A theoretical model of the interaction between phosphates in the ATP molecule and guanidinium systems

In order to understand the interaction between adenosine-5′-triphosphate (ATP) and guanidinium, as recently hypothesized in protein kinase type III inhibitors, a theoretical study has been carried out. First, the intrinsic interactions established between these two systems were studied using a model of ATP; thus, the interactions between a phosphate anion and differently substituted phenylguanidinium cations have been analysed. Then, considering the most stable complexes found with this simplified model, those formed between the phosphate groups of ATP and diaromatic guanidinium derivatives have been studied. All the calculations have been performed using ab initio MP2/6-311++G(d,p)//MP2/6-31+G(d,p) computational level utilizing the polarizable continuum model mimicking water solvation. Besides, only for ATP complexes the geometry optimization has been modified, and thus, DFT-D calculations with the ωB97XD functional were carried out. The Atoms in Molecules analysis of the electron density, natural bond orbital second-order orbital energies and electron density shift maps have been used to better understand the intermolecular interactions.