Bergenin, which has been isolated from a variety of tropical plants, has several pharmacological applications in traditional Asian medicine. Its electron-density distribution was obtained from a room-temperature low-resolution X-ray data set measured with point detection making use of multipole populations from the invariom library. Two refinement models were considered. In a first step, positional parameters and ADPs were refined with fixed library multipoles (model E1). This model was suitable to be input into a second refinement of multipoles (model E2), which converged smoothly although based on Cu Kα room-temperature data. Quantitative results of a topological analysis of the electron density from both models were compared with Hartree–Fock and density-functional calculations. With respect to the independent atom model (IAM) more information can be extracted from invariom modelling, including the electrostatic potential and hydrogen-bond energies, which are highly useful, especially for biologically active compounds. The reliability of the applied invariom formalism was assessed by a comparison of bond-topological properties of sucrose, for which high-resolution multipole and invariom densities were available. Since a conventional X-ray diffraction experiment using basic equipment was combined with the easy-to-use invariom formalism, the procedure described here for bergenin illustrates how it can be routinely applied in pharmacological research.
Supporting information
CCDC reference: 760270
Data collection: STOE software; cell refinement: STOE software; data reduction: Stoe-routine REDUC; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: Volkov et al., (2006); molecular graphics: Volkov et al., (2006); software used to prepare material for publication: Volkov et al., (2006).
Crystal data top
C14H16O9·H2O | F(000) = 728 |
Mr = 346.28 | Dx = 1.544 Mg m−3 |
Orthorhombic, P212121 | Cu Kα radiation, λ = 1.54178 Å |
Hall symbol: P 2AC 2AB | Cell parameters from 80 reflections |
a = 7.488 (1) Å | θ = 15–60° |
b = 13.934 (1) Å | µ = 1.16 mm−1 |
c = 14.275 (1) Å | T = 293 K |
V = 1489.4 (2) Å3 | Block, colourless |
Z = 4 | 0.50 × 0.38 × 0.36 mm |
Data collection top
Stoe four circle diffractometer, microVAX controlled | Rint = 0.019 |
Radiation source: fine-focus sealed tube | θmax = 65.0°, θmin = 4.4° |
No monochromator | h = −8→8 |
ω/2θ scans | k = 0→16 |
5547 measured reflections | l = 0→16 |
2531 independent reflections | 3 standard reflections every 90 min |
2467 reflections with I > 2σ(I) | intensity decay: none |
Refinement top
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)] = 0.013 | H-atom parameters not refined |
wR(F2) = 0.026 | w2 = 1/[s2(Fo2)] |
S = 1.87 | (Δ/σ)max < 0.001 |
2436 reflections | Δρmax = 0.09 e Å−3 |
289 parameters | Δρmin = −0.09 e Å−3 |
0 restraints | Absolute structure: Flack H D (1983), Acta Cryst. A39, 876-881 |
Primary atom site location: structure-invariant direct methods | Absolute structure parameter: −0.02 (12) |
Special details top
Experimental. Ni filter used |
Refinement. The high Ueq(max)/Ueq(min) ratios for some H atoms are result
of a free refinement of the H atoms against the room temperature low
resolution data set. This could have been avoided by entering constraints in
the hydrogen refinement (AFIX commands). This was, however, not wanted in this
study. |
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top | x | y | z | Uiso*/Ueq | |
O1 | 0.09469 (9) | 0.54517 (4) | 0.70334 (5) | 0.0490 (2) | |
O2 | 0.23566 (8) | 0.46031 (3) | 0.59799 (4) | 0.0338 (2) | |
O3 | 0.64579 (7) | 0.50208 (3) | 0.46534 (4) | 0.0269 (2) | |
O4 | 0.79144 (8) | 0.66321 (4) | 0.53086 (5) | 0.0412 (2) | |
O5 | 0.71597 (8) | 0.83840 (4) | 0.60482 (4) | 0.0343 (2) | |
O6 | 0.42365 (9) | 0.86746 (4) | 0.70709 (5) | 0.0423 (2) | |
O7 | 0.21037 (8) | 0.31955 (4) | 0.45427 (4) | 0.0307 (2) | |
O8 | 0.55706 (8) | 0.25544 (4) | 0.38785 (4) | 0.0318 (2) | |
O9 | 0.98285 (8) | 0.45312 (4) | 0.37933 (5) | 0.0388 (2) | |
C1 | 0.21936 (12) | 0.54087 (5) | 0.64921 (6) | 0.0320 (2) | |
C2 | 0.35520 (10) | 0.46117 (5) | 0.51925 (5) | 0.0245 (2) | |
C3 | 0.53599 (10) | 0.50105 (5) | 0.54696 (5) | 0.0242 (2) | |
C4 | 0.50983 (10) | 0.60015 (5) | 0.58644 (5) | 0.0254 (2) | |
C5 | 0.63557 (10) | 0.67356 (5) | 0.57752 (5) | 0.0273 (2) | |
C6 | 0.60151 (11) | 0.76362 (5) | 0.61761 (5) | 0.0273 (2) | |
C7 | 0.44611 (11) | 0.77859 (5) | 0.66980 (5) | 0.0295 (2) | |
C8 | 0.32216 (11) | 0.70561 (5) | 0.68053 (6) | 0.0314 (2) | |
C9 | 0.35432 (11) | 0.61731 (5) | 0.63747 (5) | 0.0273 (2) | |
C10 | 0.37522 (11) | 0.35857 (5) | 0.48535 (5) | 0.0245 (2) | |
C11 | 0.51737 (10) | 0.35269 (5) | 0.40842 (5) | 0.0244 (2) | |
C12 | 0.68882 (10) | 0.40654 (5) | 0.43547 (5) | 0.0253 (2) | |
C13 | 0.81504 (11) | 0.41451 (6) | 0.35266 (6) | 0.0315 (2) | |
C14 | 0.87567 (18) | 0.83156 (9) | 0.65681 (9) | 0.0598 (4) | |
O10 | 0.84509 (8) | 0.39232 (5) | 0.67789 (5) | 0.0376 (2) | |
H1 | 0.7881 (18) | 0.6062 (9) | 0.4996 (9) | 0.059 (4)* | |
H2 | 0.3157 (17) | 0.8738 (8) | 0.7450 (8) | 0.050 (3)* | |
H3 | 0.1425 (17) | 0.3669 (8) | 0.4237 (8) | 0.047 (3)* | |
H4 | 0.5978 (16) | 0.2282 (8) | 0.4424 (8) | 0.045 (3)* | |
H5 | 0.9904 (18) | 0.5114 (8) | 0.3584 (8) | 0.051 (3)* | |
H6 | 0.2968 (13) | 0.5063 (7) | 0.4644 (7) | 0.040 (2)* | |
H7 | 0.5954 (13) | 0.4554 (7) | 0.5991 (7) | 0.042 (3)* | |
H8 | 0.2041 (18) | 0.7148 (7) | 0.7206 (8) | 0.057 (3)* | |
H9 | 0.4150 (14) | 0.3155 (6) | 0.5435 (7) | 0.037 (2)* | |
H10 | 0.4626 (14) | 0.3849 (6) | 0.3461 (7) | 0.042 (3)* | |
H11 | 0.7543 (14) | 0.3682 (6) | 0.4933 (7) | 0.040 (3)* | |
H12 | 0.8402 (16) | 0.3459 (8) | 0.3259 (7) | 0.059 (3)* | |
H13 | 0.7535 (15) | 0.4592 (7) | 0.2988 (8) | 0.054 (3)* | |
H14 | 0.839 (3) | 0.8283 (12) | 0.7300 (14) | 0.120 (6)* | |
H15 | 0.952 (3) | 0.8935 (12) | 0.6544 (12) | 0.121 (6)* | |
H16 | 0.931 (4) | 0.7768 (16) | 0.6593 (16) | 0.188 (12)* | |
H17 | 0.9104 (17) | 0.3404 (8) | 0.6571 (8) | 0.053 (3)* | |
H18 | 0.9281 (18) | 0.4411 (9) | 0.6894 (9) | 0.062 (4)* | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
O1 | 0.0455 (4) | 0.0399 (3) | 0.0616 (4) | −0.0171 (3) | 0.0312 (3) | −0.0201 (3) |
O2 | 0.0324 (3) | 0.0260 (3) | 0.0429 (3) | −0.0089 (2) | 0.0126 (3) | −0.0065 (2) |
O3 | 0.0251 (3) | 0.0217 (2) | 0.0339 (3) | −0.0007 (2) | 0.0043 (2) | −0.0016 (2) |
O4 | 0.0311 (3) | 0.0394 (3) | 0.0530 (4) | −0.0118 (3) | 0.0144 (3) | −0.0136 (3) |
O5 | 0.0353 (3) | 0.0269 (3) | 0.0407 (3) | −0.0089 (2) | 0.0001 (3) | 0.0023 (2) |
O6 | 0.0442 (4) | 0.0211 (2) | 0.0616 (4) | −0.0030 (2) | 0.0160 (3) | −0.0075 (2) |
O7 | 0.0281 (3) | 0.0235 (2) | 0.0405 (3) | −0.0050 (2) | −0.0009 (3) | −0.0015 (2) |
O8 | 0.0340 (3) | 0.0246 (2) | 0.0367 (3) | 0.0020 (2) | −0.0017 (3) | −0.0063 (2) |
O9 | 0.0256 (3) | 0.0332 (3) | 0.0575 (4) | 0.0017 (2) | 0.0004 (3) | 0.0072 (3) |
C1 | 0.0291 (4) | 0.0275 (3) | 0.0395 (4) | −0.0063 (3) | 0.0122 (3) | −0.0061 (3) |
C2 | 0.0228 (4) | 0.0204 (3) | 0.0303 (4) | −0.0011 (3) | 0.0018 (3) | −0.0016 (3) |
C3 | 0.0233 (3) | 0.0212 (3) | 0.0282 (4) | −0.0009 (3) | −0.0001 (3) | −0.0013 (3) |
C4 | 0.0233 (4) | 0.0218 (3) | 0.0310 (4) | −0.0021 (3) | 0.0027 (3) | −0.0032 (3) |
C5 | 0.0245 (4) | 0.0251 (3) | 0.0324 (4) | −0.0047 (3) | 0.0026 (3) | −0.0035 (3) |
C6 | 0.0280 (4) | 0.0224 (3) | 0.0314 (4) | −0.0034 (3) | 0.0006 (3) | −0.0003 (3) |
C7 | 0.0297 (4) | 0.0218 (3) | 0.0370 (4) | −0.0009 (3) | 0.0028 (4) | −0.0022 (3) |
C8 | 0.0300 (4) | 0.0231 (3) | 0.0412 (4) | −0.0014 (3) | 0.0083 (4) | −0.0053 (3) |
C9 | 0.0249 (4) | 0.0219 (3) | 0.0352 (4) | −0.0031 (3) | 0.0046 (3) | −0.0041 (3) |
C10 | 0.0262 (4) | 0.0189 (3) | 0.0283 (4) | 0.0002 (3) | −0.0006 (3) | 0.0013 (3) |
C11 | 0.0247 (4) | 0.0222 (3) | 0.0262 (3) | 0.0006 (3) | −0.0018 (3) | −0.0004 (3) |
C12 | 0.0228 (4) | 0.0236 (3) | 0.0294 (4) | 0.0024 (3) | −0.0009 (3) | −0.0015 (3) |
C13 | 0.0286 (4) | 0.0305 (4) | 0.0353 (4) | 0.0023 (3) | 0.0046 (3) | −0.0031 (3) |
C14 | 0.0552 (7) | 0.0556 (6) | 0.0686 (8) | −0.0278 (6) | −0.0256 (6) | 0.0158 (5) |
O10 | 0.0294 (3) | 0.0348 (3) | 0.0485 (4) | 0.0007 (3) | 0.0037 (3) | 0.0017 (3) |
Geometric parameters (Å, º) top
O1—C1 | 1.2133 (11) | C3—C4 | 1.5042 (10) |
O2—C1 | 1.3452 (9) | C4—C9 | 1.3942 (11) |
O2—C2 | 1.4369 (10) | C4—C5 | 1.3961 (10) |
O3—C3 | 1.4261 (9) | C5—C6 | 1.4026 (10) |
O3—C12 | 1.4345 (8) | C6—C7 | 1.3974 (11) |
O4—C5 | 1.3516 (10) | C7—C8 | 1.3853 (11) |
O5—C6 | 1.3615 (10) | C8—C9 | 1.3963 (10) |
O5—C14 | 1.4106 (15) | C10—C11 | 1.5316 (11) |
O6—C7 | 1.3583 (9) | C11—C12 | 1.5363 (11) |
O7—C10 | 1.4199 (10) | C12—C13 | 1.5176 (11) |
O8—C11 | 1.4180 (9) | C2—H6 | 1.095 (10) |
O9—C13 | 1.4189 (10) | C3—H7 | 1.075 (10) |
O4—H1 | 0.911 (13) | C8—H8 | 1.061 (13) |
O6—H2 | 0.977 (12) | C10—H9 | 1.067 (10) |
O7—H3 | 0.940 (12) | C11—H10 | 1.078 (10) |
O8—H4 | 0.918 (11) | C12—H11 | 1.099 (10) |
O9—H5 | 0.867 (11) | C13—H13 | 1.091 (11) |
O10—H18 | 0.936 (13) | C13—H12 | 1.047 (11) |
O10—H17 | 0.922 (12) | C14—H16 | 0.87 (2) |
C1—C9 | 1.4778 (11) | C14—H14 | 1.08 (2) |
C2—C3 | 1.5159 (11) | C14—H15 | 1.036 (19) |
C2—C10 | 1.5167 (10) | | |
| | | |
O1···O10i | 2.8568 (10) | C14···H8ii | 3.086 (12) |
O2···O7 | 2.8446 (8) | H1···O3 | 1.865 (13) |
O3···O9 | 2.8884 (9) | H1···C3 | 2.483 (13) |
O3···O4 | 2.6655 (8) | H1···C12 | 3.022 (13) |
O4···O3 | 2.6655 (8) | H2···H8 | 2.393 (15) |
O4···C14 | 3.0221 (15) | H3···H5i | 2.494 (16) |
O4···O5 | 2.7190 (9) | H3···C13i | 2.735 (13) |
O5···O6 | 2.6621 (10) | H3···O2 | 2.893 (11) |
O5···O4 | 2.7190 (9) | H3···H6 | 2.334 (15) |
O6···O5 | 2.6621 (10) | H3···O9i | 1.809 (12) |
O7···O2 | 2.8446 (8) | H4···H9 | 2.332 (15) |
O7···O8 | 2.9045 (9) | H4···H11 | 2.389 (15) |
O7···O9i | 2.7406 (9) | H5···H3ii | 2.494 (16) |
O8···O7 | 2.9045 (9) | H6···O9i | 2.748 (10) |
O9···O7ii | 2.7406 (9) | H6···C9 | 2.947 (10) |
O9···O3 | 2.8884 (9) | H6···H3 | 2.334 (15) |
O10···C3 | 3.3385 (11) | H7···H9 | 2.501 (13) |
O10···O1ii | 2.8568 (10) | H7···H11 | 2.274 (14) |
O1···H8 | 2.514 (10) | H7···O10 | 2.352 (10) |
O1···H18i | 1.923 (13) | H8···H16i | 2.39 (3) |
O2···H3 | 2.893 (11) | H8···O1 | 2.514 (10) |
O2···H18i | 2.660 (13) | H8···C14i | 3.086 (12) |
O3···H1 | 1.865 (13) | H8···H2 | 2.393 (15) |
O4···H16 | 2.64 (2) | H9···H7 | 2.501 (13) |
O8···H12 | 2.620 (12) | H9···H4 | 2.332 (15) |
O9···H6ii | 2.748 (10) | H10···H13 | 2.505 (15) |
O9···H3ii | 1.809 (12) | H11···O10 | 2.742 (10) |
O10···H11 | 2.742 (10) | H11···H4 | 2.389 (15) |
O10···H7 | 2.352 (10) | H11···H7 | 2.274 (14) |
C3···O10 | 3.3385 (11) | H12···O8 | 2.620 (12) |
C14···O4 | 3.0221 (15) | H13···H10 | 2.505 (15) |
C1···H18i | 2.649 (13) | H16···C5 | 2.89 (3) |
C3···H1 | 2.483 (13) | H16···H8ii | 2.39 (3) |
C5···H16 | 2.89 (3) | H16···O4 | 2.64 (2) |
C9···H6 | 2.947 (10) | H18···O1ii | 1.923 (13) |
C12···H1 | 3.022 (13) | H18···O2ii | 2.660 (13) |
C13···H3ii | 2.735 (13) | H18···C1ii | 2.649 (13) |
| | | |
C1—O2—C2 | 118.34 (6) | O7—C10—C2 | 112.01 (6) |
C3—O3—C12 | 111.28 (5) | C10—C11—C12 | 111.99 (6) |
C6—O5—C14 | 114.29 (7) | O8—C11—C10 | 110.20 (6) |
C5—O4—H1 | 108.1 (8) | O8—C11—C12 | 110.10 (6) |
C7—O6—H2 | 113.7 (7) | O3—C12—C13 | 107.67 (6) |
C10—O7—H3 | 110.3 (7) | O3—C12—C11 | 109.89 (6) |
C11—O8—H4 | 106.8 (7) | C11—C12—C13 | 111.12 (6) |
C13—O9—H5 | 108.7 (9) | O9—C13—C12 | 111.73 (7) |
H17—O10—H18 | 105.9 (11) | C3—C2—H6 | 109.4 (5) |
O2—C1—C9 | 118.54 (7) | C10—C2—H6 | 110.6 (5) |
O1—C1—C9 | 124.25 (7) | O2—C2—H6 | 108.4 (5) |
O1—C1—O2 | 117.20 (7) | C2—C3—H7 | 109.5 (5) |
O2—C2—C3 | 110.81 (6) | C4—C3—H7 | 109.7 (5) |
C3—C2—C10 | 109.91 (6) | O3—C3—H7 | 109.4 (5) |
O2—C2—C10 | 107.65 (6) | C9—C8—H8 | 119.2 (6) |
C2—C3—C4 | 108.54 (6) | C7—C8—H8 | 122.0 (6) |
O3—C3—C2 | 107.78 (6) | O7—C10—H9 | 105.7 (5) |
O3—C3—C4 | 111.84 (6) | C2—C10—H9 | 108.0 (5) |
C5—C4—C9 | 119.03 (7) | C11—C10—H9 | 109.5 (6) |
C3—C4—C5 | 123.41 (7) | O8—C11—H10 | 107.9 (5) |
C3—C4—C9 | 117.51 (6) | C10—C11—H10 | 107.8 (6) |
O4—C5—C4 | 123.31 (6) | C12—C11—H10 | 108.8 (5) |
O4—C5—C6 | 116.97 (7) | C11—C12—H11 | 108.9 (5) |
C4—C5—C6 | 119.71 (7) | C13—C12—H11 | 110.1 (5) |
O5—C6—C5 | 121.03 (7) | O3—C12—H11 | 109.2 (5) |
C5—C6—C7 | 120.17 (7) | O9—C13—H12 | 106.6 (7) |
O5—C6—C7 | 118.78 (6) | C12—C13—H12 | 109.2 (6) |
O6—C7—C6 | 116.62 (7) | C12—C13—H13 | 109.1 (6) |
O6—C7—C8 | 122.88 (7) | O9—C13—H13 | 110.3 (6) |
C6—C7—C8 | 120.48 (7) | H12—C13—H13 | 109.9 (8) |
C7—C8—C9 | 118.86 (7) | O5—C14—H15 | 113.2 (11) |
C1—C9—C4 | 120.45 (7) | O5—C14—H16 | 119.0 (17) |
C1—C9—C8 | 117.86 (7) | O5—C14—H14 | 107.2 (12) |
C4—C9—C8 | 121.68 (7) | H14—C14—H16 | 92.6 (18) |
C2—C10—C11 | 110.36 (6) | H15—C14—H16 | 118 (2) |
O7—C10—C11 | 111.08 (6) | H14—C14—H15 | 102.0 (14) |
| | | |
C2—O2—C1—O1 | 166.15 (7) | C3—C4—C9—C8 | 176.94 (7) |
C2—O2—C1—C9 | −14.80 (10) | C5—C4—C9—C1 | −179.31 (7) |
C1—O2—C2—C3 | 49.41 (9) | C3—C4—C9—C1 | −1.73 (11) |
C1—O2—C2—C10 | 169.62 (7) | C3—C4—C5—O4 | 1.40 (11) |
C12—O3—C3—C2 | −68.30 (7) | C3—C4—C5—C6 | −179.13 (7) |
C12—O3—C3—C4 | 172.47 (6) | C5—C4—C9—C8 | −0.63 (11) |
C3—O3—C12—C11 | 62.48 (7) | C4—C5—C6—O5 | −175.60 (7) |
C3—O3—C12—C13 | −176.36 (6) | O4—C5—C6—O5 | 3.90 (11) |
C14—O5—C6—C5 | −74.25 (10) | O4—C5—C6—C7 | −177.66 (7) |
C14—O5—C6—C7 | 107.29 (9) | C4—C5—C6—C7 | 2.84 (11) |
O2—C1—C9—C8 | 170.94 (7) | O5—C6—C7—O6 | −2.15 (10) |
O1—C1—C9—C8 | −10.09 (12) | O5—C6—C7—C8 | 176.85 (7) |
O2—C1—C9—C4 | −10.34 (11) | C5—C6—C7—C8 | −1.63 (11) |
O1—C1—C9—C4 | 168.64 (8) | C5—C6—C7—O6 | 179.37 (7) |
O2—C2—C3—C4 | −57.25 (7) | O6—C7—C8—C9 | 178.24 (7) |
C10—C2—C3—O3 | 62.59 (7) | C6—C7—C8—C9 | −0.69 (12) |
C10—C2—C3—C4 | −176.11 (6) | C7—C8—C9—C4 | 1.84 (12) |
O2—C2—C3—O3 | −178.55 (5) | C7—C8—C9—C1 | −179.45 (7) |
O2—C2—C10—O7 | 62.06 (7) | O7—C10—C11—C12 | 172.26 (6) |
O2—C2—C10—C11 | −173.63 (6) | C2—C10—C11—O8 | 170.34 (6) |
C3—C2—C10—O7 | −177.16 (6) | O7—C10—C11—O8 | −64.82 (8) |
C3—C2—C10—C11 | −52.85 (8) | C2—C10—C11—C12 | 47.42 (8) |
O3—C3—C4—C9 | 153.20 (6) | O8—C11—C12—O3 | −174.18 (6) |
C2—C3—C4—C5 | −148.11 (7) | O8—C11—C12—C13 | 66.75 (8) |
O3—C3—C4—C5 | −29.34 (10) | C10—C11—C12—C13 | −170.27 (6) |
C2—C3—C4—C9 | 34.43 (9) | C10—C11—C12—O3 | −51.21 (8) |
C9—C4—C5—O4 | 178.82 (7) | O3—C12—C13—O9 | 67.05 (8) |
C9—C4—C5—C6 | −1.71 (11) | C11—C12—C13—O9 | −172.56 (6) |
Symmetry codes: (i) x−1, y, z; (ii) x+1, y, z. |