Synthesis, reactivity, X-ray characterization and docking studies of N7/N9-(2-pyrimidyl)-adenine derivatives

The reaction of adenine with 2-chloropyrimidine yields as a major product the unexpected N7-(2-pyrimidyl)-adenine (1) and as a minor one N9-(2-pyrimidyl)-adenine (2). Both compounds have been characterized by X-ray diffraction analysis. Moreover, we report the formation of a 1:1 co-crystal (3) composed by compound (1) and adenine that was formed serendipitously during the synthesis of (1). Unexpectedly, the treatment of (1) with Brönsted acids like HCl or HNO3 causes the opening of the imidazole ring of the N7-substituted adenine, yielding N5-(pyrimidin-2-yl)pyrimidine-4,5,6-triamine (4–7) which we have X-ray characterized in its neutral, (4), monoprotonated [nitrate salt (6)] and diprotonated forms [hydrochloride salt (5) and, also, a tetrachlorozincate salt (7)]. Finally, we have used compound (5) as ligand to synthesize and X-ray characterize its complexes with Ir(III) and Ag(I) (compounds (8) and (9), respectively), where the latter is a 2D coordination polymer and the former is a discrete mononuclear complex. We have studied the supramolecular assemblies formed in the solid state by using density functional theory (DFT) calculations. Finally, DNA-docking studies of several compounds have been carried out in order to analyze their ability to interact with the DNA. Seven new adenine derivatives have been synthesized and X-ray characterized. In some compounds an opening of the imidazole ring of the adenine occurs, yielding N5-(pyrimidin-2-yl)pyrimidine-4,5,6-triamine molecule that has been used as ligand to synthesize and X-ray characterize Ir(III) and Ag(I) complexes. DNA-docking studies of several compounds have been carried out in order to analyze their ability to interact with the DNA. [Display omitted] •N7- and N9-(2-pyrimidyl)-adenine isomers are structurally characterized.•N7-(2-pyrimidyl)-adenine in acidic conditions yields N5-(pyrimidin-2-yl)pyrimidine-4,5,6-triamine.•Ir(III) and Ag(I) complexes of N5-(pyrimidin-2-yl)pyrimidine-4,5,6-triamine have been characterized.•Supramolecular assemblies have been studied using theoretical calculations.•Molecular docking studies revel affinity of the ligands for the minor groove of ADN.