Isocyanate-Based Dendritic Building Blocks: Combinatorial Tier Construction and Macromolecular-Property Modification

Newkome, George R.; Weis, Claus D.; Moorefield, Charles N.; Baker, Gregory R.; Childs, Bradley J.; Epperson, Jon D.

doi:10.1002/(sici)1521-3773(19980216)37:3<307::aid-anie307>3.0.co;2-l

Cited by 69 publications

(20 citation statements)

References 4 publications

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“…The resulting transparent solution was stirred at room temperature. After the solution was stirred overnight, the solvent was removed to leave a crude yellow oil (n ) 14) and a crude white solid (n ) 16,18,20,22). The crude yellow oil was purified by flash column chromatography (hexane:EtOAc ) 5:1), while the crude white solid was purified by recrystalization with EtOH-H 2 O.…”

Section: Methodsmentioning

confidence: 99%

Synthesis, Critical Micelle Concentrations, and Antimycobacterial Properties of Homologous, Dendritic Amphiphiles. Probing Intrinsic Activity and the “Cutoff” Effect

et al. 2007

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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.

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Section: Methodsmentioning

confidence: 99%

Synthesis, Critical Micelle Concentrations, and Antimycobacterial Properties of Homologous, Dendritic Amphiphiles. Probing Intrinsic Activity and the “Cutoff” Effect

et al. 2007

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“…3CCb20 was prepared from the Newkome-type dendrons [9] as described in [8]. 3CCb20 amphiphile and DPPC were mixed at 0.91 : 1 molar ratio in methanol+chloroform, the solvent was evaporated under a stream of gaseous nitrogen and its traces removed by an oil vacuum pump.…”

Section: Methodsmentioning

confidence: 99%

“…One series of these novel tri-headed anionic amphiphiles, 4-[(alkoxycarbonyl)amino]-4-(2-carboxyethyl)heptanedioic acids, (abbreviation 3CCbn, n = 14-22 is the number of carbon atoms in the alkyl substituent) is constructed from the Newkome-type dendrons [9] and is a new entry into the area of multi-headed amphiphiles.…”

Section: Introductionmentioning

confidence: 99%

Synchrotron SAX and WAX diffraction study of a hydrated very long-chain, dendritic amphiphile+DPPC mixture

Karlovská

Williams

Macri

et al. 2007

Colloids and Surfaces B: Biointerfaces

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The tri-headed anionic dendritic amphiphile, 4-(2-carboxyethyl)-4-[(icosyloxycarbonyl)amino]heptanedioic acid (3CCb20), forms solid-like gel-state mixed micelles with dipalmitoylphosphatidylcholine (DPPC) in excess water at 3CCb20 : DPPC = 0.91 : 1 molar ratio. On heating, these micelles transform into fluid bilayers stacked in the liquid crystalline lamellar L α phase at about 40 °C. This phase transition and the microstructure of 3CCb20 + DPPC aggregates were studied using smalland wide-angle synchrotron X-ray diffraction. The ability of 3CCb20 to solubilize solid-like lipid bilayers could be important in microbiocidal activities of 3CCb20, including in its anti-HIV activity.Keywords: amphiphiles; DPPC; micelles; bilayers; X-ray diffraction; phase transition 3 IntroductionSaturated fatty acids have a long history as microbicides against many pathogens [1][2][3][4][5]. Measurements of inhibitory activities can be problematic because of the very low solubility of saturated fatty acids in aqueous solutions [6]. Furthermore, as the chain length increases to C 18 and beyond, the aqueous solubility becomes immeasurable. Knowing that the compounds completely dissolve in aqueous media enables speculation about how chain length affects microbiological activity. In a homologous series of compounds, antimicrobial activity can show a cut-off effect [7]. Without knowing that the amphiphiles fully dissolve in aqueous media, we cannot conclude that the cut-off effect is due to the "intrinsic" activity of the amphiphiles or due to the decreased solubility of the amphiphile in the microbiological media. The antimicrobial data for 3CCbn show that longer chains (3CCb18-22) are more active than the shorter chains (3CCb14-16). These data contrast with those of saturated fatty acids, where the most active compounds are in the range of C 8 to C 14 [1][2][3][4][5]. A dendritic structure should reduce the absorption of an amphiphile into a cell. The highly branched structure of the head group resembles the dendritic structure of glycolipids that are anchored on the outside of cells. Branching and the triple charge might retard diffusion across membranes. Given the success of very long chain amphiphiles as antimicrobials, there might be a preference for absorption of these amphiphiles on pathogens as opposed to epithelial cells resulting in the reduced irritancy.To understand molecular mechanisms in the biological activities of these compounds, their interactions with different cell constituents must be studied. Several researchers [2,5,19] have proposed that the microbicidal mechanism of action involves fatty acids interacting with membranes. Because of the long alkyl chains, 3CCbn will likely partition into biological membranes. Upon doing so, these amphiphiles will affect the structure and dynamics of the membrane. The phospholipid bilayer comprises the structural matrix of biological membranes. Understanding how amphiphiles interact with a phopholipid bilayer will provide clues to the molecular mechanism of the biological a...

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“…(Newkome et al, 1998) Condensation of two-tail amines with the isocyanate occurred at room temperature to afford good-to-high yields (step i) of triesters (not shown). Formolysis of the trimesters (step ii) produced the triacids-2(n 2 ), where n=6-10 and 3(1+n 2 ), where n=6-11-in good yields of recrystallized products.…”

Section: Project Tasksmentioning

confidence: 99%

Crosscutting Technology Development at the Center for Advanced Separation Technologies

Hull¹

2006

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Isocyanate-Based Dendritic Building Blocks: Combinatorial Tier Construction and Macromolecular-Property Modification

Cited by 69 publications

References 4 publications

Synthesis, Critical Micelle Concentrations, and Antimycobacterial Properties of Homologous, Dendritic Amphiphiles. Probing Intrinsic Activity and the “Cutoff” Effect

Synthesis, Critical Micelle Concentrations, and Antimycobacterial Properties of Homologous, Dendritic Amphiphiles. Probing Intrinsic Activity and the “Cutoff” Effect

Synchrotron SAX and WAX diffraction study of a hydrated very long-chain, dendritic amphiphile+DPPC mixture

Crosscutting Technology Development at the Center for Advanced Separation Technologies

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