Mechanochemical synthesis and structure of the tetrahydrate and mesoporous anhydrous metforminium(2+)-n,n0-1,4-phenylenedioxalamic acid (1:2) salt: The role of hydrogen bonding and n→ π charge assisted interactions: The role of hydrogen bonding and n→ π charge assisted interactions

A new organic salt of metformin, an antidiabetic drug, and N,N0-(1,4-phenylene)dioxalamic acid, was mechanochemically synthesized, purified by crystallization from solution and characterized by single X-ray crystallography. The structure revealed a salt-type crystal hydrate composed of one dicationic metformin unit, two monoanionic units of the acid and four water molecules, namely H₂Mf(HpOXA)₂ 4H₂O. X-ray powder, IR,¹³C-CPMAS, thermal and BET adsorption–desorption analyses were performed to elucidate the structure of the molecular and supramolecular structure of the anhydrous microcrystalline mesoporous solid H₂Mf(HpOXA)₂. The results suggest that their structures, conformation and hydrogen bonding schemes are very similar. To the best of our knowledge, the selective formation of the monoanion HpOXA^-, as well as its structure in the solid, is herein reported for the first time. Regular O(δ-)···C(δ), O(δ-)···N⁺ and bifacial O(δ-)···C(δ) ···O(δ-) of n→π* charge-assisted interactions are herein described in H₂MfA organic salts which could be responsible of the interactions of metformin in biologic systems. The results support the participation of n→π * charge-assisted interactions independently, and not just as a short contact imposed by the geometric constraint due to the hydrogen bonding patterns.