Mehanizam interakcije biotiola s nanočesticama zlata i srebra

doctoral thesis

• Title (english): Mechanism of interaction of biothiols with silver and gold nanoparticles
• Author: Barbara Pem
• Mentor: Ivana Vinković Vrček (mentor)
• Mentor: Valerije Vrček (komentor)
• Committee member: Mario Jug (predsjednik povjerenstva)
• Committee member: Ivana Perković (član povjerenstva)
• Committee member: Robert Vianello (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of organic chemistry); Zagreb
• Defense date and country: 2021-12-14, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy
• Universal decimal classification (UDC): 615 - Pharmacology. Therapeutics. Toxicology

Abstract

Transformacije nanočestica zlata (AuNP) i srebra (AgNP) u biološkim sustavima utječu na njihov biološki identitet, ponašanje i biološke učinke. Zbog svojeg velikog afiniteta prema sumporu, AgNP i AuNP lako stupaju u interakcije s endogenim biotiolima, pa je razumijevanje takvih interakcija preduvjet njihove uspješne biomedicinske primjene. Cilj ove doktorske disertacije bio je utvrditi mehanizam interakcije i vezanja biotiola s AgNP i AuNP kombiniranom primjenom eksperimentalnih i računalnih metoda. Nanočestice su pripremljene metodom redukcije, te su karakterizirane obzirom na oblik, raspodjelu veličina, zeta potencijal i koloidnu stabilnost pomoću mikroskopskih i spektroskopskih tehnika. Direktna interakcija s biotiolima praćena je nuklearnom magnetskom rezonancijskom spektroskopijom, a primjenom kvantno-kemijskih i molekulsko-dinamičkih metoda potvrđen je pretpostavljeni mehanizam tih interakcija. Utvrđeno je da se prilikom interakcije biotiola s atomima Ag i Au na nanopovršini događa njihova oksidativna dimerizacija u disulfide. Mehanizam oksidativne dimerizacije odvija se u dva koraka: 1) oksidacija tiolne skupine u sulfensku kiselinu posredovana reaktivnim kisikovim vrstama i 2) reakcija tiola i sulfenske kiseline uz oslobađanje vode, katalizirana s Ag i Au. Nastali disulfidi adsorbiraju na površinu AgNP i AuNP putem nekovalentnih interakcija, u kojima sudjeluju sve njihove funkcionalne skupine. Izračunom energije vezanja potvrđena je spontanost adsorpcije i veći afinitet vezanja disulfida u odnosu na tiole. Stoga je konačni produkt interakcija metalnih površina s tiolima nastanak AgNP i AuNP obloženih disulfidima. Ova saznanja pridonose razumijevanju transformacija nanočestica u prisutnosti biotiola što je važno za procjenu njihovih bioloških učinaka i sigurnosti primjene u biomedicini.

Abstract (english)

Transformations of gold and silver nanoparticles (AuNPs and AgNPs) impact their biological effects, behaviour and fate in the human body. Interaction of NPs with endogenous biothiols is one of the major events leading to those transformations, thus the understanding of their interplay is a prerequisite for biomedical applications of NPs. This study was conducted on a model system consisting of cysteine (CYS) or glutathione (GSH) and AgNPs or AuNPs, by combining experimental and theoretical approaches. NPs were prepared by the reduction method and their shape, size distribution, zeta potential and dissolution were determined by microscopy and spectroscopic techniques. Direct interaction of biothiols with Ag and Au was monitored during NP preparation by nuclear magnetic resonance spectroscopy, and the reaction mechanism and processes on the metal surface were determined by quantum-chemical and molecular dynamics methods. In the reaction mixture, simultaneously with the formation of nanoparticles, oxidative dimerization of biothiols occurs and disulphides bind to the nanoparticle surface. Mechanism of oxidative dimerization consists of two steps: 1) oxidation of the thiol group to sulfenic acid by reactive oxygen species, and 2) reaction of thiol with sulfenic acid involving the release of one water molecule (Ag and Au act as catalysts). Generated disulphides adsorb to the AgNP and AuNP surface through non-covalent interactions with participation from all functional groups. Binding energy calculations confirm the adsorption is spontaneous, and that disulphides bind with higher affinity compared to thiols. Thus, the final product of the interaction of metallic surfaces with thiols is the formation of disulphide-coated AgNPs and AuNPs. These findings contribute to the understanding of biotransformations of both biothiols and particles that are important for the application of nanoparticles in biomedicine.

• Keywords: nanočestice srebra; nanočestice zlata; cistein; glutation; nuklearna magnetska rezonancija; teorija funkcionala gustoće; molekulska dinamika
• Keywords (english): silver nanoparticles; gold nanoparticles; cysteine; glutathione; nuclear magnetic resonance; density functional theory; molecular dynamics
• Language: croatian
• URN:NBN: urn:nbn:hr:163:721515
• Promotion: 2022
• Study programme: Title: Pharmacy and biochemistry; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor znanosti (doktor znanosti)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2022-11-07 14:12:18