Nature abounds with ingenious nanoscopic machines employed to carry out all of the requisite tasks that collectively contribute to the molecular basis of life. This thesis focuses primarily on a sub-set known as "molecular walkers" which can perambulate along intracellular molecular motorways carrying out such essential tasks as vesicle transport and muscle contraction. A summary of these incredible natural motors is presented in Chapter I along with a review of the artificial small-molecule mimics reported to date. When elucidating a set of design principles for synthetic analogues, inspiration is taken from the mechanism of the biological bipedal motor protein kinesin with a focus on potential strategies to enable directional walking. Transition metal-ligand chemistry is utilised as one such strategy in Chapter II through the governance of walker-track interactions in the design, synthesis and operation of a bimetallic molecular biped. A palladium(II) moiety is selectively and intramolecularly stepped between pyridine-derivative binding sites in the track using a thermal stimulus in the presence of a coordinating solvent. Acid-base manipulations facilitate directional stepping by means of an energy ratchet mechanism allowing the track to do work on the biped unit and ultimately drive it away from equilibrium. The potential of malleable transition metal binding-event energetics is explored further in Chapter III with the design and synthesis of a platinum(II)-complexed [2]rotaxane. Thermodynamic and kinetic stimuli are investigated as means to mediate selective shuttling of a Pt-complexed macrocycle between two ligand binding sites in the thread. The substitution pattern of the ligands and the kinetic stability of the metal-ligand bonds afford exceptional metastability to the co-conformers of the molecule in the absence of an external stimulus providing the possibility for long-term information storage. In Chapter IV, a novel macrocycle is used to demonstrate the chemical orthogonality of acid-mediated hydrazone exchange with respect to the palladium(II) stepping mechanism described in Chapter II and show that two such motifs can be independently addressed within a single molecule. These linkages are then utilised as mutually exclusive chemo-selective switches to individually operate opposing feet in an unprecedented first-generation small-molecule walker-track system.

The work described in this thesis is inspired by natural-occurring molecules that are used throughout biology to perform specific, highly-selective tasks. This thesis illustrates the design, synthesis and investigation of novel molecular devices based on acyl hydrazones for the synthesis of a small molecule walker and light-driven molecular shuttles. Chapter One outlines a general overview of the design and synthesis of molecular devices, including molecular walkers and molecular shuttles. Some of the most important examples of walking molecules (both natural and synthetic) are described in detail, along with a comprehensive introduction of molecular shuttles and their synthetic mimics. Examples of stimuli-responsive molecular shuttles that have been developed are highlighted throughout the chapter. Chapter Two describes the design and synthetic progress towards a molecular walker, as well as detailing the optimisation of the synthetic steps achieved thus far. In this chapter, most of the work presented is based on the design and optimisation of the synthesis of an acyl hydrazone-based molecular walker, which will be able to walk directionally and repetitively along its conjugate track when the conditions are changed. A novel acyl hydrazone pyridine moiety is introduced to the system to achieve a high directional bias during the walking process. First, the concept and basis of the design is explained and further, the synthesis of the walker system is discussed in detail. Chapter Three illustrates the synthesis and operation of 1- and 2- station [2]-rotaxanes which exhibit all the requirements for a light-driven molecular shuttle. The effect of a new photo switchable binding station, an acyl pyridyl hydrazone, on the shuttling process is investigated by comparing the positional distribution of the macrocycle between the acyl hydrazone station and the succinamide-ester station, while the acyl hydrazone undergoes photo- and thermal isomerisation. The successful synthesis of this molecular architecture is described along with its operation, demonstrating high positional integrity and efficiency during the shuttling process.