These same Triglycerol detergents can serve as protein protecting agents in micellar media or as amphiphiles that reduce the effectiveness of antibiotic cell envelope permeability barrier in Gram negative bacteria, but each in its own particular molecular form. This manuscript proposes access-state concordance sorting of nine members of triglycerol detergent series having linear and dendritic triglycerol heads, thioether, ether, triazole, amide linkers, and C8 or C12 hydrophobic tails. This sorting involves combination of critical micelle concentration, aggregate morphology, reversed-phase HPLC linker order, HLB re-evaluation, normalized MscL-GFP recovery, and MIC-halfing against tetracycline, ciprofloxacin, and penicillin. The resulting categorization distinguishes protein recovery capacity from cell permeation potency without imposing a ranking scale for the whole set of detergents from mild to harsh. DTG-ether-C12 emerges as a best protein-recovery detergent by a combination of 0.6 mM CMC, globular aggregate morphology, and normalized MscL-GFP recovery equal to 1.00. DTG-amide-C12 and DTG-triazole-C12 retain secondary protein recovery ability by the normalized MscL-GFP recoveries of 0.62 and 0.45, respectively. LTG-triazole-C8 turns out to be the strongest MIC-potentiating detergent by halfing MIC of all three antibiotics and yielding zero normalized MscL-GFP recovery. LTG-thioether-C8 and LTG-ether-C8 constitute the second C8 class retaining normalized recoveries of 0.78 and 0.68 and halfing MIC values of tetracycline and ciprofloxacin. LTG-triazole-C12 and DTG-thioether-C12 form worm-like micelles and are ineffective in both endpoints. Therefore, linker identity only becomes predictive when considering head topology, tail length, aggregate structure, and accessibility to biology.

triglycerol detergent,membrane-protein extraction,antibiotic potentiation,critical micelle concentration,linker polarity,Gram-negative envelope,micelle morphology,HLB