Synthesis, critical micelle concentrations, and antimycobacterial properties of homologous, dendritic amphiphiles. Probing intrinsic activity and the "cutoff" effect.
Newkome-type, 1-->3 C-branched dendrons make an excellent headgroup for amphiphiles with ultralong, saturated, linear alkyl chains. Synthesis of a homologous series of five such amphiphiles from 14 to 22 carbons-RNHCONHC(CH2CH2CO2H)3, R = n-CnH2n+1, n = 14, 16, 18, 20, 22-proceeds readily. These amphiphiles are soluble in aqueous solutions of triethanolamine. Surface-tension measurements on this homologous series reveal an unusually gradual decrease in log critical micelle concentration (CMC) as the chain length increases. In fact, the tetradecyl homologue does not appear to form micelles. Further, measurements of minimal inhibitory concentration (MIC) by broth microdilution against Mycobacterium smegmatis as a function of the initial cell density provide a direct measure of the intrinsic activity (MIC0) of each homologue. The hexadecyl homologue is the most active at inhibiting growth with an MIC0 equal to 3.5 x 10-5 M, which is 100-fold below the CMC.
Sugandhi
Eko W
EW
Department of Chemistry, Virginia Tech, Blacksburg, Virginia 24061, USA.
Macri
Richard V
RV
Williams
André A
AA
Kite
Brett L
BL
Slebodnick
Carla
C
Falkinham
Joseph O
JO
Esker
Alan R
AR
Gandour
Richard D
RD
D000473:Alkanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008823:Micelles; D008826:Microbial Sensitivity Tests; D020102:Mycobacterium smegmatis / Q000187:drug effects; D013329:Structure-Activity Relationship; D013501:Surface-Active Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D000473:Alkanes; D000596:Amino Acids; D000900:Anti-Bacterial Agents; D008823:Micelles; D013501:Surface-Active Agents