Pinocembrin iz medu kot potencialni lovilec kemijskih karcinogenov - računalniški pristop

diplomsko delo visokošolskega strokovnega študijskega programa I. stopnje

Urška Vtič (Author), Urban Bren (Mentor), Veronika Furlan (Co-mentor)

Abstract

V diplomskem delu smo preučevali pinocembrin iz medu v vlogi lovilca končnih kemijskih karcinogenov s pomočjo kvantnomehanskih simulacij. Obravnavali smo devet končnih kemijskih karcinogenov: 2-cianoetilen oksid, aflatoksin B1-ekso-8,9-epoksid, β-propiolakton, etilen oksid, kloroetilen oksid, glicidamid, propilen oksid, stiren oksid in vinil karbamat epoksid. S pomočjo kvantnomehanskih simulacij z metodo Hartree-Fock, ki smo jih izvedli s programom Gaussian 09 na gruči računalnikov VRANA, smo izračunali aktivacijske proste energije pri treh različnih fleksibilnih baznih setih HF/6-31G(d), HF/6-31+G(d,p) in HF/6-311++G(d,p), ob uporabi dveh različnih modelov implicitnih topil. Grafični rezultati dokazujejo, da reakcije alkilacije med pinocembrinom in devetimi končnimi kemijskimi karcinogeni potekajo po mehanizmu nukleofilne substitucije SN2. Aktivacijske proste energije za reakcije alkilacije med kemijskimi karcinogeni in pinocembrinom, pridobljene po solvatacijskih metodah Samouglašenega reakcijskega polja in Langevinovih dipolov, pa smo primerjali z eksperimentalnimi vrednostmi aktivacijskih prostih energij med identičnimi karcinogeni in gvaninom - najreaktivnejšo bazo DNK. Na podlagi primerjave z gvaninom smo lahko določili, kako dober lovilec kemijskih karcinogenov je pinocembrin. Ugotovili smo, da pinocembrin predstavlja enakovredno učinkovit lovilec kemijskih karcinogenov v primeru etilen oksida, kloroetilen oksida in glicidamida kot gvanin, saj so izračunane aktivacijske energije podobne eksperimentalnim vrednostim za reakcije z gvaninom. V primeru 2-cianoetilen oksida, AFB1 ekso-8,9-epoksida, propilen oksida in stiren oksida pa pinocembrin ne more učinkovito zaščititi našega dednega materiala, saj je aktivacijska prosta energija pri omenjenih karcinogenih višja od eksperimentalno določene vrednosti za reakcije teh karcinogenov z gvaninom. Pinocembrin predstavlja bolj učinkovit lovilec le v primeru β-propiolaktona in vinil karbamat epoksida, kjer sta bili aktivacijski prosti energiji nižji kot v primeru reakcije z gvaninom.

Keywords

pinocembrin;med;flavonoidi;kemijski karcinogeni;aktivacijska prosta energija;kvantnomehanski izračuni;diplomske naloge;

Data

Language:	Slovenian
Year of publishing:	2021
Typology:	2.11 - Undergraduate Thesis
Organization:	UM FKKT - Faculty of Chemistry and Chemical Engineering
Publisher:	[U. Vtič]
UDC:	615.277.041(043.2)
COBISS:	77928195
Views:	243
Downloads:	30
Average score:	0 (0 votes)
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Other data

Secondary language:	English
Secondary title:	Pinocembrin from honey as a potential scavenger of chemical carcinogens - a computational approach
Secondary abstract:	In this diploma thesis we studied pinocembrin in the role of a scavenger of chemical carcinogens with the help of quantum mechanical simulations. For the simulations the following nine ultimate chemical carcinogen were used: 2-cyanoethylene oxide, aflatoxin B1-exo-8,9-epoxide, β-propiolactone, ethylene oxide, chloroethylene oxide, glycidamide, propylene oxide, styrene oxide and vinyl carbamate epoxide. With the quantum mechanical simulations at the Hartree-Fock level of theory, performed with the program Gaussian 09 on the computer cluster VRANA, we calculated the activation free energies using three different flexible basis sets: HF/6-31G(d), HF/6-31+G(d,p) and HF/6-311++G(d,p) in conjunction with two different implicit solvation models. The results in the form of images prove that the alkylation reactions between pinocembrin and ultimate chemical carcinogens follow the mechanism of nucleophilic substitution SN2. The activation free energies obtained by the solvation models Self-Consistent Reaction Field and Langevin Dipoles were compared with the experimental values of the activation free energies between identical chemical carcinogens and guanine, which represents the most reactive DNA base. Based on the comparison with guanine, we were able to determine just how efficient scavenger of chemical carcinogens is pinocembrin. We found that pinocembrin represents a similar scavenger of ultimate chemical carcinogens as guanine for ethylene oxide, chloroethylene oxide and glycidamide as guanine, because the calculated activation free energies were similar to the experimentally determined values for the reactions with guanine. In the case of 2-cyanoethylene oxide, aflatoxin B1-exo-8,9-epoxide, propylene oxide and styrene oxide pinocembrin cannot efficiently protect our DNA, because the activation free energies for these carcinoges were higher than the experimentally determined values for reactions with guanine. Pinocembrin represents an efficient scavenger only in the case of β-propiolactone and vinyl carbamate epoxide, where the calculated activation free energies were lower than the experimentally determined ones for reactions with guanine.
Secondary keywords:	pinocembrin;honey;flavonoids;chemical carcinogens;activation free energy;quantum mechemical calculations;
Type (COBISS):	Bachelor thesis/paper
Thesis comment:	Univ. v Mariboru, Fak. za kemijo in kemijsko tehnologijo
Pages:	X, 28 str.
ID:	13297415