Thermodynamic study of ethanol impact on gemcitabine binding to cucurbit[7]uril in aqueous solutions

The process of complexation of gemcitabine cation by cucurbituril Q7 was studied in an aqueous formate buffer (pH = pK(a) = 3.8) with increasing ethanol mass fraction w(EtOH) using ITC calorimetric titration technique. The equilibrium constant K and thermodynamic functions (Delta H, Delta S, Delta G) describing the process of gemcitabine binding by cucurbituril Q7 were calculated. The determined parameters indicate that in the range of ethanol mass fraction physiologically tolerated by the human body (w(EtOH) <= 0.005), the interaction energetics of cucurbituril Q7 with gemcitabine are similar to those observed in a buffer environment without the addition of alcohol. This suggests that the ethanol present in the patient's body is not a significant contraindication to the use of cucurbituril Q7 as a supramolecular gemcitabine nanocontainer for biomedical applications. However, higher ethanol mass fraction in solution clearly weaken drug interaction with cucurbituril Q7. Therefore, for potential technological applications using cucurbituril Q7 as a gemcitabine carrier, the ethanol mass fraction w(EtOH) should be lower than 0.1. (C) 2020 Elsevier Ltd.