Abacavir methanol 2.5-solvate

Pham, P.-T.T.

doi:10.1107/S1600536809027743

organic compounds

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ISSN: 2056-9890

Volume 65| Part 8| August 2009| Page o1937

doi:10.1107/S1600536809027743

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Abacavir methanol 2.5-solvate

Phuong-Truc T. Pham ^a ^*

^aDepartment of Chemistry, Penn State Worthington Scranton, 120 Ridge View Drive, Dunmore, Pennsylvania 18512, USA
^*Correspondence e-mail: ptp2@psu.edu

(Received 8 July 2009; accepted 14 July 2009; online 22 July 2009)

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, C 2
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[F² > 2σ(F²)] = 0.036
wR(F²) = 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

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
Symmetry codes: (i) -x+1, y, -z+2; (ii) $[x-{\script{1\over 2}}, y-{\script{1\over 2}}, z]$ ; (iii) -x+1, y, -z+1; (iv) $[x+{\script{1\over 2}}, y+{\script{1\over 2}}, z]$ .

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.

Supporting information

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

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

checkCIF report

Comment top

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.

Related literature top

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 top

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.

Computing details top

Data collection: SMART (Bruker, 2003); cell refinement: SAINT (Bruker, 2006); data reduction: SAINT (Bruker, 2006); 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 (Sheldrick, 2008).

Figures top

	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.

{(1S,4R)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9- yl]cyclopent-2-en-1-yl}methanol methanol 2.5-solvate top

Crystal data top

C₁₄H₁₈N₆O·2.5CH₄O	F(000) = 788
M_r = 366.45	D_x = 1.243 Mg m⁻³
Monoclinic, C2	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: C 2y	Cell parameters from 2936 reflections
a = 19.857 (4) Å	θ = 2.4–27.4°
b = 7.2552 (15) Å	µ = 0.09 mm⁻¹
c = 13.735 (3) Å	T = 173 K
β = 98.27 (3)°	Rod, colorless
V = 1958.2 (7) Å³	0.60 × 0.30 × 0.15 mm
Z = 4

Data collection top

Bruker SMART Platform CCD diffractometer	2405 independent reflections
Radiation source: normal-focus sealed tube	2231 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.024
area detector, ω scans per ϕ	θ_max = 27.5°, θ_min = 1.5°
Absorption correction: multi-scan (SADABS; Bruker, 2003)	h = −25→25
T_min = 0.948, T_max = 0.987	k = −9→9
10335 measured reflections	l = −17→17

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.036	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.099	H-atom parameters constrained
S = 1.01	w = 1/[σ²(F_o²) + (0.0623P)² + 0.4691P] where P = (F_o² + 2F_c²)/3
2405 reflections	(Δ/σ)_max < 0.001
190 parameters	Δρ_max = 0.18 e Å⁻³
1 restraint	Δρ_min = −0.19 e Å⁻³

Crystal data top

C₁₄H₁₈N₆O·2.5CH₄O	V = 1958.2 (7) Å³
M_r = 366.45	Z = 4
Monoclinic, C2	Mo Kα radiation
a = 19.857 (4) Å	µ = 0.09 mm⁻¹
b = 7.2552 (15) Å	T = 173 K
c = 13.735 (3) Å	0.60 × 0.30 × 0.15 mm
β = 98.27 (3)°

Data collection top

Bruker SMART Platform CCD diffractometer	2405 independent reflections
Absorption correction: multi-scan (SADABS; Bruker, 2003)	2231 reflections with I > 2σ(I)
T_min = 0.948, T_max = 0.987	R_int = 0.024
10335 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.036	1 restraint
wR(F²) = 0.099	H-atom parameters constrained
S = 1.01	Δρ_max = 0.18 e Å⁻³
2405 reflections	Δρ_min = −0.19 e Å⁻³
190 parameters

Special details top

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) top

	x	y	z	U_iso*/U_eq
O1	0.78278 (7)	0.9453 (2)	0.79352 (11)	0.0435 (4)
H1O	0.8119	1.0020	0.7664	0.065*
N1	0.41393 (7)	0.5553 (3)	0.92222 (10)	0.0353 (4)
H1A	0.4354	0.5494	0.9828	0.042*
H1B	0.3694	0.5669	0.9115	0.042*
N2	0.41135 (7)	0.5588 (2)	0.75419 (9)	0.0265 (3)
N3	0.40604 (7)	0.5727 (2)	0.58458 (9)	0.0302 (4)
H3N	0.4273	0.5824	0.5328	0.036*
N4	0.51700 (7)	0.5290 (2)	0.86615 (9)	0.0252 (3)
N5	0.56198 (7)	0.5232 (3)	0.62195 (9)	0.0307 (3)
N6	0.61422 (7)	0.4984 (2)	0.77840 (9)	0.0259 (3)
C1	0.44957 (8)	0.5466 (3)	0.84530 (11)	0.0253 (3)
C2	0.44332 (8)	0.5568 (3)	0.67411 (11)	0.0253 (3)
C3	0.33305 (10)	0.5746 (4)	0.57052 (13)	0.0413 (5)
H3	0.3100	0.4545	0.5796	0.050*
C4	0.29783 (13)	0.7005 (5)	0.49353 (15)	0.0589 (8)
H4A	0.2545	0.6579	0.4555	0.071*
H4B	0.3265	0.7770	0.4560	0.071*
C5	0.29839 (14)	0.7448 (5)	0.60113 (15)	0.0671 (9)
H5B	0.3274	0.8480	0.6294	0.080*
H5C	0.2554	0.7290	0.6289	0.080*
C6	0.51484 (8)	0.5376 (3)	0.68753 (11)	0.0249 (3)
C7	0.54633 (8)	0.5233 (2)	0.78383 (11)	0.0234 (3)
C8	0.61989 (8)	0.5003 (3)	0.67988 (11)	0.0295 (4)
H8	0.6621	0.4863	0.6558	0.035*
C9	0.66820 (9)	0.4790 (3)	0.86407 (11)	0.0295 (4)
H9	0.6478	0.4289	0.9210	0.035*
C10	0.70507 (9)	0.6626 (3)	0.89483 (14)	0.0346 (4)
H10A	0.7068	0.6837	0.9664	0.042*
H10B	0.6811	0.7675	0.8590	0.042*
C11	0.77807 (9)	0.6425 (3)	0.86777 (13)	0.0314 (4)
H11	0.8127	0.6785	0.9248	0.038*
C12	0.78314 (10)	0.4411 (3)	0.84697 (14)	0.0349 (4)
H12	0.8245	0.3822	0.8380	0.042*
C13	0.72425 (9)	0.3522 (3)	0.84218 (13)	0.0322 (4)
H13	0.7182	0.2250	0.8269	0.039*
C14	0.78838 (11)	0.7532 (3)	0.77666 (15)	0.0398 (5)
H14A	0.8339	0.7260	0.7589	0.048*
H14B	0.7539	0.7160	0.7208	0.048*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0336 (7)	0.0455 (9)	0.0523 (9)	−0.0024 (6)	0.0089 (6)	−0.0002 (7)
N1	0.0258 (7)	0.0635 (12)	0.0166 (6)	0.0035 (8)	0.0027 (5)	−0.0004 (8)
N2	0.0227 (6)	0.0382 (9)	0.0180 (6)	0.0001 (6)	0.0008 (5)	−0.0003 (6)
N3	0.0257 (7)	0.0492 (10)	0.0152 (6)	0.0062 (7)	0.0012 (5)	0.0002 (6)
N4	0.0262 (7)	0.0330 (8)	0.0159 (6)	0.0000 (6)	0.0018 (5)	0.0005 (6)
N5	0.0295 (7)	0.0447 (10)	0.0184 (6)	−0.0011 (7)	0.0048 (5)	0.0009 (7)
N6	0.0238 (6)	0.0370 (9)	0.0172 (6)	−0.0004 (6)	0.0034 (5)	0.0005 (6)
C1	0.0253 (7)	0.0303 (9)	0.0204 (7)	−0.0002 (7)	0.0032 (6)	−0.0003 (7)
C2	0.0280 (8)	0.0281 (9)	0.0191 (7)	−0.0002 (7)	0.0012 (6)	−0.0008 (7)
C3	0.0315 (9)	0.0679 (15)	0.0232 (8)	0.0054 (10)	−0.0006 (7)	0.0001 (9)
C4	0.0509 (13)	0.096 (2)	0.0273 (10)	0.0352 (15)	−0.0019 (9)	0.0021 (12)
C5	0.0587 (15)	0.112 (3)	0.0296 (11)	0.0447 (17)	0.0021 (10)	−0.0025 (14)
C6	0.0278 (7)	0.0304 (9)	0.0166 (7)	−0.0006 (7)	0.0036 (6)	0.0016 (7)
C7	0.0226 (7)	0.0273 (9)	0.0200 (7)	−0.0034 (7)	0.0018 (5)	0.0012 (7)
C8	0.0260 (8)	0.0441 (11)	0.0190 (7)	−0.0011 (8)	0.0051 (6)	0.0000 (8)
C9	0.0259 (8)	0.0459 (11)	0.0163 (7)	−0.0034 (8)	0.0017 (6)	−0.0001 (7)
C10	0.0254 (9)	0.0472 (12)	0.0316 (9)	−0.0024 (8)	0.0049 (7)	−0.0144 (8)
C11	0.0186 (8)	0.0504 (12)	0.0240 (8)	−0.0018 (7)	−0.0012 (6)	−0.0036 (8)
C12	0.0270 (9)	0.0460 (12)	0.0309 (9)	0.0075 (8)	0.0011 (7)	0.0055 (8)
C13	0.0329 (9)	0.0385 (10)	0.0245 (8)	0.0041 (8)	0.0015 (7)	0.0035 (8)
C14	0.0417 (11)	0.0444 (13)	0.0345 (10)	−0.0079 (9)	0.0097 (8)	−0.0045 (9)

Geometric parameters (Å, º) top

O1—C14	1.419 (3)	C4—C5	1.511 (3)
O1—H1O	0.8394	C4—H4A	0.9900
N1—C1	1.355 (2)	C4—H4B	0.9900
N1—H1A	0.8798	C5—H5B	0.9900
N1—H1B	0.8801	C5—H5C	0.9900
N2—C2	1.347 (2)	C6—C7	1.383 (2)
N2—C1	1.370 (2)	C8—H8	0.9500
N3—C2	1.346 (2)	C9—C13	1.507 (3)
N3—C3	1.434 (2)	C9—C10	1.550 (3)
N3—H3N	0.8804	C9—H9	1.0000
N4—C1	1.334 (2)	C10—C11	1.554 (2)
N4—C7	1.345 (2)	C10—H10A	0.9900
N5—C8	1.311 (2)	C10—H10B	0.9900
N5—C6	1.393 (2)	C11—C12	1.495 (3)
N6—C7	1.373 (2)	C11—C14	1.526 (3)
N6—C8	1.374 (2)	C11—H11	1.0000
N6—C9	1.480 (2)	C12—C13	1.329 (3)
C2—C6	1.412 (2)	C12—H12	0.9500
C3—C4	1.493 (3)	C13—H13	0.9500
C3—C5	1.503 (4)	C14—H14A	0.9900
C3—H3	1.0000	C14—H14B	0.9900

C14—O1—H1O	109.5	C7—C6—C2	116.10 (14)
C1—N1—H1A	120.0	N5—C6—C2	132.81 (14)
C1—N1—H1B	120.0	N4—C7—N6	126.66 (14)
H1A—N1—H1B	120.0	N4—C7—C6	127.64 (14)
C2—N2—C1	118.76 (13)	N6—C7—C6	105.69 (14)
C2—N3—C3	122.41 (14)	N5—C8—N6	114.20 (14)
C2—N3—H3N	118.8	N5—C8—H8	122.9
C3—N3—H3N	118.8	N6—C8—H8	122.9
C1—N4—C7	111.41 (13)	N6—C9—C13	111.75 (14)
C8—N5—C6	103.26 (13)	N6—C9—C10	113.26 (16)
C7—N6—C8	105.80 (13)	C13—C9—C10	104.22 (15)
C7—N6—C9	125.03 (13)	N6—C9—H9	109.2
C8—N6—C9	129.15 (14)	C13—C9—H9	109.2
N4—C1—N1	117.23 (14)	C10—C9—H9	109.2
N4—C1—N2	127.52 (14)	C9—C10—C11	105.93 (16)
N1—C1—N2	115.24 (14)	C9—C10—H10A	110.5
N3—C2—N2	118.91 (15)	C11—C10—H10A	110.5
N3—C2—C6	122.56 (14)	C9—C10—H10B	110.5
N2—C2—C6	118.54 (14)	C11—C10—H10B	110.5
N3—C3—C4	117.6 (2)	H10A—C10—H10B	108.7
N3—C3—C5	117.7 (2)	C12—C11—C14	109.71 (16)
C4—C3—C5	60.57 (16)	C12—C11—C10	103.19 (17)
N3—C3—H3	116.5	C14—C11—C10	112.74 (16)
C4—C3—H3	116.5	C12—C11—H11	110.3
C5—C3—H3	116.5	C14—C11—H11	110.3
C3—C4—C5	60.04 (16)	C10—C11—H11	110.3
C3—C4—H4A	117.8	C13—C12—C11	113.64 (19)
C5—C4—H4A	117.8	C13—C12—H12	123.2
C3—C4—H4B	117.8	C11—C12—H12	123.2
C5—C4—H4B	117.8	C12—C13—C9	111.33 (19)
H4A—C4—H4B	114.9	C12—C13—H13	124.3
C3—C5—C4	59.39 (16)	C9—C13—H13	124.3
C3—C5—H5B	117.8	O1—C14—C11	111.11 (17)
C4—C5—H5B	117.8	O1—C14—H14A	109.4
C3—C5—H5C	117.8	C11—C14—H14A	109.4
C4—C5—H5C	117.8	O1—C14—H14B	109.4
H5B—C5—H5C	115.0	C11—C14—H14B	109.4
C7—C6—N5	111.05 (14)	H14A—C14—H14B	108.0

C7—N4—C1—N1	−179.56 (17)	C9—N6—C7—C6	179.02 (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—N1	178.04 (17)	N5—C6—C7—N6	−0.4 (2)
C3—N3—C2—N2	−5.9 (3)	C2—C6—C7—N6	177.52 (17)
C3—N3—C2—C6	174.0 (2)	C6—N5—C8—N6	0.1 (2)
C1—N2—C2—N3	−178.59 (17)	C7—N6—C8—N5	−0.4 (2)
C1—N2—C2—C6	1.5 (3)	C9—N6—C8—N5	−178.85 (19)
C2—N3—C3—C4	142.2 (2)	C7—N6—C9—C13	146.99 (18)
C2—N3—C3—C5	72.8 (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—C4	107.7 (2)	C8—N6—C9—C10	82.6 (2)
C8—N5—C6—C7	0.2 (2)	N6—C9—C10—C11	−110.14 (16)
C8—N5—C6—C2	−177.3 (2)	C13—C9—C10—C11	11.53 (19)
N3—C2—C6—C7	179.77 (18)	C9—C10—C11—C12	−12.79 (19)
N2—C2—C6—C7	−0.4 (3)	C9—C10—C11—C14	105.50 (19)
N3—C2—C6—N5	−2.9 (3)	C14—C11—C12—C13	−110.41 (19)
N2—C2—C6—N5	177.0 (2)	C10—C11—C12—C13	10.0 (2)
C1—N4—C7—N6	−177.05 (18)	C11—C12—C13—C9	−2.7 (2)
C1—N4—C7—C6	1.6 (3)	N6—C9—C13—C12	116.80 (18)
C8—N6—C7—N4	179.31 (18)	C10—C9—C13—C12	−5.9 (2)
C9—N6—C7—N4	−2.1 (3)	C12—C11—C14—O1	179.07 (17)
C8—N6—C7—C6	0.4 (2)	C10—C11—C14—O1	64.7 (2)

Hydrogen-bond geometry (Å, º) top

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

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.

Experimental details

Crystal data
Chemical formula	C₁₄H₁₈N₆O·2.5CH₄O
M_r	366.45
Crystal system, space group	Monoclinic, C2
Temperature (K)	173
a, b, c (Å)	19.857 (4), 7.2552 (15), 13.735 (3)
β (°)	98.27 (3)
V (Å³)	1958.2 (7)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.09
Crystal size (mm)	0.60 × 0.30 × 0.15

Data collection
Diffractometer	Bruker SMART Platform CCD diffractometer
Absorption correction	Multi-scan (SADABS; Bruker, 2003)
T_min, T_max	0.948, 0.987
No. of measured, independent and observed [I > 2σ(I)] reflections	10335, 2405, 2231
R_int	0.024
(sin θ/λ)_max (Å⁻¹)	0.650

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.036, 0.099, 1.01
No. of reflections	2405
No. of parameters	190
No. of restraints	1
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.18, −0.19

Computer programs: SMART (Bruker, 2003), SAINT (Bruker, 2006), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1A···N4ⁱ	0.88	2.16	3.036 (2)	176.9
N1—H1B···O1ⁱⁱ	0.88	2.36	3.036 (2)	134.0
N3—H3N···N5ⁱⁱⁱ	0.88	2.21	3.016 (2)	152.4
O1—H1O···N2^iv	0.84	2.05	2.808 (2)	150.4

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.

Acknowledgements

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.

References

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