Characterization of the Effects of Alkyl Chain Asymmetry on the Ion Pair Amphiphile Bilayer Structures and the Gelation Mechanism of Cyclodextrin/Peptide Amphiphiles Complex

Abstract

Ion pair amphiphile (IPA) a lipid-like complex composed of a pair of cationic and anionic surfactants has been suggested as an inexpensive phospholipid substitute with great potentials in various pharmaceutical applications In this work we utilized molecular dynamics (MD) simulation to systematically explore the effects of various alkyl chain combinations of the alkyltrimethylammonium – alkylsulfate IPAs i e CmTMA+ – CnS– on the corresponding IPA bilayer structural and mechanical properties at the molecular level Based on the intrinsic molecular structures of the trimethylammonium and the sulfate groups and the observed transversed matching pattern the CmTMA+ – CnS– IPA alkyl chain asymmetry can be characterized by the asymmetric index ΔC = m - (n + 1) Larger |ΔC| gives rise to higher conformational fluctuations of the alkyl chains which reduces the overall packing order and the mechanical strength Besides higher total chain length leads to increased v d W interaction and thus improves the alkyl chain ordering and bilayer mechanical properties We also applied MD simulation to study the thermodynamical properties of the thermo-responsive supermolacular hydrogels comprised of β-CD and peptide amphiphiles (C16Thr20) The binding free energy of β-CD:C16Thr20 inclusion complex at 298 K and 333 K (above degelation temperature) is -29 60 and -26 33 kJ/mol respectively This result indicates the temperature at which the degelation occurs is not high enough to break apart the β-CD:C16Thr20 complex This suggests that the degelation of C16Thr20 hydrogel is mainly due to the decreased hydrogen bonding network within the structures rather than the β-CD:C16Thr20 complex dissociation Furthermore the thermodynamic analysis showed that the β-CD:C16Thr20 complex formation is mainly driven by enthalpy The free energy data of the thermodynamic cycle for the (β-CD)2:C16 inclusion complex formation illustrated that the C16 chain can form stable complex with two β-CDs consistent with the reported experimental analysis Based on the free energy data the (β-CD)2:C16 complex is more likely formed via the sequentially threading of the β-CDs onto the C16 chain

Date of Award	2016 Aug 3
Original language	English
Supervisor	Chi-cheng Chiu (Supervisor)