This fellowship will use novel instrumentation to define the role of cofactors on the structure and stability of proteins. We have recently adapted a commercially available Synapt ion mobility mass spectrometer to allow it to perform optical measurements on conformer and mass selected ions, in collaboration with Waters Corp. The heart of this instrument is the ion mobility cell, IM-MS measurements are possible in this instrument, as for any Synapt mass spectrometer, but uniquely we are able to trap ions that have been conformer selected, to allow optical measurements in a so called ‘photo SRIG’ (stacked ring ion guide). Such optical measurements can take several forms, including IR-spectroscopy, UV/Vis-spectroscopy, which will provide structural analysis of co-factors and coenzymes, photo-dissociation to sequence the proteins as well as fluorescence to probe global conformations. Molecular mechanics calculations will generate structures to compare with those determined experimentally. This MC fellow will use this novel instrument to examine the role of cofactors on the conformations of proteins, by making measurements on the cofactor alone, the apo and the holo form of the protein. The MC fellow will be trained in biological mass spectrometry, in optical methods and in molecular mechanics. They will spend a secondment at Waters developing software to best interpret the data from this instrument. This cutting edge interdisciplinary science program is world leading and will train this fellow with a set of skills highly desirable both in academia and in industry.

The aim of this project is to design, synthesize and investigate the operation of synthetic molecular machines capable of performing sophisticated tasks in chemical synthesis. The molecular machines are inspired by biological systems, where substrates are shuttled between different enzymatic sites, undergoing chemical transformations at each step. Control of substrate position allows for reactions to occur in a specific sequence, with the molecular machine dictating the selectivity of each successive chemical reaction. The project both seeks to optimize the structure of the molecular machines for use as a synthetic platform and demonstrate their usefulness for synthesis and catalysis in model reactions. The successful demonstration of this concept would mark the beginning of a fundamentally new approach for the construction of molecules.

Organoboron complexes are ubiquitous in synthesis due to their utility in functional group transformations and the Nobel Prize winning Suzuki-Miyaura reaction. Furthermore, the advent of frustrated Lewis pair chemistry and BB multiple bonds has demonstrated that organoboron compounds can activate small molecules (e.g., CO) and sigma bonds (including H2), reactivity previously thought to be the domain of transition metal catalysts. As part of the renaissance in organoboron chemistry diborane(4) compounds (R2B-BR2) have received considerable interest, particularly that react as boryl anion equivalents. Recent unpublished work at UNIMAN has developed an efficient, scalable route to a synthetically useful unsymmetric diborane(4) compound, specifically (RO)2B-BCl2(NHC), (1, NHC = N-heterocyclic Carbene). The DIBOR project will exploit this breakthrough using 1 (and new congeners synthesised in this fellowship) as key precursors to; (i) readily synthesised cationic diboranes that are strong electrophiles able to activate small molecules and sigma bonds (C-H) and to diborylate pi nucleophiles; (ii) extended homocatenated boron compounds containing both electron precise B-B and B=B bonds. Advances in (i) will generate new transition metal free routes to diborylated hydrocarbons for use as synthetic intermediates. Whilst the demonstration of H-H and C-H activation will demonstrate that individual steps are viable for future application using diboranes in catalytic sigma bond transformations. Advances in (ii) will generate fundamentally new boron entities, e.g., electron precise B4 chains containing B-B and B=B bonds. The chemistry of electron precise boranes is in its infancy but dramatic differences in reactivity to the isoelectronic hydrocarbons have already been reported. Precursor 1 is carefully designed to prevent borane cluster formation on reductive coupling thus facilitate formation of homo-catenated chains.

The proposal is to use our great synthetic control to examine the use of heterometallic cyclic coordination compounds (heterometallic rings, HRs) in two distinct application areas. One is of immediate impact: the use of the HRs as resist materials for lithography. This work has already been patented and is being developed as a means to fabricate devices that will be needed at the 7 nm node and smaller. The synthetic control also means we can make resists for extreme UV lithography (13 nm wavelength) which meet the tight specifications needed for industrial application. The second application is more long term, which is the proposal that such rings could be used as qubits in quantum information processing. Here we will build on recent work that has established a diamagnetic matrix in which complex polymetallic assembly could be incorporated. This gives us the opportunity of performing algorithms during the project and hence laying the ground-work for future developments.