Probing the effect of N-alkylation on the molecular recognition abilities of the major groove N7-binding site of purine ligands

The study of the metal binding pattern of N-methyladenines (1-, 3-, 7- or 9-Meade) towards Cu^II-iminodiacetate-like chelates is addressed on the basis of XRD crystal structures of sixteen novel ternary compounds. Except for three compounds, all others feature an square-based Cu(II) coordination, type 4 + 1, and the efficient cooperation of a CuN7 bond with an intra-molecular N6-H⋯O(coord. carboxylate) interligand interaction as the major metal-binding pattern. The three referred exceptions to this behavior are: (1) the compound [Cu(MIDA)(7Meade)(H₂O)]·4H₂O, which evidence the CuN3 binding pattern; the (2) [Cu(IDA)(1Meade)(H₂O)₂]·4H₂O, which molecular recognition consist in the CuN9 bond and a (distal aqua)⋯⋯N3(1Meade) intra-molecular interaction, within an octahedral Cu(II) center; and (3) [Cu(IDA)(9Meade)(H₂O)₂]·3H₂O, also with a 4 + 1 + 1 Cu(II) coordination, where the CuN7 bond exists along with an extremely weak N6-H⋯O(coord. carboxylate) interaction (3.33 Å, 140.2°). This former interaction is determined by packing forces that promote the participation of the N6H group in a 'trifurcated' H-bond. In conclusion, the cooperation between the CuN7 bond (not possible for 7Meade) and the intra-molecular N6-H⋯O interaction is clearly favored (a) by the H-accepting role of the O-coordinated carboxylate atoms from the iminodiacetate ligands in mer-NO₂ conformation and (b) in compounds where the Cu(II) atom exhibits an elongated square-base pyramidal coordination, type 4 + 1.