organic compounds
Santal monohydrate, an isoflavone isolated from Wyethia mollis
aDepartment of Chemistry, The University of Tennessee at Chattanooga, Chattanooga, TN 37403, USA, and bCrystallographic Systems, Bruker AXS Inc., 4565 East Cheryl Parkway, Madison, WI 53711, USA
*Correspondence e-mail: kyle-knight@utc.edu
The title compound [systematic name: 3-(3,4-dihydroxyphenyl)-5-hydroxy-7-methoxy-4H-chromen-4-one monohydrate], C16H12O6·H2O, is a monohydrate of a natural product santal isolated from Wyethia mollis. In the santal molecule, the dihedral angle between the benzoquinone and dihydroxyphenyl fragments is 53.9 (1)° and an intramolecular O—H⋯O hydrogen bond occurs. In the crystal, O—H⋯O hydrogen bonds link the components into corrugated layers parallel to the ac plane. The short distance of 3.474 (5) Å between the centroids of the benzene rings in neighbouring santal molecules reveals then existence of π–π interactions within the layers.
CCDC reference: 985329
Related literature
For the discovery and structural identification of isoflavones, see: Raudnitz & Perlmann (1935); Robertson et al. (1949). Santal was isolated following the method of Waddell et al. (1982). For the structure of the triterpene component of Wyethia mollis, see: Smith et al. (2013).
Experimental
Crystal data
|
Data collection: APEX2 (Bruker, 2009); cell SAINT (Bruker, 2009); data reduction: SAINT (Bruker, 2009); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXS97 (Sheldrick, 2008); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: OLEX2.
Supporting information
CCDC reference: 985329
10.1107/S1600536814002670/cv5443sup1.cif
contains datablock I. DOI:Structure factors: contains datablock I. DOI: 10.1107/S1600536814002670/cv5443Isup2.hkl
Supporting information file. DOI: 10.1107/S1600536814002670/cv5443Isup3.cml
Santal was isolated as described previously (Waddell et al., 1982). Suitable crystals of the title compound were obtained by slow evaporation of a water solution of the santal.
H6 was located in a difference Fourier map and refined freely. H1SA and H1SB (H2O) were located in a difference Fourier map and refined with O—H distance restrained to 0.91 (3) Å, with Uiso(H)= 1.5Ueq (O). All other H atoms were positioned geometrically, with bond distances of 0.85 Å for hydroxyl, 0.98 Å for methyl and 0.95 Å for those bound to aromatic rings and were refined as riding, with Uiso(H)= 1.2–1.5Ueq of the parent atom.
Data collection: APEX2 (Bruker, 2009); cell
SAINT (Bruker, 2009); data reduction: SAINT (Bruker, 2009); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXS97 (Sheldrick, 2008); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009).Fig. 1. View of the title compound showing the atomic numbering and 50% probability displacement ellipsoids. Dashed lines denote hydrogen bonds. |
C16H12O6·H2O | Dx = 1.484 Mg m−3 |
Mr = 318.28 | Mo Kα radiation, λ = 0.71073 Å |
Orthorhombic, Pca21 | Cell parameters from 2745 reflections |
a = 16.494 (3) Å | θ = 2.5–24.8° |
b = 13.082 (3) Å | µ = 0.12 mm−1 |
c = 6.6008 (12) Å | T = 200 K |
V = 1424.3 (5) Å3 | Prism, yellow |
Z = 4 | 0.46 × 0.41 × 0.4 mm |
F(000) = 664 |
Bruker APEXII CCD diffractometer | 2002 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.060 |
φ and ω scans | θmax = 25.0°, θmin = 2.5° |
Absorption correction: multi-scan (SADABS; Sheldrick, 2004) | h = −18→19 |
Tmin = 0.518, Tmax = 0.958 | k = −14→15 |
8545 measured reflections | l = −7→7 |
2478 independent reflections |
Refinement on F2 | 3 restraints |
Least-squares matrix: full | H atoms treated by a mixture of independent and constrained refinement |
R[F2 > 2σ(F2)] = 0.039 | w = 1/[σ2(Fo2) + (0.0829P)2] where P = (Fo2 + 2Fc2)/3 |
wR(F2) = 0.110 | (Δ/σ)max < 0.001 |
S = 0.85 | Δρmax = 0.14 e Å−3 |
2478 reflections | Δρmin = −0.18 e Å−3 |
221 parameters |
C16H12O6·H2O | V = 1424.3 (5) Å3 |
Mr = 318.28 | Z = 4 |
Orthorhombic, Pca21 | Mo Kα radiation |
a = 16.494 (3) Å | µ = 0.12 mm−1 |
b = 13.082 (3) Å | T = 200 K |
c = 6.6008 (12) Å | 0.46 × 0.41 × 0.4 mm |
Bruker APEXII CCD diffractometer | 2478 independent reflections |
Absorption correction: multi-scan (SADABS; Sheldrick, 2004) | 2002 reflections with I > 2σ(I) |
Tmin = 0.518, Tmax = 0.958 | Rint = 0.060 |
8545 measured reflections |
R[F2 > 2σ(F2)] = 0.039 | 3 restraints |
wR(F2) = 0.110 | H atoms treated by a mixture of independent and constrained refinement |
S = 0.85 | Δρmax = 0.14 e Å−3 |
2478 reflections | Δρmin = −0.18 e Å−3 |
221 parameters |
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. |
x | y | z | Uiso*/Ueq | ||
O1 | 0.00097 (18) | 0.5170 (2) | 0.8482 (5) | 0.0495 (7) | |
H1 | −0.0315 | 0.4972 | 0.9380 | 0.074* | |
O2 | 0.05990 (13) | 1.09967 (17) | 1.0156 (4) | 0.0349 (6) | |
O3 | 0.25286 (16) | 1.36978 (18) | 1.0531 (5) | 0.0496 (7) | |
O4 | 0.10095 (17) | 0.6010 (2) | 0.5878 (4) | 0.0519 (8) | |
H4 | 0.1343 | 0.6336 | 0.5166 | 0.078* | |
O5 | 0.24167 (15) | 0.88921 (18) | 0.9502 (4) | 0.0410 (6) | |
O6 | 0.34600 (14) | 1.0348 (2) | 0.9842 (4) | 0.0387 (6) | |
C1 | 0.0235 (2) | 0.6152 (3) | 0.8869 (6) | 0.0359 (8) | |
C2 | −0.0036 (2) | 0.6707 (3) | 1.0506 (6) | 0.0391 (8) | |
H2 | −0.0399 | 0.6403 | 1.1448 | 0.047* | |
C3 | 0.0222 (2) | 0.7715 (3) | 1.0786 (5) | 0.0380 (8) | |
H3 | 0.0036 | 0.8090 | 1.1928 | 0.046* | |
C4 | 0.0746 (2) | 0.8173 (2) | 0.9417 (5) | 0.0316 (7) | |
C5 | 0.1003 (2) | 0.9250 (2) | 0.9674 (5) | 0.0306 (7) | |
C6 | 0.0442 (2) | 0.9991 (3) | 0.9915 (5) | 0.0335 (7) | |
H6A | −0.0111 | 0.9788 | 0.9914 | 0.040* | |
C7 | 0.13907 (18) | 1.1317 (2) | 1.0132 (4) | 0.0282 (7) | |
C8 | 0.1518 (2) | 1.2363 (3) | 1.0322 (5) | 0.0339 (7) | |
H8 | 0.1077 | 1.2826 | 1.0432 | 0.041* | |
C9 | 0.2307 (2) | 1.2700 (3) | 1.0344 (5) | 0.0343 (8) | |
C10 | 0.1904 (3) | 1.4455 (3) | 1.0619 (9) | 0.0680 (14) | |
H10A | 0.1572 | 1.4416 | 0.9390 | 0.102* | |
H10B | 0.2150 | 1.5135 | 1.0718 | 0.102* | |
H10C | 0.1562 | 1.4332 | 1.1808 | 0.102* | |
C11 | 0.1018 (2) | 0.7603 (3) | 0.7752 (5) | 0.0342 (8) | |
H11 | 0.1380 | 0.7905 | 0.6808 | 0.041* | |
C12 | 0.0764 (2) | 0.6607 (3) | 0.7470 (5) | 0.0356 (8) | |
C13 | 0.18522 (19) | 0.9544 (2) | 0.9687 (4) | 0.0284 (7) | |
C14 | 0.20191 (18) | 1.0609 (2) | 0.9938 (4) | 0.0271 (7) | |
C15 | 0.29629 (19) | 1.2025 (3) | 1.0181 (5) | 0.0350 (8) | |
H15 | 0.3503 | 1.2278 | 1.0207 | 0.042* | |
C16 | 0.28220 (19) | 1.1001 (2) | 0.9983 (5) | 0.0297 (7) | |
O1S | 0.1966 (2) | 0.6972 (2) | 0.3142 (5) | 0.0571 (8) | |
H1SA | 0.225 (3) | 0.755 (3) | 0.345 (9) | 0.086* | |
H1SB | 0.162 (3) | 0.711 (4) | 0.214 (7) | 0.086* | |
H6 | 0.323 (2) | 0.975 (3) | 0.975 (6) | 0.044 (12)* |
U11 | U22 | U33 | U12 | U13 | U23 | |
O1 | 0.0547 (17) | 0.0299 (15) | 0.0639 (18) | −0.0135 (12) | 0.0080 (13) | −0.0013 (13) |
O2 | 0.0262 (12) | 0.0265 (12) | 0.0520 (13) | 0.0019 (10) | 0.0011 (11) | −0.0010 (11) |
O3 | 0.0511 (16) | 0.0283 (14) | 0.0694 (18) | −0.0072 (13) | −0.0025 (14) | −0.0057 (13) |
O4 | 0.0612 (19) | 0.0411 (17) | 0.0534 (16) | −0.0198 (13) | 0.0149 (13) | −0.0138 (12) |
O5 | 0.0322 (13) | 0.0305 (14) | 0.0602 (16) | 0.0054 (11) | −0.0029 (10) | −0.0060 (12) |
O6 | 0.0266 (12) | 0.0382 (15) | 0.0513 (15) | 0.0031 (11) | −0.0018 (11) | −0.0011 (11) |
C1 | 0.0334 (19) | 0.0228 (19) | 0.051 (2) | −0.0029 (14) | −0.0024 (15) | 0.0019 (15) |
C2 | 0.0356 (19) | 0.031 (2) | 0.050 (2) | −0.0014 (14) | 0.0092 (15) | 0.0066 (16) |
C3 | 0.039 (2) | 0.034 (2) | 0.0418 (19) | 0.0042 (15) | 0.0063 (15) | 0.0018 (15) |
C4 | 0.0251 (16) | 0.0293 (18) | 0.0404 (16) | −0.0022 (14) | −0.0030 (13) | 0.0021 (13) |
C5 | 0.0332 (18) | 0.0258 (18) | 0.0329 (17) | −0.0015 (13) | −0.0004 (12) | 0.0011 (12) |
C6 | 0.0295 (17) | 0.0310 (19) | 0.0401 (17) | −0.0025 (13) | 0.0017 (13) | 0.0006 (14) |
C7 | 0.0262 (16) | 0.0308 (18) | 0.0276 (14) | 0.0018 (13) | −0.0005 (13) | −0.0005 (13) |
C8 | 0.0345 (18) | 0.0284 (18) | 0.0387 (17) | 0.0032 (13) | −0.0001 (15) | −0.0023 (14) |
C9 | 0.041 (2) | 0.0302 (18) | 0.0320 (17) | −0.0054 (14) | −0.0017 (15) | −0.0026 (14) |
C10 | 0.063 (3) | 0.027 (2) | 0.114 (4) | 0.0008 (19) | −0.009 (3) | −0.012 (2) |
C11 | 0.0331 (18) | 0.0303 (19) | 0.0392 (19) | −0.0076 (14) | 0.0003 (13) | 0.0005 (13) |
C12 | 0.0366 (19) | 0.032 (2) | 0.0381 (18) | −0.0019 (15) | 0.0003 (14) | −0.0045 (14) |
C13 | 0.0280 (16) | 0.0305 (18) | 0.0268 (15) | 0.0021 (14) | −0.0009 (12) | −0.0016 (12) |
C14 | 0.0259 (16) | 0.0297 (18) | 0.0256 (15) | 0.0010 (13) | −0.0004 (12) | 0.0011 (12) |
C15 | 0.0299 (17) | 0.040 (2) | 0.0350 (16) | −0.0056 (14) | −0.0031 (14) | 0.0012 (15) |
C16 | 0.0272 (16) | 0.0359 (18) | 0.0262 (15) | 0.0020 (14) | −0.0018 (12) | −0.0002 (13) |
O1S | 0.065 (2) | 0.0485 (18) | 0.0582 (17) | −0.0161 (14) | 0.0047 (15) | −0.0012 (14) |
O1—H1 | 0.8400 | C5—C6 | 1.350 (5) |
O1—C1 | 1.362 (4) | C5—C13 | 1.453 (5) |
O2—C6 | 1.351 (4) | C6—H6A | 0.9500 |
O2—C7 | 1.371 (4) | C7—C8 | 1.390 (4) |
O3—C9 | 1.361 (4) | C7—C14 | 1.396 (4) |
O3—C10 | 1.430 (5) | C8—H8 | 0.9500 |
O4—H4 | 0.8400 | C8—C9 | 1.374 (5) |
O4—C12 | 1.370 (4) | C9—C15 | 1.401 (5) |
O5—C13 | 1.268 (4) | C10—H10A | 0.9800 |
O6—C16 | 1.359 (4) | C10—H10B | 0.9800 |
O6—H6 | 0.87 (4) | C10—H10C | 0.9800 |
C1—C2 | 1.376 (5) | C11—H11 | 0.9500 |
C1—C12 | 1.402 (5) | C11—C12 | 1.382 (5) |
C2—H2 | 0.9500 | C13—C14 | 1.430 (4) |
C2—C3 | 1.398 (5) | C14—C16 | 1.420 (4) |
C3—H3 | 0.9500 | C15—H15 | 0.9500 |
C3—C4 | 1.387 (5) | C15—C16 | 1.366 (5) |
C4—C5 | 1.480 (4) | O1S—H1SA | 0.91 (3) |
C4—C11 | 1.402 (5) | O1S—H1SB | 0.89 (3) |
C1—O1—H1 | 109.5 | O3—C9—C8 | 124.3 (3) |
C6—O2—C7 | 118.6 (2) | O3—C9—C15 | 113.8 (3) |
C9—O3—C10 | 118.3 (3) | C8—C9—C15 | 121.9 (3) |
C12—O4—H4 | 109.5 | O3—C10—H10A | 109.5 |
C16—O6—H6 | 104 (3) | O3—C10—H10B | 109.5 |
O1—C1—C2 | 123.7 (3) | O3—C10—H10C | 109.5 |
O1—C1—C12 | 116.5 (3) | H10A—C10—H10B | 109.5 |
C2—C1—C12 | 119.7 (3) | H10A—C10—H10C | 109.5 |
C1—C2—H2 | 119.9 | H10B—C10—H10C | 109.5 |
C1—C2—C3 | 120.2 (3) | C4—C11—H11 | 119.6 |
C3—C2—H2 | 119.9 | C12—C11—C4 | 120.7 (3) |
C2—C3—H3 | 119.6 | C12—C11—H11 | 119.6 |
C4—C3—C2 | 120.8 (3) | O4—C12—C1 | 116.6 (3) |
C4—C3—H3 | 119.6 | O4—C12—C11 | 123.5 (3) |
C3—C4—C5 | 121.0 (3) | C11—C12—C1 | 120.0 (3) |
C3—C4—C11 | 118.7 (3) | O5—C13—C5 | 122.0 (3) |
C11—C4—C5 | 120.3 (3) | O5—C13—C14 | 121.6 (3) |
C6—C5—C4 | 120.1 (3) | C14—C13—C5 | 116.4 (3) |
C6—C5—C13 | 118.0 (3) | C7—C14—C13 | 120.9 (3) |
C13—C5—C4 | 121.9 (3) | C7—C14—C16 | 116.8 (3) |
O2—C6—H6A | 117.2 | C16—C14—C13 | 122.3 (3) |
C5—C6—O2 | 125.6 (3) | C9—C15—H15 | 120.2 |
C5—C6—H6A | 117.2 | C16—C15—C9 | 119.6 (3) |
O2—C7—C8 | 116.3 (3) | C16—C15—H15 | 120.2 |
O2—C7—C14 | 120.4 (3) | O6—C16—C14 | 119.6 (3) |
C8—C7—C14 | 123.3 (3) | O6—C16—C15 | 119.4 (3) |
C7—C8—H8 | 121.3 | C15—C16—C14 | 121.0 (3) |
C9—C8—C7 | 117.4 (3) | H1SA—O1S—H1SB | 108 (5) |
C9—C8—H8 | 121.3 | ||
O1—C1—C2—C3 | −179.6 (3) | C5—C13—C14—C16 | 179.9 (3) |
O1—C1—C12—O4 | −1.0 (5) | C6—O2—C7—C8 | 178.0 (3) |
O1—C1—C12—C11 | 179.7 (3) | C6—O2—C7—C14 | −2.4 (4) |
O2—C7—C8—C9 | 178.7 (3) | C6—C5—C13—O5 | 178.9 (3) |
O2—C7—C14—C13 | 2.3 (4) | C6—C5—C13—C14 | −0.6 (4) |
O2—C7—C14—C16 | −178.3 (3) | C7—O2—C6—C5 | 1.0 (5) |
O3—C9—C15—C16 | −179.9 (3) | C7—C8—C9—O3 | −179.6 (3) |
O5—C13—C14—C7 | 179.8 (3) | C7—C8—C9—C15 | 0.1 (5) |
O5—C13—C14—C16 | 0.4 (4) | C7—C14—C16—O6 | 178.7 (3) |
C1—C2—C3—C4 | 0.6 (5) | C7—C14—C16—C15 | −0.8 (4) |
C2—C1—C12—O4 | 180.0 (3) | C8—C7—C14—C13 | −178.1 (3) |
C2—C1—C12—C11 | 0.7 (5) | C8—C7—C14—C16 | 1.3 (4) |
C2—C3—C4—C5 | 178.3 (3) | C8—C9—C15—C16 | 0.3 (5) |
C2—C3—C4—C11 | −0.5 (5) | C9—C15—C16—O6 | −179.5 (3) |
C3—C4—C5—C6 | −52.6 (5) | C9—C15—C16—C14 | 0.1 (5) |
C3—C4—C5—C13 | 127.1 (3) | C10—O3—C9—C8 | −3.0 (6) |
C3—C4—C11—C12 | 0.5 (5) | C10—O3—C9—C15 | 177.3 (4) |
C4—C5—C6—O2 | −179.8 (3) | C11—C4—C5—C6 | 126.2 (4) |
C4—C5—C13—O5 | −0.8 (4) | C11—C4—C5—C13 | −54.1 (5) |
C4—C5—C13—C14 | 179.7 (3) | C12—C1—C2—C3 | −0.7 (5) |
C4—C11—C12—O4 | −179.8 (3) | C13—C5—C6—O2 | 0.5 (5) |
C4—C11—C12—C1 | −0.6 (5) | C13—C14—C16—O6 | −1.9 (4) |
C5—C4—C11—C12 | −178.3 (3) | C13—C14—C16—C15 | 178.6 (3) |
C5—C13—C14—C7 | −0.8 (4) | C14—C7—C8—C9 | −0.9 (5) |
D—H···A | D—H | H···A | D···A | D—H···A |
O1—H1···O4i | 0.84 | 1.98 | 2.777 (4) | 157 |
O4—H4···O1S | 0.84 | 1.88 | 2.708 (4) | 169 |
O1S—H1SA···O5ii | 0.91 (3) | 1.97 (3) | 2.855 (4) | 164 (5) |
O6—H6···O5 | 0.87 (4) | 1.76 (4) | 2.577 (4) | 155 (4) |
Symmetry codes: (i) −x, −y+1, z+1/2; (ii) −x+1/2, y, z−1/2. |
D—H···A | D—H | H···A | D···A | D—H···A |
O1—H1···O4i | 0.84 | 1.98 | 2.777 (4) | 156.8 |
O4—H4···O1S | 0.84 | 1.88 | 2.708 (4) | 168.7 |
O1S—H1SA···O5ii | 0.91 (3) | 1.97 (3) | 2.855 (4) | 164 (5) |
O6—H6···O5 | 0.87 (4) | 1.76 (4) | 2.577 (4) | 155 (4) |
Symmetry codes: (i) −x, −y+1, z+1/2; (ii) −x+1/2, y, z−1/2. |
Acknowledgements
Acknowledgements are made to the National Science Foundation MRI Program (CHE-0951711) and the Grote Chemistry Fund at the University of Tennessee at Chattanooga for their generous support of our work. The authors would like to thank Dr Daron Janzen for helpful discussions.
References
Bruker (2009). APEX2 and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339–341. Web of Science CrossRef CAS IUCr Journals Google Scholar
Raudnitz, H. & Perlmann, G. (1935). Ber. Dtsch Chem. Ges. B, 68, 1862–1866. CrossRef Google Scholar
Robertson, A., Suckling, C. W. & Whalley, W. B. (1949). J. Chem. Soc. pp. 1571–1578. CrossRef Web of Science Google Scholar
Sheldrick, G. M. (2004). SADABS. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Smith, C. T., Noll, B., Waddell, T. G. & Knight, K. S. (2013). Nat. Prod. Commun. 8, 299–300. Web of Science CAS PubMed Google Scholar
Waddell, T. G., Thomasson, M. H., Moore, M. W., White, H. W., Swanson-Bean, D., Green, M. E., Van, H. G. S. & Fales, H. M. (1982). Phytochemistry, 21, 1631–1633. CrossRef CAS Web of Science Google Scholar
This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.
Santal, C16H12O6, is an isoflavone isolated from Wyethia mollis, a species once used in folk medicine to treat contusions, pain, fevers, and colds. Santal (Figure 1), has a benzoquinone core with an appended dihydroxyphenyl group. The benzoquinone core is substituted with hydroxyl and methoxy substituents. In the santal molecule of the title compound, which is a monohydrate, the flat planes created by the benzoquinone core and the dihydroxyphenyl group are twisted dramatically relative to each other with a dihedral angle of 53.9 (1)°. The torsion angle C11—C4—C5—C13 is 54.1 (5)°. This twisting breaks conjugation between the rings, but is likely necessitated by steric interactions between O5 and H11.
The molecule stacks together with the benzoquinone rings parallel to each other and with the dihydroxyphenyl rings pointing in toward the center of the unit cell. The crystal structure shows the presence of linking external water molecules. The water interacts uniquely with three separate santal molecules. It acts as a hydrogen bond donor (H1SA) with O5 and as a hydrogen bond acceptor with O4H of a second santal molecule (Table 1). The second hydrogen on the water (H1SB) is stabilized by interaction with the electron rich π system of the dihydroxyphenyl ring of a third santal molecule. Additionally, O4 acts as a hydrogen bond acceptor to O1H in another santal unit. There is an intramolecular hydrogen bond in which the hydroxyl group at O6 acts as the donor and O5 as the acceptor (Table 1).
In the crystal, intermolecular O—H···O hydrogen bonds link all moieties into corrugated layers parallel to ac plane. The short distances of 3.474 (5) Å between the centroids of benzene rings from the neighbouring santal molecules reveal an existence of π–π interactions inside the layers.