Applications of macrocycles: From nucleic acid sensors to controlling molecular motion

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Wilkinson, Edward ORCID: https://orcid.org/0000-0002-4987-6965 (2021). Applications of macrocycles: From nucleic acid sensors to controlling molecular motion. University of Birmingham. Ph.D.

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Abstract

Macrocycles have long been key molecular cornerstones of many fundamental processes found in nature and have risen to prominence over the last 60 years in the field of chemistry research, with their rich coordination chemistry seeing them used for a variety of applications. The work herein employs macrocycles and their complexes in two areas; firstly in the development of a switchable system which exhibits controlled molecular-level motion, and secondly as a component of a electrochemical nucleic acid sensing system capable of detecting important cancer biomarkers.
Harnessing molecular motion is considered vital for the development of next generation nanotechnology. In this thesis, the design, synthesis and study of a novel ball-bearing rotary system is described that employs the coordination chemistry of crown ethers to control the rate of rotation about the axis of a (η4-tetraarylcyclobutadiene)(η5-cyclopentadienyl)cobalt(I) sandwich complex core. Chemical inputs, in the form of pH changes and metal cations, were employed to exert switchable control over molecular motion, as evidenced by variable temperature 1H NMR experiments and the subsequent calculation of kinetic parameters.
In 2016, Tucker and co-workers reported a nucleic acid probe modified with a copper cyclidene complex capable of electrochemically distinguishing between target DNA strands containing the four canonical nucleobases at one locus. The work herein details the synthesis of the cyclidene macrocycle and its transition metal complexes, and establishes the synthetic route for their incorporation into DNA. The sensing ability of the previously reported sensing system is explored as part of a SAM on the electrode surface, leading to the synthesis and study of a hetero-bimetallic and ratiometric sensing probe that can rapidly detect key cancer
biomarkers at low femtomolar levels. The ability to discriminate between nucleobases at such low concentrations raises the exciting possibility of biomarker detection without the need for amplification, highlighting the potential of this sensing system to act as a valuable medical tool in the diagnosis and management of genetic diseases.
Additionally, a variety of other cyclidene-modified DNA systems are synthesised and characterised, with strands varying in length and number of metal atoms, whilst the previously problematic electrochemical visualisation of the nickel complex is addressed. This research expands the previously reported family of metal-modified nucleic acids and provides the foundations for their electrochemical properties to be explored in a wider range of applications such as molecular wires.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):