Colloidal and antibacterial properties of novel triple-headed, double-tailed amphiphiles: exploring structure-activity relationships and synergistic mixtures.
Two novel series of tris-cationic, tripled-headed, double-tailed amphiphiles were synthesized and the effects of tail length and head group composition on the critical aggregation concentration (CAC), thermodynamic parameters, and minimum inhibitory concentration (MIC) against six bacterial strains were investigated. Synergistic antibacterial combinations of these amphiphiles were also identified. Amphiphiles in this study are composed of a benzene core with three benzylic ammonium bromide groups, two of which have alkyl chains, each 8-16 carbons in length. The third head group is a trimethylammonium or pyridinium. Log of critical aggregation concentration (log[CAC]) and heat of aggregation (ΔHagg) were both inversely proportional to the length of the linear hydrocarbon chains. Antibacterial activity increases with tail length until an optimal tail length of 12 carbons per chain, above which, activity decreased. The derivatives with two 12 carbon chains had the best antibacterial activity, killing all tested strains at concentrations of 1-2μM for Gram-positive and 4-16μM for Gram-negative bacteria. The identity of the third head group (trimethylammonium or pyridinium) had minimal effect on colloidal and antibacterial activity. The antibacterial activity of several binary combinations of amphiphiles from this study was higher than activity of individual amphiphiles, indicating that these combinations are synergistic. These amphiphiles show promise as novel antibacterial agents that could be used in a variety of applications.
James Madison University, Department of Biology, 951 Carrier Drive, MSC 7801, Harrisonburg, VA 22807, USA; James Madison University, Department of Chemistry and Biochemistry, 901 Carrier Drive, MSC 4501, Harrisonburg, VA 22807, USA.
John N
JN
Marafino
James Madison University, Department of Biology, 951 Carrier Drive, MSC 7801, Harrisonburg, VA 22807, USA.
Tara M
TM
Gallagher
James Madison University, Department of Chemistry and Biochemistry, 901 Carrier Drive, MSC 4501, Harrisonburg, VA 22807, USA.
Jhosdyn
J
Barragan
James Madison University, Department of Biology, 951 Carrier Drive, MSC 7801, Harrisonburg, VA 22807, USA.
Brandi L
BL
Volkers
James Madison University, Department of Biology, 951 Carrier Drive, MSC 7801, Harrisonburg, VA 22807, USA.
Jade E
JE
LaDow
James Madison University, Department of Biology, 951 Carrier Drive, MSC 7801, Harrisonburg, VA 22807, USA.
Kyle
K
Bonifer
James Madison University, Department of Chemistry and Biochemistry, 901 Carrier Drive, MSC 4501, Harrisonburg, VA 22807, USA.
Gabriel
G
Fitzgerald
James Madison University, Department of Biology, 951 Carrier Drive, MSC 7801, Harrisonburg, VA 22807, USA.
Jason L
JL
Floyd
James Madison University, Department of Chemistry and Biochemistry, 901 Carrier Drive, MSC 4501, Harrisonburg, VA 22807, USA.
Kristin
K
McKenna
James Madison University, Department of Biology, 951 Carrier Drive, MSC 7801, Harrisonburg, VA 22807, USA.
Nicholas T
NT
Minahan
James Madison University, Department of Chemistry and Biochemistry, 901 Carrier Drive, MSC 4501, Harrisonburg, VA 22807, USA.
Brenna
B
Walsh
James Madison University, Department of Biology, 951 Carrier Drive, MSC 7801, Harrisonburg, VA 22807, USA. Electronic address: seiferkx@jmu.edu.
Kyle
K
Seifert
James Madison University, Department of Chemistry and Biochemistry, 901 Carrier Drive, MSC 4501, Harrisonburg, VA 22807, USA. Electronic address: carankl@jmu.edu.
Kevin L
KL
Caran
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001409:Bacillus cereus / Q000187:drug effects / Q000254:growth & development; D001555:Benzene Derivatives / Q000138:chemical synthesis / Q000494:pharmacology*; D001965:Bromides / Q000737:chemistry; D003102:Colloids; D004357:Drug Synergism; D013293:Enterococcus faecalis / Q000187:drug effects / Q000254:growth & development; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development; D005427:Flocculation; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000254:growth & development; D000644:Quaternary Ammonium Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development; D013292:Streptococcus agalactiae / Q000187:drug effects / Q000254:growth & development; D013329:Structure-Activity Relationship; D013501:Surface-Active Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D013696:Temperature; D013816:Thermodynamics
D000900:Anti-Bacterial Agents; D001555:Benzene Derivatives; D001965:Bromides; D003102:Colloids; D000644:Quaternary Ammonium Compounds; D013501:Surface-Active Agents; C051470:ammonium bromide
Amphiphile; Antibacterial; Bacteria; Cationic amphiphiles; Chain length; Critical aggregation concentration; Critical micelle concentration; Enthalpy of aggregate formation; Enthalpy of micelle formation; Entropy of aggregate formation; Entropy of micelle formation; Gram-negative; Gram-positive; Isothermal titration calorimetry; Micelle; Minimum inhibitory concentration; Multi-headed amphiphile; Polycephalic amphiphile; Surfactant; Synergy; Thermodynamics of aggregate formation; Thermodynamics of micelle formation; Tricephalic amphiphile; Triple-headed amphiphile