Fig. 3. Thermodynamic profiles for adenosine and compound 4. (a) Computational van't Hoff plots based on binding free energies relative to 3-deazaadenosine calculated at different temperatures for adenosine and compound 4. (b) Thermodynamic profiles show that the relative free energy change at 300 K for adenosine and compound 4 is driven by enthalpy. (c) Decomposition of the relative binding enthalpy for adenosine and compound 4 into contributions from the ligand and from within the surroundings. The ligand contribution is the driving force for adenosine whereas changes from within the surroundings dominate for compound 4. The calculated energies and uncertainties in (b) and (c) are also shown in Table S2.†.