Adenosine hypodiphosphate ester,an analogue of ADP: analysis of the adenine–hypodiphosphate interaction mode in hypodiphosphate nucleotides and adenine salts

Adenosine diphosphate (ADP) plays a crucial role in cell biochemistry, especially in metabolic pathways and energy storage. ADP itself, as well as many of its analogues, such as adenosine hypodiphosphate (AhDP), has been studied extensively, in particular in terms of enzymatic activity. However, structural studies in the solid state, especially for AhDP, are still missing. An analogue of ADP, i.e. adenosine hypodiphosphate ester, has been synthesized and characterized in the crystalline form as two hydrated sodium salts of 2′:3′‐isopropylideneadenosine 5′‐hypodiphosphate (H₃AhDP, C₁₃H₁₉N₅O₉P₂ for the neutral form), namely pentasodium tetrakis(2′:3′‐isopropylideneadenosine 5′‐hypodiphosphate) tetracosahydrate, 5Na⁺·3C₁₃H₁₈N₅O₉P₂⁻·C₁₃H₁₇N₅O₉P₂²⁻·24H₂O or Na₅(H₂AhDP)₃(HAhDP)·24H₂O, (I), and sodium tetrakis(2′:3′‐isopropylideneadenosine 5′‐hypodiphosphate) pentadecahydrate, Na⁺·C₁₃H₂₀N₅O₉P₂⁺·2C₁₃H₁₈N₅O₉P₂⁻·C₁₃H₁₉N₅O₉P₂·15H₂O or Na(H₄AhDP)(H₃AhDP)(H₂AhDP)₂·15H₂O, (II). Crystal structure analyses of (I) and (II) reveal two nucleoside hypodiphosphate ions in the asymmetric units with different ionization states of the hypodiphosphate unit and adenine base. For all AhDP nucleotides, the same anti conformation about the N‐glycosidic bond and similar puckering of the ribose ring have been found. AhDP geometry and interactions have been compared to ADP nucleotides deposited in the Cambridge Structural Database. The adenine–hypodiphosphate interactions, identified as defining nucleotide self‐assembly, have been analysed in model systems, i.e. the adenine (Ade) salts of hypodiphosphoric acid, namely bis(adeninium) hypodiphosphate dihydrate, 2C₅H₆N₅⁺·H₂P₂O₆²⁻·2H₂O or (AdeH)₂(H₂P₂O₆)·2H₂O, (III), and bis(adeninium) hypodiphosphate, 2C₅H₆N₅⁺·H₂P₂O₆²⁻ or (AdeH)₂(H₂P₂O₆), (IV).