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Dissertation Information for Hailling Zhang

NAME:
- Hailling Zhang

DEGREE:
- Ph.D.

DISCIPLINE:
- Chemistry

SCHOOL:
- Emory University (USA) (2006)

ADVISORS:
- Fred M. Menger

COMMITTEE MEMBERS:
- Dennis C. Liotta
- Lanny S. Liebeskind

MPACT Status: Fully Complete

Title: Part I. Peptoads, a group of amphiphilic long-chain tri-amides. Part II. Molecular dynamics simulations of self-assembly of peptoad and taxol dissolution. Part III. Self-adhesion among phospholipid vesicles

Abstract: Part I . Eleven tri-amide bearing long alkyl chains have been synthesized to produce a new class of amphiphilic compounds (dubbed \"peptoad\"). The properties of these molecules have been investigated by X-ray analysis, solubility studies, light and electron microscopy, surface tensiometry, light scattering, drug dissolution, and molecular dynamics. In the solid state the peptoads assemble in layers with both intra- and inter-layer hydrogen-bonding coupled to side-by-side proximity of the hydrocarbon chains. Peptoads with a terminal primary amide, and a total of three amide NH sites, are water-insoluble owing presumably to attractive forces in the solid state. However, peptoads with terminal -CONMe 2 groups, and two internal amide NH sites, are water-soluble at room temperature. This solubility is critically dependent upon the chain-length. For example, a C 7 -chained peptoad is 1600 times more soluble than its C 9 analog.High concentrations (6-8 M) of C 7 peptoads in water are clear and viscous but do not gel. Light microscopy shows long fibers floating in an isotropic liquid. Water-soluble peptoads are highly surface active, lowering water\'s surface tension as effectively as a soap with a much longer chain. Surface tension plots show a \"critical aggregation number\", but it is believed from light scattering and molecular dynamics that the aggregates grow continuously as more peptoad is added to the water. In answer to the inevitable (but valid) question, \"What possible good are they?\", it can be pointed out that a peptoad solubilizes a water-insoluble drug, taxol, as efficiently as does Cremophor EL, a commercial excipient widely used with taxol and other non-polar drugs. Peptoads, being small molecules, and consisting of hydrolyzable amide groups, are likely biodegradable and less prone to the hypersensitivity and neurotoxicity found with Cremophor EL. Part II . Molecular dynamics simulations of peptoad-G self-assembly and taxol dissolution have been carried out with GROMACS (3.1.2) simulation package. A 10 ns simulation of 108 peptoad G molecules, 20,001 water molecules in a 8.8 nm 3 cubic box produced a spherical clump that contain 97 of peptoad molecules. The diameter of the clump is about 4 nm, which is similar to the size of normal micelle formed from conventional surfactants. The terminal dimehtyl amide exclusively located on the surface of the clump and amide groups lie, on the average, external to the hydrocarbon chains. However, there is considerable disorder with no indication of molecular packing similar to that found in the X-ray pictures. It indicated that intermolecular hydrogen-bonding interaction is one of the major driving forces for self-assembly. Two spherical aggregates will collide and fuse into an oval aggregate, and a cylindrical clump was formed with higher concentration simulation. A bicontinuous phase was generated by the taxol dissolution simulation where system with a much higher G concentration was simulated. Taxol was \"wrapped\" by G molecules by sitting in the conjunction of cylindrical clumps, to minimize the possibility of exposing to water. Moreover, about 3-6 hydrogen bonds formed between G and taxol molecules also stabilized taxol in aqueous solution. The hydrogen-bonding sites switched on different functional groups quickly due large amount of hydrogen-bonding acceptors and donors.

MPACT Scores for Hailling Zhang

A = 0
C = 0
A+C = 0
T = 0
G = 0
W = 0
TD = 0
TA = 0
calculated 2008-03-16 15:56:45

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