Interaction of caffeine dimers with water molecules

Stability of caffeine dimers in the presence of surrounding water molecules was investigated by performing ab initio calculations at B3LYP/CBSB7 level of theory. Dimers were constructed by placing geometry optimized monomers at different relative orientations. These dimers were then fully geometry optimized at the same level of theory. Dimer–water interaction was modeled in two ways. Dimers were geometry optimized in aqueous medium using polarizable conductor calculation model. The energy, enthalpy and Gibbs energy of dimer formation was then calculated. It was found that the thermodynamic parameters are much deviated from experimental values. Caffeine dimer water interactions were also modeled by placing water molecules around the dimer at locations where hydrogen bonds could form. In this manner, the number of water molecules was increased up to six. It was observed that the water molecules form hydrogen bonds with both the caffeine molecules. The caffeine–caffeine inter-plane distance increased from 3.6 Å for isolated caffeine dimers (gas phase) up to 3.9 Å for dimer water clusters. Formation energy change (ΔE) of caffeine dimers, depending on their relative orientation in gas phase, ranged from −5.2 to −6.0 kcal mol−1. The average energy change, enthalpy change and Gibbs energy change for dimer formation in gas phase are −5.9, −3.9 and 8.4 kcal mol−1 respectively. Average formation energy change decreased to −13.7 kcal mol−1 for dimer–water clusters. The average standard Gibbs energy change of dimer–water cluster formation is positive and observed to be 14.9 kcal mol−1. Compared to formation energy changes, relatively large fluctuations were observed with Gibbs energy changes.