the NMR-spectroscopy until dynamic equilibrium is reached. From obtained experimental data, kobs and Keq can be determined, as well as ΔG‡. By use of DFT calculations, three reaction pathways, formerly described in literature, were considered and modelled. These reaction pathways are considered as potential transacylation mechanisms if the calculated energy barriers are lower or close to the experimental ones. Only the SN2-like reaction mechanism involving DMSO as a nucleophilic reactant agrees well with experimental data. It was also determined that C6-substituent of purine ring has a great influence on reaction kinetics. Isomerization of acylated purines in polar organic solvent, DMSO, is of great importance for treating or dissolving acylated purines in it. Transacylation is not limited to organometallic-nucleobase conjugates only and could possibly be important in many other purine-acyl derivatives, as well as some other heterocyclic systems in general.

• Keywords: ferocen; purinske baze; transacilacija; DFT metode; računalna studija
• Keywords (english): ferrocene; purine nucleobases; transacylation; DFT methods; computational study
• Language: croatian
• URN:NBN: urn:nbn:hr:163:616608
• 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: 2021-05-12 13:03:50