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doctoral thesis
Structure, biological activity and mechanism of action of newly synthesized quaternary ammonium compounds
2025. urn:nbn:hr:166:788336
Crnčević, Doris
University of Split
Faculty of Science
Department of Physics

Cite this document

Crnčević, D. (2025). Structure, biological activity and mechanism of action of newly synthesized quaternary ammonium compounds (Doctoral thesis). Split: University of Split, Faculty of Science. Retrieved from https://urn.nsk.hr/urn:nbn:hr:166:788336

Crnčević, Doris. "Structure, biological activity and mechanism of action of newly synthesized quaternary ammonium compounds." Doctoral thesis, University of Split, Faculty of Science, 2025. https://urn.nsk.hr/urn:nbn:hr:166:788336

Crnčević, Doris. "Structure, biological activity and mechanism of action of newly synthesized quaternary ammonium compounds." Doctoral thesis, University of Split, Faculty of Science, 2025. https://urn.nsk.hr/urn:nbn:hr:166:788336

Crnčević, D. (2025). 'Structure, biological activity and mechanism of action of newly synthesized quaternary ammonium compounds', Doctoral thesis, University of Split, Faculty of Science, accessed 03 April 2025, https://urn.nsk.hr/urn:nbn:hr:166:788336

Crnčević D. Structure, biological activity and mechanism of action of newly synthesized quaternary ammonium compounds [Doctoral thesis]. Split: University of Split, Faculty of Science; 2025 [cited 2025 April 03] Available at: https://urn.nsk.hr/urn:nbn:hr:166:788336

D. Crnčević, "Structure, biological activity and mechanism of action of newly synthesized quaternary ammonium compounds", Doctoral thesis, University of Split, Faculty of Science, Split, 2025. Available at: https://urn.nsk.hr/urn:nbn:hr:166:788336

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Metadata
TitleStructure, biological activity and mechanism of action of newly synthesized quaternary ammonium compounds
Title (croatian)Struktura, biološka aktivnost i mehanizam djelovanja novosintetiziranih kvaternih amonijevih spojeva
AuthorDoris Crnčević
MentorMatilda Šprung (mentor)
Committee memberRenata Odžak (predsjednik povjerenstva)
Committee memberStjepan Orhanović (član povjerenstva)
Committee memberRosana Ribić (član povjerenstva)
GranterUniversity of Split
Faculty of Science
(Department of Physics)
Split
Defense date and country2025-03-14, Croatia
Scientific / art field,
discipline and subdiscipline		NATURAL SCIENCES
Chemistry
Universal decimal classification
(UDC)		577 - Biochemistry. Molecular biology. Biophysics
Abstract
This thesis investigates the development of novel quaternary ammonium compounds (QACs) with the aim of addressing the growing concerns regarding bacterial resistance and environmental impacts associated with conventional QACs. The research focusses on two different QAC series: traditional derivatives based on pyridine-4-aldoxime and biodegradable "soft" variants derived from 3-substituted quinuclidine. While the structural modifications of the traditional QACs resulted in potent antiviral... More properties, their antibacterial efficacy was impaired, possibly due to an increased polarity of the backbone that hinders electrostatic interactions with the bacterial membrane. Consequently, the polarity of the amide bond in the "soft" QAC variants was diminished by the addition of long hydrocarbon chains in its extension, resulting in compounds with a dual mechanism of action, lower toxicity and an improved biodegradability profile. In addition, the research emphasizes the importance of fine-tuning the hydrophobic/hydrophilic ratio, as demonstrated by the example of 3-aminoquinuclidine derived QACs in which the amino functional group mimics bis-QAC by protonation under physiological conditions. These derivatives showed potent bactericidal activity against a variety of bacterial strains, including the ability to disrupt biofilm formation and induce bacterial cell death by destabilization of the membrane and generation of the reactive oxygen species. Taken together, the obtained results and the established structure-activity relationships provide valuable insights for the rational design and synthesis of next-generation QACs with improved efficacy, biosafety profile and potential therapeutic applications. Less
Abstract (croatian)
Ova doktorska disertacija rezultirala je razvojem novih kvaternih amonijevih spojeva (QAC) s ciljem rješavanja rastućeg problema razvoja bakterijske rezistencije te negativnog ekološkog učinka uzrokovanog konvencionalnim QAC derivatima. Istraživanje se fokusira na dvije različite QAC serije: tradicionalne derivate temeljene na piridinijevom-4-aldoksimu i biorazgradive "meke" varijante 3-supstituiranog kinuklidina. Dok su strukturne modifikacije tradicionalnih QAC rezultirale snažnim... More antivirusnim svojstvima, isti su pokazali smanjenu antibakterijsku učinkovitost, koju je moguće pripisati povećanoj polarnosti okosnice što može ometati povoljne elektrostatske interakcije s bakterijskom membranom. Posljedično, polarnost amidne veze u "mekim" QAC varijantama smanjena je dodatkom dugih alkilnih lanaca u njenom produžetku, što je rezultiralo spojevima s dvostrukim mehanizmom djelovanja, nižom toksičnošću i poboljšanim profilom biorazgradivosti. Osim toga, istraživanje naglašava važnost optimalnog podešavanja omjera hidrofobno/hidrofilno, a isto je pokazano na primjeru QAC deriviranih na okosnici 3-aminokinuklidina u kojima protonirana amino skupima pruža mogućnost oponašanja bis-QAC. Ovi derivati su pokazali snažnu baktericidnu aktivnost, uključujući sposobnost inhibicije stvaranja biofilma i induciranja smrti bakterijske stanice destabilizacijom membrane i generiranjem reaktivnih vrsta kisika. Rezultati ovog istraživanja, zajedno sa zaključcima utjecaja strukture na aktivnost, omogućuju daljnji racionalan dizajn i sintezu novih QAC varijanti s poboljšanom učinkovitošću, biosigurnosnim profilom i potencijalnom terapeutskom primjenom. Less
Keywords
Keywords (croatian)
Languageenglish
URN:NBNurn:nbn:hr:166:788336
Study programmeTitle: Doctoral Study of Biophysics
Study programme type: university
Study level: postgraduate
Academic / professional title: doktor/doktorica znanosti u području prirodnih znanosti (doktor/doktorica znanosti u području prirodnih znanosti)
Type of resourceText
Extent108 str. ; 30 cm
File originBorn digital
Access conditionsOpen access
Terms of useLicence In copyright icon
Created on2025-03-19 11:39:00
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