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

Abstract

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.

Keywords: Adenine complexes; Ag(I) complexes; DFT calculations; Docking studies; Ir(III) complexes; Supramolecular chemistry.