Iridium(III) coordination of N(6) modified adenine derivatives with aminoacid chains

In this manuscript we report the preparation of three N⁶-aminoacid-adenine-derivatives: N-(7H-purin-6-yl)glycine·0.5H₂O (N⁶-GlyAde), N-(7H-purin-6-yl)-β-alanine·1.5H₂O (N⁶-β-AlaAde) and N-(7H-purin-6-yl)-γ-aminobutyric·2H₂O (N⁶-GabaAde) and the synthesis and X-ray characterization of three Ir(III) NAMI-A derivatives (NAMI-A is [imidazoleH][trans-Ru^IIICl₄(DMSO-κS)(imidazole)]) [trans-Ir^IIICl₄(DMSO-κS)(N³-H)-(7H-purin-6-yl)glycine-κN⁹] (1), [trans-Ir^IIICl₄(DMSO-κS)(N³-H)-(7H-purin-6-yl)-β-alanine-κN⁹] hydrate (2) and [trans-Ir^IIICl₄(DMSO-κS)(N³-H)-(7H-purin-6-yl)-γ-aminobutyryl-κN⁹] (3). In all complexes the metal center shows octahedral geometry with coordination to four chlorido ligands and one S coordinated dimethylsulfoxide (DMSO-κS). The coordination sphere of the metal is completed by the modified adenine molecule which is bound via N(9) and protonated at N(3). In two complexes the importance of lone pair (lp)-π interactions involving the adenine ring have been studied using density functional theory (DFT) calculations and the Bader's theory of atoms in molecules. Furthermore, the ability of complexes (1-3) to affect the cell viability was evaluated against three different cancer cell lines: human lung carcinoma cells (A549), human cervical carcinoma cells (HeLa) and human breast cancer cells (MCF7). We have also analyzed their ability to cleave the DNA experimentally and their affinity for two models of DNA has been studied using molecular docking simulations.