DNA as a Vehicle for Chemistry and Assembly

Allott, Benjamin (2025). DNA as a Vehicle for Chemistry and Assembly. University of Birmingham. Ph.D.

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Abstract

This thesis delves into the intricacies of DNA Templated Synthesis (DTS) and investigates the self-assembly of octahedral patchy colloids in computer simulations. A common theme for both strands of research is DNA, which can be used to functionalise the patches to encode a hierarchy of interactions that could as well be specific for programming distinct self-assembly pathways. Our experimental study reveals and measures how a unique protective effect present in DTS can shield a labile thioester-TAMRA from hydrolysis. We show that protection is enhanced when the abasic site is located across the minor groove, specifically the -3 position. It is proven that this protective effect occurs via the interaction of the TAMRA moiety with an abasic site, with variations in the degree of protection according to the relative position of the abasic site to that of the TAMRA linker. This protective effect was discovered and measured in the hopes that it could enhance the synthesis of long-chain polymers via DTS. This experimental chapter is complemented by the following molecular dynamics study concerned with modelling this unique effect. The study employs models of the short-TAMRA linker at abasic sites +3 and -3, with TAMRA represented either as the lactone or zwitterion resonance form at neutral or physiological salt concentrations. Neutral salt concentration conditions involve sufficient sodium ions to neutralise the negative charge of the DNA phosphate backbone. In contrast, physiological salt concentration not only neutralises this charge but also includes additional sodium and chloride ions in equal proportions to mimic physiological conditions. We hypothesise, based on both experimental and computational studies, that the protective effect necessitates physiological salt concentration and initially requires the lactone resonance form for insertion. This dual approach of experimental and computational research provided a detailed understand- ing of how the protection mechanism is manifested. The study of self-assembly of octahedral patchy colloids explores how different self-assembly pathways can be programmed to yield simple cubic crystals and whether the quality of the crystals self-assembled differs in those cases. To this end, the four patches on a plane are distinguished from the remaining two across the plane, the former referred to as equatorial patches (labelled E) and the latter axial patches (labelled A), in terms of the strength of interactions between the patches within a given type. Different scenarios are considered in computer simulations: equatorial-bias (E-E interaction strengths 5 times stronger than A-A interaction strengths) and axial-bias (A-A interaction strengths 5 times stronger than E-E interaction strengths, with and without interactions between different types of patches, along with the control scenario (no distinction between patch-patch interactions). We show marginally better-quality crystals are produced via equatorial biasing with no (E-A interaction), with the control scenario of no biasing being a close second and characterisations of the crystallisation pathways in the different scenarios. Our findings suggest that uniform growth of the largest crystalline cluster in all three dimensions favours the formation of good-quality simple cubic crystals. This study elucidates key parameters influencing the self-assembly of simple cubic crystals from octahedral patchy colloids. This thesis not only advances knowledge of DTS and colloidal self-assembly but sets the stage for future explorations, developing these phenomena for material and drug development.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):