Crystal Structure of Abacavir Hemisulfate: A Nucleoside Analog Reverse Transcriptase Inhibitor

Abstract

The title compound, Abacavir hemisulfate Systematic name: {(1S,4R)-4-2-amino-6-(cyclopropylamino)- 9H-purin-9-yl]cyclopentene}-1-methanol hemisulfate, C(14)H(19)N(6)O(+)](2) SO(4)(2-), (I), crystallizes in the monoclinic space group C2 with unit cell parameters a = 18.7498(7), b = 8.3577(5), c = 13.2563(5), angstrom, beta = 130.575(3)degrees, Z = 2. In the asymmetric unit, the compound crystallizes with two C(14)H(19)N(6)O(+) cations and one SO(4)(2-) anion connected by strong intermolecular N-H center dot center dot center dot O hydrogen bond interactions between two of these C(14)H(19)N(6)O(+) cations. Additional strong O-H center dot center dot center dot O hydrogen bond intermolecular interactions are observed between the C(14)H(19)N(6)O(+) and SO(4)(2-), cation-anion, units, respectively. The C(14)H(19)N(6)O(+)](2) SO(4)(2-) units link themselves into an infinite O-H center dot center dot center dot O-H center dot center dot center dot O-H one dimensional chain diagonally along the 101] plane of the unit cell. The dihedral angle between the mean planes of the 5-membered imidazole ring fused to the 6-membered pyrimidine ring is 2.6(8)degrees making it a nonplanar purin-9-yl ring. The dihedral angle between the mean planes of the imidazole and pyrimidine rings with those of the cyclopropane and cyclopentene rings are 63.3(7)degrees, 61.2(2)degrees and 63.2(2)degrees, 63.87 degrees, respectively. Intermolecular O-H center dot center dot center dot O and N-H center dot center dot center dot O hydrogen bond interactions influence the cyclopropane twist angle and therefore play a role in stabilizing crystal packing in the unit cell. The geometries of the C(14)H(19)N(6)O(+), SO(4)(2-), cation-anion pair, were optimized means of density functional theory (DFT) molecular orbital theoretical calculation at the B3-LYP/6-311 + G(d,p) level and compared to the crystallographic results providing support for these observations.