Makenna Schierling
- B.Sc. (University of Victoria, 2024)
Topic
Kinetics of extended sulfo-pillar[6]arenes for the reversal of neuromuscular blockers
Department of Chemistry
Date & location
- Monday, August 10, 2026
- 9:00 A.M.
- Elliott Building, Room 226
Examining Committee
Supervisory Committee
- Dr. Fraser Hof, Department of Chemistry, University of Victoria (Co-Supervisor)
- Dr. Cornelia Bohne, Department of Chemistry, UVic (Co-Supervisor)
- Dr. Scott McIndoe, Department of Chemistry, UVic (Member)
External Examiner
- Dr. David Goodlett, Department of Biochemistry and Microbiology, UVic
Chair of Oral Examination
- Dr. Leslee Francis Pelton, Department of Curriculum and Instruction, UVic
Abstract
Host-guest chemistry focuses on noncovalent interactions between a macrocyclic host and a guest molecule which has proven to be relevant in many medical and material applications. Sulfo-pillar[n]arenes are a relatively new macrocycle (first synthesized in 2020) that have demonstrated exceptionally high affinity for illicit drugs, neuromuscular blockers, and direct oral anticoagulants allowing for their development as reversal agents for these substances. This work studies sulfo-pillar[n]arenes which can be used as an antidote for non-depolarizing steroidal neuromuscular blocking agents (NMBAs). In Chapter 2, the affinity of extended sulfo-pillar[6]arene (A1A2sP6) for NMBAs is measured through the host’s intrinsic fluorescence. A1A2sP6 shows nanomolar affinity for NMBAs, proving to bind stronger than the parent host, sulfo-pillar[6]arene (sP6). Another finding is that sP6 is shown to aggregate at higher concentrations which prevents comparison to previous studies with this host and NMBAs. Additionally in Chapter 2, a new method of deprotection in the sP6 synthetic pathway is successfully developed due to a shortage of the reagent used in the published procedure, therefore leading to a simplified route to this key intermediate. In Chapter 3, the mechanism of host-guest complexation is determined from stopped flow experiments. A1A2sP6 and NMBA complexation is found to have multi-component kinetics. The mechanism is determined to be the fast formation of an exclusion complex, followed by the slower conversion to an inclusion complex. This mechanism is concluded from an offset in initial intensity observed during the stopped flow experiments, in which the formation of exclusion complex is faster than the resolution of the instrument. Overall, this work increases understanding of the binding parameters of the host A1A2sP6, demonstrating its potential for rapidly sequestering NMBAs with high affinity in physiological conditions.