Computer simulations of self-assembling nanofibers from thiophene-peptide oligomers

Polythiophenes are conductive polymers with outstanding semiconducting, optical, electroluminescent and processing properties making them a promising compound class for applications in organic electronics, sensor design, etc. The ability to organize molecules into various functional structures at micro and nano scale in a controlled fashion is now seen as an important challenge which will contribute to the ongoing technological revolution in the field of nanotechnology. A perspective approach towards the design of such structures is the chemical conjugation of synthetic polymers with specific biopolymers which are known to self-assemble into well ordered supramolecular aggregates. In the lab of Prof. Bäuerle, University of Ulm, several new hybrid compounds have been recently synthesized containing the oligothiophene moiety conjugated with a -sheet forming peptide, which are known to self-assemble into amyloid-like fibrillar structures similar to those featured in many human diseases (Alzheimer, type II diabetes, etc.). These compounds were indeed shown to self-assemble into fibrillar aggregates (molecular nanowires) in organic solvent. However, the structure of the aggregates as well as the rational understanding of the self-assembly principles and their properties remained elusive. In this thesis we aimed at applying an arsenal of theoretical approaches, including molecular mechanics, molecular dynamics, crystalline packing prediction, dissipative particle dynamics, quantum chemistry calculations, etc. to deduce the possible atomistic models for the arrangement of the molecules in the observed fibrils, study their morphological, conformational and conducting properties, as well as develop a methodology for computer simulations of these complex systems. The thesis is organized as follows; in Introduction the motivation and aims of the thesis are presented. Chapter 1 surveys our current understanding of the amyloid fibril structure, formation and properties, the application of amyloid-like fibrils as a scaffold for new nanomaterials as well as available information on the thiophene-peptide conjugates. The theory and practical issues behind the computer simulations methods based on molecular mechanics are surveyed in Chapter 2. Starting from Chapter 3 original results are presented, beginning with the discussion of challenges encountered during the computer simulations of large fibrillar aggregates at atomistic level. In Chapter 4 an original attempt to predict the structure of fibrillar aggregates based on crystalline structure prediction algorithms and subsequent large scale atomistic simulations of the aggregates are presented. In Chapter 5 an original combined experimental/theoretical methodology based on multi-scale atomistic simulations of fibrillar aggregates in solvent, vacuum and on the substrate as well as virtual AFM simulations is developed. Using this methodology the relations between the intermolecular arrangement and supramolecular morphology of the fibrils were studied and a most probable structural model for the experimentally observed fibrils was devised. We also discuss the basic principles of fibrillar organization and advice further strategies for experimental study and design of conducting nanowires formed by thiophene-peptide diblock oligomers. Chapter 6 is devoted to quantum mechanical consideration of charge transfer along the molecular wires formed by oligothiophene stacks within the fibrillar aggregates in terms of semiclassical Marcus theory of charge transfer. The high dependence of charge mobility on the peculiarities of molecular arrangement is elucidated.