Cinchoninium L-tartrate tetrahydrate

The title compound, (3R,4S,8R,9S)-cinchoninium (2R,3R)-tartrate tetrahydrate, C₁₉H₂₃N₂O⁺·C₄H₅O₆^-·4H₂O, is a hydrated salt of cinchonine. In the cinchoninium cation, the geometry around the quinuclidinic N atom is typical of a protonated N atom, and the bond lengths and angles in the tartrate moiety clearly indicate the mono-ionized form. The relative orientation of the quinoline and quinuclidine systems is that most frequently observed in structures of cinchona salts and corresponds to one of the energy minima calculated for this type of mol­ecule in the gas phase. An extended network of intermolecular hydrogen bonds spreads parallel to the bc plane separating apolar layers.

S1. Comment

Compounds containing heterocyclic nitrogen systems are very important to mankind as they are often associated with substances that show physiological activity. In particular, naturally occurring alkaloids of the cinchona group have for a long time been used as antimalarial, antibacterial and cardioactive agents (Verpoorte et al., 1988; Carroll et al., 1991; Karle & Karle, 1992; Oleksyn & Serda, 1993; Chiou, et al., 1996). Many factors can influence the biological activity of these substances and the action mechanism is still not completely understood. In particular, the activity seems to be strongly correlated with the stereochemistry of the adjacent C8 and C9 chiral centres and 8,9-threo-isomers have been shown to possess minimal biological activity (Dijkstra et al., 1989; Karle & Karle, 1992; Oleksyn & Serda, 1993; Fujii et al., 2000). In addition, the ability of the amino and hydroxyl groups at C8 and C9 to form intermolecular hydrogen bonds with the receptors is also considered essential for the biological activity, which is completely lost when these groups are engaged in intramolecular hydrogen bonds. Apart from the biological activity, this class of substances has been used, after the pioneering studies of Pasteur (1853) and McKenzie (1899), as effective resolving agents of racemic mixtures of carboxylic acids (Fogassy et al., 1986; Dijkstra et al., 1989; Ryttersgaard & Larsen, 1998) and, more recently, as chiral control elements in various asymmetric processes (Corey et al., 1997; Thiel et al., 2001, and references therein).

Several adducts formed by cinchona alkaloids with carboxylic acids have been studied crystallographically in the last decade (Larsen et al., 1993; Oleksyn & Serda, 1993; Gjerløv & Larsen, 1997a,b; Ryttersgaard & Larsen, 1998). The present structure of (3R,4S,8R,9S)-cinchoninium (2R,3R)-tartrate tetrahydrate, (I), underlines the stereochemical features of the alkaloid moiety and its characteristic mode of interaction with other molecules in the crystal.

Fig. 1 shows a perspective view of the asymmetric unit in the cell. All the bond lengths and angles are in the expected ranges (Pniewska & Suszko-Purzycka, 1989, and references therein; Ryttersgaard & Larsen, 1998). In particular, the geometry around N1 in the quinuclidinic moiety is typical of a protonated nitrogen (Oleksyn et al., 1978, 1979). Likewise, the values of the bond lengths and angles in the tartrate anion clearly indicate that only the C4A carboxyl group is ionized. In the cinchona cation, N1⁺ is anti oriented with respect to the quinoline ring and the orientation of quinoline and quinuclidine moieties is well described by the torsion angles N1—C8—C9—C16 and C8—C9—C16—C15 of -170.9 (2) and -108.8 (3)°, respectively. This conformation corresponds to one of the energy minima calculated in the gas phase for this alkaloid family (Dupont et al., 1985; Carroll et al., 1991) and is the most frequently observed in the crystal structures of cinchona salts (Oleksyn & Serda, 1993). The quinoline system is only roughly planar. With respect to the best plane through the non-H atoms of the bicyclic system, the deviations are within 0.054 (3) Å. This finding, together with the values of the bond lengths and angles, is consistent with the low aromaticity of the bicyclic system (Gdaniec et al., 1989; Oleksyn & Serda, 1993). The quinuclidine system is in a boat conformation, slightly distorted toward a twist-boat form, so that the methylene groups are \sim12° twisted around the N1···C4 line. This twisting is more pronounced in the N1-protonated cinchona alkaloids (Oleksyn et al., 1992; Oleksyn & Serda, 1993). The vinyl group is oriented to form a dihedral angle of 137.6 (4)° with the C2—C3 bond, according to the experimental and theoretical results for correlated structures (Karle & Karle, 1981; Carroll et al., 1991; Ryttersgaard & Larsen, 1998). The hydroxyl O atom at C9 forms a O12—C9—C8—N1 torsion angle of 68.5 (2)°.

The tartrate anion adopts the usual extended trans conformation (Ryttersgaard & Larsen, 1998). The value of -175.4 (2)° for the backbone torsion angle (C1A—C2A—C3A—C4A) is well within the variance of ±16° around 180° found for 90 tartrate structures in a search of the Cambridge Structural Database (Version 5.21, April 2001; Allen & Kennard, 1993).

In the crystal, the molecular arrangement is ruled by numerous intermolecular hydrogen bonds that involve all the potential donor groups. The geometry of the hydrogen-bonding interactions is given in Table 2 and in Fig. 2. In particular, the tartrate anions are interconnected through a short hydrogen bond between the carboxylic hydroxyl and carboxylate carbonyl groups, giving rise to anion chains parallel to the b axis and encircling the screw axis at a = 1/2, c = 0. Such a head-to-tail chain arrangement is rather common in tartrate structures with a translational period of about 7 Å (Fogassy et al., 1986, and references therein). Further hydrogen-bonding interactions interconnect, along the a direction, cinchoninium and tartrate ions in an infinite sequence of alternating cations and anions. In both chain motifs, the crystal water W1 is involved as a donor and acceptor in four hydrogen bonds. The remaining water molecules are arranged around the screw axis at a and c = 1/2, and are joined by a network of hydrogen bonds which act as a bridge along the c direction between the screw-related tartrate moieties. In this manner, the molecular arrangement forms, along the a axis, an alternating sequence of polar (a = 1/2) and apolar layers (a = 0). In the hydrophobic layers, all distances are greater than (>3.5 Å) the sum of van der Waals radii. The vinyl groups point towards the quinoline systems of neighbouring screw-related cations with a C11···N13(2 - x, 1/2 + y, 1 - z) distance of 3.688 (4) Å.

Related literature

For related literature, see: Allen & Kennard (1993); Carroll et al. (1991); Chiou et al. (1996); Corey et al. (1997); Dijkstra et al. (1989); Dupont et al. (1985); Fogassy et al. (1986); Fujii et al. (2000); Gdaniec et al. (1989); Gjerløv & Larsen (1997a, 1997b); Karle & Karle (1981, 1992); Larsen et al. (1993); McKenzie (1899); Oleksyn & Serda (1993); Oleksyn et al. (1978, 1979, 1992); Pasteur (1853); Pniewska & Suszko-Purzycka (1989); Ryttersgaard & Larsen (1998); Thiel et al. (2001); Verpoorte et al. (1988).

S2. Experimental

Single crystals of (I) were selected directly from the Artificial Crystal Collection of the mineralogist Arcangelo Scacchi (1810–1893) preserved in the `Real Museo Mineralogico' of Naples. Identical crystals were obtained dissolving a fraction of the original sample in methanol by slow evaporation (about three weeks) at 277 K. Crystals of compound (I) were also obtained from equimolar amounts of cinchonine and L-tartaric acid (Fluka products) dissolved in a (5:1 molar ratio) methanol and water mixture.

S3. Refinement

All H atoms were observed in difference Fourier maps and included at idealized positions in the final refinements as fixed atoms, with U_iso(H) = U_eq(parent atom). Alkyl H atoms and hydroxyl and water H atoms were constrained to lie 1.02 and 0.98 Å, respectively, from their parent atoms.

Computing details

Data collection: CAD-4 Software (Enraf-Nonius, 1989); cell refinement: CAD-4 Software; data reduction: SDP (Enraf-Nonius, 1985); program(s) used to solve structure: SIR92 (Altomare et al., 1993); program(s) used to refine structure: SDP; molecular graphics: ORTEP-3 (Farrugia, 1997); software used to prepare material for publication: PARST (Nardelli, 1983, 1995).

Figures

	Fig. 1. Perspective view of the asymmetric unit of (I) with the atomic labelling for non-H atoms. Displacement ellipsoids are drawn at the 30% probability level.
	Fig. 2. The crystal packing projected onto the ac plane. Only the H-atoms involved in hydrogen bonding are reported. Dotted lines indicate hydrogen bonds.

(I)

Crystal data

C19H23N2O^+·C4H5O6^−·4H2O	F(000) = 552.0
Mr = 516.54	Dx = 1.332 Mg m^−3
Monoclinic, P21	Cu Kα radiation, λ = 1.54180 Å
Hall symbol: P 2yb	Cell parameters from 25 reflections
a = 12.802 (7) Å	θ = 25.4–31.3°
b = 7.0425 (10) Å	µ = 0.90 mm^−1
c = 14.97 (1) Å	T = 291 K
β = 107.44 (3)°	Rectangular prism, light brown
V = 1287.6 (11) Å^3	0.42 × 0.22 × 0.09 mm
Z = 2

Data collection

Enraf-Nonius CAD-4 diffractometer	4833 reflections with I > 2.5σ(I)
Radiation source: monochromated	Rint = 0.030
Graphite monochromator	θmax = 75.7°
ω–θ scans as suggested by peak–shape analysis implemented in the CAD–4 Software (Enraf–Nonius, 1989)	h = 0→16
Absorption correction: ψ scan (North et al., 1968)	k = −6→8
Tmin = 0.828, Tmax = 0.999	l = −18→17
5316 measured reflections	3 standard reflections every 200 min
5096 independent reflections	intensity decay: none

Refinement

Refinement on F	Weighting scheme based on measured s.u.'s w = 1/[σ^2(Fo) + (0.02Fo)^2 + 1.0] (Killean & Lawrence, 1969)
Least-squares matrix: full	(Δ/σ)max = 0.013
R[F^2 > 2σ(F^2)] = 0.046	Δρmax = 0.24 e Å^−3
wR(F^2) = 0.054	Δρmin = −0.24 e Å^−3
S = 0.99	Extinction correction: Stout & Jensen (1968)
4833 reflections	Extinction coefficient: 1.6E-6 (2)
326 parameters	Absolute structure: The absolute configuration was chosen according to that of the known cinchonine (Oleksyn et al., 1978) and is supported by the refined Rogers parameter (Rogers, 1981).
H-atom parameters constrained	Rogers parameter: 0.998 (6)

Special details

Experimental. Systematic absences and intensity statistics led to the unique assignment of the space group P2₁.

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

	x	y	z	Uiso*/Ueq
O1A	0.37406 (15)	1.0	0.04386 (12)	0.0514 (5)
O2A	0.34068 (18)	1.0185 (3)	0.18120 (14)	0.0756 (7)
O3A	0.35200 (12)	0.6341 (3)	0.20232 (11)	0.0468 (5)
O4A	0.56094 (12)	0.7101 (2)	0.18894 (12)	0.0454 (5)
O5A	0.39932 (14)	0.3596 (2)	0.04026 (11)	0.0434 (5)
O6A	0.55698 (14)	0.3441 (3)	0.15490 (12)	0.0481 (5)
O12	0.80269 (12)	0.8184 (3)	0.27065 (11)	0.0422 (5)
N1	0.71031 (14)	0.4529 (3)	0.32195 (13)	0.0390 (5)
N13	1.13715 (15)	0.6244 (4)	0.18754 (15)	0.0531 (7)
C1A	0.35839 (17)	0.9267 (3)	0.11926 (16)	0.0390 (7)
C2A	0.36457 (16)	0.7106 (3)	0.11979 (15)	0.0357 (6)
C3A	0.47478 (15)	0.6484 (3)	0.11094 (14)	0.0322 (6)
C4A	0.47871 (17)	0.4318 (3)	0.10335 (15)	0.0353 (6)
C2	0.69065 (19)	0.5921 (4)	0.39195 (16)	0.0457 (7)
C3	0.7681 (2)	0.5474 (4)	0.48896 (16)	0.0549 (8)
C4	0.8617 (2)	0.4221 (4)	0.47665 (18)	0.0526 (8)
C5	0.8125 (3)	0.2269 (4)	0.44253 (19)	0.0587 (9)
C6	0.7099 (2)	0.2539 (4)	0.36053 (18)	0.0518 (8)
C7	0.9046 (2)	0.5116 (4)	0.40160 (17)	0.0502 (8)
C8	0.82054 (16)	0.4829 (4)	0.30602 (15)	0.0384 (6)
C9	0.81849 (16)	0.6380 (4)	0.23423 (15)	0.0370 (5)
C10	0.8101 (3)	0.7288 (5)	0.54176 (19)	0.0731 (12)
C11	0.8213 (4)	0.7655 (5)	0.6256 (2)	0.0880 (15)
C14	1.1054 (2)	0.7673 (4)	0.2291 (2)	0.0573 (9)
C15	1.0019 (2)	0.7775 (4)	0.24359 (18)	0.0492 (8)
C16	0.92782 (17)	0.6336 (4)	0.21191 (15)	0.0391 (7)
C17	0.95699 (17)	0.4801 (4)	0.16229 (14)	0.0399 (7)
C18	0.88653 (19)	0.3273 (4)	0.12187 (16)	0.0476 (7)
C19	0.9248 (2)	0.1802 (5)	0.08043 (19)	0.0596 (9)
C20	1.0329 (2)	0.1765 (5)	0.07636 (18)	0.0595 (9)
C21	1.10103 (19)	0.3230 (5)	0.11130 (17)	0.0554 (8)
C22	1.06519 (18)	0.4800 (4)	0.15461 (15)	0.0439 (7)
O1W	0.66257 (14)	1.0236 (3)	0.13183 (12)	0.0470 (6)
O2W	0.4355 (2)	0.3362 (4)	0.33029 (16)	0.0821 (8)
O3W	0.4201 (3)	0.5775 (5)	0.47701 (19)	0.1065 (12)
O4W	0.5880 (3)	0.4001 (4)	0.62119 (17)	0.1148 (14)
H2	0.65263	0.47159	0.26251	0.0390*
H3	0.61158	0.58113	0.39301	0.0457*
H4	0.70482	0.72680	0.37336	0.0457*
H5	0.72799	0.47519	0.52790	0.0549*
H6	0.92387	0.41000	0.53771	0.0526*
H7	0.79319	0.15844	0.49552	0.0587*
H8	0.86799	0.14810	0.42178	0.0587*
H9	0.70860	0.15688	0.30964	0.0518*
H10	0.64237	0.23623	0.38248	0.0518*
H11	0.97660	0.44856	0.40241	0.0502*
H12	0.91711	0.65328	0.41454	0.0502*
H13	0.84255	0.36606	0.27559	0.0384*
H14	0.75547	0.61485	0.17471	0.0370*
H15	0.83205	0.83399	0.50409	0.0731*
H16	0.85087	0.89456	0.65260	0.0880*
H17	0.80091	0.66649	0.66727	0.0880*
H18	1.15854	0.87716	0.25215	0.0573*
H19	0.98215	0.89122	0.27749	0.0492*
H20	0.80749	0.32687	0.12361	0.0476*
H21	0.87342	0.07076	0.05187	0.0596*
H22	1.06001	0.06325	0.04705	0.0595*
H23	1.17889	0.32132	0.10662	0.0554*
H4A	0.30231	0.66219	0.06455	0.0357*
H5A	0.48422	0.70836	0.05181	0.0322*
H1	0.77397	0.90830	0.21914	0.0422*
H1A	0.35745	1.13504	0.04776	0.0514*
H2A	0.27353	0.64705	0.19442	0.0468*
H3A	0.60292	0.80917	0.16901	0.0454*
H1W	0.63673	0.99689	0.06452	0.0470*
H2W	0.63931	1.15129	0.14373	0.0470*
H3W	0.40983	0.20971	0.30620	0.0821*
H4W	0.40232	0.42921	0.28132	0.0821*
H5W	0.46750	0.55200	0.54059	0.1065*
H6W	0.42033	0.45741	0.44402	0.1065*
H7W	0.60939	0.35346	0.68583	0.1148*
H8W	0.58398	0.28514	0.58339	0.1148*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1A	0.0790 (9)	0.0202 (7)	0.0631 (8)	0.0022 (7)	0.0337 (7)	0.0031 (7)
O2A	0.1252 (12)	0.0379 (10)	0.0902 (10)	0.0119 (10)	0.0725 (7)	−0.0058 (9)
O3A	0.0470 (6)	0.0423 (9)	0.0626 (8)	0.0010 (7)	0.0336 (5)	0.0105 (7)
O4A	0.0356 (7)	0.0329 (8)	0.0641 (9)	−0.0038 (7)	0.0095 (7)	−0.0001 (8)
O5A	0.0589 (8)	0.0238 (7)	0.0471 (7)	−0.0010 (7)	0.0153 (6)	−0.0002 (7)
O6A	0.0603 (8)	0.0284 (8)	0.0550 (8)	0.0127 (7)	0.0163 (7)	−0.0011 (7)
O12	0.0441 (7)	0.0356 (8)	0.0505 (7)	0.0061 (7)	0.0199 (5)	0.0018 (7)
N1	0.0386 (7)	0.0385 (10)	0.0452 (8)	−0.0013 (8)	0.0205 (6)	−0.0009 (8)
N13	0.0442 (8)	0.0589 (13)	0.0665 (10)	0.0009 (9)	0.0321 (7)	0.0105 (10)
C1A	0.0385 (9)	0.0260 (10)	0.0591 (11)	0.0024 (8)	0.0245 (7)	−0.0019 (9)
C2A	0.0381 (9)	0.0231 (10)	0.0521 (10)	−0.0010 (8)	0.0228 (7)	0.0020 (8)
C3A	0.0323 (8)	0.0244 (10)	0.0447 (9)	−0.0020 (7)	0.0187 (6)	0.0026 (8)
C4A	0.0436 (9)	0.0264 (10)	0.0399 (9)	0.0039 (8)	0.0187 (7)	0.0007 (8)
C2	0.0519 (10)	0.0447 (14)	0.0504 (10)	0.0034 (10)	0.0304 (7)	−0.0013 (10)
C3	0.0838 (14)	0.0460 (15)	0.0439 (10)	−0.0090 (13)	0.0329 (9)	−0.0042 (10)
C4	0.0609 (13)	0.0528 (15)	0.0449 (11)	−0.0043 (12)	0.0170 (10)	0.0094 (11)
C5	0.0854 (17)	0.0385 (14)	0.0568 (13)	0.0026 (13)	0.0285 (11)	0.0103 (11)
C6	0.0692 (14)	0.0344 (13)	0.0582 (12)	−0.0097 (11)	0.0291 (10)	−0.0011 (10)
C7	0.0426 (10)	0.0586 (15)	0.0498 (11)	0.0027 (11)	0.0144 (9)	0.0122 (12)
C8	0.0329 (8)	0.0391 (12)	0.0486 (10)	0.0052 (8)	0.0205 (7)	0.0040 (9)
C9	0.0356 (8)	0.0368 (11)	0.0435 (9)	0.0036 (9)	0.0195 (7)	0.0030 (9)
C10	0.128 (3)	0.0491 (17)	0.0420 (12)	−0.0019 (17)	0.0258 (13)	−0.0126 (12)
C11	0.149 (3)	0.065 (2)	0.0493 (14)	−0.015 (2)	0.0294 (16)	−0.0208 (14)
C14	0.0509 (11)	0.0482 (15)	0.0826 (15)	−0.0085 (10)	0.0349 (10)	0.0016 (13)
C15	0.0488 (11)	0.0385 (13)	0.0685 (13)	−0.0050 (10)	0.0300 (9)	0.0008 (11)
C16	0.0360 (8)	0.0427 (12)	0.0428 (9)	0.0034 (9)	0.0184 (7)	0.0068 (9)
C17	0.0402 (9)	0.0462 (13)	0.0392 (9)	0.0015 (9)	0.0208 (7)	0.0042 (9)
C18	0.0463 (10)	0.0531 (14)	0.0472 (10)	−0.0013 (12)	0.0197 (8)	−0.0046 (11)
C19	0.0664 (14)	0.0574 (17)	0.0580 (13)	0.0007 (14)	0.0231 (10)	−0.0152 (13)
C20	0.0704 (13)	0.0605 (17)	0.0564 (12)	0.0136 (13)	0.0323 (9)	−0.0076 (12)
C21	0.0547 (10)	0.0677 (17)	0.0542 (11)	0.0173 (12)	0.0323 (8)	0.0044 (13)
C22	0.0439 (9)	0.0512 (14)	0.0439 (9)	0.0063 (10)	0.0243 (7)	0.0084 (10)
O1W	0.0591 (8)	0.0311 (8)	0.0488 (8)	0.0097 (7)	0.0131 (7)	−0.0016 (7)
O2W	0.1006 (14)	0.0712 (14)	0.0781 (12)	0.0076 (14)	0.0324 (10)	0.0021 (13)
O3W	0.136 (2)	0.100 (2)	0.0865 (14)	0.0033 (18)	0.0371 (14)	−0.0259 (15)
O4W	0.194 (3)	0.092 (2)	0.0579 (12)	−0.0093 (19)	0.0371 (14)	0.0161 (12)

Geometric parameters (Å, º)

O1A—C1A	1.310 (3)	C6—H10	1.020
O1A—H1A	0.980	C7—C8	1.524 (3)
O2A—C1A	1.206 (3)	C7—H11	1.020
O3A—C2A	1.401 (3)	C7—H12	1.020
O3A—H2A	0.980	C8—C9	1.527 (3)
O4A—C3A	1.413 (2)	C8—H13	1.020
O4A—H3A	0.980	C9—C16	1.534 (3)
O5A—C4A	1.268 (3)	C9—H14	1.020
O6A—C4A	1.232 (3)	C10—C11	1.247 (5)
O12—C9	1.421 (3)	C10—H15	1.020
O12—H1	0.980	C11—H16	1.020
N1—C2	1.510 (3)	C11—H17	1.020
N1—C6	1.516 (3)	C14—C15	1.406 (4)
N1—C8	1.515 (3)	C14—H18	1.020
N1—H2	0.980	C15—C16	1.372 (3)
N13—C14	1.310 (4)	C15—H19	1.020
N13—C22	1.362 (3)	C16—C17	1.424 (4)
C1A—C2A	1.524 (3)	C17—C18	1.418 (4)
C2A—C3A	1.521 (3)	C17—C22	1.424 (3)
C2A—H4A	1.020	C18—C19	1.371 (4)
C3A—C4A	1.532 (3)	C18—H20	1.020
C3A—H5A	1.020	C19—C20	1.404 (4)
C2—C3	1.526 (3)	C19—H21	1.020
C2—H3	1.020	C20—C21	1.351 (4)
C2—H4	1.020	C20—H22	1.020
C3—C4	1.543 (4)	C21—C22	1.425 (4)
C3—C10	1.514 (4)	C21—H23	1.020
C3—H5	1.020	O1W—H1W	0.980
C4—C5	1.535 (4)	O1W—H2W	0.980
C4—C7	1.527 (4)	O2W—H3W	0.980
C4—H6	1.020	O2W—H4W	0.980
C5—C6	1.518 (4)	O3W—H5W	0.980
C5—H7	1.020	O3W—H6W	0.980
C5—H8	1.020	O4W—H7W	0.980
C6—H9	1.020	O4W—H8W	0.980
O1A···O2A	2.226 (3)	C7···H8	2.636
O1A···C2A	2.354 (3)	C7···H13	2.084
O1A···C3A	2.833 (2)	C7···H15	3.037
O1A···H4A	2.602	C8···C16	2.481 (4)
O1A···H5A	2.474	C8···C17	3.152 (4)
O2A···O3A	2.724 (3)	C8···H2	2.052
O2A···C2A	2.410 (3)	C8···H4	2.657
O2A···H4A	3.012	C8···H8	2.881
O2A···H1A	2.229	C8···H9	2.715
O2A···H2A	2.779	C8···H11	2.099
O3A···O4A	2.793 (3)	C8···H12	2.099
O3A···C1A	2.421 (3)	C8···H14	2.107
O3A···C3A	2.375 (3)	C8···H20	2.901
O3A···C4A	2.880 (3)	C9···C15	2.511 (4)
O3A···O2W	2.826 (3)	C9···C17	2.586 (4)
O3A···H4A	1.978	C9···C18	3.042 (4)
O3A···H4W	1.854	C9···H2	2.569
O4A···O6A	2.625 (3)	C9···H4	2.943
O4A···O12	3.064 (3)	C9···H11	3.027
O4A···N1	2.936 (3)	C9···H12	2.617
O4A···C1A	2.918 (3)	C9···H13	2.008
O4A···C2A	2.415 (3)	C9···H19	2.679
O4A···C4A	2.405 (3)	C9···H20	2.724
O4A···C2	3.108 (3)	C9···H1	1.981
O4A···O1W	2.822 (3)	C9···H3A	2.900
O4A···H2	2.154	C10···H3	3.018
O4A···H3	3.065	C10···H4	2.477
O4A···H4	2.825	C10···H5	2.051
O4A···H14	2.649	C10···H6	2.687
O4A···H5A	1.993	C10···H12	2.711
O4A···H1	2.975	C10···H16	1.967
O4A···H1W	3.094	C10···H17	1.967
O5A···O6A	2.226 (2)	C11···H5	2.589
O5A···C2A	2.836 (3)	C11···H15	1.927
O5A···C3A	2.362 (3)	C14···C16	2.402 (4)
O5A···H4A	2.547	C14···C17	2.750 (4)
O5A···H5A	2.671	C14···C22	2.293 (4)
O6A···N1	2.784 (3)	C14···H19	2.112
O6A···C3A	2.392 (3)	C15···C17	2.404 (4)
O6A···C6	3.178 (3)	C15···C22	2.733 (4)
O6A···H2	1.928	C15···H12	3.187
O6A···H9	2.859	C15···H18	2.092
O6A···H14	3.119	C15···H1	2.977
O6A···H5A	2.995	C16···C18	2.514 (4)
O6A···H4W	3.179	C16···C22	2.430 (4)
O12···N1	3.026 (3)	C16···H11	3.026
O12···C2	3.075 (3)	C16···H12	3.080
O12···C7	2.946 (3)	C16···H13	2.505
O12···C8	2.418 (3)	C16···H14	2.112
O12···C15	2.715 (4)	C16···H19	2.081
O12···C16	2.424 (3)	C16···H20	2.751
O12···O1W	2.719 (2)	C16···H1	2.786
O12···H2	3.087	C17···C19	2.414 (4)
O12···H4	2.346	C17···C20	2.814 (4)
O12···H12	2.499	C17···C21	2.460 (4)
O12···H14	1.991	C17···H13	2.675
O12···H19	2.326	C17···H14	2.807
O12···H3A	2.555	C17···H20	2.121
N1···C3	2.476 (3)	C18···C20	2.422 (4)
N1···C4	2.545 (3)	C18···C21	2.798 (4)
N1···C5	2.468 (3)	C18···C22	2.440 (4)
N1···C7	2.450 (3)	C18···H13	2.542
N1···C9	2.536 (3)	C18···H14	2.887
N1···H3	2.086	C18···H21	2.070
N1···H4	2.086	C19···C21	2.386 (4)
N1···H5	3.027	C19···C22	2.780 (4)
N1···H8	3.018	C19···H20	2.079
N1···H9	2.092	C19···H22	2.108
N1···H10	2.092	C20···C22	2.413 (4)
N1···H12	2.953	C20···H21	2.099
N1···H13	2.104	C20···H23	2.057
N1···H14	2.694	C21···H22	2.060
N13···C15	2.394 (4)	C22···H23	2.124
N13···C16	2.812 (4)	O1W···H14	3.108
N13···C17	2.444 (3)	O1W···H5A	3.152
N13···C21	2.388 (4)	O1W···H1	1.812
N13···H18	2.005	O1W···H3A	1.852
N13···H23	2.588	O2W···O3W	2.830 (4)
C1A···C3A	2.488 (3)	O2W···H3	2.770
C1A···H4A	2.075	O2W···H10	2.623
C1A···H5A	2.637	O2W···H6W	1.965
C1A···H1A	1.814	O3W···O4W	2.839 (4)
C1A···H2A	2.657	O3W···H3	3.072
C1A···H3A	3.105	O3W···H4W	3.054
C2A···C4A	2.503 (3)	O3W···H8W	3.029
C2A···H5A	2.078	O4W···H5	2.635
C2A···H1A	3.170	O4W···H5W	1.966
C2A···H2A	1.894	O4W···H6W	2.897
C2A···H3A	2.998	H2···H3	2.303
C2A···H4W	3.051	H2···H4	2.401
C3A···H2	2.964	H2···H9	2.371
C3A···H4A	2.109	H2···H10	2.476
C3A···H2A	3.183	H2···H13	2.493
C3A···H3A	1.968	H2···H14	2.349
C4A···H2	2.745	H2···H3A	2.735
C4A···H4A	2.699	H3···H5	2.247
C4A···H5A	2.104	H3···H10	2.473
C4A···H3A	3.102	H3···H4W	2.904
C4A···H4W	3.101	H3···H6W	2.908
C2···C4	2.484 (4)	H4···H5	2.858
C2···C5	2.986 (4)	H4···H12	2.651
C2···C6	2.454 (4)	H4···H15	2.268
C2···C7	2.758 (4)	H4···H1	2.995
C2···C8	2.509 (4)	H4···H3A	3.001
C2···C10	2.498 (4)	H5···H6	2.510
C2···H2	2.036	H5···H7	2.480
C2···H5	2.113	H5···H10	2.710
C2···H10	2.575	H5···H15	2.928
C2···H12	2.849	H5···H17	2.423
C2···H15	2.679	H5···H8W	2.607
C3···C5	2.478 (4)	H6···H7	2.388
C3···C6	2.768 (4)	H6···H8	2.486
C3···C7	2.490 (4)	H6···H11	2.335
C3···C8	3.043 (4)	H6···H12	2.499
C3···C11	2.485 (4)	H6···H15	3.193
C3···H3	2.099	H7···H9	2.666
C3···H4	2.099	H7···H10	2.221
C3···H6	2.139	H8···H9	2.221
C3···H7	2.756	H8···H10	2.838
C3···H10	2.897	H8···H11	2.595
C3···H12	2.591	H8···H13	2.612
C3···H15	2.165	H9···H13	2.428
C3···H17	2.708	H10···H3W	2.857
C4···C6	2.485 (4)	H11···H13	2.221
C4···C8	2.486 (4)	H12···H13	2.853
C4···C10	2.537 (5)	H12···H15	2.340
C4···H4	3.028	H12···H19	2.955
C4···H5	2.108	H13···H14	2.363
C4···H7	2.108	H13···H20	2.200
C4···H8	2.108	H14···H20	2.334
C4···H10	3.035	H14···H1	2.162
C4···H11	2.101	H14···H3A	2.365
C4···H12	2.101	H15···H16	2.205
C4···H13	2.972	H15···H17	2.846
C4···H15	2.970	H16···H17	1.767
C5···C7	2.493 (4)	H18···H19	2.401
C5···C8	2.750 (4)	H19···H1	2.546
C5···H5	2.587	H20···H21	2.379
C5···H6	2.123	H21···H22	2.412
C5···H9	2.094	H22···H23	2.367
C5···H10	2.094	H4A···H5A	2.415
C5···H11	2.822	H4A···H2A	2.087
C5···H13	2.816	H5A···H3A	2.072
C6···C7	2.994 (4)	H5A···H1W	2.785
C6···C8	2.443 (4)	H1···H3A	2.205
C6···H2	2.096	H1···H1W	2.529
C6···H3	2.738	H1···H2W	2.451
C6···H5	2.900	H2A···H4W	2.341
C6···H7	2.093	H3A···H1W	2.188
C6···H8	2.093	H3A···H2W	2.504
C6···H13	2.534	H3W···H6W	2.674
C7···C9	2.575 (4)	H4W···H6W	2.385
C7···C10	3.118 (5)	H5W···H7W	2.759
C7···C16	3.066 (4)	H5W···H8W	2.365
C7···H4	2.893	H6W···H8W	2.756
C7···H6	2.103
C1A—O1A—H1A	103.8	C5—C6—H10	109.6
C2A—O3A—H2A	104.0	H9—C6—H10	109.5
C3A—O4A—H3A	109.3	C4—C7—C8	109.1 (2)
C9—O12—H1	109.8	C4—C7—H11	109.6
C2—N1—C6	108.4 (2)	C4—C7—H12	109.6
C2—N1—C8	112.1 (2)	C8—C7—H11	109.6
C2—N1—H2	107.8	C8—C7—H12	109.6
C6—N1—C8	107.4 (2)	H11—C7—H12	109.5
C6—N1—H2	112.5	N1—C8—C7	107.4 (2)
C8—N1—H2	108.8	N1—C8—C9	113.0 (2)
C14—N13—C22	118.2 (3)	N1—C8—H13	110.7
O1A—C1A—O2A	124.3 (2)	C7—C8—C9	115.1 (2)
O1A—C1A—C2A	112.1 (2)	C7—C8—H13	108.3
O2A—C1A—C2A	123.5 (2)	C9—C8—H13	102.2
O3A—C2A—C1A	111.7 (2)	O12—C9—C8	110.1 (2)
O3A—C2A—C3A	108.7 (2)	O12—C9—C16	110.2 (2)
O3A—C2A—H4A	108.5	O12—C9—H14	108.2
C1A—C2A—C3A	109.6 (2)	C8—C9—C16	108.3 (2)
C1A—C2A—H4A	107.6	C8—C9—H14	110.0
C3A—C2A—H4A	110.7	C16—C9—H14	109.9
O4A—C3A—C2A	110.8 (2)	C3—C10—C11	128.0 (3)
O4A—C3A—C4A	109.4 (2)	C3—C10—H15	116.0
O4A—C3A—H5A	108.9	C11—C10—H15	116.0
C2A—C3A—C4A	110.2 (2)	C10—C11—H16	120.0
C2A—C3A—H5A	108.1	C10—C11—H17	120.0
C4A—C3A—H5A	109.4	H16—C11—H17	120.0
O5A—C4A—O6A	125.8 (2)	N13—C14—C15	123.6 (3)
O5A—C4A—C3A	114.7 (2)	N13—C14—H18	118.2
O6A—C4A—C3A	119.5 (2)	C15—C14—H18	118.2
N1—C2—C3	109.3 (2)	C14—C15—C16	119.6 (3)
N1—C2—H3	109.5	C14—C15—H19	120.2
N1—C2—H4	109.5	C16—C15—H19	120.2
C3—C2—H3	109.5	C9—C16—C15	119.5 (2)
C3—C2—H4	109.5	C9—C16—C17	121.9 (2)
H3—C2—H4	109.5	C15—C16—C17	118.6 (2)
C2—C3—C4	108.1 (2)	C16—C17—C18	124.5 (2)
C2—C3—C10	110.5 (2)	C16—C17—C22	117.1 (2)
C2—C3—H5	110.7	C18—C17—C22	118.4 (2)
C4—C3—C10	112.2 (3)	C17—C18—C19	119.9 (3)
C4—C3—H5	109.0	C17—C18—H20	120.0
C10—C3—H5	106.5	C19—C18—H20	120.0
C3—C4—C5	107.2 (2)	C18—C19—C20	121.6 (3)
C3—C4—C7	108.4 (2)	C18—C19—H21	119.2
C3—C4—H6	111.5	C20—C19—H21	119.2
C5—C4—C7	109.1 (2)	C19—C20—C21	120.0 (3)
C5—C4—H6	110.8	C19—C20—H22	120.0
C7—C4—H6	109.7	C21—C20—H22	120.0
C4—C5—C6	109.0 (2)	C20—C21—C22	120.7 (3)
C4—C5—H7	109.6	C20—C21—H23	119.7
C4—C5—H8	109.6	C22—C21—H23	119.7
C6—C5—H7	109.6	N13—C22—C17	122.6 (2)
C6—C5—H8	109.6	N13—C22—C21	118.0 (2)
H7—C5—H8	109.5	C17—C22—C21	119.4 (2)
N1—C6—C5	108.8 (2)	H1W—O1W—H2W	109.6
N1—C6—H9	109.6	H3W—O2W—H4W	108.1
N1—C6—H10	109.6	H5W—O3W—H6W	103.7
C5—C6—H9	109.6	H7W—O4W—H8W	104.1
H1A—O1A—C1A—O2A	−7.8	C3—C4—C5—H8	169.4
H1A—O1A—C1A—C2A	172.0	C7—C4—C5—C6	−67.8 (3)
H2A—O3A—C2A—C1A	75.0	C7—C4—C5—H7	172.3
H2A—O3A—C2A—C3A	−163.9	C7—C4—C5—H8	52.2
H2A—O3A—C2A—H4A	−43.5	H6—C4—C5—C6	171.3
H3A—O4A—C3A—C2A	−110.7	H6—C4—C5—H7	51.4
H3A—O4A—C3A—C4A	127.6	H6—C4—C5—H8	−68.7
H3A—O4A—C3A—H5A	8.0	C3—C4—C7—C8	−72.4 (3)
H1—O12—C9—C8	−158.6	C3—C4—C7—H11	167.6
H1—O12—C9—C16	81.9	C3—C4—C7—H12	47.5
H1—O12—C9—H14	−38.3	C5—C4—C7—C8	44.0 (3)
C6—N1—C2—C3	49.5 (3)	C5—C4—C7—H11	−75.9
C6—N1—C2—H3	−70.5	C5—C4—C7—H12	164.0
C6—N1—C2—H4	169.4	H6—C4—C7—C8	165.6
C8—N1—C2—C3	−68.9 (2)	H6—C4—C7—H11	45.7
C8—N1—C2—H3	171.2	H6—C4—C7—H12	−74.5
C8—N1—C2—H4	51.1	C4—C5—C6—N1	17.2 (3)
H2—N1—C2—C3	171.4	C4—C5—C6—H9	137.1
H2—N1—C2—H3	51.5	C4—C5—C6—H10	−102.7
H2—N1—C2—H4	−68.6	H7—C5—C6—N1	137.2
C2—N1—C6—C5	−70.7 (3)	H7—C5—C6—H9	−102.9
C2—N1—C6—H9	169.4	H7—C5—C6—H10	17.3
C2—N1—C6—H10	49.3	H8—C5—C6—N1	−102.7
C8—N1—C6—C5	50.6 (3)	H8—C5—C6—H9	17.2
C8—N1—C6—H9	−69.3	H8—C5—C6—H10	137.4
C8—N1—C6—H10	170.5	C4—C7—C8—N1	23.1 (3)
H2—N1—C6—C5	170.3	C4—C7—C8—C9	149.9 (2)
H2—N1—C6—H9	50.4	C4—C7—C8—H13	−96.5
H2—N1—C6—H10	−69.8	H11—C7—C8—N1	143.1
C2—N1—C8—C7	44.3 (3)	H11—C7—C8—C9	−90.2
C2—N1—C8—C9	−83.7 (2)	H11—C7—C8—H13	23.5
C2—N1—C8—H13	162.4	H12—C7—C8—N1	−96.8
C6—N1—C8—C7	−74.6 (2)	H12—C7—C8—C9	29.9
C6—N1—C8—C9	157.4 (2)	H12—C7—C8—H13	143.6
C6—N1—C8—H13	43.5	N1—C8—C9—O12	68.5 (2)
H2—N1—C8—C7	163.4	N1—C8—C9—C16	−170.9 (2)
H2—N1—C8—C9	35.4	N1—C8—C9—H14	−50.6
H2—N1—C8—H13	−78.5	C7—C8—C9—O12	−55.4 (3)
C22—N13—C14—C15	1.6 (4)	C7—C8—C9—C16	65.3 (3)
C22—N13—C14—H18	−178.4	C7—C8—C9—H14	−174.5
C14—N13—C22—C17	1.0 (4)	H13—C8—C9—O12	−172.5
C14—N13—C22—C21	−178.7 (3)	H13—C8—C9—C16	−51.9
O1A—C1A—C2A—O3A	177.7 (2)	H13—C8—C9—H14	68.3
O1A—C1A—C2A—C3A	57.1 (2)	O12—C9—C16—C15	11.8 (3)
O1A—C1A—C2A—H4A	−63.3	O12—C9—C16—C17	−170.9 (2)
O2A—C1A—C2A—O3A	−2.6 (3)	C8—C9—C16—C15	−108.8 (3)
O2A—C1A—C2A—C3A	−123.1 (3)	C8—C9—C16—C17	68.6 (3)
O2A—C1A—C2A—H4A	116.4	H14—C9—C16—C15	130.9
O3A—C2A—C3A—O4A	−59.0 (2)	H14—C9—C16—C17	−51.7
O3A—C2A—C3A—C4A	62.3 (2)	C3—C10—C11—H16	180.0
O3A—C2A—C3A—H5A	−178.2	C3—C10—C11—H17	0.0
C1A—C2A—C3A—O4A	63.3 (2)	H15—C10—C11—H16	0.0
C1A—C2A—C3A—C4A	−175.4 (2)	H15—C10—C11—H17	180.0
C1A—C2A—C3A—H5A	−55.9	N13—C14—C15—C16	−1.2 (4)
H4A—C2A—C3A—O4A	−178.1	N13—C14—C15—H19	178.8
H4A—C2A—C3A—C4A	−56.9	H18—C14—C15—C16	178.9
H4A—C2A—C3A—H5A	62.7	H18—C14—C15—H19	−1.1
O4A—C3A—C4A—O5A	174.3 (2)	C14—C15—C16—C9	175.5 (2)
O4A—C3A—C4A—O6A	−7.7 (3)	C14—C15—C16—C17	−2.0 (4)
C2A—C3A—C4A—O5A	52.3 (3)	H19—C15—C16—C9	−4.5
C2A—C3A—C4A—O6A	−129.7 (2)	H19—C15—C16—C17	178.0
H5A—C3A—C4A—O5A	−66.4	C9—C16—C17—C18	5.8 (4)
H5A—C3A—C4A—O6A	111.6	C9—C16—C17—C22	−173.1 (2)
N1—C2—C3—C4	17.9 (3)	C15—C16—C17—C18	−176.8 (2)
N1—C2—C3—C10	141.0 (2)	C15—C16—C17—C22	4.3 (3)
N1—C2—C3—H5	−101.3	C16—C17—C18—C19	−176.0 (3)
H3—C2—C3—C4	137.9	C16—C17—C18—H20	4.0
H3—C2—C3—C10	−99.0	C22—C17—C18—C19	2.9 (4)
H3—C2—C3—H5	18.6	C22—C17—C18—H20	−177.1
H4—C2—C3—C4	−102.1	C16—C17—C22—N13	−4.0 (4)
H4—C2—C3—C10	21.0	C16—C17—C22—C21	175.7 (2)
H4—C2—C3—H5	138.7	C18—C17—C22—N13	177.1 (2)
C2—C3—C4—C5	−70.2 (3)	C18—C17—C22—C21	−3.2 (4)
C2—C3—C4—C7	47.5 (3)	C17—C18—C19—C20	−0.3 (4)
C2—C3—C4—H6	168.4	C17—C18—C19—H21	179.7
C10—C3—C4—C5	167.8 (3)	H20—C18—C19—C20	179.7
C10—C3—C4—C7	−74.6 (3)	H20—C18—C19—H21	−0.3
C10—C3—C4—H6	46.3	C18—C19—C20—C21	−2.0 (5)
H5—C3—C4—C5	50.2	C18—C19—C20—H22	178.0
H5—C3—C4—C7	167.8	H21—C19—C20—C21	178.0
H5—C3—C4—H6	−71.3	H21—C19—C20—H22	−2.0
C2—C3—C10—C11	137.6 (4)	C19—C20—C21—C22	1.6 (4)
C2—C3—C10—H15	−42.4	C19—C20—C21—H23	−178.4
C4—C3—C10—C11	−101.7 (4)	H22—C20—C21—C22	−178.4
C4—C3—C10—H15	78.3	H22—C20—C21—H23	1.6
H5—C3—C10—C11	17.4	C20—C21—C22—N13	−179.3 (3)
H5—C3—C10—H15	−162.6	C20—C21—C22—C17	1.0 (4)
C3—C4—C5—C6	49.4 (3)	H23—C21—C22—N13	0.7
C3—C4—C5—H7	−70.5	H23—C21—C22—C17	−179.0

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O4A—H3A···O12	0.98	2.56	3.064 (3)	112
O4A—H3A···O1W	0.98	1.85	2.822 (3)	170
O12—H1···O1W	0.98	1.81	2.719 (2)	152
N1—H2···O4A	0.98	2.15	2.936 (3)	136
N1—H2···O6A	0.98	1.93	2.784 (3)	144
O2W—H4W···O3A	0.98	1.85	2.826 (3)	171
O3W—H5W···O4W	0.98	1.97	2.839 (4)	147
O3W—H6W···O2W	0.98	1.97	2.831 (4)	146
O2W—H3W···O4W^i	0.98	2.43	3.191 (4)	134
O4W—H7W···O2A^i	0.98	2.23	2.943 (4)	129
O4W—H7W···O3A^i	0.98	2.22	3.141 (3)	156
O4W—H8W···O3W^i	0.98	1.71	2.691 (4)	177
O2W—H3W···O2A^ii	0.98	2.26	3.136 (3)	148
O1W—H1W···O5A^iii	0.98	1.78	2.716 (3)	158
O1W—H2W···O6A^iv	0.98	1.76	2.705 (3)	162
O1A—H1A···O5A^iv	0.98	1.68	2.556 (2)	146
O3A—H2A···N13^v	0.98	1.73	2.693 (3)	169

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