Redetermination of rifampicin penta­hydrate revealing a zwitterionic form of the anti­biotic

Rifampicin belongs to the family of naphthalenic ansamycin anti­biotics. The first crystal structure of rifampicin in the form of the penta­hydrate was reported in 1975 [Gadret, Goursolle, Leger & Colleter (1975). Acta Cryst. B31, 1454–1462] with the rifampicin mol­ecule assumed to be neutral. Redetermination of this crystal structure now shows that one of the phenol –OH groups is deprotonated, with the proton transferred to a piperazine N atom, confirming earlier spectroscopic results that indicated a zwitterionic form for the mol­ecule, namely (2S,12Z,14E,16S,17S,18R,19R,20R,21S,22R,23S,24E)-21-acetyloxy-6,9,17,19-tetra­hydroxy-23-meth­oxy-2,4,12,16,18,20,22-hepta­methyl-8-[(E)-N-(4-methyl­piperazin-4-ium-1-yl)formimido­yl]-1,11-dioxo-1,2-dihydro-2,7-(ep­oxy­penta­deca[1,11,13]trienimino)­naphtho­[2,1-b]furan-5-olate penta­hy­drate, C₄₃H₅₈N₄O₁₂·5H₂O. The mol­ecular structure of this anti­biotic is stabilized by a system of four intra­molecular O—H...O and N—H...N hydrogen bonds. Four of the symmetry-independent water mol­ecules are arranged via hydrogen bonds into helical chains extending along [100], whereas the fifth water mol­ecule forms only one hydrogen bond, to the amide group O atom. The rifampicin mol­ecules inter­act via O—H...O hydrogen bonds, generating chains along [001]. Rifampicin penta­hydrate is isostructural with recently reported rifampicin trihydrate methanol disolvate.