The increased development of microorganisms capable of resisting the most common antimicrobial substances, in recent years, is a phenomenon that has long been of concern to various global health organizations. The development of resistance to adverse substances is a natural mechanism, which microorganisms have exploited since ancient times. With the onset of industrialization in the early 20th century and the discovery of powerful antibiotic drugs, mankind has been able to significantly improve its lifestyle. The result of decades of irresponsible use and wastage of these antimicrobial substances in the environment, however, has inevitably led to the generation of antibiotic-resistant microorganisms. Humanity, if it wants to better contain this phenomenon, in the future will have to act with more conscience, limiting waste, using products that better preserve the environment and developing new effective antimicrobial substances. In this Ph.D. work we describe the synthesis of novel antimicrobial quaternary ammonium salts (QACs) by exploiting the high reactivity of chloro triazines. Several triazine QACs were synthesized and their antimicrobial activity was investigated. In the first instance, we focused on the synthesis of a library of morpholino-triazine QACs directly inspired by the structure of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methyl-morpholinium chloride or DMTMM. Then evaluating its efficacy against Gram-positive and Gram-negative bacterial strains such as Staphylococcus aureus and Escherichia coli. Next, we moved on to the synthesis of a library of imidazole-triazine QACs that showed superior performance compared to the first morpholino-triazine QACs, both in terms of yield and antimicrobial activity. Finally, the synthesis of various blockcopolymers based on 2-N-morpholinoethyl methylmethacrylate (MEMA) and their use in the preparation of polymeric QACs and antimicrobial surfaces was described.

L’aumento dello sviluppo di microorganismi in grado di resistere alle più comuni sostanze antimicrobiche negli ultimi anni è un fenomeno che da tempo preoccupa le varie organizzazioni della salute mondiale. Lo sviluppo della resistenza alle sostanze avverse è un meccanismo naturale, che i microorganismi hanno sfruttato fin dall’antichità. Con l’avvio verso l’industrializzazione ai primi del XX secolo e la scoperta di potenti farmaci antibiotici, l’umanità ha potuto notevolmente migliorare il suo stile di vita. Il risultato di decenni di utilizzo irresponsabile e sperpero nell’ambiente di queste sostanze antimicrobiche però ha inevitabilmente portato alla generazione di microorganismi antibiotico resistenti. L’umanità, se meglio vuole arginare questo fenomeno, in futuro dovrà agire con più coscienza, limitando gli sprechi, utilizzando prodotti che meglio preservino l’ambiente e sviluppando nuove sostanze antimicrobiche efficaci. In questa lavoro di dottorato si descrive la sintesi di nuovi sali d’ammonio quaternario antimicrobici (QACs), sfruttando la grande reattività dalle cloro triazine. Diversi QACs triazinici sono stati sintetizzati e la loro attività antimicrobica è stata investigata. In prima istanza ci si è concentrati sulla sintesi di una libreria di QACs morfolino-triazinici di diretta ispirazione alla struttura della 4-(4,6-dimetossi-1,3,5-triazin-2-il)-4-metil-morfolinio cloruro o DMTMM. Valutandone poi l’efficacia contro ceppi batterici Gram-positivi e Gram-negativi come Staphylococcus aureus ed Escherichia coli. Successivamente si è passati alla sintesi di una libreria di QACs imidazolo-triazinici che hanno mostrato prestazioni superiori rispetto ai primi QACs morfolino-triazinici, sia in termini di resa delle reazioni che in termini di attività antimicrobica. Infine, è stata descritta la sintesi di vari polimeri a blocchi basati sulla 2-N-morfolinoetil metilmetacrilato (MEMA) e il loro utilizzo nella preparazione di QACs polimerici e superfici antimicrobiche.

SYNTHESIS AND USE OF TRIAZINYL QACs AS ANTIMICROBIAL AGENTS / Morandini, Andrea. - (2021 Apr 15).

SYNTHESIS AND USE OF TRIAZINYL QACs AS ANTIMICROBIAL AGENTS

MORANDINI, ANDREA
2021-04-15

Abstract

The increased development of microorganisms capable of resisting the most common antimicrobial substances, in recent years, is a phenomenon that has long been of concern to various global health organizations. The development of resistance to adverse substances is a natural mechanism, which microorganisms have exploited since ancient times. With the onset of industrialization in the early 20th century and the discovery of powerful antibiotic drugs, mankind has been able to significantly improve its lifestyle. The result of decades of irresponsible use and wastage of these antimicrobial substances in the environment, however, has inevitably led to the generation of antibiotic-resistant microorganisms. Humanity, if it wants to better contain this phenomenon, in the future will have to act with more conscience, limiting waste, using products that better preserve the environment and developing new effective antimicrobial substances. In this Ph.D. work we describe the synthesis of novel antimicrobial quaternary ammonium salts (QACs) by exploiting the high reactivity of chloro triazines. Several triazine QACs were synthesized and their antimicrobial activity was investigated. In the first instance, we focused on the synthesis of a library of morpholino-triazine QACs directly inspired by the structure of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methyl-morpholinium chloride or DMTMM. Then evaluating its efficacy against Gram-positive and Gram-negative bacterial strains such as Staphylococcus aureus and Escherichia coli. Next, we moved on to the synthesis of a library of imidazole-triazine QACs that showed superior performance compared to the first morpholino-triazine QACs, both in terms of yield and antimicrobial activity. Finally, the synthesis of various blockcopolymers based on 2-N-morpholinoethyl methylmethacrylate (MEMA) and their use in the preparation of polymeric QACs and antimicrobial surfaces was described.
15-apr-2021
33
2019/2020
Settore CHIM/04 - Chimica Industriale
Università degli Studi di Trieste
File in questo prodotto:
File Dimensione Formato  
PhD Final Thesis Andrea Morandini.pdf

accesso aperto

Descrizione: Tesi finale
Tipologia: Tesi di dottorato
Dimensione 7.38 MB
Formato Adobe PDF
7.38 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11368/2988358
 Avviso

Registrazione in corso di verifica.
La registrazione di questo prodotto non è ancora stata validata in ArTS.

Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact