20.500.12556/DKUM-97263 Preučevanje antioksidativne aktivnosti polifenola arzanola s pomočjo kvantno-mehanskih izračunov magistrsko delo Study of the antioxidant activity of the polyphenol arzanol by quantum-mechanical calculations Antioksidanti, zlasti polifenoli, imajo izrazito sposobnost lovljenja prostih radikalov, kar zmanjša njihovo reaktivnost ter škodljive učinke. Med rastlinami z izrazito antioksidativno aktivnostjo izstopa smilj (Helichrysum italicum), ki vsebuje številne polifenolne spojine, med katerimi prevladuje arzanol kot ključna bioaktivna spojina. Poleg antioksidativnega delovanja izkazujejo ekstrakti smilja tudi protivnetne, antikarcinogene in protivirusne učinke, zaradi česar se pogosto uporabljajo v pripravkih za nego kože in celjenje ran. Čeprav so znanstvene študije potrdile, da ima arzanol številne pozitivne zdravstvene učinke, mehanizmi njegovega antioksidativnega delovanja v znanstveni literaturi ostajajo neraziskani. V magistrskem delu smo zato s kvantno-mehanskimi simulacijami preučili mehanizme reakcij arzanola v nevtralni, monoanionski in dianionski obliki s prostimi radikali CCl₃OO•, HOO• in CH₃O• ter ocenili njegovo učinkovitost lovljenja teh radikalov. Obravnavali smo mehanizme HAT, RAF, SET, SPLET in SET-PT ter določili termodinamsko ugodnost in kinetične lastnosti posameznih reakcij. Izračuni so bili izvedeni s programom Gaussian 16 v skladu s protokolom QM-ORSA, pri čemer smo uporabili DFT funkcional M06-2X, fleksibilni bazni set 6-311++G(d,p) in solvatacijski model SMD. Rezultati v veliki meri potrjujejo zastavljeno hipotezo, da sta mehanizma HAT in RAF med termodinamsko ugodnimi reakcijskimi potmi za vse tri obravnavane radikale, pri čemer HAT prevladuje z večjim deležem ugodnih reakcijskih mest (85,19 %) v primerjavi z RAF (30,95 %). Termodinamsko najugodnejše reakcije so potekle med dianionsko obliko arzanola in radikalom CH₃O•. Termodinamski rezultati hkrati kažejo na pomembno vlogo mehanizma SPLET, ki izkazuje večji delež ugodnih mest kot RAF (59,26 %). Termodinamsko najugodnejši reakcijski mesti sta 11a (HAT in SPLET) in 9 (RAF) v vseh treh protolitskih oblikah arzanola. Nadaljnja analiza kinetičnih izračunov je pokazala, da večina HAT reakcij na arzanolu poteče brez energijske bariere, s hitrostjo difuzije (1,91·10⁹ M⁻¹·s⁻¹), kar potrjuje tudi zastavljeno hipotezo, da so aktivacijske proste energije najnižje pri HAT mehanizmu. Arzanol se je izkazal kot najučinkovitejši lovilec radikala CCl₃OO•, s celokupno konstanto reakcijske hitrosti 4,09·10¹⁰ M⁻¹·s⁻¹. Pri tem sta bila ključna mehanizma SPLET in RAF, medtem ko je v primeru radikalov HOO• in CH₃O• prevladal mehanizem HAT. Na podlagi izračuna relativne antioksidativne aktivnosti lahko potrdimo tudi, da je arzanol 20-krat učinkovitejši lovilec radikala CCl₃OO• kot referenčni antioksidant Trolox. Verjamemo, da ta magistrska naloga postavlja trden temelj za nadaljnje računalniške in eksperimentalne študije antioksidativne aktivnosti arzanola ter njegove potencialne uporabe v farmacevtski, živilski in kozmetični industriji. Antioxidants, particularly polyphenols, exhibit a pronounced ability to scavenge free radicals, thereby reducing their reactivity and harmful effects. Among plants with pronounced antioxidant activity, Helichrysum italicum stands out as it contains numerous polyphenolic compounds, among which arzanol predominates as a key bioactive compound. In addition to their antioxidant activity, Helichrysum italicum extracts exhibit anti-inflammatory, anticarcinogenic, and antiviral effects, which is why they are often used in skin care and wound healing products. Although scientific studies have confirmed that arzanol exerts various beneficial health effects, the mechanisms of its antioxidant activity remain unexplored in the scientific literature. Therefore, in the Master's thesis, we investigated the reaction mechanisms of arzanol in its neutral, monoanionic, and dianionic forms with the free radicals CCl₃OO•, HOO•, and CH₃O• using quantum-mechanical simulations and evaluated its efficiency in the scavenging of these radicals. The HAT, RAF, SET, SPLET, and SET-PT mechanisms were examined and the thermodynamic favorability and kinetic properties of individual reactions were determined. Calculations were performed using the Gaussian 16 software package in accordance with the QM-ORSA protocol, using the M06-2X DFT functional, the 6-‍311++G(d,p) flexible basis set, and the SMD solvation model. The results largely support the initial hypothesis that the HAT and RAF mechanisms form thermodynamically favorable reaction pathways for all three radicals, with HAT prevailing due to a greater proportion of favorable reaction sites (85.19%) compared to RAF (30.95%). The most thermodynamically favorable reactions occurred between the dianionic form of arzanol and the CH₃O• radical. Thermodynamic findings also highlight the important role of the SPLET mechanism, which exhibits a greater proportion of favorable sites than RAF (59.26%). The thermodynamically most favorable reaction sites were 11a (HAT and SPLET) and 9 (RAF) in all three protonation forms of arzanol. Further analysis of kinetic calculations revealed that most HAT reactions on arzanol proceed without an energy barrier, at diffusion-‍controlled rates (1.91·10⁹ M⁻¹·s⁻¹), thereby supporting the hypothesis that activation free energies are the lowest for the HAT mechanism. Arzanol proved to be the most effective scavenger of the CCl₃OO• radical, with an overall reaction rate constant of 4.09·10¹⁰ M⁻¹·s⁻¹. The key mechanisms in this case were SPLET and RAF, whereas HAT predominated in the case of HOO• and CH₃O• radicals. Based on the calculation of relative antioxidant activity, we can also confirm that arzanol is a 20-times more effective scavenger of the CCl₃OO• radical than the reference antioxidant Trolox. We believe that this Master's thesis sets a solid foundation for further computational and experimental studies of the antioxidant activity of arzanol and its potential applications in the pharmaceutical, food, and cosmetic industries. smilj arzanol antioksidativni mehanizmi prosti radikali aktivacijska prosta energija kvantno-mehanski izračuni Helichrysum italicum arzanol antioxidative mechanisms free radicals activation free energy quantum-mechanical calculations true true false [K. Fingušt] Slovenski jezik Angleški jezik Magistrsko delo/naloga 2026-02-25 18:12:28 2026-05-06 08:42:15 2026-05-23 03:05:41 0000-00-00 00:00:00 2026 0 Maribor 0 Maribor 1 spletni vir (1 datoteka PDF (XIII, 77 str.)) 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 66.094.3.097.8:547.56(043.2) 279041027 MAG_Fingust_Katja_2026.pdf MAG_Fingust_Katja_2026.pdf 1 14CD8527F96CC3A80FBC7BBCD9D86573 ef45a078e03f25b6ca0f8419c83d4b1349bd6c07e162cc3eb2b1b1d13c065893 40c62cdb-4865-11f1-8e35-00155d0001a1 https://dk.um.si/Dokument.php?lang=slv&id=205775 Fakulteta za kemijo in kemijsko tehnologijo 0 0 0