39249-27-9Relevant articles and documents
Positionally isomeric organic gelators: Structure-gelation study, racemic versus enantiomeric gelators, and solvation effects
Caplar, Vesna,Frkanec, Leo,Vujicic, Natasa Sijakovic,Zinic, Mladen
supporting information; experimental part, p. 3066 - 3082 (2010/07/11)
Low molecular weight gelator molecules consisting of aliphatic acid, amino acid (phenylglycine), and ω-aminoaliphatic acid units have been designed. By varying the number of methylene units in the aliphatic and ωaminoaliphatic acid chains, as defined by descriptors m and n, respectively, a series of positionally isomeric gelators having different positions of the peptidic hydrogen-bonding unit within the gelator molecule has been obtained. The gelation properties of the positional isomers have been determined in relation to a defined set of twenty solvents of different structure and polarity and analyzed in terms of gelator versatility (G ver) and effectiveness (Geff). The results of gelation tests have shown that simple synthetic optimizations of a "lead gelator molecule" by variation of m and n, end-group polarity (carboxylic acid versus sodium carboxylate), and stereochemistry (racemate versus optically pure form) allowed the identification of gelators with tremendously improved versatility (Gver) and effectiveness (Geff). Dramatic differences in Geff values of up to 70 times could be observed between pure racemate/enantiomer pairs of some gelators, which were manifested even in the gelation of very similar solvents such as isomeric xylenes. The combined results of spectroscopic (1H NMR, FTIR), electron microscopy (TEM), and X-ray diffraction studies suggest similar organization of the positionally isomeric gelators at the molecular level, comprising parallel β-sheet hydrogen-bonded primary assemblies that form inversed bilayers at a higher organizational level. Differential scanning calorimetry (DSC) studies of selected enantiomer/racemate gelator pairs and their o- and p-xylene gels revealed the simultaneous presence of different polymorphs in the racemate gels. The increased gelation effectiveness of the racemate compared to that of the single enantiomer is most likely a consequence of its spontaneous resolution into enantiomeric bilayers and their subsequent organization into polymorphic aggregates of different energy. The latter determine the gel fiber thickness and solvent immobilization capacity of the formed gel network.
Synthesis and siderophore and antibacterial activity of N5-acetyl-N5-hydroxy-L-ornithine-derived siderophore-β-lactam conjugates: Iron-transport-mediated drug delivery
Dolence,Minnick,Lin,Miller,Payne
, p. 968 - 978 (2007/10/02)
N5-Acetyl-N5-hydroxy-L-ornithyl-N5-acetyl-N5-hydroxy-L-ornithyl- N5-acetyl-N5-hydroxy-L-ornithine, the functionally instrumental component of the albomycins and ferrichromes, has been incorporated as a ''carrier'' substructure into both carbacephalosporin and oxamazin type β-lactam antibiotics. The previously synthesized protected version of this tripeptide (14) was coupled with various β-lactam analogues 17, 19, 24, and 25 to give protected conjugates 21, 22, 26, and 27. Final deprotection by hydrogenolysis provided the deprotected siderophore-β-lactam antibiotic conjugates 1-4. The growth-promoting ability of each has been evaluated using either the siderophore-deficient mutant Shigella flexneri SA 100 or S. flexneri SA240 (SA 100 iucD:Tn5). Measurement of the growth-promoting activity using two isogenic Escherichia coli strains differing only in the presence or absence of fhuA (hydroxamate ferrichrome receptor) suggests uptake by the hydroxamate iron-transport system. The antibacterial activity of these conjugates has been investigated, and the potential for use of the ferrichrome iron-transport system as a means of drug delivery is discussed.
