Abacavir methanol 2.5-solvate

Phuong-Truc T Pham

doi:10.1107/S1600536809027743

. 2009 Jul 22;65(Pt 8):o1937. doi: 10.1107/S1600536809027743

Abacavir methanol 2.5-solvate

Phuong-Truc T Pham ^a,^*

PMCID: PMC2977439 PMID: 21583619

Abstract

The structure of abacavir (systematic name: {(1S,4R)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]cyclopent-2-en-1-yl}methanol), C₁₄H₁₈N₆O·2.5CH₃OH, consists of hydrogen-bonded ribbons which are further held together by additional hydrogen bonds involving the hydroxyl group and two N atoms on an adjacent purine. The asymmetric unit also contains 2.5 molecules of methanol solvate which were grossly disordered and were excluded using SQUEEZE subroutine in PLATON [Spek, (2009 ▶). Acta Cryst. D65, 148–155].

Related literature

For a related structure, see: Huang et al. (2007 ▶). For the synthesis, see: Vince & Hua (1990 ▶). For an X-ray powder diffraction analysis of abacavir hemisulfate, see: Monger & Varlashkin (2005 ▶).

Experimental

Crystal data

C₁₄H₁₈N₆O·2.5CH₄O
M _r = 366.45
Monoclinic,
a = 19.857 (4) Å
b = 7.2552 (15) Å
c = 13.735 (3) Å
β = 98.27 (3)°
V = 1958.2 (7) Å³
Z = 4
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 173 K
0.60 × 0.30 × 0.15 mm

Data collection

Bruker SMART Platform CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2003 ▶) T _min = 0.948, T _max = 0.987
10335 measured reflections
2405 independent reflections
2231 reflections with I > 2σ(I)
R _int = 0.024

Refinement

R[F ² > 2σ(F ²)] = 0.036
wR(F ²) = 0.099
S = 1.01
2405 reflections
190 parameters
1 restraint
H-atom parameters constrained
Δρ_max = 0.18 e Å⁻³
Δρ_min = −0.19 e Å⁻³

Data collection: SMART (Bruker, 2003 ▶); cell refinement: SAINT (Bruker, 2006 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXTL.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536809027743/pv2180sup1.cif

e-65-o1937-sup1.cif^{(18.8KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809027743/pv2180Isup2.hkl

e-65-o1937-Isup2.hkl^{(115.8KB, hkl)}

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1A⋯N4ⁱ	0.88	2.16	3.036 (2)	177
N1—H1B⋯O1ⁱⁱ	0.88	2.36	3.036 (2)	134
N3—H3N⋯N5ⁱⁱⁱ	0.88	2.21	3.016 (2)	152
O1—H1O⋯N2^iv	0.84	2.05	2.808 (2)	150

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) ; (iv) .

Acknowledgments

This work was supported in part by the MRSEC Program of the National Science Foundation under Award Number DMR-0212302, Research Development Grants from the Pennsylvania State University and funding from the Drug Research Center at the University of Minnesota. The author also acknowledges Benjamin E. Kucera, Victor G. Young, Jr, Aalo Gupta and the X-ray Crystallographic Laboratory at the University of Minnesota.

supplementary crystallographic information

Comment

Abacavir is a potent anti-HIV drug which acquires its activity through inhibiting the viral reverse transcriptase. The crystal structure of this biologically important drug is not known. An X-ray powder diffraction analysis of abacavir hemisulfate, however, has been reported (Monger & Varlashkin, 2005). The structure of abacavir (Fig. 1) contains wide cylindrical channels that are parallel to the c axis (Fig. 2). The lattice is held together by hydrogen bonds (details are in Table 1). The absolute configuration around C9 and C11 of abacavir was assigned as R and S, respectively, based on the synthetic procedures. The large voids in the lattice of abacavir appear to hold methanol solvate molecules but attempts to model the solvent were unsuccessful.

Experimental

Abacavir was prepared according to literature procedure (Vince & Hua, 1990). The compound was dissolved in a minimal amount of hot methanol and the solution was then placed in a chamber saturated with dichloromethane at room temperature, covered and allowed to crystallize for two weeks. The resulting clear colorless rod shaped crystals were washed with cold methanol, dried then collected and a suitable crystal was selected for structural determination.