A High Affinity and Selective Recognition Element for Kynurenic Acid

Kynurenic acid (KynA) is a byproduct of tryptophan (Trp) metabolism as well as an important neuroprotective biomolecule. KynA acts as a distinct biomarker for many neurological diseases since concentrations above or below an established equilibrium are associated with clinically diagnosed schizophrenia and depression, respectively. Currently, the only way to quantify KynA at physiological concentration levels is through high performance liquid chromatography (HPLC) analysis with extensive sample preparation. This technique is also very expensive and time consuming. A more efficient sensing system can achieve the same results utilizing a macrocyclic resorcin[4]arene receptor with inherent photophysical properties. This advancement is necessary as increasing amounts of research is associating KynA with depression, especially in women on oral contraceptives. Having access to point of care testing for KynA blood levels can help guide physicians when diagnosing patients and prescribing medications. In this thesis research, a naphthalene functionalized resorcin[4]arene based receptor (Np-NAR(Cl)4) displays high affinity and selectivity for KynA over Trp in a host-guest complex. The interactions are tested using Nuclear Magnetic Resonance (NMR) for qualitative screening, Isothermal Calorimetry (ITC) for quantitative thermodynamic parameters, Ultraviolet-Visible (UV-Vis) and Fluorescence Spectroscopy for visualizing binding across a range of pathological and physiological concentrations.