The crystal structures of granisetron [systematic name: 1-methyl-
N-(9-methyl-9-azabicyclo[3.3.1]nonan-7-yl)indazole-3-carboxamide], C
18H
24N
4O, (I), an antinauseant and antiemetic agent, and its Co
II complex, diaqua[1-methyl-
N-(9-methyl-9-azoniabicyclo[3.3.1]nonan-7-yl)indazole-3-carboxamide]cobalt(II) tetrachloride dodecahydrate, [Co(C
18H
25N
4O)
2(H
2O)
2]Cl
4·12H
2O, (II), have been determined by X-ray diffraction. The granisetron molecule is in an extended conformation in both structures. Twisting of the central carboxamide group facilitates the Co
II coordination in (II). The Co
II atom is located on an inversion centre. The azabicyclononane ring adopts a chair–boat conformation in both structures. The molecules in (I) are linked into centrosymmetric dimers and form tetracyclic rings through C—H
O hydrogen-bonding interactions. The simultaneous presence of free chloride ions in conjunction with a number of hydration water molecules in (II) provides interesting hydrogen-bond patterns. This study can aid in the investigation of the properties of metal complexes with active pharmaceuticals in which the drug molecules play the role of a ligand.
Supporting information
CCDC references: 774021; 774022
Crystals of granisetron, (I) (Pharmacology Department, IICT, Hyderabad) (25 mg), were obtained from the acetonitrile solution (5 ml) on slow evaporation.
Compound (II) was prepared by the reaction of two equivalents of (I) with one
equivalent of CoCl2.6H2O in water–methanol (1:1 v/v). A
drop of 0.1 N HCl was added and the reaction mixture was heated to 323 K in a
temperature-controlled bath, stirred for 6 h. The resulting solution was
cooled to room temperature and allowed to stand for 3 d for crystallization.
On standing, bluish green crystals suitable for X-ray analysis were obtained.
All N-bound H atoms were located in difference Fourier maps and their positions
and isotropic displacement parameters were located and refined. All other H
atoms were located in a difference density map but were positioned
geometrically and included as riding atoms, with C—H distances in the ranges
0.93–0.97 Å and with Uiso(H) values of 1.2Ueq(C). The
water H atoms of (II) were located in difference Fourier maps and their
positions were refined. The isotropic displacement parameters were set equal
to 1.2 times the equivalent isotropic displacement parameter of the parent
atoms. The geometries of the water molecules were restrained with
O3W—H5W = O3W—H6W = O4W—H7W =
O5W—H9W = O5W—H10W = 0.89 (1) Å,
N4—H4N = 0.82 (1) Å and H5W···H10W = 2.19 (1) Å. To
avoid close contacts between the water H atoms a mild anti-bumping restraint
was applied.
For both compounds, data collection: SMART (Bruker, 2001); cell refinement: SAINT (Bruker, 2001); data reduction: SAINT (Bruker, 2001); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: DIAMOND (Brandenburg & Putz, 2005) and Mercury (Macrae et al., 2008)'; software used to prepare material for publication: SHELXL97 (Sheldrick, 2008).
(I) 1-methyl-
N-(9-methyl-9-azabicyclo[3.3.1]nonan-7-yl)indazole-
3-carboxamide
top
Crystal data top
C18H24N4O | F(000) = 1344 |
Mr = 312.41 | Dx = 1.236 Mg m−3 |
Orthorhombic, Pbca | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: -P 2ac 2ab | Cell parameters from 6917 reflections |
a = 13.7930 (12) Å | θ = 2.4–27.5° |
b = 13.5544 (12) Å | µ = 0.08 mm−1 |
c = 17.9574 (16) Å | T = 294 K |
V = 3357.2 (5) Å3 | Block, colorless |
Z = 8 | 0.18 × 0.16 × 0.09 mm |
Data collection top
Bruker SMART APEX CCD area-detector diffractometer | 2559 reflections with I > 2σ(I) |
Radiation source: sealed tube | Rint = 0.039 |
Graphite monochromator | θmax = 25.0°, θmin = 2.3° |
ω scan | h = −16→16 |
29671 measured reflections | k = −16→16 |
2950 independent reflections | l = −21→21 |
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)] = 0.043 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.128 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.07 | w = 1/[σ2(Fo2) + (0.0662P)2 + 0.786P] where P = (Fo2 + 2Fc2)/3 |
2950 reflections | (Δ/σ)max = 0.001 |
214 parameters | Δρmax = 0.19 e Å−3 |
0 restraints | Δρmin = −0.15 e Å−3 |
Crystal data top
C18H24N4O | V = 3357.2 (5) Å3 |
Mr = 312.41 | Z = 8 |
Orthorhombic, Pbca | Mo Kα radiation |
a = 13.7930 (12) Å | µ = 0.08 mm−1 |
b = 13.5544 (12) Å | T = 294 K |
c = 17.9574 (16) Å | 0.18 × 0.16 × 0.09 mm |
Data collection top
Bruker SMART APEX CCD area-detector diffractometer | 2559 reflections with I > 2σ(I) |
29671 measured reflections | Rint = 0.039 |
2950 independent reflections | |
Refinement top
R[F2 > 2σ(F2)] = 0.043 | 0 restraints |
wR(F2) = 0.128 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.07 | Δρmax = 0.19 e Å−3 |
2950 reflections | Δρmin = −0.15 e Å−3 |
214 parameters | |
Special details top
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 (Å2) top | x | y | z | Uiso*/Ueq | |
C1 | 0.74556 (11) | 0.76275 (12) | −0.05107 (9) | 0.0558 (4) | |
C2 | 0.70954 (14) | 0.75326 (14) | −0.12399 (11) | 0.0721 (5) | |
H2 | 0.6629 | 0.7064 | −0.1360 | 0.087* | |
C3 | 0.74633 (15) | 0.81610 (16) | −0.17628 (11) | 0.0756 (6) | |
H3 | 0.7232 | 0.8121 | −0.2248 | 0.091* | |
C4 | 0.81734 (14) | 0.88619 (15) | −0.15963 (10) | 0.0687 (5) | |
H4 | 0.8402 | 0.9274 | −0.1971 | 0.082* | |
C5 | 0.85394 (12) | 0.89519 (12) | −0.08888 (9) | 0.0564 (4) | |
H5 | 0.9015 | 0.9416 | −0.0780 | 0.068* | |
C6 | 0.81752 (10) | 0.83235 (10) | −0.03348 (8) | 0.0488 (4) | |
C7 | 0.83531 (10) | 0.81552 (10) | 0.04340 (8) | 0.0468 (4) | |
C8 | 0.90579 (10) | 0.86740 (11) | 0.09161 (8) | 0.0462 (3) | |
C9 | 0.97510 (11) | 0.88338 (11) | 0.21671 (8) | 0.0504 (4) | |
H9 | 1.0330 | 0.9055 | 0.1899 | 0.060* | |
C10 | 0.92999 (13) | 0.97256 (12) | 0.25396 (10) | 0.0621 (4) | |
H10A | 0.8676 | 0.9543 | 0.2748 | 0.075* | |
H10B | 0.9191 | 1.0236 | 0.2171 | 0.075* | |
C11 | 0.99597 (13) | 1.01359 (12) | 0.31674 (9) | 0.0598 (4) | |
H11 | 1.0101 | 1.0829 | 0.3056 | 0.072* | |
C12 | 0.94672 (14) | 1.00873 (17) | 0.39356 (11) | 0.0790 (6) | |
H12A | 0.9864 | 1.0433 | 0.4297 | 0.095* | |
H12B | 0.8844 | 1.0417 | 0.3911 | 0.095* | |
C13 | 0.93215 (15) | 0.90399 (18) | 0.41867 (10) | 0.0805 (6) | |
H13A | 0.9103 | 0.9036 | 0.4700 | 0.097* | |
H13B | 0.8822 | 0.8734 | 0.3885 | 0.097* | |
C14 | 1.02409 (15) | 0.84514 (15) | 0.41235 (10) | 0.0717 (5) | |
H14A | 1.0101 | 0.7761 | 0.4217 | 0.086* | |
H14B | 1.0698 | 0.8674 | 0.4498 | 0.086* | |
C15 | 1.06939 (12) | 0.85605 (12) | 0.33538 (9) | 0.0551 (4) | |
H15 | 1.1320 | 0.8218 | 0.3360 | 0.066* | |
C16 | 1.00641 (12) | 0.80833 (12) | 0.27390 (9) | 0.0577 (4) | |
H16A | 1.0431 | 0.7565 | 0.2496 | 0.069* | |
H16B | 0.9495 | 0.7786 | 0.2964 | 0.069* | |
C17 | 1.16487 (14) | 1.00376 (16) | 0.35829 (11) | 0.0727 (5) | |
H17A | 1.1482 | 1.0022 | 0.4102 | 0.109* | |
H17B | 1.1734 | 1.0710 | 0.3427 | 0.109* | |
H17C | 1.2240 | 0.9679 | 0.3505 | 0.109* | |
C18 | 0.66213 (14) | 0.62723 (14) | 0.02181 (13) | 0.0804 (6) | |
H18A | 0.6038 | 0.6371 | −0.0063 | 0.121* | |
H18B | 0.6463 | 0.6199 | 0.0736 | 0.121* | |
H18C | 0.6944 | 0.5688 | 0.0045 | 0.121* | |
N1 | 0.72573 (9) | 0.71193 (10) | 0.01223 (8) | 0.0590 (4) | |
N2 | 0.78034 (9) | 0.74335 (9) | 0.06993 (7) | 0.0537 (3) | |
N3 | 0.90949 (11) | 0.83846 (11) | 0.16275 (7) | 0.0585 (4) | |
H3N | 0.8722 (15) | 0.7959 (15) | 0.1777 (12) | 0.081 (7)* | |
N4 | 1.08735 (9) | 0.95860 (10) | 0.31500 (7) | 0.0529 (3) | |
O1 | 0.95708 (9) | 0.93278 (9) | 0.06647 (6) | 0.0667 (4) | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
C1 | 0.0492 (8) | 0.0512 (8) | 0.0671 (10) | 0.0066 (7) | −0.0157 (7) | −0.0113 (7) |
C2 | 0.0642 (10) | 0.0699 (11) | 0.0823 (13) | 0.0043 (9) | −0.0317 (10) | −0.0195 (10) |
C3 | 0.0761 (12) | 0.0887 (13) | 0.0618 (11) | 0.0143 (11) | −0.0228 (9) | −0.0127 (10) |
C4 | 0.0680 (11) | 0.0824 (12) | 0.0556 (10) | 0.0122 (9) | −0.0054 (8) | −0.0073 (9) |
C5 | 0.0527 (9) | 0.0612 (9) | 0.0553 (9) | 0.0059 (7) | −0.0007 (7) | −0.0096 (7) |
C6 | 0.0423 (7) | 0.0499 (8) | 0.0543 (8) | 0.0059 (6) | −0.0065 (6) | −0.0127 (7) |
C7 | 0.0393 (7) | 0.0462 (7) | 0.0549 (8) | 0.0002 (6) | −0.0024 (6) | −0.0102 (6) |
C8 | 0.0398 (7) | 0.0501 (8) | 0.0488 (8) | −0.0023 (6) | 0.0012 (6) | −0.0093 (6) |
C9 | 0.0480 (8) | 0.0566 (8) | 0.0465 (8) | −0.0096 (7) | −0.0038 (6) | −0.0062 (6) |
C10 | 0.0622 (10) | 0.0666 (10) | 0.0576 (9) | 0.0100 (8) | −0.0171 (8) | −0.0080 (8) |
C11 | 0.0699 (10) | 0.0517 (8) | 0.0579 (10) | 0.0073 (8) | −0.0175 (8) | −0.0093 (7) |
C12 | 0.0625 (11) | 0.1083 (16) | 0.0660 (11) | 0.0236 (11) | −0.0138 (9) | −0.0354 (11) |
C13 | 0.0665 (12) | 0.1261 (18) | 0.0488 (10) | −0.0149 (12) | 0.0056 (8) | −0.0097 (10) |
C14 | 0.0801 (13) | 0.0814 (12) | 0.0535 (10) | −0.0120 (10) | −0.0115 (9) | 0.0095 (9) |
C15 | 0.0501 (8) | 0.0591 (9) | 0.0560 (9) | 0.0058 (7) | −0.0077 (7) | −0.0004 (7) |
C16 | 0.0605 (9) | 0.0549 (9) | 0.0577 (9) | −0.0024 (7) | −0.0027 (7) | −0.0041 (7) |
C17 | 0.0626 (10) | 0.0884 (13) | 0.0671 (11) | −0.0193 (10) | −0.0134 (9) | −0.0071 (10) |
C18 | 0.0631 (11) | 0.0623 (10) | 0.1158 (17) | −0.0183 (9) | −0.0248 (11) | −0.0011 (11) |
N1 | 0.0477 (7) | 0.0517 (7) | 0.0776 (9) | −0.0057 (6) | −0.0176 (6) | −0.0085 (7) |
N2 | 0.0452 (7) | 0.0513 (7) | 0.0647 (8) | −0.0020 (6) | −0.0089 (6) | −0.0064 (6) |
N3 | 0.0589 (8) | 0.0686 (9) | 0.0481 (7) | −0.0240 (7) | −0.0046 (6) | −0.0035 (6) |
N4 | 0.0475 (7) | 0.0599 (8) | 0.0512 (7) | −0.0067 (6) | −0.0075 (5) | −0.0039 (6) |
O1 | 0.0652 (7) | 0.0802 (8) | 0.0545 (6) | −0.0285 (6) | −0.0052 (5) | 0.0006 (6) |
Geometric parameters (Å, º) top
C1—N1 | 1.357 (2) | C11—H11 | 0.9800 |
C1—C6 | 1.405 (2) | C12—C13 | 1.503 (3) |
C1—C2 | 1.406 (2) | C12—H12A | 0.9700 |
C2—C3 | 1.365 (3) | C12—H12B | 0.9700 |
C2—H2 | 0.9300 | C13—C14 | 1.502 (3) |
C3—C4 | 1.397 (3) | C13—H13A | 0.9700 |
C3—H3 | 0.9300 | C13—H13B | 0.9700 |
C4—C5 | 1.372 (2) | C14—C15 | 1.524 (2) |
C4—H4 | 0.9300 | C14—H14A | 0.9700 |
C5—C6 | 1.403 (2) | C14—H14B | 0.9700 |
C5—H5 | 0.9300 | C15—N4 | 1.459 (2) |
C6—C7 | 1.421 (2) | C15—C16 | 1.547 (2) |
C7—N2 | 1.3261 (19) | C15—H15 | 0.9800 |
C7—C8 | 1.4795 (19) | C16—H16A | 0.9700 |
C8—O1 | 1.2205 (18) | C16—H16B | 0.9700 |
C8—N3 | 1.337 (2) | C17—N4 | 1.457 (2) |
C9—N3 | 1.4591 (19) | C17—H17A | 0.9600 |
C9—C16 | 1.509 (2) | C17—H17B | 0.9600 |
C9—C10 | 1.515 (2) | C17—H17C | 0.9600 |
C9—H9 | 0.9800 | C18—N1 | 1.455 (2) |
C10—C11 | 1.552 (2) | C18—H18A | 0.9600 |
C10—H10A | 0.9700 | C18—H18B | 0.9600 |
C10—H10B | 0.9700 | C18—H18C | 0.9600 |
C11—N4 | 1.465 (2) | N1—N2 | 1.3500 (18) |
C11—C12 | 1.539 (3) | N3—H3N | 0.82 (2) |
| | | |
N1—C1—C6 | 107.14 (13) | H12A—C12—H12B | 108.0 |
N1—C1—C2 | 131.47 (16) | C14—C13—C12 | 111.47 (16) |
C6—C1—C2 | 121.35 (17) | C14—C13—H13A | 109.3 |
C3—C2—C1 | 116.86 (17) | C12—C13—H13A | 109.3 |
C3—C2—H2 | 121.6 | C14—C13—H13B | 109.3 |
C1—C2—H2 | 121.6 | C12—C13—H13B | 109.3 |
C2—C3—C4 | 122.52 (17) | H13A—C13—H13B | 108.0 |
C2—C3—H3 | 118.7 | C13—C14—C15 | 111.28 (15) |
C4—C3—H3 | 118.7 | C13—C14—H14A | 109.4 |
C5—C4—C3 | 121.09 (19) | C15—C14—H14A | 109.4 |
C5—C4—H4 | 119.5 | C13—C14—H14B | 109.4 |
C3—C4—H4 | 119.5 | C15—C14—H14B | 109.4 |
C4—C5—C6 | 118.09 (16) | H14A—C14—H14B | 108.0 |
C4—C5—H5 | 121.0 | N4—C15—C14 | 112.94 (14) |
C6—C5—H5 | 121.0 | N4—C15—C16 | 108.35 (13) |
C5—C6—C1 | 120.07 (14) | C14—C15—C16 | 112.13 (14) |
C5—C6—C7 | 136.46 (14) | N4—C15—H15 | 107.7 |
C1—C6—C7 | 103.46 (14) | C14—C15—H15 | 107.7 |
N2—C7—C6 | 111.64 (12) | C16—C15—H15 | 107.7 |
N2—C7—C8 | 121.07 (14) | C9—C16—C15 | 111.39 (13) |
C6—C7—C8 | 127.28 (14) | C9—C16—H16A | 109.3 |
O1—C8—N3 | 122.97 (14) | C15—C16—H16A | 109.3 |
O1—C8—C7 | 120.63 (14) | C9—C16—H16B | 109.3 |
N3—C8—C7 | 116.40 (13) | C15—C16—H16B | 109.3 |
N3—C9—C16 | 110.38 (13) | H16A—C16—H16B | 108.0 |
N3—C9—C10 | 111.80 (13) | N4—C17—H17A | 109.5 |
C16—C9—C10 | 110.79 (13) | N4—C17—H17B | 109.5 |
N3—C9—H9 | 107.9 | H17A—C17—H17B | 109.5 |
C16—C9—H9 | 107.9 | N4—C17—H17C | 109.5 |
C10—C9—H9 | 107.9 | H17A—C17—H17C | 109.5 |
C9—C10—C11 | 111.46 (13) | H17B—C17—H17C | 109.5 |
C9—C10—H10A | 109.3 | N1—C18—H18A | 109.5 |
C11—C10—H10A | 109.3 | N1—C18—H18B | 109.5 |
C9—C10—H10B | 109.3 | H18A—C18—H18B | 109.5 |
C11—C10—H10B | 109.3 | N1—C18—H18C | 109.5 |
H10A—C10—H10B | 108.0 | H18A—C18—H18C | 109.5 |
N4—C11—C12 | 112.16 (13) | H18B—C18—H18C | 109.5 |
N4—C11—C10 | 107.86 (12) | N2—N1—C1 | 111.74 (13) |
C12—C11—C10 | 112.15 (16) | N2—N1—C18 | 119.64 (15) |
N4—C11—H11 | 108.2 | C1—N1—C18 | 128.40 (15) |
C12—C11—H11 | 108.2 | C7—N2—N1 | 106.02 (13) |
C10—C11—H11 | 108.2 | C8—N3—C9 | 122.39 (14) |
C13—C12—C11 | 111.61 (15) | C8—N3—H3N | 119.7 (15) |
C13—C12—H12A | 109.3 | C9—N3—H3N | 117.8 (15) |
C11—C12—H12A | 109.3 | C17—N4—C15 | 113.03 (14) |
C13—C12—H12B | 109.3 | C17—N4—C11 | 113.97 (13) |
C11—C12—H12B | 109.3 | C15—N4—C11 | 109.48 (13) |
| | | |
N1—C1—C2—C3 | −178.88 (17) | C13—C14—C15—N4 | 55.6 (2) |
C6—C1—C2—C3 | −1.3 (3) | C13—C14—C15—C16 | −67.2 (2) |
C1—C2—C3—C4 | 0.8 (3) | N3—C9—C16—C15 | −175.41 (13) |
C2—C3—C4—C5 | 0.0 (3) | C10—C9—C16—C15 | −51.01 (18) |
C3—C4—C5—C6 | −0.4 (3) | N4—C15—C16—C9 | −5.56 (19) |
C4—C5—C6—C1 | −0.1 (2) | C14—C15—C16—C9 | 119.75 (16) |
C4—C5—C6—C7 | 178.40 (16) | C6—C1—N1—N2 | −0.32 (18) |
N1—C1—C6—C5 | 179.05 (13) | C2—C1—N1—N2 | 177.50 (17) |
C2—C1—C6—C5 | 1.0 (2) | C6—C1—N1—C18 | −174.77 (16) |
N1—C1—C6—C7 | 0.13 (16) | C2—C1—N1—C18 | 3.1 (3) |
C2—C1—C6—C7 | −177.96 (15) | C6—C7—N2—N1 | −0.30 (16) |
C5—C6—C7—N2 | −178.54 (16) | C8—C7—N2—N1 | −179.49 (12) |
C1—C6—C7—N2 | 0.10 (16) | C1—N1—N2—C7 | 0.39 (17) |
C5—C6—C7—C8 | 0.6 (3) | C18—N1—N2—C7 | 175.37 (14) |
C1—C6—C7—C8 | 179.23 (14) | O1—C8—N3—C9 | 0.4 (2) |
N2—C7—C8—O1 | 178.94 (14) | C7—C8—N3—C9 | −179.65 (13) |
C6—C7—C8—O1 | −0.1 (2) | C16—C9—N3—C8 | −148.15 (15) |
N2—C7—C8—N3 | −1.0 (2) | C10—C9—N3—C8 | 88.04 (19) |
C6—C7—C8—N3 | 179.97 (14) | C14—C15—N4—C17 | 69.64 (18) |
N3—C9—C10—C11 | 174.32 (14) | C16—C15—N4—C17 | −165.52 (14) |
C16—C9—C10—C11 | 50.75 (19) | C14—C15—N4—C11 | −58.57 (17) |
C9—C10—C11—N4 | 6.0 (2) | C16—C15—N4—C11 | 66.27 (16) |
C9—C10—C11—C12 | −118.02 (17) | C12—C11—N4—C17 | −69.98 (19) |
N4—C11—C12—C13 | −54.7 (2) | C10—C11—N4—C17 | 166.04 (15) |
C10—C11—C12—C13 | 66.90 (19) | C12—C11—N4—C15 | 57.71 (17) |
C11—C12—C13—C14 | 50.3 (2) | C10—C11—N4—C15 | −66.28 (16) |
C12—C13—C14—C15 | −50.5 (2) | | |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
N3—H3N···N2 | 0.82 (2) | 2.42 (2) | 2.7591 (17) | 106.0 (17) |
C5—H5···O1i | 0.93 | 2.60 | 3.520 (2) | 172 |
C18—H18A···O1ii | 0.96 | 2.48 | 3.343 (2) | 149 |
Symmetry codes: (i) −x+2, −y+2, −z; (ii) x−1/2, −y+3/2, −z. |
(II) diaqua[1-methyl-
N-(9-methyl-9-azoniabicyclo[3.3.1]nonan-7-yl)indazole-
3-carboxamide]cobalt(II) tetrachloride dodecahydrate
top
Crystal data top
[Co(C18H25N4O)2(H2O)2]Cl4·12H2O | Z = 1 |
Mr = 1079.79 | F(000) = 573 |
Triclinic, P1 | Dx = 1.380 Mg m−3 |
Hall symbol: -P 1 | Mo Kα radiation, λ = 0.71073 Å |
a = 9.6311 (9) Å | Cell parameters from 6762 reflections |
b = 9.9794 (9) Å | θ = 2.4–27.5° |
c = 16.0133 (14) Å | µ = 0.61 mm−1 |
α = 92.611 (1)° | T = 294 K |
β = 103.449 (1)° | Block, blue green |
γ = 118.037 (1)° | 0.12 × 0.10 × 0.07 mm |
V = 1299.5 (2) Å3 | |
Data collection top
Bruker SMART APEX CCD area-detector diffractometer | 4220 reflections with I > 2σ(I) |
Radiation source: sealed tube | Rint = 0.020 |
Graphite monochromator | θmax = 25.0°, θmin = 1.3° |
ω scan | h = −11→11 |
12536 measured reflections | k = −11→11 |
4552 independent reflections | l = −19→19 |
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)] = 0.038 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.114 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.10 | w = 1/[σ2(Fo2) + (0.0644P)2 + 0.4633P] where P = (Fo2 + 2Fc2)/3 |
4552 reflections | (Δ/σ)max = 0.001 |
355 parameters | Δρmax = 0.51 e Å−3 |
8 restraints | Δρmin = −0.21 e Å−3 |
Crystal data top
[Co(C18H25N4O)2(H2O)2]Cl4·12H2O | γ = 118.037 (1)° |
Mr = 1079.79 | V = 1299.5 (2) Å3 |
Triclinic, P1 | Z = 1 |
a = 9.6311 (9) Å | Mo Kα radiation |
b = 9.9794 (9) Å | µ = 0.61 mm−1 |
c = 16.0133 (14) Å | T = 294 K |
α = 92.611 (1)° | 0.12 × 0.10 × 0.07 mm |
β = 103.449 (1)° | |
Data collection top
Bruker SMART APEX CCD area-detector diffractometer | 4220 reflections with I > 2σ(I) |
12536 measured reflections | Rint = 0.020 |
4552 independent reflections | |
Refinement top
R[F2 > 2σ(F2)] = 0.038 | 8 restraints |
wR(F2) = 0.114 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.10 | Δρmax = 0.51 e Å−3 |
4552 reflections | Δρmin = −0.21 e Å−3 |
355 parameters | |
Special details top
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 (Å2) top | x | y | z | Uiso*/Ueq | |
Co1 | 0.0000 | 0.5000 | 0.5000 | 0.03051 (13) | |
C1 | 0.1416 (2) | 0.9653 (2) | 0.45480 (13) | 0.0335 (4) | |
C2 | 0.1443 (3) | 1.0861 (3) | 0.41260 (14) | 0.0425 (5) | |
H2 | 0.0528 | 1.0739 | 0.3703 | 0.051* | |
C3 | 0.2897 (3) | 1.2235 (3) | 0.43730 (16) | 0.0492 (6) | |
H3 | 0.2962 | 1.3072 | 0.4116 | 0.059* | |
C4 | 0.4294 (3) | 1.2415 (3) | 0.50042 (16) | 0.0470 (5) | |
H4 | 0.5263 | 1.3358 | 0.5140 | 0.056* | |
C5 | 0.4264 (3) | 1.1247 (2) | 0.54208 (14) | 0.0399 (5) | |
H5 | 0.5194 | 1.1381 | 0.5837 | 0.048* | |
C6 | 0.2781 (2) | 0.9826 (2) | 0.52036 (13) | 0.0332 (4) | |
C7 | 0.2228 (2) | 0.8344 (2) | 0.54413 (12) | 0.0316 (4) | |
C8 | 0.2966 (2) | 0.7632 (2) | 0.60517 (13) | 0.0321 (4) | |
C9 | 0.4983 (2) | 0.7840 (2) | 0.73599 (13) | 0.0336 (4) | |
H9 | 0.5018 | 0.6999 | 0.7042 | 0.040* | |
C10 | 0.6738 (2) | 0.9054 (2) | 0.78658 (14) | 0.0381 (5) | |
H10A | 0.6743 | 0.9981 | 0.8081 | 0.046* | |
H10B | 0.7417 | 0.9316 | 0.7472 | 0.046* | |
C11 | 0.7496 (3) | 0.8511 (3) | 0.86453 (14) | 0.0406 (5) | |
H11 | 0.8520 | 0.8601 | 0.8576 | 0.049* | |
C12 | 0.7881 (3) | 0.9436 (3) | 0.95290 (16) | 0.0513 (6) | |
H12A | 0.8448 | 0.9100 | 0.9979 | 0.062* | |
H12B | 0.8611 | 1.0518 | 0.9539 | 0.062* | |
C13 | 0.6348 (3) | 0.9256 (4) | 0.97312 (17) | 0.0629 (7) | |
H13A | 0.6636 | 0.9770 | 1.0324 | 0.076* | |
H13B | 0.5872 | 0.9741 | 0.9339 | 0.076* | |
C14 | 0.5096 (3) | 0.7566 (4) | 0.96301 (17) | 0.0670 (8) | |
H14A | 0.4084 | 0.7480 | 0.9699 | 0.080* | |
H14B | 0.5505 | 0.7127 | 1.0088 | 0.080* | |
C15 | 0.4737 (3) | 0.6652 (3) | 0.87457 (16) | 0.0529 (6) | |
H15 | 0.3997 | 0.5558 | 0.8735 | 0.063* | |
C16 | 0.3928 (3) | 0.7173 (3) | 0.79780 (15) | 0.0460 (5) | |
H16A | 0.2882 | 0.6297 | 0.7648 | 0.055* | |
H16B | 0.3711 | 0.7948 | 0.8210 | 0.055* | |
C17 | 0.7062 (5) | 0.6073 (4) | 0.9224 (2) | 0.0767 (9) | |
H17A | 0.8054 | 0.6221 | 0.9107 | 0.115* | |
H17B | 0.6296 | 0.4988 | 0.9131 | 0.115* | |
H17C | 0.7309 | 0.6526 | 0.9818 | 0.115* | |
C18 | −0.1449 (3) | 0.7401 (3) | 0.38038 (14) | 0.0415 (5) | |
H18A | −0.1373 | 0.7203 | 0.3228 | 0.062* | |
H18B | −0.1919 | 0.8062 | 0.3811 | 0.062* | |
H18C | −0.2132 | 0.6444 | 0.3964 | 0.062* | |
N1 | 0.0191 (2) | 0.81538 (19) | 0.44255 (10) | 0.0327 (4) | |
N2 | 0.0691 (2) | 0.73667 (18) | 0.49555 (10) | 0.0319 (4) | |
N3 | 0.4264 (2) | 0.8518 (2) | 0.67239 (11) | 0.0353 (4) | |
H3N | 0.451 (3) | 0.940 (3) | 0.6856 (16) | 0.040 (7)* | |
N4 | 0.6321 (3) | 0.6832 (2) | 0.86195 (13) | 0.0464 (5) | |
H4N | 0.614 (3) | 0.629 (2) | 0.8155 (8) | 0.051 (8)* | |
O1 | 0.23222 (17) | 0.61935 (15) | 0.59165 (9) | 0.0372 (3) | |
Cl1 | 0.09237 (9) | 0.27909 (9) | 0.84636 (5) | 0.0684 (2) | |
Cl2 | −0.48031 (9) | 0.19184 (8) | 0.77707 (5) | 0.0633 (2) | |
O1W | −0.1061 (2) | 0.4952 (2) | 0.59903 (11) | 0.0465 (4) | |
H1W | −0.071 (4) | 0.566 (4) | 0.636 (2) | 0.056 (9)* | |
H2W | −0.132 (4) | 0.420 (4) | 0.626 (2) | 0.059 (10)* | |
O2W | −0.1872 (3) | 0.2656 (2) | 0.69237 (14) | 0.0626 (5) | |
H3W | −0.110 (4) | 0.279 (4) | 0.734 (2) | 0.075 (10)* | |
H4W | −0.261 (5) | 0.254 (4) | 0.720 (2) | 0.077 (12)* | |
O3W | 0.0717 (4) | 0.5947 (4) | 0.88118 (19) | 0.1003 (8) | |
H5W | 0.083 (4) | 0.512 (2) | 0.878 (3) | 0.120* | |
H6W | 0.073 (5) | 0.644 (4) | 0.9296 (14) | 0.120* | |
O4W | −0.3881 (3) | 0.5154 (3) | 0.71325 (15) | 0.0724 (6) | |
H7W | −0.2785 (13) | 0.564 (4) | 0.726 (2) | 0.087* | |
H8W | −0.420 (5) | 0.423 (5) | 0.725 (3) | 0.087* | |
O5W | −0.1708 (5) | 0.3080 (4) | 0.9432 (2) | 0.1148 (10) | |
H9W | −0.260 (6) | 0.273 (8) | 0.897 (3) | 0.134* | |
H10W | −0.105 (4) | 0.310 (4) | 0.912 (3) | 0.134* | |
O6W | −0.0351 (3) | 0.7003 (3) | 0.74328 (15) | 0.0687 (6) | |
H11W | 0.038 (6) | 0.799 (5) | 0.759 (3) | 0.082 (16)* | |
H12W | −0.003 (4) | 0.672 (3) | 0.784 (2) | 0.082 (9)* | |
O7W | 0.1531 (4) | 1.0101 (3) | 0.7879 (2) | 0.0846 (7) | |
H13W | 0.248 (5) | 1.053 (5) | 0.787 (3) | 0.102 (13)* | |
H14W | 0.138 (4) | 1.074 (4) | 0.802 (2) | 0.102 (11)* | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
Co1 | 0.0310 (2) | 0.0286 (2) | 0.0267 (2) | 0.01287 (16) | 0.00363 (15) | 0.00369 (15) |
C1 | 0.0388 (11) | 0.0362 (11) | 0.0293 (10) | 0.0209 (9) | 0.0112 (8) | 0.0073 (8) |
C2 | 0.0536 (13) | 0.0465 (13) | 0.0359 (11) | 0.0313 (11) | 0.0118 (10) | 0.0147 (10) |
C3 | 0.0685 (16) | 0.0401 (12) | 0.0464 (13) | 0.0293 (12) | 0.0215 (12) | 0.0205 (10) |
C4 | 0.0493 (13) | 0.0368 (12) | 0.0489 (13) | 0.0141 (10) | 0.0191 (11) | 0.0098 (10) |
C5 | 0.0390 (11) | 0.0373 (11) | 0.0393 (11) | 0.0166 (10) | 0.0093 (9) | 0.0069 (9) |
C6 | 0.0368 (10) | 0.0347 (11) | 0.0297 (10) | 0.0196 (9) | 0.0082 (8) | 0.0059 (8) |
C7 | 0.0337 (10) | 0.0307 (10) | 0.0284 (10) | 0.0166 (8) | 0.0044 (8) | 0.0041 (8) |
C8 | 0.0313 (10) | 0.0333 (11) | 0.0303 (10) | 0.0162 (9) | 0.0062 (8) | 0.0050 (8) |
C9 | 0.0332 (10) | 0.0316 (10) | 0.0315 (10) | 0.0159 (9) | 0.0021 (8) | 0.0053 (8) |
C10 | 0.0324 (10) | 0.0385 (11) | 0.0357 (11) | 0.0140 (9) | 0.0041 (9) | 0.0072 (9) |
C11 | 0.0298 (10) | 0.0464 (12) | 0.0413 (12) | 0.0183 (9) | 0.0042 (9) | 0.0090 (10) |
C12 | 0.0409 (12) | 0.0580 (15) | 0.0384 (12) | 0.0196 (11) | −0.0049 (10) | −0.0004 (11) |
C13 | 0.0601 (16) | 0.093 (2) | 0.0358 (13) | 0.0422 (16) | 0.0065 (11) | −0.0029 (13) |
C14 | 0.0499 (15) | 0.107 (2) | 0.0403 (14) | 0.0343 (16) | 0.0151 (11) | 0.0243 (14) |
C15 | 0.0378 (12) | 0.0576 (15) | 0.0460 (14) | 0.0113 (11) | 0.0071 (10) | 0.0219 (12) |
C16 | 0.0304 (11) | 0.0549 (14) | 0.0390 (12) | 0.0133 (10) | 0.0034 (9) | 0.0116 (10) |
C17 | 0.098 (2) | 0.077 (2) | 0.0588 (17) | 0.0541 (19) | 0.0020 (16) | 0.0234 (15) |
C18 | 0.0384 (11) | 0.0463 (12) | 0.0353 (11) | 0.0224 (10) | −0.0001 (9) | 0.0053 (9) |
N1 | 0.0340 (9) | 0.0357 (9) | 0.0278 (8) | 0.0191 (8) | 0.0038 (7) | 0.0064 (7) |
N2 | 0.0351 (9) | 0.0313 (9) | 0.0280 (8) | 0.0176 (7) | 0.0043 (7) | 0.0052 (7) |
N3 | 0.0368 (9) | 0.0276 (9) | 0.0344 (9) | 0.0152 (8) | −0.0001 (7) | 0.0025 (7) |
N4 | 0.0521 (12) | 0.0455 (11) | 0.0388 (11) | 0.0264 (10) | 0.0026 (9) | 0.0113 (9) |
O1 | 0.0370 (8) | 0.0283 (7) | 0.0373 (8) | 0.0142 (6) | −0.0008 (6) | 0.0046 (6) |
Cl1 | 0.0646 (4) | 0.0795 (5) | 0.0538 (4) | 0.0335 (4) | 0.0095 (3) | 0.0097 (3) |
Cl2 | 0.0726 (4) | 0.0520 (4) | 0.0709 (4) | 0.0322 (3) | 0.0278 (4) | 0.0074 (3) |
O1W | 0.0564 (10) | 0.0414 (9) | 0.0395 (9) | 0.0197 (8) | 0.0203 (8) | 0.0061 (8) |
O2W | 0.0595 (12) | 0.0738 (13) | 0.0537 (12) | 0.0303 (11) | 0.0187 (11) | 0.0245 (10) |
O3W | 0.114 (2) | 0.123 (2) | 0.0755 (16) | 0.0700 (19) | 0.0217 (15) | 0.0200 (16) |
O4W | 0.0908 (15) | 0.0661 (13) | 0.0740 (14) | 0.0498 (13) | 0.0217 (12) | 0.0187 (11) |
O5W | 0.125 (3) | 0.115 (2) | 0.083 (2) | 0.045 (2) | 0.0269 (17) | 0.0024 (16) |
O6W | 0.0835 (15) | 0.0594 (13) | 0.0554 (13) | 0.0353 (12) | 0.0086 (11) | −0.0003 (10) |
O7W | 0.0685 (17) | 0.0609 (15) | 0.106 (2) | 0.0253 (14) | 0.0103 (14) | 0.0031 (13) |
Geometric parameters (Å, º) top
Co1—O1Wi | 2.0679 (16) | C13—H13A | 0.9700 |
Co1—O1W | 2.0680 (16) | C13—H13B | 0.9700 |
Co1—O1i | 2.0938 (14) | C14—C15 | 1.522 (4) |
Co1—O1 | 2.0938 (14) | C14—H14A | 0.9700 |
Co1—N2 | 2.1414 (16) | C14—H14B | 0.9700 |
Co1—N2i | 2.1414 (16) | C15—N4 | 1.513 (3) |
C1—N1 | 1.369 (3) | C15—C16 | 1.544 (3) |
C1—C2 | 1.402 (3) | C15—H15 | 0.9800 |
C1—C6 | 1.410 (3) | C16—H16A | 0.9700 |
C2—C3 | 1.373 (4) | C16—H16B | 0.9700 |
C2—H2 | 0.9300 | C17—N4 | 1.508 (3) |
C3—C4 | 1.410 (4) | C17—H17A | 0.9600 |
C3—H3 | 0.9300 | C17—H17B | 0.9600 |
C4—C5 | 1.361 (3) | C17—H17C | 0.9600 |
C4—H4 | 0.9300 | C18—N1 | 1.461 (3) |
C5—C6 | 1.411 (3) | C18—H18A | 0.9600 |
C5—H5 | 0.9300 | C18—H18B | 0.9600 |
C6—C7 | 1.422 (3) | C18—H18C | 0.9600 |
C7—N2 | 1.336 (3) | N1—N2 | 1.340 (2) |
C7—C8 | 1.477 (3) | N3—H3N | 0.80 (3) |
C8—O1 | 1.251 (2) | N4—H4N | 0.832 (10) |
C8—N3 | 1.323 (3) | O1W—H1W | 0.78 (3) |
C9—N3 | 1.466 (3) | O1W—H2W | 0.85 (4) |
C9—C10 | 1.526 (3) | O2W—H3W | 0.82 (4) |
C9—C16 | 1.532 (3) | O2W—H4W | 0.89 (4) |
C9—H9 | 0.9800 | O3W—H5W | 0.88 (3) |
C10—C11 | 1.547 (3) | O3W—H6W | 0.89 (3) |
C10—H10A | 0.9700 | O4W—H7W | 0.90 (3) |
C10—H10B | 0.9700 | O4W—H8W | 0.87 (4) |
C11—N4 | 1.510 (3) | O5W—H9W | 0.90 (5) |
C11—C12 | 1.519 (3) | O5W—H10W | 0.89 (4) |
C11—H11 | 0.9800 | O6W—H11W | 0.88 (5) |
C12—C13 | 1.515 (4) | O6W—H12W | 0.78 (3) |
C12—H12A | 0.9700 | O7W—H13W | 0.81 (4) |
C12—H12B | 0.9700 | O7W—H14W | 0.75 (4) |
C13—C14 | 1.515 (4) | | |
| | | |
O1Wi—Co1—O1W | 179.999 (1) | H12A—C12—H12B | 107.9 |
O1Wi—Co1—O1i | 89.36 (7) | C14—C13—C12 | 110.9 (2) |
O1W—Co1—O1i | 90.64 (7) | C14—C13—H13A | 109.5 |
O1Wi—Co1—O1 | 90.64 (7) | C12—C13—H13A | 109.5 |
O1W—Co1—O1 | 89.36 (7) | C14—C13—H13B | 109.5 |
O1i—Co1—O1 | 180.0 | C12—C13—H13B | 109.5 |
O1Wi—Co1—N2 | 87.53 (7) | H13A—C13—H13B | 108.1 |
O1W—Co1—N2 | 92.47 (7) | C13—C14—C15 | 112.1 (2) |
O1i—Co1—N2 | 102.86 (6) | C13—C14—H14A | 109.2 |
O1—Co1—N2 | 77.14 (6) | C15—C14—H14A | 109.2 |
O1Wi—Co1—N2i | 92.47 (7) | C13—C14—H14B | 109.2 |
O1W—Co1—N2i | 87.53 (7) | C15—C14—H14B | 109.2 |
O1i—Co1—N2i | 77.14 (6) | H14A—C14—H14B | 107.9 |
O1—Co1—N2i | 102.86 (6) | N4—C15—C14 | 109.5 (2) |
N2—Co1—N2i | 180.0 | N4—C15—C16 | 108.47 (18) |
N1—C1—C2 | 130.0 (2) | C14—C15—C16 | 112.8 (2) |
N1—C1—C6 | 107.33 (17) | N4—C15—H15 | 108.7 |
C2—C1—C6 | 122.6 (2) | C14—C15—H15 | 108.7 |
C3—C2—C1 | 116.2 (2) | C16—C15—H15 | 108.7 |
C3—C2—H2 | 121.9 | C9—C16—C15 | 113.37 (19) |
C1—C2—H2 | 121.9 | C9—C16—H16A | 108.9 |
C2—C3—C4 | 122.0 (2) | C15—C16—H16A | 108.9 |
C2—C3—H3 | 119.0 | C9—C16—H16B | 108.9 |
C4—C3—H3 | 119.0 | C15—C16—H16B | 108.9 |
C5—C4—C3 | 121.8 (2) | H16A—C16—H16B | 107.7 |
C5—C4—H4 | 119.1 | N4—C17—H17A | 109.5 |
C3—C4—H4 | 119.1 | N4—C17—H17B | 109.5 |
C4—C5—C6 | 118.1 (2) | H17A—C17—H17B | 109.5 |
C4—C5—H5 | 121.0 | N4—C17—H17C | 109.5 |
C6—C5—H5 | 121.0 | H17A—C17—H17C | 109.5 |
C1—C6—C5 | 119.19 (19) | H17B—C17—H17C | 109.5 |
C1—C6—C7 | 103.91 (17) | N1—C18—H18A | 109.5 |
C5—C6—C7 | 136.78 (19) | N1—C18—H18B | 109.5 |
N2—C7—C6 | 110.37 (17) | H18A—C18—H18B | 109.5 |
N2—C7—C8 | 114.05 (17) | N1—C18—H18C | 109.5 |
C6—C7—C8 | 135.48 (18) | H18A—C18—H18C | 109.5 |
O1—C8—N3 | 122.08 (18) | H18B—C18—H18C | 109.5 |
O1—C8—C7 | 118.23 (17) | N2—N1—C1 | 110.69 (16) |
N3—C8—C7 | 119.69 (18) | N2—N1—C18 | 121.13 (16) |
N3—C9—C10 | 109.80 (16) | C1—N1—C18 | 128.15 (17) |
N3—C9—C16 | 110.59 (17) | C7—N2—N1 | 107.67 (16) |
C10—C9—C16 | 111.11 (17) | C7—N2—Co1 | 112.82 (12) |
N3—C9—H9 | 108.4 | N1—N2—Co1 | 137.07 (13) |
C10—C9—H9 | 108.4 | C8—N3—C9 | 120.90 (18) |
C16—C9—H9 | 108.4 | C8—N3—H3N | 119.0 (18) |
C9—C10—C11 | 113.12 (17) | C9—N3—H3N | 118.1 (18) |
C9—C10—H10A | 109.0 | C17—N4—C11 | 113.7 (2) |
C11—C10—H10A | 109.0 | C17—N4—C15 | 113.6 (2) |
C9—C10—H10B | 109.0 | C11—N4—C15 | 109.84 (18) |
C11—C10—H10B | 109.0 | C17—N4—H4N | 96.9 (14) |
H10A—C10—H10B | 107.8 | C11—N4—H4N | 111.4 (16) |
N4—C11—C12 | 109.24 (19) | C15—N4—H4N | 110.8 (19) |
N4—C11—C10 | 108.64 (16) | C8—O1—Co1 | 115.47 (12) |
C12—C11—C10 | 113.79 (19) | Co1—O1W—H1W | 123 (2) |
N4—C11—H11 | 108.3 | Co1—O1W—H2W | 120 (2) |
C12—C11—H11 | 108.3 | H1W—O1W—H2W | 103 (3) |
C10—C11—H11 | 108.3 | H3W—O2W—H4W | 100 (3) |
C13—C12—C11 | 112.30 (19) | H5W—O3W—H6W | 125 (4) |
C13—C12—H12A | 109.1 | H7W—O4W—H8W | 107 (4) |
C11—C12—H12A | 109.1 | H9W—O5W—H10W | 95 (6) |
C13—C12—H12B | 109.1 | H11W—O6W—H12W | 98 (4) |
C11—C12—H12B | 109.1 | H13W—O7W—H14W | 105 (4) |
| | | |
N1—C1—C2—C3 | −177.4 (2) | C6—C1—N1—C18 | −178.50 (19) |
C6—C1—C2—C3 | 1.3 (3) | C6—C7—N2—N1 | −1.8 (2) |
C1—C2—C3—C4 | 1.1 (3) | C8—C7—N2—N1 | −178.89 (16) |
C2—C3—C4—C5 | −1.8 (4) | C6—C7—N2—Co1 | 163.58 (13) |
C3—C4—C5—C6 | 0.1 (3) | C8—C7—N2—Co1 | −13.5 (2) |
N1—C1—C6—C5 | 175.93 (18) | C1—N1—N2—C7 | 1.3 (2) |
C2—C1—C6—C5 | −3.0 (3) | C18—N1—N2—C7 | 179.65 (18) |
N1—C1—C6—C7 | −0.7 (2) | C1—N1—N2—Co1 | −158.72 (15) |
C2—C1—C6—C7 | −179.66 (19) | C18—N1—N2—Co1 | 19.6 (3) |
C4—C5—C6—C1 | 2.2 (3) | O1Wi—Co1—N2—C7 | −85.32 (14) |
C4—C5—C6—C7 | 177.5 (2) | O1W—Co1—N2—C7 | 94.68 (14) |
C1—C6—C7—N2 | 1.6 (2) | O1i—Co1—N2—C7 | −174.10 (13) |
C5—C6—C7—N2 | −174.2 (2) | O1—Co1—N2—C7 | 5.90 (13) |
C1—C6—C7—C8 | 177.8 (2) | O1Wi—Co1—N2—N1 | 74.02 (19) |
C5—C6—C7—C8 | 2.0 (4) | O1W—Co1—N2—N1 | −105.98 (19) |
N2—C7—C8—O1 | 18.0 (3) | O1i—Co1—N2—N1 | −14.8 (2) |
C6—C7—C8—O1 | −158.1 (2) | O1—Co1—N2—N1 | 165.2 (2) |
N2—C7—C8—N3 | −161.30 (18) | O1—C8—N3—C9 | −1.7 (3) |
C6—C7—C8—N3 | 22.6 (3) | C7—C8—N3—C9 | 177.58 (18) |
N3—C9—C10—C11 | 171.16 (18) | C10—C9—N3—C8 | 160.76 (19) |
C16—C9—C10—C11 | 48.5 (2) | C16—C9—N3—C8 | −76.3 (2) |
C9—C10—C11—N4 | 6.4 (3) | C12—C11—N4—C17 | −67.7 (3) |
C9—C10—C11—C12 | −115.5 (2) | C10—C11—N4—C17 | 167.6 (2) |
N4—C11—C12—C13 | −57.2 (3) | C12—C11—N4—C15 | 60.9 (2) |
C10—C11—C12—C13 | 64.4 (3) | C10—C11—N4—C15 | −63.8 (2) |
C11—C12—C13—C14 | 52.9 (3) | C14—C15—N4—C17 | 67.9 (3) |
C12—C13—C14—C15 | −52.5 (3) | C16—C15—N4—C17 | −168.6 (2) |
C13—C14—C15—N4 | 56.7 (3) | C14—C15—N4—C11 | −60.7 (3) |
C13—C14—C15—C16 | −64.2 (3) | C16—C15—N4—C11 | 62.8 (2) |
N3—C9—C16—C15 | −171.68 (19) | N3—C8—O1—Co1 | 166.61 (16) |
C10—C9—C16—C15 | −49.5 (3) | C7—C8—O1—Co1 | −12.7 (2) |
N4—C15—C16—C9 | −4.9 (3) | O1Wi—Co1—O1—C8 | 91.25 (15) |
C14—C15—C16—C9 | 116.6 (2) | O1W—Co1—O1—C8 | −88.75 (15) |
C2—C1—N1—N2 | 178.5 (2) | N2—Co1—O1—C8 | 3.93 (14) |
C6—C1—N1—N2 | −0.3 (2) | N2i—Co1—O1—C8 | −176.07 (14) |
C2—C1—N1—C18 | 0.3 (3) | | |
Symmetry code: (i) −x, −y+1, −z+1. |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
N3—H3N···Cl2ii | 0.80 (3) | 2.56 (3) | 3.324 (2) | 161 (2) |
N4—H4N···O4Wiii | 0.83 (1) | 1.94 (1) | 2.761 (3) | 170 (3) |
O1W—H1W···O6W | 0.78 (3) | 1.99 (3) | 2.740 (3) | 163 (3) |
O1W—H2W···O2W | 0.85 (4) | 1.85 (4) | 2.696 (3) | 176 (3) |
O2W—H3W···Cl1 | 0.82 (4) | 2.33 (4) | 3.145 (2) | 171 (3) |
O2W—H4W···Cl2 | 0.89 (4) | 2.32 (4) | 3.204 (2) | 171 (3) |
O3W—H5W···Cl1 | 0.88 (3) | 2.40 (3) | 3.280 (3) | 171 (4) |
O3W—H6W···O5Wiv | 0.89 (3) | 1.96 (2) | 2.719 (4) | 141 (3) |
O4W—H7W···O6W | 0.90 (3) | 2.02 (3) | 2.908 (4) | 170 (4) |
O4W—H8W···Cl2 | 0.87 (4) | 2.34 (4) | 3.207 (2) | 172 (4) |
O5W—H9W···Cl2 | 0.90 (5) | 2.28 (6) | 3.177 (4) | 178 (7) |
O5W—H10W···Cl1 | 0.89 (4) | 2.50 (4) | 3.374 (4) | 168 (4) |
O6W—H11W···O7W | 0.88 (5) | 1.83 (5) | 2.699 (4) | 168 (4) |
O6W—H12W···O3W | 0.78 (3) | 1.91 (3) | 2.686 (4) | 178 (3) |
O7W—H13W···Cl2ii | 0.81 (4) | 2.37 (4) | 3.174 (3) | 175 (4) |
O7W—H14W···Cl1v | 0.75 (4) | 2.40 (4) | 3.151 (4) | 179 (4) |
C9—H9···O4Wiii | 0.98 | 2.51 | 3.371 (3) | 146 |
C17—H17C···Cl1vi | 0.96 | 2.74 | 3.601 (3) | 150 |
C18—H18C···O1i | 0.96 | 2.57 | 3.356 (3) | 139 |
Symmetry codes: (i) −x, −y+1, −z+1; (ii) x+1, y+1, z; (iii) x+1, y, z; (iv) −x, −y+1, −z+2; (v) x, y+1, z; (vi) −x+1, −y+1, −z+2. |
Experimental details
| (I) | (II) |
Crystal data |
Chemical formula | C18H24N4O | [Co(C18H25N4O)2(H2O)2]Cl4·12H2O |
Mr | 312.41 | 1079.79 |
Crystal system, space group | Orthorhombic, Pbca | Triclinic, P1 |
Temperature (K) | 294 | 294 |
a, b, c (Å) | 13.7930 (12), 13.5544 (12), 17.9574 (16) | 9.6311 (9), 9.9794 (9), 16.0133 (14) |
α, β, γ (°) | 90, 90, 90 | 92.611 (1), 103.449 (1), 118.037 (1) |
V (Å3) | 3357.2 (5) | 1299.5 (2) |
Z | 8 | 1 |
Radiation type | Mo Kα | Mo Kα |
µ (mm−1) | 0.08 | 0.61 |
Crystal size (mm) | 0.18 × 0.16 × 0.09 | 0.12 × 0.10 × 0.07 |
|
Data collection |
Diffractometer | Bruker SMART APEX CCD area-detector diffractometer | Bruker SMART APEX CCD area-detector diffractometer |
Absorption correction | – | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 29671, 2950, 2559 | 12536, 4552, 4220 |
Rint | 0.039 | 0.020 |
(sin θ/λ)max (Å−1) | 0.595 | 0.595 |
|
Refinement |
R[F2 > 2σ(F2)], wR(F2), S | 0.043, 0.128, 1.07 | 0.038, 0.114, 1.10 |
No. of reflections | 2950 | 4552 |
No. of parameters | 214 | 355 |
No. of restraints | 0 | 8 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.19, −0.15 | 0.51, −0.21 |
Selected geometric parameters (Å, º) for (I) topC8—O1 | 1.2205 (18) | C15—N4 | 1.459 (2) |
C8—N3 | 1.337 (2) | C17—N4 | 1.457 (2) |
C9—N3 | 1.4591 (19) | N1—N2 | 1.3500 (18) |
C11—N4 | 1.465 (2) | | |
| | | |
N3—C8—C7 | 116.40 (13) | C8—N3—C9 | 122.39 (14) |
C7—N2—N1 | 106.02 (13) | C15—N4—C11 | 109.48 (13) |
| | | |
C9—C10—C11—N4 | 6.0 (2) | C16—C15—N4—C11 | 66.27 (16) |
C13—C14—C15—N4 | 55.6 (2) | C12—C11—N4—C15 | 57.71 (17) |
N4—C15—C16—C9 | −5.56 (19) | C10—C11—N4—C15 | −66.28 (16) |
C14—C15—N4—C11 | −58.57 (17) | | |
Hydrogen-bond geometry (Å, º) for (I) top
D—H···A | D—H | H···A | D···A | D—H···A |
N3—H3N···N2 | 0.82 (2) | 2.42 (2) | 2.7591 (17) | 106.0 (17) |
C5—H5···O1i | 0.93 | 2.60 | 3.520 (2) | 172.0 |
C18—H18A···O1ii | 0.96 | 2.48 | 3.343 (2) | 149.3 |
Symmetry codes: (i) −x+2, −y+2, −z; (ii) x−1/2, −y+3/2, −z. |
Selected geometric parameters (Å, º) for (II) topCo1—O1W | 2.0680 (16) | C9—N3 | 1.466 (3) |
Co1—O1 | 2.0938 (14) | C11—N4 | 1.510 (3) |
Co1—N2 | 2.1414 (16) | C15—N4 | 1.513 (3) |
C8—O1 | 1.251 (2) | C17—N4 | 1.508 (3) |
C8—N3 | 1.323 (3) | N1—N2 | 1.340 (2) |
| | | |
N3—C8—C7 | 119.69 (18) | C8—N3—C9 | 120.90 (18) |
C7—N2—N1 | 107.67 (16) | C11—N4—C15 | 109.84 (18) |
| | | |
C9—C10—C11—N4 | 6.4 (3) | C12—C11—N4—C15 | 60.9 (2) |
N4—C11—C12—C13 | −57.2 (3) | C10—C11—N4—C15 | −63.8 (2) |
C13—C14—C15—N4 | 56.7 (3) | C14—C15—N4—C11 | −60.7 (3) |
N4—C15—C16—C9 | −4.9 (3) | C16—C15—N4—C11 | 62.8 (2) |
Hydrogen-bond geometry (Å, º) for (II) top
D—H···A | D—H | H···A | D···A | D—H···A |
N3—H3N···Cl2i | 0.80 (3) | 2.56 (3) | 3.324 (2) | 161 (2) |
N4—H4N···O4Wii | 0.832 (10) | 1.938 (11) | 2.761 (3) | 170 (3) |
O1W—H1W···O6W | 0.78 (3) | 1.99 (3) | 2.740 (3) | 163 (3) |
O1W—H2W···O2W | 0.85 (4) | 1.85 (4) | 2.696 (3) | 176 (3) |
O2W—H3W···Cl1 | 0.82 (4) | 2.33 (4) | 3.145 (2) | 171 (3) |
O2W—H4W···Cl2 | 0.89 (4) | 2.32 (4) | 3.204 (2) | 171 (3) |
O3W—H5W···Cl1 | 0.88 (3) | 2.40 (3) | 3.280 (3) | 171 (4) |
O3W—H6W···O5Wiii | 0.89 (3) | 1.96 (2) | 2.719 (4) | 141 (3) |
O4W—H7W···O6W | 0.90 (3) | 2.02 (3) | 2.908 (4) | 170 (4) |
O4W—H8W···Cl2 | 0.87 (4) | 2.34 (4) | 3.207 (2) | 172 (4) |
O5W—H9W···Cl2 | 0.90 (5) | 2.28 (6) | 3.177 (4) | 178 (7) |
O5W—H10W···Cl1 | 0.89 (4) | 2.50 (4) | 3.374 (4) | 168 (4) |
O6W—H11W···O7W | 0.88 (5) | 1.83 (5) | 2.699 (4) | 168 (4) |
O6W—H12W···O3W | 0.78 (3) | 1.91 (3) | 2.686 (4) | 178 (3) |
O7W—H13W···Cl2i | 0.81 (4) | 2.37 (4) | 3.174 (3) | 175 (4) |
O7W—H14W···Cl1iv | 0.75 (4) | 2.40 (4) | 3.151 (4) | 179 (4) |
C9—H9···O4Wii | 0.98 | 2.51 | 3.371 (3) | 145.9 |
C17—H17C···Cl1v | 0.96 | 2.74 | 3.601 (3) | 150.1 |
C18—H18C···O1vi | 0.96 | 2.57 | 3.356 (3) | 139.2 |
Symmetry codes: (i) x+1, y+1, z; (ii) x+1, y, z; (iii) −x, −y+1, −z+2; (iv) x, y+1, z; (v) −x+1, −y+1, −z+2; (vi) −x, −y+1, −z+1. |
Selected topographical X-ray structural features of the
title compound (I) and (II) and other related structures
(Å). topRef | d1 | d2 | d3 | D |
(I) | 4.19 | 4.82 | 8.83 | 0.17 |
(II) | 5.09 | 4.86 | 8.52 | 0.67 |
a | 4.30 | 6.35 | 9.72 | 0.94 |
b | 3.66 | 4.20 | 7.04 | 0.99 |
c | 4.28 | 5.66 | 8.94 | 0.91 |
d1 = distance between the aromatic ring centroid and linker
carboxamide O1 , d2 = distance between O1 and basic N4 atom,
d3 = distance between the aromatic ring centroid and basic N4 atom,
D = deviation of the basic N4 with respect to the aromatic ring.
(I) and (II) present work
(a)ondansetron HCl (Chandra Mohan & Ravikumar, 1995)
(b) palonosetron HCl (Ravikumar & Sridhar, 2007b)
(c) analogue structure (Fludzinski et al., 1987). |
As their name implies, 5-HT3 antagonists prevent serotonin from binding to 5-HT3 receptors. Such receptors are present mostly on the ends of afferent branches of the vagus nerve, which send signals directly to the brain's vomiting centre in the medulla oblongata, and in the chemoreceptor trigger zone of the brain, which receives input from nausea-inducing agents in the bloodstream and communicates with the vomiting centre. By preventing activation of these receptors, 5-HT3 antagonists interrupt one of the pathways that lead to nausea and/or vomiting. All 5-HT3 antagonists are identified by the setron, according to WHO's Anatomical Therapeutic Chemical Classification System, and are classified among antiemetic agents. Although these agents share a common mechanism of action in preventing chemotherapy-induced nausea and vomiting (CINV), there are differences in their pharmacological profiles. The major differences are found in their chemical structure, 5-HT3 receptor affinity, dose–response curve and pharmacokinetic profile (Gan, 2005).
Granisetron, BRL 43694, is an indazole derivative developed by the British drug company Beecham (Sanger & Nelson, 1989; Plosker & Goa, 1991). It is unique among the 5-HT3 receptor antagonists because it is not metabolized via the cytochrome P450 (CYP) 2D6 pathway (Tan, 2003). Granisetron is well tolerated with adverse events of mild severity including headache, asthenia and constipation. Overall, data demonstrate that granisetron is an efficacious, safe and cost-effective member of the 5-HT3 receptor antagonist class for the prevention of CINV. Granisetron is usually administered as a hydrochloride salt and is produced by Hoffmann–La Roche under the trade name Kytril. It was approved in the UK in 1991 and in the US in 1994 by the Food and Drug Administration.
Several drugs have chelating properties. When co-administered with nutritional supplements, viz vitamins and minerals, chelating drugs can combine with metal ions in the gastrointestinal (GI) tract to form complexes that are poorly absorbed. Hence, attempts have been made to form metal- coordinated complexes with the biologically active molecules, to try to improve the properties known to be superior in terms of potency, stability, reduced side effects, or targeted delivery.
As part of our structural studies on pharmaceutical compounds (Ravikumar & Sridhar, 2006a,b, 2007a,b; Ravikumar et al., 2008; Sridhar & Ravikumar, 2009) and further stimulated by the studies on drug–metal interactions, the crystal structures of granisetron, (I), and its cobalt complex, (II), were determined.
The molecular structures of (I) and (II) are shown in Figs.1 and 2, respectively, while selected geometric parameters are presented in Tables 1 and 3. The overall structure of the granisetron molecule in (I) and (II) may be described as a planar indazole ring linked by the coplanar carboxamide group to the flexible azabicyclo ring system. In both structures (I) and (II), the two stereogenic centres, C11 and C15, are of the same chirality, corresponding to the RS/SR diastereoisomer. The molecule in both structures is in extended conformation [C7—C8—N3—C9, -179.7 (1) (I) and 177.6 (2)° (II)]. A striking difference between the two structures is the orientation of the central carboxamide group. In chelating granisetron, (II), the carboxamide group is in a cis orientation while in the free form, (I), it is trans. The metal coordination in (II) leads to a significant change in the bond angles around atoms C7 and C8. Also, an intramolecular hydrogen bond N3—H···N1 seen in (I) is not observed in (II). The CoII coordination polyhedron is a slightly distorted octahedron, with the CoII ion at the centre of inversion. The distortion arises from the O1W—Co—O1Wi axis which is not perpendicular to the coordination plane [O1/N2/O1i/N2i/Co, symmetry code: (i) -x, -y + 1, -z + 1]. The two bidendate ligands lie trans to one another and are coordinated to the CoII ion through the indazole N2 atoms and the carboxamide O1 atoms, to form a five-membered ring in the equatorial plane. Two water O1W atoms complete the octahedron at the axial positions. An overlay of the granisetron molecules of (I) and (II) with an analogous structure (azabicyloc[3.3.1]nonane ring is replaced by azabicyclo[3.2.1]octane ring at N3; Fludzinski et al., 1987), superimposing the planar indazole systems, reveals the conformational flexibility (Fig. 3).
The conformation of the azabicyclo ring system expressed by the torsion angles C—C—N4—C and N4—C—C—C in (I) and (II) is chair–boat. The protonation at N4 of the azabicyclo ring (quinuclidinium) in (II) does not additionally influence its conformation.
The crystal packing in (I) is influenced by the centrosymmetric C—H···O dimerization between carboxamide O1 and C5 of the indazole ring (Table 2). The dimers are further linked by a C—H···O hydrogen bond formed by the C18 of the azabicyclo ring with the carboxamide O1, resulting in a cyclic centrosymmetric tetramer formation, resembling a square-grid mesh (Fig. 4). The presence of water molecules and Cl ions in (II) provides a unique medium for hydrogen bonding (Table 4). All water molecules act as both donor and acceptor, and along with Cl ions form different OW···Cl ring clusters (Fig. 5). These pseudo-ring patterns are fused and form a continuous hydrogen-bonding network. The granisetron ligands connect the above-mentioned ring patterns through the amide N3—H···Cl2 and the protonated N4 of the azabicyclo ring (N4—H···O4W). The crystal packing of (II) thus exhibits a framework architecture formed by the combination of coordination and hydrogen-bonded assemblies of Cl ions and water molecules. Weak C—H···O and C—H···Cl interactions are also observed.
A number of pharmacophore models and alignments of antagonists binding to the 5-HT3 receptors have been proposed (Hibert et al., 1990; Lopez-Rodriguez et al., 1997). It appears that 5-HT3 receptor antagonists can share a pharmacophore, made up of the structural features of an aromatic moiety, a coplanar carbonyl function (with the O atom situated at an approximate distance of 3–4 Å from the centroid of the aromatic ring) and a basic N atom (situated at an average distance of 5.5 Å from the oxygen of the carbonyl group and 7–8 Å from the centroid of the aromatic ring) which is almost aligned in the same plane as the aromatic ring. Viewing [Comparing] the present structures of (I) and (II) with those of other setrons (Chandra Mohan & Ravikumar, 1995; Ravikumar & Sridhar, 2007b) in the light of the above pharmacophore model, the geometric parameters deduced are listed in Table 5. Significant similarities in these derived structural parameters can be seen. However, it is difficult from this limited set of data to suggest what structural parameters contribute to the observed pharmacological differences. Considering the diversity seen in the chemical structure of the setrons, the structural features observed may still be useful for further development of the 5-HT3 receptor antagonists.
In conclusion, the crystal structures of free granisetron, (I), and its cobalt complex, (II), reveal the rotational flexibility of the carboxamide group despite linking the rigid and bulky groups, which [the carboxamide group?] can easily change its orientation under the influence of weak interactions. An interplay of hydrogen- bonding interactions between the water molecules of hydration and Cl ions in (II) may mimic those found in solution for the salt or solvated molecule of (I).