Reproduction of experimental data for stacked caffeine dimers using various computational methods.

Reliable description of stacking interaction of aromatic molecules is important for the understanding structure, stability, and functions of biopolymers. The caffeine molecule is an ideal object for this study as the stacking interactions are the preferential ones for self-associations of this hydrophobic molecule without H-bond donor groups. The analysis of anhydrous caffeine crystal structures revealed five types of caffeine stacking dimers. Geometry optimization of these dimers was performed using two molecular mechanics force fields, ab-initio method Møller Plesset of the second order (MP2), and density functional theory (DFT) with different functionals. The comparison of geometric parameters of the caffeine dimers obtained using different theoretical methods with those in crystals enables us to suggest the methods providing the most reliable stacking characteristics. These methods are: the MP2 with Basis Set Superposition Error correction (MP2/CP), Poltev force field, along with PBE0-DH, SCAN and PBE-D3 functionals of DFT. For the methods, which give the dimer interaction energy close to that obtained by MP2/CP method, the evaluated sublimation enthalpy values are shown to be close to the experimental data. Additionally, MP2/CP, Poltev FF and PBE0-DH functional showed to be the methods that describe well both the energy and geometry of the caffeine stacking dimer.