Redetermination and comparative structural study of isopimpinellin: a new inhibitor against the Leishmania APRT enzyme

The title compound (alternative name 5,8-di­methoxy­psoralen), C₁₃H₁₀O₅, is a natural product extracted from Adiscanthus fusciflorus (Rutaceae). Our biochemical tests show that this compound has inhibitory activity against the enzyme adenine phospho­ribosyl­transferase (APRT) from Leishmania, a tropical parasite causing endemic disease in poor countries. It crystallizes in the centrosymmetric space group P2₁/c, with one mol­ecule in the asymmetric unit, and has at least two C—H...O intermolecular interactions, leading to the formation of centrosymmetric dimers.

Key indicators

• Single-crystal X-ray study
• T = 120 K
• Mean [sigma](C-C) = 0.002 Å
• R factor = 0.044
• wR factor = 0.124
• Data-to-parameter ratio = 12.4

checkCIF/PLATON results

No syntax errors found



Alert level C
PLAT790_ALERT_4_C Centre of Gravity not Within Unit Cell: Resd.  #          1
              C13 H10 O5

   0 ALERT level A = In general: serious problem
   0 ALERT level B = Potentially serious problem
   1 ALERT level C = Check and explain
   0 ALERT level G = General alerts; check

   0 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   0 ALERT type 2 Indicator that the structure model may be wrong or deficient
   0 ALERT type 3 Indicator that the structure quality may be low
   1 ALERT type 4 Improvement, methodology, query or suggestion

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Computing details

Data collection: COLLECT (Nonius, 1998); cell refinement: HKL SCALEPACK (Otwinowski & Minor, 1997); data reduction: HKL DENZO (Otwinowski & Minor, 1997) and SCALEPACK; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997) and PLATON (Spek, 2002); software used to prepare material for publication: WinGX publication routines (Farrugia, 1999).

(I)

Crystal data

C13H10O5	F(000) = 512
Mr = 246.21	Dx = 1.53 Mg m^−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 2772 reflections
a = 16.9357 (5) Å	θ = 1.0–27.5°
b = 4.3669 (1) Å	µ = 0.12 mm^−1
c = 16.2558 (4) Å	T = 120 K
β = 117.218 (1)°	Prism, light yellow
V = 1069.10 (5) Å^3	0.28 × 0.16 × 0.05 mm
Z = 4

Data collection

KappaCCD diffractometer	Rint = 0.023
φ and ω scans	θmax = 27.5°, θmin = 2.5°
4114 measured reflections	h = −21→22
2450 independent reflections	k = −4→5
1841 reflections with I > 2σ(I)	l = −21→20

Refinement

Refinement on F^2	0 restraints
Least-squares matrix: full	All H-atom parameters refined
R[F^2 > 2σ(F^2)] = 0.044	w = 1/[σ^2(Fo^2) + (0.0713P)^2 + 0.1752P] where P = (Fo^2 + 2Fc^2)/3
wR(F^2) = 0.124	(Δ/σ)max < 0.001
S = 1.04	Δρmax = 0.23 e Å^−3
2450 reflections	Δρmin = −0.3 e Å^−3
197 parameters

Special details

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes)

are estimated using the full covariance matrix. The cell e.s.d.'s are taken

into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

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

	x	y	z	Uiso*/Ueq
O1	0.25821 (7)	−0.3321 (2)	0.15311 (7)	0.0290 (3)
O2	0.08783 (6)	−1.0025 (3)	0.24125 (7)	0.0324 (3)
O3	0.33339 (8)	0.0004 (2)	0.11387 (8)	0.0366 (3)
O4	0.09680 (7)	−0.6081 (3)	0.10486 (7)	0.0350 (3)
O5	0.39331 (6)	−0.8340 (2)	0.44430 (7)	0.0268 (3)
C1	0.33592 (11)	−0.1792 (3)	0.17207 (10)	0.0288 (3)
C2	0.41263 (10)	−0.2493 (3)	0.25869 (11)	0.0283 (3)
C3	0.40727 (9)	−0.4432 (3)	0.31994 (10)	0.0249 (3)
C4	0.32509 (9)	−0.5916 (3)	0.30127 (9)	0.0231 (3)
C5	0.31677 (9)	−0.7921 (3)	0.36502 (9)	0.0231 (3)
C6	0.23412 (9)	−0.9258 (3)	0.34167 (9)	0.0239 (3)
C7	0.16400 (9)	−0.8570 (3)	0.25405 (10)	0.0268 (3)
C8	0.16904 (9)	−0.6663 (3)	0.18827 (10)	0.0271 (3)
C9	0.25149 (9)	−0.5312 (3)	0.21538 (10)	0.0248 (3)
C10	0.19474 (10)	−1.1281 (4)	0.38392 (11)	0.0289 (3)
C11	0.10984 (10)	−1.1639 (4)	0.32247 (11)	0.0336 (4)
C12	0.39212 (10)	−1.0369 (4)	0.51305 (10)	0.0271 (3)
C13	0.09892 (11)	−0.7760 (4)	0.02912 (11)	0.0371 (4)
H12A	0.3524 (14)	−0.951 (5)	0.5385 (13)	0.056*
H12B	0.4561 (14)	−1.050 (5)	0.5612 (13)	0.056*
H12C	0.3734 (13)	−1.249 (5)	0.4877 (13)	0.056*
H13A	0.1549 (14)	−0.721 (5)	0.0262 (13)	0.056*
H13B	0.0463 (14)	−0.713 (5)	−0.0271 (14)	0.056*
H13C	0.0966 (13)	−1.003 (6)	0.0418 (13)	0.056*
H3	0.4575 (11)	−0.486 (4)	0.3790 (11)	0.028 (4)*
H2	0.4666 (12)	−0.144 (4)	0.2690 (11)	0.034 (4)*
H11	0.0613 (11)	−1.279 (4)	0.3229 (11)	0.032 (4)*
H10	0.2229 (11)	−1.225 (4)	0.4447 (12)	0.035 (4)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0350 (6)	0.0248 (5)	0.0288 (5)	0.0057 (4)	0.0159 (5)	0.0061 (4)
O2	0.0219 (5)	0.0350 (6)	0.0388 (6)	−0.0003 (4)	0.0127 (4)	0.0017 (5)
O3	0.0556 (7)	0.0274 (6)	0.0362 (6)	0.0048 (5)	0.0292 (5)	0.0063 (5)
O4	0.0284 (5)	0.0386 (6)	0.0300 (6)	0.0096 (5)	0.0065 (4)	0.0029 (5)
O5	0.0241 (5)	0.0284 (6)	0.0247 (5)	−0.0007 (4)	0.0084 (4)	0.0040 (4)
C1	0.0405 (8)	0.0210 (7)	0.0331 (8)	0.0032 (6)	0.0239 (7)	−0.0006 (6)
C2	0.0334 (8)	0.0228 (7)	0.0352 (8)	−0.0001 (6)	0.0213 (7)	−0.0009 (6)
C3	0.0266 (7)	0.0213 (7)	0.0290 (7)	0.0032 (6)	0.0146 (6)	−0.0012 (6)
C4	0.0250 (7)	0.0204 (7)	0.0255 (7)	0.0041 (5)	0.0129 (6)	0.0005 (6)
C5	0.0224 (6)	0.0206 (7)	0.0256 (7)	0.0036 (5)	0.0105 (6)	−0.0010 (6)
C6	0.0241 (7)	0.0208 (7)	0.0278 (7)	0.0036 (6)	0.0126 (6)	0.0004 (6)
C7	0.0222 (7)	0.0250 (7)	0.0338 (8)	0.0025 (6)	0.0134 (6)	−0.0018 (6)
C8	0.0241 (7)	0.0278 (8)	0.0256 (7)	0.0081 (6)	0.0082 (6)	0.0023 (6)
C9	0.0304 (7)	0.0209 (7)	0.0260 (7)	0.0059 (6)	0.0155 (6)	0.0026 (6)
C10	0.0292 (7)	0.0272 (8)	0.0337 (8)	−0.0004 (6)	0.0173 (6)	0.0013 (6)
C11	0.0289 (7)	0.0354 (9)	0.0398 (8)	−0.0015 (7)	0.0186 (7)	0.0019 (7)
C12	0.0314 (8)	0.0244 (7)	0.0248 (7)	0.0012 (6)	0.0122 (6)	0.0029 (6)
C13	0.0330 (9)	0.0427 (10)	0.0291 (8)	0.0024 (8)	0.0085 (7)	0.0015 (7)

Geometric parameters (Å, º)

O1—C9	1.3781 (17)	C4—C5	1.412 (2)
O1—C1	1.3789 (19)	C5—C6	1.3993 (19)
O2—C7	1.3658 (17)	C6—C7	1.4078 (19)
O2—C11	1.3888 (19)	C6—C10	1.455 (2)
O3—C1	1.2145 (18)	C7—C8	1.388 (2)
O4—C8	1.3721 (17)	C8—C9	1.389 (2)
O4—C13	1.447 (2)	C10—C11	1.333 (2)
O5—C5	1.3590 (16)	C10—H10	0.976 (18)
O5—C12	1.4336 (17)	C11—H11	0.966 (18)
C1—C2	1.446 (2)	C12—H12A	1.01 (2)
C2—C3	1.341 (2)	C12—H12B	1.01 (2)
C2—H2	0.966 (18)	C12—H12C	1.00 (2)
C3—C4	1.436 (2)	C13—H13A	1.00 (2)
C3—H3	0.967 (16)	C13—H13B	0.98 (2)
C4—C9	1.4072 (19)	C13—H13C	1.02 (2)
C9—O1—C1	122.16 (11)	O4—C8—C7	122.09 (13)
C7—O2—C11	105.49 (11)	O4—C8—C9	123.19 (13)
C8—O4—C13	112.89 (11)	C7—C8—C9	114.68 (13)
C5—O5—C12	118.37 (11)	O1—C9—C8	116.35 (12)
O3—C1—O1	116.64 (14)	O1—C9—C4	120.91 (13)
O3—C1—C2	126.23 (14)	C8—C9—C4	122.74 (13)
O1—C1—C2	117.13 (12)	C11—C10—C6	106.74 (14)
C3—C2—C1	121.37 (14)	C11—C10—H10	124.6 (10)
C3—C2—H2	123.4 (10)	C6—C10—H10	128.7 (10)
C1—C2—H2	115.2 (10)	C10—C11—O2	112.42 (14)
C2—C3—C4	121.06 (14)	C10—C11—H11	133.3 (10)
C2—C3—H3	122.2 (10)	O2—C11—H11	114.3 (10)
C4—C3—H3	116.7 (10)	O5—C12—H12A	109.8 (12)
C9—C4—C5	120.26 (13)	O5—C12—H12B	104.3 (12)
C9—C4—C3	117.27 (13)	H12A—C12—H12B	112.6 (16)
C5—C4—C3	122.48 (13)	O5—C12—H12C	111.4 (11)
O5—C5—C6	127.08 (12)	H12A—C12—H12C	111.6 (17)
O5—C5—C4	114.05 (12)	H12B—C12—H12C	106.9 (17)
C6—C5—C4	118.87 (12)	O4—C13—H13A	108.2 (12)
C5—C6—C7	117.50 (13)	O4—C13—H13B	106.6 (12)
C5—C6—C10	137.99 (13)	H13A—C13—H13B	111.5 (16)
C7—C6—C10	104.50 (12)	O4—C13—H13C	107.7 (11)
O2—C7—C8	123.24 (13)	H13A—C13—H13C	111.6 (17)
O2—C7—C6	110.85 (12)	H13B—C13—H13C	111.1 (17)
C8—C7—C6	125.91 (13)
C9—O1—C1—O3	−177.04 (12)	C6—C7—C8—C9	−1.5 (2)
C9—O1—C1—C2	3.43 (19)	C1—O1—C9—C8	178.98 (12)
O3—C1—C2—C3	177.32 (14)	C1—O1—C9—C4	−1.16 (19)
O1—C1—C2—C3	−3.2 (2)	O4—C8—C9—O1	−0.4 (2)
C1—C2—C3—C4	0.7 (2)	C7—C8—C9—O1	−177.84 (12)
C2—C3—C4—C9	1.7 (2)	O4—C8—C9—C4	179.73 (12)
C2—C3—C4—C5	−178.70 (13)	C7—C8—C9—C4	2.3 (2)
C12—O5—C5—C6	0.3 (2)	C5—C4—C9—O1	178.89 (12)
C12—O5—C5—C4	−179.20 (11)	C3—C4—C9—O1	−1.45 (19)
C9—C4—C5—O5	178.82 (12)	C5—C4—C9—C8	−1.3 (2)
C3—C4—C5—O5	−0.82 (19)	C3—C4—C9—C8	178.39 (13)
C9—C4—C5—C6	−0.8 (2)	C5—C6—C10—C11	179.33 (17)
C3—C4—C5—C6	179.60 (12)	C7—C6—C10—C11	0.24 (16)
O5—C5—C6—C7	−178.03 (13)	C6—C10—C11—O2	0.09 (18)
C4—C5—C6—C7	1.49 (19)	C7—O2—C11—C10	−0.40 (17)
O5—C5—C6—C10	3.0 (3)	O1—O2—O4—O5	2.02 (5)
C4—C5—C6—C10	−177.52 (16)	O2—O4—O5—C1	−177.46 (5)
C11—O2—C7—C8	−178.94 (14)	O4—O5—C1—C2	−177.19 (11)
C11—O2—C7—C6	0.55 (15)	O5—C1—C2—C3	0.57 (9)
C5—C6—C7—O2	−179.81 (12)	C1—C2—C3—C4	0.7 (2)
C10—C6—C7—O2	−0.50 (15)	C2—C3—C4—C5	−178.70 (13)
C5—C6—C7—C8	−0.3 (2)	C3—C4—C5—C6	179.60 (12)
C10—C6—C7—C8	178.98 (14)	C4—C5—C6—C7	1.49 (19)
C13—O4—C8—C7	−103.24 (16)	C5—C6—C7—C8	−0.3 (2)
C13—O4—C8—C9	79.52 (18)	C6—C7—C8—C9	−1.5 (2)
O2—C7—C8—O4	0.4 (2)	C7—C8—C9—C10	−0.14 (9)
C6—C7—C8—O4	−179.00 (13)	C8—C9—C10—C11	−1.91 (12)
O2—C7—C8—C9	177.88 (12)	C9—C10—C11—C12	27.4 (17)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C12—H12B···O5^i	1.01 (2)	2.64 (2)	3.420 (1)	134.2 (14)
C13—H13B···O4^ii	0.98 (2)	2.58 (2)	3.455 (2)	149.4 (16)
C12—H12A···O3^iii	1.01 (2)	2.41 (2)	3.264 (1)	141.3 (16)
C12—H12C···O3^iv	1.00 (2)	2.67 (2)	3.043 (1)	102.0 (13)
C11—H11···O2^v	0.96 (1)	2.45 (1)	3.360 (1)	156.7 (13)

Symmetry codes: (i) −x+1, −y−2, −z+1; (ii) −x, −y−1, −z; (iii) x, −y−1/2, z+1/2; (iv) x, −y−3/2, z+1/2; (v) −x, y−1/2, −z+1/2.