Juan Pablo Diaz Duran

Topic

Multi-responsive calixarene hosts for the detection of drug molecules

Department of Chemistry

Date & location

• Tuesday, April 23, 2024
• 2:00 P.M.
• Elliott Building, Room 230

Examining Committee

Supervisory Committee

• Dr. Fraser Hof, Department of Chemistry, University of Victoria (Supervisor)
• Dr. David Leitch, Department of Chemistry, UVic (Member)

External Examiner

• Dr. Mariya Goncheva, Department of Biochemistry and Microbiology, UVic

Chair of Oral Examination

• Dr. Jon Husson, School of Earth and Ocean Sciences, UVic

Abstract

The field of host-guest systems is advancing toward a wide variety of biologically relevant applications such as drug delivery, encapsulating agents, sensing target molecules of interest, and acting as therapeutics themselves. Calixarenes are a family of macrocyclic hosts that have been able to fill many of these roles, including novel systems that can act as therapeutic drug reversal agents and powerful chemosensors. In this work we present a new series of Stilbene-calix[4]arene (StiCx) molecules that can act as fluorescent sensors for small cationic drug molecules. The reaction by which these are constructed was optimized to synthesize a small library of compounds, by introducing a phenylacetylene “arm” with different substituents onto the calixarene scaffold, followed by in situ semi-reduction to obtain the corresponding stilbene. We also studied the ability of these molecules to bind and detect small drug molecules, with detection based on the change of fluorescent intensity of the host upon binding. We find that the new StiCx system can have either a turn-on or turn-off response depending on the identity of the target, which has the advantage of giving information-rich outputs of a mixture. This system is also capable of differentiating different analytes based on the fluorescence response using multivariate statistical treatment of the data. The mechanisms of guest binding and sensing by StiCx sensors were studied using different NMR and optical spectroscopy techniques. This work provides novel chemo-sensors for future use in drug detection, as well as providing insight into their mechanisms of action.