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

[Display omitted] •Cucurbit[7]uril (Q7) cavity is stronger solvated by ethanol than water.•In aqueous solution with wEtOH ≤ 0.15 macrocycle Q7 binds gemcitabine (Gem).•Q7–Gem binding is exothermic and thermodynamically spontaneous.•EtOH as cosolvent weakens the driving force of Gem complexation with Q7.•At wEtOH = 0.25 cucurbituril Q7 does not complex Gem. The process of complexation of gemcitabine cation by cucurbituril Q7 was studied in an aqueous formate buffer (pH = pKa=3.8) with increasing ethanol mass fraction wEtOH using ITC calorimetric titration technique. The equilibrium constant K and thermodynamic functions (ΔH,ΔS,ΔG) 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 (wEtOH ≤ 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 nano-container 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 wEtOH should be lower than 0.1.