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, [C₁₄H₁₉N₆O⁺]₂ SO₄ 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), Å, β = 130.575(3)°, Z = 2. In the asymmetric unit, the compound crystallizes with two C₁₄H₁₉N₆O⁺ cations and one SO₄ ²⁻ anion connected by strong intermolecular N–H···O hydrogen bond interactions between two of these C₁₄H₁₉N₆O⁺ cations. Additional strong O–H···O hydrogen bond intermolecular interactions are observed between the C₁₄H₁₉N₆O⁺ and SO₄ ²⁻, cation–anion, units, respectively. The [C₁₄H₁₉N₆O⁺]₂ SO₄ ²⁻ units link themselves into an infinite O–H···O–H···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)° 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)°, 61.2(2)° and 63.2(2)°, 63.87°, respectively. Intermolecular O–H···O and N–H···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 C₁₄H₁₉N₆O⁺, SO₄ 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.

Graphical Abstract

Crystal structure of Abacavir hemisulfate is reported and its geometric and packing parameters described and compared to a DFT computational calculation.