Grant: Research Tools and Instruments

Methods to quantify chirality are complex since enantiomers have identical physical properties. The use of optical rotation in a quantitative sense is unreliable on small scales and highly sensitive to impurities. Chiral shift reagents are not always effective, require tedious titration into a sample and are not helpful for reactions that are highly selective. Chromatography with chiral stationary phases is by far the best alternative, and the use of super critical fluids is essential to increase the speed and efficiency of separation. In our experience, compounds elute 2-5 times faster using SFC compared to traditional HPLC. Since this instrument will be shared between multiple groups, speed of analysis and development of reaction conditions is essential. A major part of the Crudden lab studies the development of enantioselective and enantiospecific cross coupling reactions. This project previously relied upon a 10 year old SFC-HPLC to separate and identify enantiomers after catalytic CC bond connections. After functioning well for 9 years, this instrument suffered a series of breakdowns, was sent back to the parent company for repair over the COVID shutdown, and is still not functioning after being returned to us. For the time being, this leaves us unable to measure chirality in our samples, which is threatening the work of an MSc student, two PhD students, and two postdoctoral fellows. Another program that will be impossible without the requested infrastructure is the use of chiral nanoclusters in catalysis. Crudden has spent the last 6 years developing the use of carbon-based NHC ligands in materials science, culminating in the successful synthesis of a series of nanoclusters, most recently describing two chiral nanoclusters. The next step is the application of these in synthesis, which will not be possible without the requested infrastructure. The Stamplecoskie group has significant experience in nanoclusters and has recently prepared a chiral Ag29 cluster, but cannot use it for anything without the requested infrastructure. Queen's is developing a strength in bio-organic chemistry and the programs of three key members of this program (Zechel, Howe and Ross) will be severely impacted without access to chiral chromatography. New hire Howe is investigating directed evolution of enzymes, including the preparation of designer enzymes to prepare chiral molecules with enzyme-level specificity. Zechel is studying iron-dependent oxygenases for use in stereospecific C-H activation, and Ross needs access to this instrument to determine stereochemistry of amino acids as part of her work in structure determination of low abundance bioactive peptides from bacterial sources. None of this work will be possible without access to the requested infrastructure, which will also serve as an excellent training ground for HQP in the five groups, and a touchpoint for interactions between HQP from these different research areas.