Let’s do the twist: chiral information transfer in self-assembled supramolecular functionalised coiled-coils

Liebnitz, Danielle Aria (2026) Let’s do the twist: chiral information transfer in self-assembled supramolecular functionalised coiled-coils. PhD thesis, University of Glasgow.

Abstract

Chirality is an inherent feature of life and can be found across many natural systems, from DNA to snail shells. This concept spans from the molecular level, up to visible phenomena at the macroscale, with each step in this increasing scale influencing the next as a result of chiral information transfer. Despite the prevalence of chirality across the scientific field, the exact mechanisms and controls of chiral information transfer are poorly understood.

To aid in the understanding of these mechanisms, a model system taking advantage of the innate chiral information transfer in the self-assembly of peptide sequences, known as coiled coils, has been developed and investigated in this work. By modifying these sequences to feature an aromatic chelating unit at the N-terminus, this work demonstrates a cooperative relationship in which the aromatic chelating units (2,2′-bipyridine and 8-hydroxyquinoline) enhance the α-helical character of the peptide assembly, while the chiral information from the peptide is simultaneously transmitted to the complex, resulting in a chiral bias for onehandedness of the resulting complex.

After discussion of the relevant literature in Chapter 1, Chapter 2 of this work introduces the chiral information transfer exhibited by the coiled coils onto the coordination complex. This chapter focuses on the stabilisation of a homotrimeric coiled coil peptide sequence by the introduction of an aromatic chelating unit (bipyridine/phenanthroline) to the N-terminus of the peptide sequence. It was found that the sequences resulted in the preferential formation of the Δ-[tris-bpy]-peptide and Δ-[tris-phen]-peptide complexes in response to coordination with first row transition metals, Co²⁺, Ni²⁺, Cu²⁺ and Zn²⁺. Furthermore, a cooperative relationship between the degree of coiled coil helicity and the degree of chiral bias in the resulting complex has been uncovered, with sequences with more helical character exhibiting more chiral preference as a result. Through comparison to non-helical sequences, it was shown that the chirality of the complex occurs as a result of the helicity of the peptide and not the inherent chirality of the amino acid subunits.

In Chapter 3, the structural tolerances of this cooperative relationship have been investigated. By variation of sequence length, helical content, register position and the distance of the 2,2′-bipyridine from a chiral centre on the peptide, 17 coiled coil forming peptides were synthesised and investigated. By altering these aspects of the structure, it was found that preference for the Δ- and Λ-isomers of the complex can be controlled by altering the register position of the chelating unit, with the d-position being found to favour the Δ-isomer and the e-position favouring the Λ-isomer. Furthermore, the strength of this preference can be controlled by altering the proximity of the chelate to a chiral centre. The identity of the achiral spacers, however, have been found to be an important factor, their ability to H-bond in an i-i+4 pattern being crucial for continuation of the α-helical turns.

In Chapter 4 an alternate chelating unit, 8-hydroxyquinoline, is investigated. The coordination of this ligand to transition metal ion Co²⁺, and p-block metal ions Ga³⁺ and Al³⁺ has been investigated and analysed by circular dichroism and UV-absorbance spectroscopy. The preferential formation of Δ-tris-(8HQ-peptide) and Λ-tris-(8HQ-peptide) complexes were found to be controlled by alteration of the 8-HQ register position, with 8-HQ in the dposition favouring the Λ-isomer and 8-HQ in the e-position favouring the Δ-isomer. The behaviour of these systems in response to pH was also investigated in this chapter and aims to show that the differences between the 2,2′-bipyridine and the 8-HQ chiral preferences are as a result of H-bonding interactions between the 8-HQ chelating units and the peptides.

Graphical Abstract – Cartoon representation of the transfer of chiral information in the systems investigated in this thesis. The information is transferred from the point chirality in the amino acid structures (L-AAs), to helical chirality in the secondary structure (P-Helices), to folding of the super-secondary structure into the opposite handedness helical chirality (M-Supercoiling) and finally, controlling the directionality of an 6-coordinate complex at the N-terminus of the sequence (Λ/Δ).

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Additional Information: Supported by funding from the Leverhulme Trust.
• Subjects: Q Science > QD Chemistry
• Colleges/Schools: College of Science and Engineering > School of Chemistry
• Funder's Name: Leverhulme Trust (LEVERHUL)
• Supervisor's Name: Thomson, Dr. Drew and Forgan, Professor Ross
• Date of Award: 2026
• Depositing User: Theses Team
• Unique ID: glathesis:2026-85695
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 16 Jan 2026 12:04
• Last Modified: 16 Jan 2026 12:06
• Thesis DOI: 10.5525/gla.thesis.85695
• URI: https://theses.gla.ac.uk/id/eprint/85695