Crystal structure of [Rh2(μ-OAc)2(μ-HNOCCF3)2(theophylline)2]·6H2O. Metal bonding to theophylline at the unexpected N(9) site due to the crystal packing effect and a review on intra-molecular interligand interactions affecting metal bonding properties of theophylline

Reaction of theophylline with [Rh₂(μ-OAc)₂(μ-HNOCCF₃)₂] gave [Rh₂(μ-OAc)₂(μ-HNOCCF₃)₂(theophylline)₂]·6H₂O (1), whose crystal structure was determined by single-crystal X-ray diffraction. The dirhodium core, where the two different acetato and acetamidato ligands bridging the Rh‒Rh bond are in a trans configuration, is occupied at either axial-side by two theophylline ligands through N(9) with the formation of two kinds of intra-molecular interligand C−H (theophylline)···O hydrogen bonds, one being a bifurcated hydrogen bond between the C(3)-methyl hydrogen as a donor and the acetato and amidato oxygens as acceptors and the other between the C(8) hydrogen and the acetato oxygen. In the crystal lattice, a discrete, hydrogen-bonding, cyclic hexameric water cluster with the flattened chair conformation is sandwiched between theophylline bases, providing the first water hexagon that intercalates between aromatic rings. The participation of the acetamidato NH group in the formation of a hydrogen bond with a water molecule belonging to the water hexagon that governs the crystal packing makes it impossible for the acetamidato ligand to form an intra-molecular hydrogen bond with O(6), causing the failure of the metal bonding to theophylline through N(7). A critical review on metal bonding properties of theophylline observed in so far reported crystal structures is given, emphasizing the significance of intra-molecular interligand interactions (H-bonding, electrostatic repulsion, and steric constraint) as a factor that could affect metal binding sites/modes of theophylline.