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Antimicrobial resistance (AMR) is likely to be one of the greatest challenges faced by humanity and if nothing changes it is projected to kill one person every 5 seconds by 2050. Despite this, there are few new therapeutic options in development and so there is a need for new solutions to be identified. One new strategy is the reverse antibiotic approach originally published by Akamatsu and co-workers. Here treatment with the first antibiotic leads to resistance so a new antibiotic is needed. Resistance to the second antibiotic can only be achieved by a back-mutation thus re-sensitising the bacteria to the first antibiotic. The bacteria will be trapped in an 'evolutionary loop' where it will always be sensitive to either the first or second antibiotic. Work outlined in this thesis will look to investigate and develop one of the key series of antibiotics in the reverse antibiotic approach, the Nybomycin family of natural products. A new robust and scalable synthetic route that facilitated the synthesis of the best literature compound DNM-2, as well as novel analogues to probe the SAR, is reported. The whole cell inhibition of these compounds is reported as well as selected analogue's enzymatic inhibition of the key biological targets. The ability of the series to inhibit Gram-negative bacteria was also explored and led to the discovery that the series is a substrate for efflux via the AcrAB/TolC efflux channel. However, the compounds are active in E. coli if TolC or AcrB is removed. After initial profiling, aqueous solubility was found to be the major hurdle in the development of the series. This was addressed using medicinal chemistry techniques as well as computational chemistry to aid in the design of novel analogues. This led to the discovery of 6DNM-2-L1A, the most potent and soluble analogue tested to date.

This study examines the role of privately owned country houses in political and cultural discourse in Britain between 1950 and 2000. It expands existing scholarship on how and why policy affecting country houses has developed, and contextualises these developments broadly within cultural and political changes of the late-twentieth century. The thesis situates privately owned country houses within the broader history of the rise of the 'heritage industry' and heritage preservation policy in Britain. It utilises the Historic House Association's (HHA's) archives, and the personal archives of some of its key figures, which have not been studied by researchers before. This approach contributes unprecedented detail to the study of built heritage preservation policy changes, and particularly to our understanding of how aristocrats have influenced modern politics via the heritage sector. Existing accounts of the country house's "survival" in twentieth-century Britain are predominantly cultural. This perspective in isolation obscures critical dynamics within governments, and between governments and lobbyists. Relationships between country house lobbyists and Treasury and Inland Revenue officials, which long outlasted individual governments, were essential in the development of crucial taxation exemptions for heritage. The conditional exemption of heritage properties from Capital Transfer Tax in 1975/76, under Wilson's government, set a critical precedent for the special treatment of historic houses under taxation, which was expanded during the 1980s. This became the foundation of the cross-party political principle that country houses are best maintained in private hands, although Wilson's cabinet had not truly resolved their objections to granting country house owners financial privileges. Governments' subsequent expansion of public aid for privately owned houses and collections was rooted in this political principle. During the 1980s and 1990s, the importance of "saving" country houses and their collections was taken for granted by both the public and governments-even under the allegedly heritage-averse New Labour.