Versatile Association Behavior in Mixtures of Oppositely Charged Amphiphiles : From DNA-Like Assembly of Supramolecular Helices to Coacervation in Chiral Surfactant Systems

Abstract: As biological surfactants, bile salts (BSs), play important roles in biological processes, i.e., food digestion, but also in BS-related diseases, as well as in applications. In this thesis, the main focus was to gain a fundamental understanding of the intermolecular interactions between BSs and cationic block copolymers with the purpose of developing new BS sequestrants that are used in the treatment of BS-related diseases. In addition, the studies also aimed to explore the unique co-assembled structures formed in mixtures of BS and either block copolymers or chiral gemini surfactants of opposite charge, which can be used for biomedical applications. The versatile association behavior, thermodynamic interactions, different morphologies and supramolecular structures of the complexes formed in these oppositely charged amphiphile systems were investigated by dynamic and static light scattering, isothermal titration calorimetry, high-sensitive differential scanning calorimetry, small angle X-ray scattering, cryogenic (cryo-) transmission electron microscopy and cryo-electron tomography, turbidimetric titration, and electrophoretic mobility measurements. Based on these studies, this thesis is divided into three parts.The studies on the oppositely charged block copolymer-BS systems are summarized first. Two cationic diblock copolymers with the same charged block of poly((3-acrylamidopropyl)trimethylammonium chloride) (PAMPTMA(+)) but with different nonionic blocks, either the thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) or methoxy poly(ethylene glycol) (MPEG), and two homopolymers (PAMPTMA(+)130 and PNIPAMm) were explored in terms of their interactions with the bile salt sodium deoxycholate (NaDC) in water at 25 °C. The experimental studies showed that single supramolecular helices were formed in the PAMPTMA(+)130-NaDC system, while they condensed into different hierarchical arrangements, i.e., orderly parallel structures and DNA-like hexagonally packed bundles or toroids when using the diblock copolymers. The chirality of BS molecules and the supramolecular chirality of the helices obtained in different polymer-NaDC systems enabled the mixed co-assemblies the ability to load drugs, highlighting their potential use in drug encapsulation and delivery. Moreover, the observed heat-induced phase transition in the PNIPAM120-b-PAMPTMA(+)30-NaDC system demonstrated the formation of composition-controlled thermoresponsive mixed aggregates, which are appealing in stimulating responsive-related applications.The co-assembly in PNIPAM65-b-PAMPTMA(+)20 block copolymer-sodium dodecyl sulfate (SDS) system was studied in the second part of the thesis. It was found that SDS interacts with both blocks of the copolymer and associates in a step-wise process involving both electrostatic and hydrophobic interactions, which stands in contrast to the copolymer-NaDC system where the NaDC preferentially interacts with PAMPTMA(+) blocks. This is reflected in both a different mixed complex structure and a divergent thermoresponsive behavior compared to the PNIPAM120-b-PAMPTMA(+)30-NaDC system.Lastly, the study on the mixtures of NaDC and three gemini surfactants 1,4-bis(dodecyl-N,N-dimethylammonium bromide)-2,3-butanediol (12-4(OH)2-12), including two chiral ones ((2S,3S)-12-4(OH)2-12 and (2R,3R)-12-4(OH)2-12) and the racemate ((±)-12-4(OH)2-12), revealed different aqueous phase behaviors including coacervation. It was found that the BS can recognize the gemini surfactants by showing either an enhanced, switched, or induced chirality in (2S,3S)-12-4(OH)2-12-NaDC, (2R,3R)-12-4(OH)2-12-NaDC, and (±)-12-4(OH)2-12-NaDC mixtures, respectively.