Can β-Cyclodextrin Function as a Nonenzymatic Biosensor for Creatinine? Exploring Host–Guest Interactions

Chronic kidney disease (CKD) is a global health crisis affecting approximately 10% of the population, with diabetes being the leading cause. Early detection of CKD is crucial, since creatinine is a key biomarker for this purpose. This study explores the potential of β-cyclodextrin (β-CD) as a nonenzymatic biosensor for creatinine by investigating host–guest interactions. The thermodynamic behavior of creatinine in binary and ternary aqueous solutions at 310.15 K was examined using density measurements to obtain volumetric properties, while osmotic pressure measurements provided insights into water activity and activity coefficients. The McMillan–Mayer and Kirkwood–Buff theories were applied to obtain virial coefficients and pair distribution functions to understand molecular interactions. We also examined the binding constant of the creatinine−β-CD complex and the transfer Gibbs free-energy changes for aqueous ternary solutions containing creatinine and β-CD (or NaCl). The findings highlight the significant role of hydrophobic interactions and hydration in the creatinine−β-CD system. This research provides fundamental insights into the structural and thermodynamic properties of creatinine, which are essential for the development of effective biosensors. The results underscore the potential of CD-based sensors as valuable tools for CKD management and pave the way for future advancements in electrochemical nonenzymatic creatinine biosensors.