Ionic Cocrystals of Pharmaceutical Compounds: Sodium Complexes of Carbamazepine

Three inorganic cocrystal (ICC) forms of carbamazepine (CBZ) have been synthesized, and their crystal structures are described. [Na­(CBZ)4(MeOH)]­[I]·H2O, [Na­(CBZ)5]­[I3], and [Na­(CBZ)5]­[C13H10N]­[IBr2]2 are the first CBZ structures that contain metal cations, and the latter example also contains acridinium, which is a known metabolite of CBZ. All three Na complexes have distorted square pyramidal NaO5 coordination geometries but different conformations of the four basal ligands and different hydrogen bonding interactions for the apical ligand. The hydrogen bonded synthons that have been identified for other species that contain neutral CBZ molecules are absent in all these Na containing ICC phases and are replaced by Na–O dative bonds. However, previously identified nonpolar supramolecular constructs in the form of stacks and dimers are shared with other CBZ containing structures.本研究成功合成了三种卡马西平（carbamazepine, CBZ）无机共晶体（inorganic cocrystal, ICC），并对其晶体结构进行了详细表征与报道。[Na­(CBZ)4(MeOH)]­[I]·H2O、[Na­(CBZ)5]­[I3]以及[Na­(CBZ)5]­[C13H10N]­[IBr2]2为首批含金属阳离子的卡马西平晶体结构，其中第三种配合物还含有吖啶鎓（acridinium）——一种已知的卡马西平代谢产物。三种钠基配合物均具有畸变的四方锥型NaO5配位几何构型，但四个基底配体的构象以及顶端配体的氢键相互作用均存在差异。此前在含中性卡马西平分子的体系中被确认的氢键合成子（hydrogen bonded synthons），在所有含钠的无机共晶体相中均未出现，取而代之的是Na–O配位键（dative bonds）。不过，此前报道的以堆叠体与二聚体形式存在的非极性超分子构建体（supramolecular constructs），在其他含卡马西平的晶体结构中仍被保留。