Crystal Structure of a Second Polymorph of Gabapentin Hydrochloride Hemihydrate with a Three-Center Bifurcated Hydrogen Bond

Abstract

AbstractGabapentin hydrochloride hemihydrate, a derivative of Gabapentin [or 1-(aminomethyl) cyclohexaneacetic acid; Gpn, C 6 H 17 NO 2 ], is a salt of C 9 H 18 NO 2 + Cl − 0.5 H 2 O, which crystallizes in the monoclinic space group I 2/a with unit cell parameters a = 13.2467(3), b = 6.5552(2), c = 26.0094(8) A, β = 96.561(3)°, Z = 8. The crystal structure and bonding network is compared to its isostructural and previously reported polymorphic derivative, Gpn hydrochloride hemihydrate [C 9 H 17 NO 2 HCl ½ H 2 O]. Both of these derivatives exhibit extensive inter and intra molecular hydrogen bonding networks between the NH 3 + group and neighboring Cl − , water and carboxyl oxygen atoms as well as similar interactions between the chloride anion and nearby water and carboxyl oxygen atoms. A unique and relatively rare three-center hydrogen bond configuration (with a bifurcated chlorine Cl − ···H-(N,O) and Cl − ···H-O acceptor hydrogen bonds) as well as N-H···O donor hydrogen bonds can be seen linking the molecules into chains along the [1 0 1] plane of the unit cell.Graphical AbstractCrystal structure of a second polymorph of gabapentin hydrochloride hemihydrate is reported and its geometric and packing parameters described and compared to the first polymorph and to a MOPAC computational calculation.[IMAGE]