PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of actaeInternational Union of Crystallographysearchopen accessarticle submissionjournal home pagethis article
 
Acta Crystallogr Sect E Struct Rep Online. 2009 August 1; 65(Pt 8): o1937.
Published online 2009 July 22. doi:  10.1107/S1600536809027743
PMCID: PMC2977439

Abacavir methanol 2.5-solvate

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 [triangle]). Acta Cryst. D65, 148–155].

Related literature

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

An external file that holds a picture, illustration, etc.
Object name is e-65-o1937-scheme1.jpg

Experimental

Crystal data

  • C14H18N6O·2.5CH4O
  • M r = 366.45
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-65-o1937-efi1.jpg
  • 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 [triangle]) 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
  • Δρmax = 0.18 e Å−3
  • Δρmin = −0.19 e Å−3

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

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

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

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

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

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.

Refinement

The program PLATON (Spek, 2009) indicated solvent accessible void space of 688.7 Å3, corresponding to 179 electrons in a unit cell, equivalent to ten molecules of methanol solvate. Since the solvent molecules were grossly disordered and could not be modeled, their contribution was excluded using the subroutine SQUEEZE. H atoms were placed in idealized positions and treated as riding atoms with distances: O—H = 0.84, N—H 0.88 and C—H in the range 0.95–1.00 Å and Uiso(H) = 1.2Ueq(parent atom). An absolute structure could not be determined by anoimalous dispersion effects; Friedel pairs (2405) were therefore merged.

Figures

Fig. 1.
The molecular structure of abacavir with atomic lables; thermal displacement ellipsoids have been plotted at 50% probability level.
Fig. 2.
Crystal packing of abacavir molecules in the unit cell viewed along the a axis.

Crystal data

C14H18N6O·2.5CH4OF(000) = 788
Mr = 366.45Dx = 1.243 Mg m3
Monoclinic, C2Mo Kα radiation, λ = 0.71073 Å
Hall symbol: C 2yCell parameters from 2936 reflections
a = 19.857 (4) Åθ = 2.4–27.4°
b = 7.2552 (15) ŵ = 0.09 mm1
c = 13.735 (3) ÅT = 173 K
β = 98.27 (3)°Rod, colorless
V = 1958.2 (7) Å30.60 × 0.30 × 0.15 mm
Z = 4

Data collection

Bruker SMART Platform CCD diffractometer2405 independent reflections
Radiation source: normal-focus sealed tube2231 reflections with I > 2σ(I)
graphiteRint = 0.024
area detector, ω scans per [var phi]θmax = 27.5°, θmin = 1.5°
Absorption correction: multi-scan (SADABS; Bruker, 2003)h = −25→25
Tmin = 0.948, Tmax = 0.987k = −9→9
10335 measured reflectionsl = −17→17

Refinement

Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.036Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.099H-atom parameters constrained
S = 1.01w = 1/[σ2(Fo2) + (0.0623P)2 + 0.4691P] where P = (Fo2 + 2Fc2)/3
2405 reflections(Δ/σ)max < 0.001
190 parametersΔρmax = 0.18 e Å3
1 restraintΔρmin = −0.19 e Å3

Special details

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.
Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > 2sigma(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2)

xyzUiso*/Ueq
O10.78278 (7)0.9453 (2)0.79352 (11)0.0435 (4)
H1O0.81191.00200.76640.065*
N10.41393 (7)0.5553 (3)0.92222 (10)0.0353 (4)
H1A0.43540.54940.98280.042*
H1B0.36940.56690.91150.042*
N20.41135 (7)0.5588 (2)0.75419 (9)0.0265 (3)
N30.40604 (7)0.5727 (2)0.58458 (9)0.0302 (4)
H3N0.42730.58240.53280.036*
N40.51700 (7)0.5290 (2)0.86615 (9)0.0252 (3)
N50.56198 (7)0.5232 (3)0.62195 (9)0.0307 (3)
N60.61422 (7)0.4984 (2)0.77840 (9)0.0259 (3)
C10.44957 (8)0.5466 (3)0.84530 (11)0.0253 (3)
C20.44332 (8)0.5568 (3)0.67411 (11)0.0253 (3)
C30.33305 (10)0.5746 (4)0.57052 (13)0.0413 (5)
H30.31000.45450.57960.050*
C40.29783 (13)0.7005 (5)0.49353 (15)0.0589 (8)
H4A0.25450.65790.45550.071*
H4B0.32650.77700.45600.071*
C50.29839 (14)0.7448 (5)0.60113 (15)0.0671 (9)
H5B0.32740.84800.62940.080*
H5C0.25540.72900.62890.080*
C60.51484 (8)0.5376 (3)0.68753 (11)0.0249 (3)
C70.54633 (8)0.5233 (2)0.78383 (11)0.0234 (3)
C80.61989 (8)0.5003 (3)0.67988 (11)0.0295 (4)
H80.66210.48630.65580.035*
C90.66820 (9)0.4790 (3)0.86407 (11)0.0295 (4)
H90.64780.42890.92100.035*
C100.70507 (9)0.6626 (3)0.89483 (14)0.0346 (4)
H10A0.70680.68370.96640.042*
H10B0.68110.76750.85900.042*
C110.77807 (9)0.6425 (3)0.86777 (13)0.0314 (4)
H110.81270.67850.92480.038*
C120.78314 (10)0.4411 (3)0.84697 (14)0.0349 (4)
H120.82450.38220.83800.042*
C130.72425 (9)0.3522 (3)0.84218 (13)0.0322 (4)
H130.71820.22500.82690.039*
C140.78838 (11)0.7532 (3)0.77666 (15)0.0398 (5)
H14A0.83390.72600.75890.048*
H14B0.75390.71600.72080.048*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
O10.0336 (7)0.0455 (9)0.0523 (9)−0.0024 (6)0.0089 (6)−0.0002 (7)
N10.0258 (7)0.0635 (12)0.0166 (6)0.0035 (8)0.0027 (5)−0.0004 (8)
N20.0227 (6)0.0382 (9)0.0180 (6)0.0001 (6)0.0008 (5)−0.0003 (6)
N30.0257 (7)0.0492 (10)0.0152 (6)0.0062 (7)0.0012 (5)0.0002 (6)
N40.0262 (7)0.0330 (8)0.0159 (6)0.0000 (6)0.0018 (5)0.0005 (6)
N50.0295 (7)0.0447 (10)0.0184 (6)−0.0011 (7)0.0048 (5)0.0009 (7)
N60.0238 (6)0.0370 (9)0.0172 (6)−0.0004 (6)0.0034 (5)0.0005 (6)
C10.0253 (7)0.0303 (9)0.0204 (7)−0.0002 (7)0.0032 (6)−0.0003 (7)
C20.0280 (8)0.0281 (9)0.0191 (7)−0.0002 (7)0.0012 (6)−0.0008 (7)
C30.0315 (9)0.0679 (15)0.0232 (8)0.0054 (10)−0.0006 (7)0.0001 (9)
C40.0509 (13)0.096 (2)0.0273 (10)0.0352 (15)−0.0019 (9)0.0021 (12)
C50.0587 (15)0.112 (3)0.0296 (11)0.0447 (17)0.0021 (10)−0.0025 (14)
C60.0278 (7)0.0304 (9)0.0166 (7)−0.0006 (7)0.0036 (6)0.0016 (7)
C70.0226 (7)0.0273 (9)0.0200 (7)−0.0034 (7)0.0018 (5)0.0012 (7)
C80.0260 (8)0.0441 (11)0.0190 (7)−0.0011 (8)0.0051 (6)0.0000 (8)
C90.0259 (8)0.0459 (11)0.0163 (7)−0.0034 (8)0.0017 (6)−0.0001 (7)
C100.0254 (9)0.0472 (12)0.0316 (9)−0.0024 (8)0.0049 (7)−0.0144 (8)
C110.0186 (8)0.0504 (12)0.0240 (8)−0.0018 (7)−0.0012 (6)−0.0036 (8)
C120.0270 (9)0.0460 (12)0.0309 (9)0.0075 (8)0.0011 (7)0.0055 (8)
C130.0329 (9)0.0385 (10)0.0245 (8)0.0041 (8)0.0015 (7)0.0035 (8)
C140.0417 (11)0.0444 (13)0.0345 (10)−0.0079 (9)0.0097 (8)−0.0045 (9)

Geometric parameters (Å, °)

O1—C141.419 (3)C4—C51.511 (3)
O1—H1O0.8394C4—H4A0.9900
N1—C11.355 (2)C4—H4B0.9900
N1—H1A0.8798C5—H5B0.9900
N1—H1B0.8801C5—H5C0.9900
N2—C21.347 (2)C6—C71.383 (2)
N2—C11.370 (2)C8—H80.9500
N3—C21.346 (2)C9—C131.507 (3)
N3—C31.434 (2)C9—C101.550 (3)
N3—H3N0.8804C9—H91.0000
N4—C11.334 (2)C10—C111.554 (2)
N4—C71.345 (2)C10—H10A0.9900
N5—C81.311 (2)C10—H10B0.9900
N5—C61.393 (2)C11—C121.495 (3)
N6—C71.373 (2)C11—C141.526 (3)
N6—C81.374 (2)C11—H111.0000
N6—C91.480 (2)C12—C131.329 (3)
C2—C61.412 (2)C12—H120.9500
C3—C41.493 (3)C13—H130.9500
C3—C51.503 (4)C14—H14A0.9900
C3—H31.0000C14—H14B0.9900
C14—O1—H1O109.5C7—C6—C2116.10 (14)
C1—N1—H1A120.0N5—C6—C2132.81 (14)
C1—N1—H1B120.0N4—C7—N6126.66 (14)
H1A—N1—H1B120.0N4—C7—C6127.64 (14)
C2—N2—C1118.76 (13)N6—C7—C6105.69 (14)
C2—N3—C3122.41 (14)N5—C8—N6114.20 (14)
C2—N3—H3N118.8N5—C8—H8122.9
C3—N3—H3N118.8N6—C8—H8122.9
C1—N4—C7111.41 (13)N6—C9—C13111.75 (14)
C8—N5—C6103.26 (13)N6—C9—C10113.26 (16)
C7—N6—C8105.80 (13)C13—C9—C10104.22 (15)
C7—N6—C9125.03 (13)N6—C9—H9109.2
C8—N6—C9129.15 (14)C13—C9—H9109.2
N4—C1—N1117.23 (14)C10—C9—H9109.2
N4—C1—N2127.52 (14)C9—C10—C11105.93 (16)
N1—C1—N2115.24 (14)C9—C10—H10A110.5
N3—C2—N2118.91 (15)C11—C10—H10A110.5
N3—C2—C6122.56 (14)C9—C10—H10B110.5
N2—C2—C6118.54 (14)C11—C10—H10B110.5
N3—C3—C4117.6 (2)H10A—C10—H10B108.7
N3—C3—C5117.7 (2)C12—C11—C14109.71 (16)
C4—C3—C560.57 (16)C12—C11—C10103.19 (17)
N3—C3—H3116.5C14—C11—C10112.74 (16)
C4—C3—H3116.5C12—C11—H11110.3
C5—C3—H3116.5C14—C11—H11110.3
C3—C4—C560.04 (16)C10—C11—H11110.3
C3—C4—H4A117.8C13—C12—C11113.64 (19)
C5—C4—H4A117.8C13—C12—H12123.2
C3—C4—H4B117.8C11—C12—H12123.2
C5—C4—H4B117.8C12—C13—C9111.33 (19)
H4A—C4—H4B114.9C12—C13—H13124.3
C3—C5—C459.39 (16)C9—C13—H13124.3
C3—C5—H5B117.8O1—C14—C11111.11 (17)
C4—C5—H5B117.8O1—C14—H14A109.4
C3—C5—H5C117.8C11—C14—H14A109.4
C4—C5—H5C117.8O1—C14—H14B109.4
H5B—C5—H5C115.0C11—C14—H14B109.4
C7—C6—N5111.05 (14)H14A—C14—H14B108.0
C7—N4—C1—N1−179.56 (17)C9—N6—C7—C6179.02 (18)
C7—N4—C1—N2−0.2 (3)N5—C6—C7—N4−179.26 (18)
C2—N2—C1—N4−1.3 (3)C2—C6—C7—N4−1.3 (3)
C2—N2—C1—N1178.04 (17)N5—C6—C7—N6−0.4 (2)
C3—N3—C2—N2−5.9 (3)C2—C6—C7—N6177.52 (17)
C3—N3—C2—C6174.0 (2)C6—N5—C8—N60.1 (2)
C1—N2—C2—N3−178.59 (17)C7—N6—C8—N5−0.4 (2)
C1—N2—C2—C61.5 (3)C9—N6—C8—N5−178.85 (19)
C2—N3—C3—C4142.2 (2)C7—N6—C9—C13146.99 (18)
C2—N3—C3—C572.8 (3)C8—N6—C9—C13−34.8 (3)
N3—C3—C4—C5−107.9 (3)C7—N6—C9—C10−95.7 (2)
N3—C3—C5—C4107.7 (2)C8—N6—C9—C1082.6 (2)
C8—N5—C6—C70.2 (2)N6—C9—C10—C11−110.14 (16)
C8—N5—C6—C2−177.3 (2)C13—C9—C10—C1111.53 (19)
N3—C2—C6—C7179.77 (18)C9—C10—C11—C12−12.79 (19)
N2—C2—C6—C7−0.4 (3)C9—C10—C11—C14105.50 (19)
N3—C2—C6—N5−2.9 (3)C14—C11—C12—C13−110.41 (19)
N2—C2—C6—N5177.0 (2)C10—C11—C12—C1310.0 (2)
C1—N4—C7—N6−177.05 (18)C11—C12—C13—C9−2.7 (2)
C1—N4—C7—C61.6 (3)N6—C9—C13—C12116.80 (18)
C8—N6—C7—N4179.31 (18)C10—C9—C13—C12−5.9 (2)
C9—N6—C7—N4−2.1 (3)C12—C11—C14—O1179.07 (17)
C8—N6—C7—C60.4 (2)C10—C11—C14—O164.7 (2)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
N1—H1A···N4i0.882.163.036 (2)177
N1—H1B···O1ii0.882.363.036 (2)134
N3—H3N···N5iii0.882.213.016 (2)152
O1—H1O···N2iv0.842.052.808 (2)150

Symmetry codes: (i) −x+1, y, −z+2; (ii) x−1/2, y−1/2, z; (iii) −x+1, y, −z+1; (iv) x+1/2, y+1/2, z.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: PV2180).

References

  • Bruker (2003). SMART and SADABS Bruker AXS Inc., Madison, Wisconsin, USA.
  • Bruker (2006). SAINT Bruker AXS Inc., Madison, Wisconsin, USA.
  • Huang, W., Miller, M. J., De Clerq, E. & Balzarini, J. (2007). Org. Biomol. Chem.5, 1164–1166. [PubMed]
  • Monger, G. & Varlashkin, P. (2005). Powder Diffr.20, 241–245.
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]
  • Spek, A. L. (2009). Acta Cryst. D65, 148–155. [PMC free article] [PubMed]
  • Vince, R. & Hua, M. (1990). J. Med. Chem.33, 17–21. [PubMed]

Articles from Acta Crystallographica Section E: Structure Reports Online are provided here courtesy of International Union of Crystallography