Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

ORCID

http://orcid.org/0000-0003-3171-8579

Date of Award

Spring 2017

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Department of Biology

Advisor(s)

Kyle Seifert

Kevin Caran

James Herrick

Abstract

Antibiotic resistant infections are responsible for approximately 23,000 deaths every year in the United States alone. The formation of bacterial biofilms makes resistant bacteria difficult to eliminate completely using chemical treatment. Therefore, novel antimicrobial compounds such as amphiphiles are essential to slow or stop the spread of resistant bacteria. Several novel series of amphiphiles were synthesized, and discrete aspects of their chemical structure were altered to investigate the relationship between structure and antibacterial activity. Minimum inhibitory concentration (MIC) assays were used to measure antibacterial activity against two Gram-negative and five Gram-positive bacteria, and the most effective compounds were tested for biofilm disruption activity against Pseudomonas aeruginosa using a Crystal Violet assay. For the tris-cationic M-E,n,n; M-DMAP,n,n; M-IQ,n,n; and M-4PP,n,n series, twelve carbons per tail was the ideal tail length for antibacterial activity, having MIC values as low as 4-8 μM against Gram-negative species and 2-4 μM against Gram-positive species. The 12-carbon derivatives also disrupted up to 70% of established P. aeruginosa biofilms at concentrations comparable to tobramycin and benzalkonium chloride. Hofmeister counterion substitution of one single-tailed and one double-tailed compound (M-1,1,18 and M-1,12,12, respectively) resulted in a notable 8-fold decrease in the MIC against P. aeruginosa when the bromide counterion was replaced with chloride, and a 16-fold decrease when the counterion was substituted with iodide. Finally, in order to determine the effect of charge distribution in the head group, three bis-cationic (oX-n,n; mX-n,n; and pX-n,n) and three tetra-cationic series (oX-(2,n)2; mX-(2,n)2; and pX-(2,n)2) of double-tailed amphiphiles of varying tail lengths were synthesized and tested for their x MIC values. For all three series of bis-cationic amphiphiles, as well as the mX-(2,n)2 and pX-(2,n)2 series, the 12-carbon derivatives had the lowest MIC values. However, the oX-(2,n)2 series had an ideal tail length of 8 carbons per tail. This further understanding of the relationship between structure and function of antimicrobial amphiphiles can be used to create more effective disinfectants and antibiotics. Continuing research into novel antibacterial compounds and biofilm disrupting agents is essential to combat the growing problem of antibiotic resistance.

Available for download on Thursday, April 18, 2019

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