Peroxosolvates of purine derivatives: structural insights into possible H₂O₂-purine interactions in biological systems

Hydrogen peroxide, a mediator of oxidative stress, promotes DNA damage. However, its direct interaction with purine derivatives was not previously studied. Five novel peroxosolvates of purine derivatives were synthesized: theophylline peroxosolvate, C₇H₈N₄O₂·H₂O₂ (1); theobromine peroxosolvate, C₇H₈N₄O₂·H₂O₂ (2); hypoxanthine peroxosolvates, 2(C₅H₄N₄O)·H₂O₂ (3) and 2(C₅H₄N₄O)·3(H₂O₂) (4); 6-benzylaminopurine peroxosolvate, C₁₂H₁₁N₅·2(H₂O₂) (5). Their crystal structures, determined by X-ray analysis, reveal hydrogen bonding between H₂O₂ and the purine bases. In most structures, C–H⋯O H-bonds are significant in forming two-dimensional layered motifs. Unusual cyclic (H₂O₂)₂ dimers were observed in two structures, with a new type of H₂O₂ “pendulum” disorder identified in one. Solid-state DFT calculations quantified intermolecular interaction energies: ∼35 kJ mol⁻¹ for N–H⋯O 00000000 00000000 00000000 00000000 11111111 00000000 11111111 00000000 00000000 00000000 C, 22 kJ mol⁻¹ for N–H⋯N, and ∼20 kJ mol⁻¹ for C–H⋯OC contacts. The crystallographically characterized peroxosolvates provide structural insights into the non-oxidative interaction of H₂O₂ with purine bases. These models offer crucial benchmark data for computational studies of H₂O₂ adducts with purine derivatives.