Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270106021706/gz3007sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S0108270106021706/gz3007Isup2.hkl |
CCDC reference: 618622
Compound (I) was used as supplied, from a batch produced by the Federal University of Pernambuco, Brazil, following the procedure of Hooker et al. (1936), and purified by ethanolic recrystallizations. Its 1H and 13C NMR spectra were completely assigned by two-dimensional NMR experiments using two-dimensional 1H-detected heteronuclear one-bond (HMQC) and multiplebond (HMBC) techniques, as follows: 1H NMR (CDCl3, 750 MHz, δ, p.p.m.): 1.468 (s, 6H, CH3), 1.854 (t, 2H, CH2), 2.573 (t, 2H, CH2), 7.503 (t, 1H, Ar), 7.638 (t, 1H, Ar), 7.796–7.822 (d, 1H, Ar), 8.049–8.070 (d, 1H, Ar); 13C NMR (CDCl3, 750 MHz, δ, p.p.m.): 16.169 (s), 26.768 (s), 31.621 (s), 79.252 (s), 112.729 (s) 124.040 (s), 128.566(s), 130.16 (s), 130.631 (s), 132.64 (s), 134.736 (s), 161.990 (s), 178.568 (s), 179.854 (s). The purity of (I) was confirmed by high-performance liquid chromatography (HPLC) (Waters M600, photodiode array detector) and differential scanning calorimetry (DSC Q100, TA Instruments, Delaware, USA). HPLC results showed a purity of approximately 100%. No impurities or degradation products were detected. DSC thermograms showed a single peak at 430 K, corresponding to the characteristic melting point of the drug (Krishna et al., 2004) with an enthalpy of 109 J g−1.
H atoms were positioned [geometrically?] and treated as riding, with C—H = 0.95–0.99 Å and with Uiso(H) = 1.2Ueq(C), or 1.5Ueq(C) for methyl H. [Please check added text and correct as necessary]
Data collection: COLLECT (Nonius, 1999); cell refinement: SCALEPACK (Otwinowski & Minor, 1997); data reduction: XPREP (Bruker, 2006); program(s) used to solve structure: SIR97 (Altomare et al., 1999); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997) and Mercury (Macrae et al., 2006); software used to prepare material for publication: WinGX (Farrugia, 1999) and PLATON (Spek, 2003).
C15H14O3 | F(000) = 1024 |
Mr = 242.26 | Dx = 1.363 Mg m−3 Dm = 1.311 (5) Mg m−3 Dm measured by helium air pycnometer |
Orthorhombic, Pbca | Cu Kα radiation, λ = 1.5418 Å |
Hall symbol: -P 2ac 2ab | Cell parameters from 2245 reflections |
a = 12.8995 (6) Å | θ = 1.0–90° |
b = 6.8681 (3) Å | µ = 0.77 mm−1 |
c = 26.6419 (13) Å | T = 120 K |
V = 2360.34 (19) Å3 | Prism, orange |
Z = 8 | 0.31 × 0.13 × 0.13 mm |
Nonius KappaCCD 2000 area-detector diffractometer | 2300 independent reflections |
Graphite monochromator | 2001 reflections with I > 2σ(I) |
Detector resolution: 14 pixels mm-1 | Rint = 0.062 |
CCD scans | θmax = 69.4°, θmin = 3.3° |
Absorption correction: multi-scan (SADABS; Sheldrick, 2006) | h = 0→15 |
Tmin = 0.775, Tmax = 0.905 | k = 0→8 |
2300 measured reflections | l = 0→30 |
Refinement on F2 | Secondary atom site location: difference Fourier map |
Least-squares matrix: full | Hydrogen site location: inferred from neighbouring sites |
R[F2 > 2σ(F2)] = 0.061 | H-atom parameters constrained |
wR(F2) = 0.170 | w = 1/[σ2(Fo2) + (0.1016P)2 + 0.9714P] where P = (Fo2 + 2Fc2)/3 |
S = 1.12 | (Δ/σ)max = 0.001 |
2077 reflections | Δρmax = 0.28 e Å−3 |
166 parameters | Δρmin = −0.30 e Å−3 |
0 restraints | Extinction correction: SHELXL97 (Sheldrick, 1997), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4 |
Primary atom site location: structure-invariant direct methods | Extinction coefficient: 0.0048 (9) |
C15H14O3 | V = 2360.34 (19) Å3 |
Mr = 242.26 | Z = 8 |
Orthorhombic, Pbca | Cu Kα radiation |
a = 12.8995 (6) Å | µ = 0.77 mm−1 |
b = 6.8681 (3) Å | T = 120 K |
c = 26.6419 (13) Å | 0.31 × 0.13 × 0.13 mm |
Nonius KappaCCD 2000 area-detector diffractometer | 2300 independent reflections |
Absorption correction: multi-scan (SADABS; Sheldrick, 2006) | 2001 reflections with I > 2σ(I) |
Tmin = 0.775, Tmax = 0.905 | Rint = 0.062 |
2300 measured reflections |
R[F2 > 2σ(F2)] = 0.061 | 0 restraints |
wR(F2) = 0.170 | H-atom parameters constrained |
S = 1.12 | Δρmax = 0.28 e Å−3 |
2077 reflections | Δρmin = −0.30 e Å−3 |
166 parameters |
Experimental. density measurement: helium air pycnometer (Quantachrome MPY-2). |
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. |
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 > σ(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. |
x | y | z | Uiso*/Ueq | ||
C1 | 0.65816 (13) | 0.1797 (2) | 0.56624 (6) | 0.0249 (4) | |
C2 | 0.59415 (14) | 0.1663 (2) | 0.52434 (6) | 0.0271 (4) | |
H2 | 0.521 | 0.1698 | 0.5284 | 0.033* | |
C3 | 0.63655 (14) | 0.1477 (3) | 0.47649 (6) | 0.0312 (4) | |
H3 | 0.5923 | 0.1401 | 0.4481 | 0.037* | |
C4 | 0.74317 (15) | 0.1403 (3) | 0.47023 (6) | 0.0323 (5) | |
H4 | 0.7718 | 0.1245 | 0.4376 | 0.039* | |
C5 | 0.80787 (14) | 0.1559 (2) | 0.51154 (7) | 0.0312 (4) | |
H5 | 0.8809 | 0.1517 | 0.5072 | 0.037* | |
C6 | 0.76602 (13) | 0.1779 (2) | 0.55955 (6) | 0.0257 (4) | |
C7 | 0.83561 (13) | 0.2022 (2) | 0.60334 (7) | 0.0286 (4) | |
C8 | 0.78484 (13) | 0.2167 (2) | 0.65577 (6) | 0.0272 (4) | |
C9 | 0.67304 (14) | 0.2162 (2) | 0.65950 (6) | 0.0264 (4) | |
C10 | 0.61423 (13) | 0.1955 (2) | 0.61724 (6) | 0.0245 (4) | |
C11 | 0.62401 (14) | 0.2237 (3) | 0.71052 (6) | 0.0304 (5) | |
H11A | 0.6174 | 0.3607 | 0.7216 | 0.036* | |
H11B | 0.6681 | 0.1538 | 0.735 | 0.036* | |
C12 | 0.51723 (13) | 0.1292 (3) | 0.70824 (6) | 0.0298 (4) | |
H12A | 0.5255 | −0.0135 | 0.7048 | 0.036* | |
H12B | 0.4801 | 0.1547 | 0.7401 | 0.036* | |
C13 | 0.45260 (13) | 0.2046 (3) | 0.66488 (6) | 0.0277 (4) | |
O14 | 0.51065 (9) | 0.18309 (17) | 0.61713 (4) | 0.0266 (4) | |
C15 | 0.35698 (14) | 0.0795 (3) | 0.65719 (7) | 0.0349 (5) | |
H15A | 0.3195 | 0.1242 | 0.6273 | 0.052* | |
H15B | 0.3118 | 0.09 | 0.6866 | 0.052* | |
H15C | 0.3779 | −0.0566 | 0.6526 | 0.052* | |
C16 | 0.42503 (13) | 0.4184 (3) | 0.66966 (6) | 0.0316 (5) | |
H16A | 0.4887 | 0.4953 | 0.6728 | 0.047* | |
H16B | 0.3818 | 0.4378 | 0.6995 | 0.047* | |
H16C | 0.3868 | 0.4601 | 0.6398 | 0.047* | |
O17 | 0.84203 (9) | 0.22549 (18) | 0.69258 (5) | 0.0341 (4) | |
O18 | 0.92912 (9) | 0.2132 (2) | 0.59969 (5) | 0.0377 (4) |
U11 | U22 | U33 | U12 | U13 | U23 | |
C1 | 0.0268 (9) | 0.0195 (8) | 0.0285 (9) | −0.0003 (6) | 0.0007 (6) | 0.0003 (6) |
C2 | 0.0263 (8) | 0.0245 (8) | 0.0305 (9) | 0.0004 (7) | 0.0000 (7) | −0.0006 (6) |
C3 | 0.0372 (10) | 0.0282 (9) | 0.0280 (9) | −0.0024 (7) | 0.0011 (7) | −0.0013 (7) |
C4 | 0.0384 (10) | 0.0275 (9) | 0.0309 (9) | −0.0020 (7) | 0.0088 (7) | −0.0009 (7) |
C5 | 0.0295 (9) | 0.0237 (9) | 0.0404 (10) | −0.0015 (7) | 0.0079 (7) | 0.0014 (7) |
C6 | 0.0242 (9) | 0.0190 (8) | 0.0339 (9) | −0.0006 (6) | 0.0029 (7) | 0.0022 (6) |
C7 | 0.0233 (9) | 0.0214 (8) | 0.0409 (10) | −0.0004 (6) | −0.0008 (7) | 0.0051 (7) |
C8 | 0.0270 (9) | 0.0208 (9) | 0.0339 (9) | −0.0003 (6) | −0.0046 (7) | 0.0031 (6) |
C9 | 0.0261 (9) | 0.0241 (9) | 0.0292 (9) | 0.0003 (6) | −0.0026 (7) | 0.0021 (6) |
C10 | 0.0212 (9) | 0.0207 (8) | 0.0316 (10) | −0.0004 (6) | 0.0005 (6) | 0.0005 (6) |
C11 | 0.0295 (9) | 0.0352 (10) | 0.0264 (9) | 0.0013 (7) | −0.0030 (7) | 0.0011 (7) |
C12 | 0.0280 (9) | 0.0330 (9) | 0.0285 (9) | 0.0008 (7) | 0.0024 (6) | 0.0029 (7) |
C13 | 0.0221 (8) | 0.0336 (10) | 0.0273 (9) | −0.0015 (7) | 0.0035 (6) | −0.0014 (6) |
O14 | 0.0200 (6) | 0.0332 (7) | 0.0266 (7) | −0.0003 (5) | 0.0021 (4) | −0.0019 (5) |
C15 | 0.0288 (9) | 0.0409 (11) | 0.0350 (9) | −0.0075 (8) | 0.0017 (7) | −0.0009 (8) |
C16 | 0.0286 (9) | 0.0348 (10) | 0.0314 (9) | 0.0042 (7) | −0.0009 (7) | −0.0029 (7) |
O17 | 0.0291 (7) | 0.0338 (8) | 0.0394 (8) | −0.0018 (5) | −0.0095 (5) | 0.0027 (5) |
O18 | 0.0224 (7) | 0.0427 (8) | 0.0480 (9) | −0.0017 (5) | 0.0003 (5) | 0.0094 (6) |
C1—C6 | 1.403 (2) | C11—H11A | 0.99 |
C1—C10 | 1.476 (2) | C11—H11B | 0.99 |
C2—C1 | 1.392 (2) | C12—H12A | 0.99 |
C2—C3 | 1.393 (2) | C12—H12B | 0.99 |
C2—H2 | 0.95 | C13—C12 | 1.516 (2) |
C3—C4 | 1.386 (3) | C13—C16 | 1.516 (2) |
C3—H3 | 0.95 | C13—C15 | 1.517 (2) |
C4—H4 | 0.95 | O14—C10 | 1.339 (2) |
C5—C4 | 1.385 (3) | O14—C13 | 1.483 (2) |
C5—C6 | 1.396 (2) | C15—H15A | 0.98 |
C5—H5 | 0.95 | C15—H15B | 0.98 |
C7—C6 | 1.482 (2) | C15—H15C | 0.98 |
C7—C8 | 1.546 (2) | C16—H16A | 0.98 |
C9—C10 | 1.365 (2) | C16—H16B | 0.98 |
C9—C8 | 1.446 (3) | C16—H16C | 0.98 |
C9—C11 | 1.500 (2) | O17—C8 | 1.229 (2) |
C11—C12 | 1.524 (2) | O18—C7 | 1.212 (2) |
C1—C6—C7 | 119.99 (15) | H12A—C12—H12B | 107.8 |
C1—C2—C3 | 120.48 (16) | C12—C11—H11B | 109.8 |
C1—C2—H2 | 119.8 | C12—C11—H11A | 109.8 |
C2—C3—H3 | 119.9 | C12—C13—C16 | 113.32 (14) |
C2—C1—C6 | 119.07 (16) | C12—C13—C15 | 110.90 (15) |
C2—C1—C10 | 121.03 (16) | C13—C16—H16A | 109.5 |
C3—C2—H2 | 119.8 | C13—C16—H16B | 109.5 |
C3—C4—H4 | 120 | C13—C15—H15A | 109.5 |
C4—C3—C2 | 120.20 (16) | C13—C15—H15B | 109.5 |
C4—C3—H3 | 119.9 | C13—C12—C11 | 112.47 (14) |
C4—C5—C6 | 120.21 (16) | C13—C12—H12A | 109.1 |
C4—C5—H5 | 119.9 | C13—C16—H16C | 109.5 |
C5—C6—C1 | 120.06 (16) | C13—C15—H15C | 109.5 |
C5—C6—C7 | 119.95 (15) | C13—C12—H12B | 109.1 |
C5—C4—C3 | 119.94 (16) | O14—C13—C16 | 106.66 (13) |
C5—C4—H4 | 120 | O14—C13—C15 | 103.78 (13) |
C6—C5—H5 | 119.9 | O14—C13—C12 | 110.00 (13) |
C6—C1—C10 | 119.90 (15) | O14—C10—C9 | 124.27 (15) |
C6—C7—C8 | 117.52 (15) | O14—C10—C1 | 112.11 (14) |
C8—C9—C11 | 118.87 (15) | H15A—C15—H15C | 109.5 |
C9—C11—C12 | 109.28 (14) | H15B—C15—H15C | 109.5 |
C9—C11—H11A | 109.8 | H15A—C15—H15B | 109.5 |
C9—C10—C1 | 123.61 (16) | C16—C13—C15 | 111.66 (15) |
C9—C11—H11B | 109.8 | H16A—C16—H16B | 109.5 |
C9—C8—C7 | 118.98 (15) | H16A—C16—H16C | 109.5 |
C10—C9—C8 | 119.87 (16) | H16B—C16—H16C | 109.5 |
C10—C9—C11 | 121.11 (16) | O17—C8—C9 | 122.98 (17) |
C10—O14—C13 | 119.70 (12) | O17—C8—C7 | 118.04 (16) |
H11A—C11—H11B | 108.3 | O18—C7—C6 | 123.14 (16) |
C11—C12—H12B | 109.1 | O18—C7—C8 | 119.33 (16) |
C11—C12—H12A | 109.1 | ||
C1—C2—C3—C4 | 0.7 (3) | C10—C9—C8—O17 | −176.46 (15) |
C2—C1—C6—C7 | 176.82 (14) | C10—C9—C11—C12 | 21.8 (2) |
C2—C1—C10—C9 | −177.53 (15) | C10—O14—C13—C12 | −31.2 (2) |
C2—C1—C10—O14 | 3.8 (2) | C10—O14—C13—C16 | 92.07 (16) |
C2—C1—C6—C5 | −2.3 (2) | C10—O14—C13—C15 | −149.89 (15) |
C2—C3—C4—C5 | −1.5 (3) | C10—C1—C6—C5 | 177.73 (14) |
C3—C2—C1—C6 | 1.2 (2) | C10—C9—C8—C7 | 2.5 (2) |
C3—C2—C1—C10 | −178.80 (15) | C10—C1—C6—C7 | −3.2 (2) |
C4—C5—C6—C1 | 1.5 (2) | C11—C9—C10—O14 | 0.9 (2) |
C4—C5—C6—C7 | −177.61 (15) | C11—C9—C10—C1 | −177.57 (15) |
C6—C1—C10—O14 | −176.17 (14) | C11—C9—C8—O17 | −0.9 (2) |
C6—C1—C10—C9 | 2.5 (2) | C11—C9—C8—C7 | 178.03 (14) |
C6—C7—C8—O17 | 175.82 (15) | C13—O14—C10—C9 | 4.0 (2) |
C6—C7—C8—C9 | −3.2 (2) | C13—O14—C10—C1 | −177.38 (12) |
C6—C5—C4—C3 | 0.4 (3) | O14—C13—C12—C11 | 54.01 (19) |
C8—C9—C11—C12 | −153.65 (15) | C15—C13—C12—C11 | 168.23 (15) |
C8—C7—C6—C5 | −177.36 (14) | C16—C13—C12—C11 | −65.27 (19) |
C8—C7—C6—C1 | 3.6 (2) | O18—C7—C6—C5 | 3.4 (2) |
C8—C9—C10—O14 | 176.37 (14) | O18—C7—C6—C1 | −175.63 (15) |
C8—C9—C10—C1 | −2.1 (2) | O18—C7—C8—O17 | −5.0 (2) |
C9—C11—C12—C13 | −48.9 (2) | O18—C7—C8—C9 | 176.05 (15) |
Experimental details
Crystal data | |
Chemical formula | C15H14O3 |
Mr | 242.26 |
Crystal system, space group | Orthorhombic, Pbca |
Temperature (K) | 120 |
a, b, c (Å) | 12.8995 (6), 6.8681 (3), 26.6419 (13) |
V (Å3) | 2360.34 (19) |
Z | 8 |
Radiation type | Cu Kα |
µ (mm−1) | 0.77 |
Crystal size (mm) | 0.31 × 0.13 × 0.13 |
Data collection | |
Diffractometer | Nonius KappaCCD 2000 area-detector diffractometer |
Absorption correction | Multi-scan (SADABS; Sheldrick, 2006) |
Tmin, Tmax | 0.775, 0.905 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 2300, 2300, 2001 |
Rint | 0.062 |
(sin θ/λ)max (Å−1) | 0.607 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.061, 0.170, 1.12 |
No. of reflections | 2077 |
No. of parameters | 166 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.28, −0.30 |
Computer programs: COLLECT (Nonius, 1999), SCALEPACK (Otwinowski & Minor, 1997), XPREP (Bruker, 2006), SIR97 (Altomare et al., 1999), SHELXL97 (Sheldrick, 1997), ORTEP-3 for Windows (Farrugia, 1997) and Mercury (Macrae et al., 2006), WinGX (Farrugia, 1999) and PLATON (Spek, 2003).
C9—C10 | 1.365 (2) | O14—C10 | 1.339 (2) |
C9—C11 | 1.500 (2) | O14—C13 | 1.483 (2) |
C11—C12 | 1.524 (2) | O17—C8 | 1.229 (2) |
C13—C12 | 1.516 (2) | O18—C7 | 1.212 (2) |
C9—C11—C12 | 109.28 (14) | C13—C12—C11 | 112.47 (14) |
C10—O14—C13 | 119.70 (12) | O14—C13—C12 | 110.00 (13) |
D···A | Distance D···Aa | Angle D—H···Ab |
C11···O17i | 3.507 (2) | 142 |
C12···O17iii | 3.340 (2) | 143 |
C12···O17iv | 3.539 (2) | 165 |
C16···O18i | 3.334 (2) | 125 |
C3···O18ii | 3.492 (2) | 147 |
Notes: (a) distance between donor and acceptor atoms; (b) angle between donor, H atoms and acceptor atom. [Symmetry codes: (i) −x + 3/2+, y + 1/2, z; (ii) x − 1/2, −y + 1/2, −z + 1; (iii) −x + 3/2, y − 1/2, z; (iv) x − 1/2, y,-z + 3/2.] |
The title compound (systematic name: 3,4-dihydro-2,2-dimethyl-2H-naphthol[1,2-b]pyran-5,6-dione), (I), is a naphthoquinone which can be isolated on a small scale from South American trees of the families Bigoniaceae and Verbenaceae (Burnett & Thomson, 1968). It can be produced chemically on a large scale from lapachol, following the procedures developed by Hooker (1892). These consist of cyclization in sulfuric acid by nucleophilic attack on the O atom of the lapachol isoprenyl side chain, followed by further recrystallizations (Hooker et al., 1936). A research group at the Federal University of Pernambuco, Brazil, first noted the activity of (I) against several micro-organisms (Lima et al., 1962; D'Alburquerque, 1968) and tumour cells (Ferreira de Santana et al., 1968; D'Alburquerque et al., 1972). In recent years, compound (I) has become very interesting as a potential agent against several diseases. It has antifungal, antiviral, antipsoriatic and anti-inflammatory activities (Guiraud et al., 1994; Li et al., 1993; Mueller et al., 1999). It is also active against parasites such as Tripanosoma cruzi, the etiologic agent of Chagas disease (Pinto et al., 2000). But it is its antineoplastic activity that has generated the greatest expectations of this molecule. In vitro and in vivo studies have shown that (I) inhibits conventional therapy-resistant tumours, particularly malignant neoplasms with a slow cell cycle, such as prostate, colon and some ovarian and breast cancers (Planchon et al., 1995; Li et al., 2003; Park et al., 2005). 300 research articles and nearly 40 patents have been published on the subject in the last 15 years. Thus, its excellent pharmacological potential suggests that this drug could shortly be included in the therapeutic arsenal.
In this paper, we report the molecular and crystal structures of (I) (Fig. 1). Some X-ray data from structural derivatives of (I) have previously been reported (De Simone et al., 2002; Reibenspies et al., 1989; Di Chenna et al., 2001). It should be noted that the most similar structure already reported, 3-bromoβ-lapachone (De Simone et al., 2002), presents the benzo and quinone rings lying in the same plane, and the heterocycle is in a distorted half-chair conformation. In the present case, the structure of (I) also has benzo and quinone rings, designated A and B, respectively. A Cremer & Pople (1975) analysis of the six-membered non-planar ring, C?, gives ring-puckering parameters ϕ = 248.4 (3)° and θ = 52.4 (2)° and a puckering amplitude Q = 0.4497 (19) Å. Thus, the conformation of the ring is between the half-chair (H) and envelope (E) symmetrical forms.
The main differences between the reported analogues and compound (I) seem to be the strategy of self-assembly through weak intermolecular interactions. In the case of (I), the two planar rings in the molecule at (x, y, z) stack above the symmetry-related rings of the molecule at (−x + 1/2, y − 1/2, z), with distances of 3.659 and 3.509 Å between the centroids of rings A and B, respectively, a perpendicular distance between the rings of 3.432 Å, and centroid offsets of 1.270 and 0.731 Å, respectively. Fig. 2 shows this stacking interaction, which generates stacked molecules running almost parallel to the [010] direction. The supramolecular structure also contains a weak intermolecular C—H···O hydrogen bond between atoms O17 and O18 and aromatic and non-aromatic H atoms of symmetry-related molecules. Table 1 presents the geometric parameters of these weak interactions.
As reported previously, the strategy of self-assembly through these weak interactions is of central importance for efficient and specific biological reactions, and for the design of new supramolecules possessing interesting structural and physical or chemical properties. As an example, we have found that, by changing the crystal growing conditions of this molecule, we can dramatically modify its dissolution rate (Landin et al., 2005). This could be explained according to the different preferred orientations achieved. Further studies will be reported in subsequent publications.