4-Acetamido-3,3,5,5-[²H₄]-2,2,6,6-tetra­([²H₃]methyl)piperidin-1-yloxyl 0.33-hydrate

The asymmetric unit of the title compound, C₁₁H₅D₁₆N₂O₂·0.33H₂O, is formed by three crystallographically independent piperidin-1-yloxyl mol­ecules and a mol­ecule of water. The mol­ecules are crosslinked by nine hydrogen bonds into layers parallel with the ac plane. The water mol­ecule contributes to the stability of the low-symmetry arrangement by four hydrogen bonds.

S1. Comment

Recent advances in electron spin resonance (ESR) technology [i.e. extension of ESR to high fields and very high frequencies (HF-ESR), development of two-dimensional Fourier transform ESR imaging with very short pulsed field gradients] bring very powerful experimental techniques to bear for the desired analysis of the nanosecond-scale dynamics of macromolecular systems (LaConte et al., 2002). The nitroxide radical 2,2,6,6-tetramethylpiperidin-1-yloxyl is a favourite spin label for site-directed mutagenesis of proteins, with the aim of following local motions in macromolecules. Intact interaction of the magnetic moment of an unpaired electron with the nuclear magnetic moment of nitrogen alone gives, in principle, a simple and sharp ESR spectrum. However, magnetic moments of hydrogen nuclei of methyl groups closely surrounding the nitroxy group invoke undesired hyperfine interactions. This effect can be suppressed by deuteration of the piperidine ring, because of thesmaller magnetic moment of the deuterium nucleus in comparison with a proton. It significantly simplifies the analysis of both fast- and slow-motion spectra. The method has broad utilization in biological (Bennati & Prisner, 2005), physicochemical (Mizuochi et al., 1997) or synthetic (Bossmann et al., 1996) studies.

The title compound, (I), belongs to this group of stable radicals and has been used in our institute as a paramagnetic tracer for electron spin resonance imaging (ESRI) for monitoring diffusion processes, with numerous practical applications such as drug delivery systems and transport across membranes. It has also contributed significantly to understanding polymer dynamics (Pilař et al., 1999).

The compound crystallizes in the centrosymmetric space group P1. Three independent molecules, A, B and C (the letters are appended to the atom labels), and one molecule of water were refined in the asymmetric unit. An overall view of the first molecule, with displacement ellipsoids and labelling scheme, is shown in Fig. 1. The main geometric features of all molecules are given in Tables 2 and 3.

The main part of the compound, the piperidine ring, adopts a chair conformation, with angles between the planes C2/C3/C5/C6 and C2/N1/C6 of 31.7 (1), 30.6 (1) and 33.4 (1)° for molecules A, B and C, respectively, and between the planes C2/C3/C5/C6 and C3/C4/C5 of 52.2 (1), 53.9 (1) and 52.5 (1)° for molecules A, B and C, respectively. This is in agreement with piperidine ring puckering observed in another structure with a methacrylamide substituent (Duskova et al., 2006) and fits well with the average geometry of piperidine rings resulting from 114 hits found in the Cambridge Structural Database (Version 5.26; Allen, 2002). The linked acetylamine chain (CH₃CONH–) occupies an equatorial position with respect to the ring and is almost ideally planar in all three molecules.

In order to elucidate the influence of crystal packing on molecular conformation, the symmetrically independent molecules A, B and C were superimposed on all the non-H atoms using the program package CCP4 (Collaborative Computational Project, Number 4, 1994). The resulting r.m.s. deviations were 0.055, 0.073 and 0.071 Å for A–B, A–C and B–C aligments of all non-H atoms, respectively. The largest deviation, the O12A···O12C distance of 0.264 Å, corresponding to about 9° deviation in the C═O bond direction, is caused by different directions of hydrogen bonds formed by the carbonyl atom O12 (Fig. 2). This is in accord with different values of the C3—C4—N10—C11 torsion angle of 91.0 (2), 94.4 (2) and 99.8 (2)° for molecules A, B and C, respectively. Other differences are observed in the conformations of the methyl groups of C8, C9 and C13. The angular differences between the extreme cases of orientations of the methyl groups (Fig. 2) are ca 24.1, 9.7 and 7.7° for the methyl groups of atoms C13, C9 and C8, respectively. This is probably caused by stress induced by the hydrogen bonds. Atoms O12 and N10 of molecules A, B and C are involved in strong hydrogen bonding and the H atoms on atoms C13 and C9 of molecule C and on C8 of molecule A participate in weak intermolecular interactions. Surprisingly, only the single oxygen radical of molecule C is involved in intermolecular interactions defining the arrangement of the molecules in the crystal structure. It forms a strong hydrogen contact to a water molecule and a weak one to methyl atom C13 of molecule C. The oxygen radicals O7 of the other two molecules (A and B) do not form any hydrogen bonds in the crystal structure. This behaviour is different from that of an analogous compound, 3,3,5,5-[²H₄]-4-methacrylamido-2,2,6,6-tetra([²H₃]methyl)piperidin-1-yloxyl (Duskova et al., 2006), where the oxygen radical plays an essential role in the formation of a chain of molecules.

The mobilities of D atoms surrounding the nitroxyl group are significantly restricted, so that one C—D bond of each deuterated methyl group tends to orient parallel to the N—O bond (antiparallel dipoles). However, this cannot be fully satisfied, due to the puckering of the piperidine ring. Considering molecule A, the nitroxy groups is directed between two methyl groups, resulting in a C8···C14 distance of 4.679 (2) Å, compared with a distance of 3.517 (2) Å for the opposite pair of atoms, C9 and C15. Viewed in the direction of the nitroxide bond, the methyl groups form a trapezoid with an approximate mirror symmetry. In spite of this, the deuterated methyl groups are rotated so that the D atoms are divided into three groups with almost identical distances to the oxygen radical. The closest four D atoms in all three molecules have distances to the nitroxy atom O7 in the range 2.48–2.71 Å, the next four in the range 2.95–3.44 Å, and the last four methyl D atoms are at distances in the range 3.67–3.82 Å. The axial D atoms on C3 and C5 have identical distances of 3.90–3.93 Å. Irrespective of the steric hindrances imposed by the 2,2,6,6 methyl groups, the nitroxide radical forms two hydrogen bonds, to a solvent water molecule and to a methyl group of the neighboring antiparallel-oriented molecule.

Molecules A, B and C are joined via one weak and four strong hydrogen bonds, with hydrogen–acceptor distances N10A—H···O12B = 2.01 (2), N10C—H···O12A = 1.97 (2), N10B—H···O(water) = 2.06 (2), O12C···H—O(water) = 1.94 (3) and C13C—H···O12A = 2.65 Å. In this way, chains of molecules ···B···A···C···O···B··· are generated parallel to the c direction (Fig. 3). Another set of three hydrogen bonds connects these chains into layers parallel with ab. These involve hydrogen bonds C13C—H···O7C = 2.65, O(water)—H···O7C = 2.00 (3) and C9C—H···O(water) = 2.61 (2) Å (Fig. 3).

A very weak C—H···O contact of 2.57 (2) Å between molecules A and B connects two neighbouring layers, forming bilayers in the b direction. Neighbouring bilayers related by a centre of symmetry interact only via van der Waals contacts between pairs of molecules A–B and B–A, i.e. by weak polar interactions of atom C5B and methyl groups C14B and C15B with atom O7A, and also of methyl groups C14A and C15A with amino group N10B.

S2. Experimental

4-Acetamido-3,3,5,5-[²H₄]-2,2,6,6-tetra([²H₃]methyl)piperidine (1 g), sodium ethylenediaminetetraacetate (0.1 g) and sodium tungstate dihydrate (0.1 g) were dissolved in methanol (5 ml) and water (3 ml) with 30% hydrogen peroxide (1.7 ml). The mixture was kept at laboratory temperature for 4 d. After the methanol had evaporated, the product was recrystallized from a dichloromethane–hexane mixture (1:1).

S3. Refinement

Two strong reflections, 001 and 010, were omitted from the refinement because the beam stop influenced the accuracy of their measurement. The D atoms of the piperidine ring were refined as H atoms. First, all H atoms were added in their ideal geometric positions, as implemented in SHELXL97 (Sheldrick, 1997). In subsequent steps, all constraints for D atoms were released for free refinement, including their isotropic displacement parameters. The H atoms on atom C13 in all three molecules were refined as a rigid group, with U_iso(H) = 1.5U_eq(C). The positions of the H atoms of a single water molecule were clearly identified in the electron-density map and were refined freely with isotropic displacement parameters.

Computing details

Data collection: COLLECT (Nonius, 1998) and DENZO (Otwinowski & Minor, 1997); cell refinement: COLLECT and DENZO; data reduction: COLLECT and DENZO; program(s) used to solve structure: SHELXS97 (Sheldrick, 1990); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: DIAMOND (Brandenburg & Putz, 2005); software used to prepare material for publication: SHELXL97 and DIAMOND.

Figures

	Fig. 1. The atom-numbering scheme for molecule A. The interplanar angles characterizing the chair conformation of the piperidine ring are clarified. Displacement ellipsoids are drawn at the 50% probability level. An identical numbering scheme is applied for molecules B and C. For the purpose of this figure, the suffixes of the atom names identifying individual molecules have been omitted.
	Fig. 2. Overlap of A (red), B (blue) and C (yellow) molecules. Significant differences in the conformations of the methyl groups are correlated with rotation of the carbonyl group C11═O12. H and D atoms of the most flexible methyl groups are drawn as spheres.
	Fig. 3. Part of the crystal structure of (I), showing the molecular packing. Symmetrically independent molecules are marked by capital letters and by their respective symmetry operators. Dashed lines indicate hydrogen bonds which are responsible for formation of the layer parallel to ac.

4-Acetamido-3,3,5,5-[²H₄]-2,2,6,6-tetra([²H₃]methyl)piperidin-1-yloxyl 0.33-hydrate

Crystal data

C11H5D16N2O2·0.33H2O	Z = 6
Mr = 235.34	F(000) = 722
TriclinicP1	Dx = 1.266 Mg m^−3
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71070 Å
a = 10.6940 (3) Å	Cell parameters from 36138 reflections
b = 11.7120 (3) Å	θ = 1.0–27.5°
c = 16.0480 (5) Å	µ = 0.08 mm^−1
α = 109.351 (1)°	T = 150 K
β = 101.678 (1)°	Irregular, red
γ = 90.325 (1)°	0.2 × 0.1 × 0.1 mm
V = 1851.41 (9) Å^3

Data collection

Nonius KappaCCD area-detector diffractometer	6918 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.055
Graphite monochromator	θmax = 27.5°, θmin = 1.9°
φ and ω scans	h = 0→13
35956 measured reflections	k = −15→15
8420 independent reflections	l = −20→20

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.048	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.140	H atoms treated by a mixture of independent and constrained refinement
S = 1.05	w = 1/[σ^2(Fo^2) + (0.1025P)^2 + 1.9749P] where P = (Fo^2 + 2Fc^2)/3
8420 reflections	(Δ/σ)max = 0.001
663 parameters	Δρmax = 0.29 e Å^−3
0 restraints	Δρmin = −0.28 e Å^−3

Special details

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F² against all reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

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

	x	y	z	Uiso*/Ueq
N1A	−0.14768 (11)	−0.19819 (11)	0.11928 (8)	0.0217 (3)
C2A	−0.10408 (13)	−0.31362 (13)	0.13216 (10)	0.0223 (3)
C3A	0.02115 (14)	−0.34365 (13)	0.10016 (11)	0.0227 (3)
H1A	0.0028 (16)	−0.3762 (15)	0.0342 (12)	0.020 (4)*
H2A	0.0545 (17)	−0.4107 (16)	0.1206 (12)	0.026 (4)*
C4A	0.12033 (14)	−0.23576 (13)	0.13106 (10)	0.0211 (3)
H3A	0.1490 (16)	−0.2046 (15)	0.2005 (11)	0.019 (4)*
C5A	0.06178 (14)	−0.13905 (14)	0.09486 (10)	0.0228 (3)
H4A	0.1238 (19)	−0.0660 (19)	0.1114 (13)	0.038 (5)*
H5A	0.0411 (15)	−0.1745 (14)	0.0290 (11)	0.017 (4)*
C6A	−0.05908 (14)	−0.09311 (13)	0.12814 (10)	0.0213 (3)
O7A	−0.26091 (10)	−0.17264 (10)	0.13163 (8)	0.0314 (3)
C8A	−0.20714 (16)	−0.41538 (15)	0.07429 (14)	0.0317 (4)
H6A	−0.1809 (18)	−0.4937 (18)	0.0830 (13)	0.034 (5)*
H7A	−0.2207 (19)	−0.4242 (18)	0.0113 (15)	0.037 (5)*
H8A	−0.289 (2)	−0.4010 (19)	0.0919 (14)	0.041 (5)*
C9A	−0.08954 (17)	−0.30095 (17)	0.23181 (12)	0.0307 (4)
H9A	−0.0684 (18)	−0.3804 (18)	0.2408 (13)	0.032 (5)*
H10A	−0.026 (2)	−0.2390 (19)	0.2714 (14)	0.037 (5)*
H11A	−0.172 (2)	−0.2813 (18)	0.2503 (13)	0.038 (5)*
N10A	0.23482 (12)	−0.27244 (12)	0.09560 (9)	0.0217 (3)
H18A	0.2357 (17)	−0.2770 (16)	0.0410 (13)	0.026 (4)*
C11A	0.33513 (14)	−0.31190 (13)	0.14028 (10)	0.0231 (3)
O12A	0.33929 (11)	−0.31779 (12)	0.21619 (8)	0.0335 (3)
C13A	0.44402 (16)	−0.34666 (16)	0.09277 (13)	0.0305 (4)
H19A	0.4666	−0.4262	0.0917	0.039 (5)*
H20A	0.4186	−0.3465	0.0319	0.051 (6)*
H21A	0.5168	−0.2892	0.1244	0.052 (6)*
C14A	−0.12905 (16)	−0.02484 (15)	0.06853 (11)	0.0267 (3)
H12A	−0.1523 (18)	−0.0767 (17)	0.0052 (13)	0.029 (5)*
H13A	−0.2046 (19)	0.0057 (18)	0.0901 (13)	0.035 (5)*
H14A	−0.0683 (19)	0.0469 (18)	0.0745 (13)	0.035 (5)*
C15A	−0.02582 (16)	−0.00846 (15)	0.22706 (11)	0.0276 (3)
H15A	−0.1054 (18)	0.0210 (16)	0.2508 (12)	0.029 (5)*
H16A	0.0213 (18)	−0.0488 (17)	0.2663 (13)	0.033 (5)*
H17A	0.0263 (19)	0.0634 (19)	0.2316 (13)	0.036 (5)*
N1B	0.61828 (12)	−0.18040 (11)	0.78811 (9)	0.0244 (3)
C2B	0.58367 (14)	−0.29879 (14)	0.79719 (11)	0.0260 (3)
C3B	0.43801 (14)	−0.32692 (14)	0.77012 (11)	0.0241 (3)
H1B	0.4099 (17)	−0.3516 (16)	0.7065 (13)	0.023 (4)*
H2B	0.4176 (18)	−0.3931 (17)	0.7905 (13)	0.030 (5)*
C4B	0.36358 (13)	−0.21897 (13)	0.80999 (10)	0.0207 (3)
H3B	0.3861 (16)	−0.1936 (15)	0.8760 (12)	0.019 (4)*
C5B	0.39503 (14)	−0.11894 (14)	0.77470 (11)	0.0234 (3)
H4B	0.3452 (18)	−0.0482 (18)	0.7979 (13)	0.032 (5)*
H5B	0.3695 (17)	−0.1496 (16)	0.7077 (13)	0.025 (4)*
C6B	0.53724 (14)	−0.07459 (13)	0.80326 (10)	0.0213 (3)
O7B	0.73880 (11)	−0.15473 (11)	0.79702 (9)	0.0372 (3)
C8B	0.64581 (18)	−0.39721 (16)	0.73294 (16)	0.0399 (5)
H6B	0.614 (2)	−0.399 (2)	0.6741 (16)	0.045 (6)*
H7B	0.627 (2)	−0.473 (2)	0.7412 (14)	0.042 (5)*
H8B	0.743 (2)	−0.379 (2)	0.7467 (15)	0.051 (6)*
C9B	0.63577 (18)	−0.29397 (18)	0.89417 (14)	0.0379 (4)
H9B	0.595 (2)	−0.239 (2)	0.9377 (14)	0.039 (5)*
H10B	0.728 (2)	−0.276 (2)	0.9083 (15)	0.052 (6)*
H11B	0.618 (2)	−0.377 (2)	0.8990 (15)	0.046 (6)*
N10B	0.22627 (12)	−0.25405 (12)	0.78331 (9)	0.0226 (3)
H18B	0.1862 (18)	−0.2563 (16)	0.7330 (13)	0.025 (4)*
C11B	0.16324 (14)	−0.28998 (13)	0.83490 (10)	0.0230 (3)
O12B	0.21542 (11)	−0.29206 (11)	0.91060 (8)	0.0326 (3)
C13B	0.02255 (15)	−0.32707 (16)	0.79651 (12)	0.0314 (4)
H19B	0.0047	−0.3451	0.7322	0.047*
H20B	−0.0266	−0.2619	0.8233	0.047*
H21B	−0.0001	−0.3978	0.8095	0.047*
C14B	0.56499 (17)	−0.00369 (16)	0.74389 (12)	0.0295 (3)
H12B	0.5125 (18)	0.0686 (18)	0.7534 (13)	0.033 (5)*
H13B	0.5424 (18)	−0.0534 (18)	0.6792 (14)	0.033 (5)*
H14B	0.654 (2)	0.0292 (19)	0.7610 (14)	0.044 (6)*
C15B	0.57383 (16)	0.00604 (15)	0.90299 (11)	0.0265 (3)
H15B	0.5233 (19)	0.0784 (18)	0.9121 (13)	0.036 (5)*
H16B	0.668 (2)	0.0369 (18)	0.9201 (13)	0.035 (5)*
H17B	0.5576 (17)	−0.0379 (17)	0.9399 (13)	0.029 (5)*
N1C	0.81996 (11)	−0.20859 (11)	0.46042 (8)	0.0214 (3)
C2C	0.77299 (14)	−0.32254 (14)	0.47107 (11)	0.0253 (3)
C3C	0.63028 (14)	−0.35161 (14)	0.42626 (11)	0.0261 (3)
H1C	0.6199 (17)	−0.3813 (16)	0.3579 (12)	0.024 (4)*
H2C	0.5994 (17)	−0.4142 (17)	0.4446 (12)	0.027 (4)*
C4C	0.55080 (14)	−0.24249 (14)	0.45116 (10)	0.0231 (3)
H3C	0.5541 (16)	−0.2119 (16)	0.5162 (12)	0.023 (4)*
C5C	0.60171 (14)	−0.14547 (14)	0.42052 (11)	0.0240 (3)
H4C	0.5541 (18)	−0.0726 (18)	0.4334 (12)	0.031 (5)*
H5C	0.5929 (16)	−0.1783 (15)	0.3523 (12)	0.022 (4)*
C6C	0.74258 (14)	−0.10166 (13)	0.46341 (10)	0.0224 (3)
O7C	0.94257 (10)	−0.18538 (10)	0.47978 (8)	0.0299 (3)
C8C	0.84757 (18)	−0.42541 (16)	0.42266 (15)	0.0372 (4)
H6C	0.816 (2)	−0.500 (2)	0.4246 (14)	0.045 (6)*
H7C	0.936 (2)	−0.413 (2)	0.4529 (16)	0.053 (6)*
H8C	0.8412 (19)	−0.4317 (18)	0.3562 (14)	0.035 (5)*
C9C	0.79691 (17)	−0.3069 (2)	0.57180 (13)	0.0367 (4)
H9C	0.744 (2)	−0.249 (2)	0.6054 (15)	0.048 (6)*
H10C	0.890 (2)	−0.277 (2)	0.6028 (15)	0.051 (6)*
H11C	0.783 (2)	−0.385 (2)	0.5754 (15)	0.047 (6)*
N10C	0.41633 (12)	−0.27733 (12)	0.40567 (9)	0.0241 (3)
H18C	0.3961 (18)	−0.2845 (17)	0.3474 (14)	0.032 (5)*
C11C	0.32679 (14)	−0.30199 (14)	0.44554 (10)	0.0255 (3)
O12C	0.34864 (11)	−0.29327 (13)	0.52631 (8)	0.0398 (3)
C13C	0.19437 (15)	−0.34011 (17)	0.38599 (12)	0.0304 (3)
H19C	0.1369	−0.2799	0.4074	0.053 (6)*
H20C	0.1645	−0.4166	0.3877	0.045 (6)*
H21C	0.1972	−0.3480	0.3249	0.044 (6)*
C14C	0.79241 (16)	−0.03321 (16)	0.40917 (13)	0.0298 (3)
H12C	0.743 (2)	0.036 (2)	0.4092 (14)	0.043 (5)*
H13C	0.7862 (17)	−0.0847 (17)	0.3467 (14)	0.029 (5)*
H14C	0.881 (2)	−0.0033 (18)	0.4349 (14)	0.037 (5)*
C15C	0.76135 (17)	−0.01808 (17)	0.56222 (12)	0.0327 (4)
H15C	0.715 (2)	0.056 (2)	0.5659 (14)	0.043 (6)*
H16C	0.856 (2)	0.0088 (19)	0.5860 (14)	0.044 (6)*
H17C	0.7333 (17)	−0.0582 (17)	0.5977 (13)	0.028 (5)*
O1	0.13294 (12)	−0.26369 (12)	0.60071 (8)	0.0307 (3)
H1	0.194 (2)	−0.275 (2)	0.5746 (16)	0.049 (6)*
H2	0.075 (2)	−0.234 (2)	0.5666 (17)	0.057 (7)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
N1A	0.0150 (6)	0.0228 (6)	0.0280 (6)	0.0030 (5)	0.0036 (5)	0.0103 (5)
C2A	0.0175 (7)	0.0218 (7)	0.0295 (8)	0.0034 (5)	0.0040 (6)	0.0120 (6)
C3A	0.0210 (7)	0.0215 (7)	0.0270 (8)	0.0035 (6)	0.0065 (6)	0.0092 (6)
C4A	0.0170 (7)	0.0261 (7)	0.0209 (7)	0.0031 (5)	0.0044 (5)	0.0085 (6)
C5A	0.0215 (7)	0.0243 (7)	0.0248 (8)	0.0022 (6)	0.0059 (6)	0.0107 (6)
C6A	0.0196 (7)	0.0208 (7)	0.0238 (7)	0.0009 (5)	0.0036 (6)	0.0086 (6)
O7A	0.0177 (5)	0.0318 (6)	0.0480 (7)	0.0065 (4)	0.0095 (5)	0.0163 (5)
C8A	0.0227 (8)	0.0253 (8)	0.0458 (10)	−0.0006 (6)	0.0041 (7)	0.0125 (7)
C9A	0.0310 (9)	0.0369 (9)	0.0321 (9)	0.0080 (7)	0.0115 (7)	0.0190 (7)
N10A	0.0180 (6)	0.0295 (7)	0.0201 (6)	0.0041 (5)	0.0057 (5)	0.0106 (5)
C11A	0.0194 (7)	0.0231 (7)	0.0261 (7)	0.0003 (5)	0.0033 (6)	0.0082 (6)
O12A	0.0304 (6)	0.0467 (7)	0.0273 (6)	0.0080 (5)	0.0033 (5)	0.0191 (5)
C13A	0.0196 (8)	0.0322 (9)	0.0399 (10)	0.0039 (6)	0.0086 (7)	0.0113 (7)
C14A	0.0276 (8)	0.0259 (8)	0.0280 (8)	0.0056 (6)	0.0046 (7)	0.0119 (7)
C15A	0.0283 (8)	0.0266 (8)	0.0249 (8)	0.0019 (6)	0.0041 (6)	0.0060 (6)
N1B	0.0173 (6)	0.0244 (6)	0.0310 (7)	0.0002 (5)	0.0068 (5)	0.0079 (5)
C2B	0.0197 (7)	0.0212 (7)	0.0354 (8)	0.0014 (5)	0.0031 (6)	0.0093 (6)
C3B	0.0198 (7)	0.0228 (7)	0.0290 (8)	−0.0002 (6)	0.0037 (6)	0.0089 (6)
C4B	0.0164 (7)	0.0256 (7)	0.0199 (7)	0.0002 (5)	0.0023 (5)	0.0086 (6)
C5B	0.0195 (7)	0.0259 (8)	0.0260 (8)	0.0029 (6)	0.0035 (6)	0.0114 (6)
C6B	0.0202 (7)	0.0214 (7)	0.0232 (7)	0.0027 (5)	0.0054 (6)	0.0082 (6)
O7B	0.0179 (6)	0.0330 (6)	0.0603 (8)	0.0001 (5)	0.0127 (5)	0.0127 (6)
C8B	0.0270 (9)	0.0249 (9)	0.0632 (14)	0.0041 (7)	0.0145 (9)	0.0059 (8)
C9B	0.0304 (9)	0.0386 (10)	0.0452 (11)	−0.0021 (8)	−0.0071 (8)	0.0238 (9)
N10B	0.0166 (6)	0.0310 (7)	0.0213 (6)	0.0010 (5)	0.0018 (5)	0.0116 (5)
C11B	0.0232 (7)	0.0225 (7)	0.0254 (7)	0.0029 (6)	0.0075 (6)	0.0094 (6)
O12B	0.0331 (6)	0.0429 (7)	0.0275 (6)	0.0017 (5)	0.0064 (5)	0.0194 (5)
C13B	0.0221 (8)	0.0340 (9)	0.0419 (9)	0.0003 (6)	0.0087 (7)	0.0169 (7)
C14B	0.0310 (9)	0.0314 (9)	0.0290 (8)	−0.0020 (7)	0.0062 (7)	0.0142 (7)
C15B	0.0292 (8)	0.0249 (8)	0.0242 (8)	−0.0007 (6)	0.0052 (6)	0.0071 (6)
N1C	0.0152 (6)	0.0246 (6)	0.0256 (6)	0.0026 (5)	0.0031 (5)	0.0108 (5)
C2C	0.0194 (7)	0.0273 (8)	0.0335 (8)	0.0027 (6)	0.0039 (6)	0.0168 (7)
C3C	0.0207 (7)	0.0250 (8)	0.0335 (9)	0.0006 (6)	0.0027 (6)	0.0128 (7)
C4C	0.0166 (7)	0.0298 (8)	0.0212 (7)	0.0002 (6)	0.0013 (6)	0.0081 (6)
C5C	0.0189 (7)	0.0248 (7)	0.0280 (8)	0.0034 (6)	0.0022 (6)	0.0103 (6)
C6C	0.0191 (7)	0.0214 (7)	0.0262 (7)	0.0032 (5)	0.0031 (6)	0.0083 (6)
O7C	0.0156 (5)	0.0354 (6)	0.0421 (7)	0.0023 (4)	0.0039 (5)	0.0189 (5)
C8C	0.0271 (9)	0.0261 (9)	0.0601 (13)	0.0075 (7)	0.0093 (8)	0.0168 (8)
C9C	0.0264 (9)	0.0544 (12)	0.0396 (10)	0.0021 (8)	0.0026 (8)	0.0322 (9)
N10C	0.0168 (6)	0.0336 (7)	0.0203 (6)	0.0004 (5)	0.0005 (5)	0.0093 (5)
C11C	0.0194 (7)	0.0308 (8)	0.0269 (8)	0.0046 (6)	0.0046 (6)	0.0106 (6)
O12C	0.0216 (6)	0.0727 (9)	0.0287 (6)	0.0032 (6)	0.0052 (5)	0.0221 (6)
C13C	0.0193 (8)	0.0406 (10)	0.0308 (9)	0.0005 (7)	0.0025 (6)	0.0133 (7)
C14C	0.0266 (8)	0.0278 (8)	0.0389 (10)	0.0008 (7)	0.0042 (7)	0.0183 (7)
C15C	0.0290 (9)	0.0326 (9)	0.0299 (9)	0.0010 (7)	0.0047 (7)	0.0029 (7)
O1	0.0234 (6)	0.0457 (7)	0.0277 (6)	0.0057 (5)	0.0049 (5)	0.0190 (5)

Geometric parameters (Å, º)

N1A—O7A	1.2872 (16)	C8B—H8B	1.02 (2)
N1A—C2A	1.4970 (18)	C9B—H9B	0.95 (2)
N1A—C6A	1.4997 (18)	C9B—H10B	0.97 (2)
C2A—C8A	1.528 (2)	C9B—H11B	1.02 (2)
C2A—C9A	1.532 (2)	N10B—C11B	1.3306 (19)
C2A—C3A	1.531 (2)	N10B—H18B	0.826 (19)
C3A—C4A	1.525 (2)	C11B—O12B	1.2383 (18)
C3A—H1A	0.975 (17)	C11B—C13B	1.507 (2)
C3A—H2A	0.989 (18)	C13B—H19B	0.9600
C4A—N10A	1.4606 (19)	C13B—H20B	0.9600
C4A—C5A	1.520 (2)	C13B—H21B	0.9600
C4A—H3A	1.029 (17)	C14B—H12B	1.01 (2)
C5A—C6A	1.530 (2)	C14B—H13B	0.99 (2)
C5A—H4A	1.01 (2)	C14B—H14B	0.98 (2)
C5A—H5A	0.975 (17)	C15B—H15B	0.99 (2)
C6A—C14A	1.529 (2)	C15B—H16B	1.02 (2)
C6A—C15A	1.534 (2)	C15B—H17B	0.942 (19)
C8A—H6A	1.01 (2)	N1C—O7C	1.2902 (16)
C8A—H7A	0.96 (2)	N1C—C2C	1.4970 (18)
C8A—H8A	0.97 (2)	N1C—C6C	1.4979 (18)
C9A—H9A	1.01 (2)	C2C—C8C	1.527 (2)
C9A—H10A	0.95 (2)	C2C—C9C	1.532 (2)
C9A—H11A	0.99 (2)	C2C—C3C	1.533 (2)
N10A—C11A	1.3388 (19)	C3C—C4C	1.525 (2)
N10A—H18A	0.863 (19)	C3C—H1C	1.017 (18)
C11A—O12A	1.2347 (19)	C3C—H2C	0.956 (18)
C11A—C13A	1.504 (2)	C4C—N10C	1.4623 (18)
C13A—H19A	0.9600	C4C—C5C	1.517 (2)
C13A—H20A	0.9600	C4C—H3C	0.979 (18)
C13A—H21A	0.9600	C5C—C6C	1.531 (2)
C14A—H12A	0.97 (2)	C5C—H4C	0.98 (2)
C14A—H13A	0.97 (2)	C5C—H5C	1.016 (17)
C14A—H14A	1.03 (2)	C6C—C14C	1.526 (2)
C15A—H15A	1.018 (19)	C6C—C15C	1.534 (2)
C15A—H16A	0.97 (2)	C8C—H6C	0.95 (2)
C15A—H17A	0.98 (2)	C8C—H7C	0.95 (2)
N1B—O7B	1.2901 (16)	C8C—H8C	1.03 (2)
N1B—C2B	1.4935 (19)	C9C—H9C	0.98 (2)
N1B—C6B	1.4980 (19)	C9C—H10C	1.02 (2)
C2B—C9B	1.525 (2)	C9C—H11C	0.95 (2)
C2B—C8B	1.527 (2)	N10C—C11C	1.333 (2)
C2B—C3B	1.533 (2)	N10C—H18C	0.89 (2)
C3B—C4B	1.524 (2)	C11C—O12C	1.2388 (19)
C3B—H1B	0.946 (18)	C11C—C13C	1.510 (2)
C3B—H2B	0.975 (19)	C13C—H19C	0.9600
C4B—N10B	1.4596 (18)	C13C—H20C	0.9600
C4B—C5B	1.523 (2)	C13C—H21C	0.9600
C4B—H3B	0.978 (17)	C14C—H12C	0.97 (2)
C5B—C6B	1.531 (2)	C14C—H13C	0.97 (2)
C5B—H4B	0.99 (2)	C14C—H14C	0.97 (2)
C5B—H5B	0.991 (18)	C15C—H15C	0.99 (2)
C6B—C14B	1.524 (2)	C15C—H16C	1.01 (2)
C6B—C15B	1.532 (2)	C15C—H17C	0.938 (19)
C8B—H6B	0.93 (2)	O1—H1	0.84 (3)
C8B—H7B	0.97 (2)	O1—H2	0.89 (3)
O7A—N1A—C2A	115.78 (11)	H6B—C8B—H7B	112.4 (19)
O7A—N1A—C6A	115.87 (11)	C2B—C8B—H8B	111.2 (13)
C2A—N1A—C6A	124.21 (11)	H6B—C8B—H8B	107.2 (18)
N1A—C2A—C8A	107.81 (12)	H7B—C8B—H8B	109.5 (17)
N1A—C2A—C9A	109.14 (13)	C2B—C9B—H9B	114.1 (13)
C8A—C2A—C9A	109.16 (14)	C2B—C9B—H10B	108.1 (13)
N1A—C2A—C3A	110.20 (11)	H9B—C9B—H10B	112.1 (19)
C8A—C2A—C3A	108.61 (13)	C2B—C9B—H11B	109.2 (12)
C9A—C2A—C3A	111.82 (12)	H9B—C9B—H11B	104.6 (17)
C4A—C3A—C2A	114.35 (12)	H10B—C9B—H11B	108.5 (18)
C4A—C3A—H1A	107.9 (10)	C11B—N10B—C4B	122.51 (13)
C2A—C3A—H1A	109.4 (10)	C11B—N10B—H18B	117.9 (13)
C4A—C3A—H2A	112.0 (10)	C4B—N10B—H18B	119.5 (13)
C2A—C3A—H2A	107.1 (10)	O12B—C11B—N10B	122.67 (14)
H1A—C3A—H2A	105.8 (14)	O12B—C11B—C13B	121.20 (13)
N10A—C4A—C5A	109.19 (12)	N10B—C11B—C13B	116.13 (13)
N10A—C4A—C3A	110.38 (12)	C11B—C13B—H19B	109.5
C5A—C4A—C3A	108.15 (12)	C11B—C13B—H20B	109.5
N10A—C4A—H3A	106.6 (9)	H19B—C13B—H20B	109.5
C5A—C4A—H3A	112.4 (9)	C11B—C13B—H21B	109.5
C3A—C4A—H3A	110.1 (9)	H19B—C13B—H21B	109.5
C4A—C5A—C6A	113.78 (12)	H20B—C13B—H21B	109.5
C4A—C5A—H4A	112.1 (12)	C6B—C14B—H12B	109.1 (11)
C6A—C5A—H4A	107.1 (12)	C6B—C14B—H13B	111.6 (11)
C4A—C5A—H5A	107.2 (9)	H12B—C14B—H13B	108.0 (16)
C6A—C5A—H5A	109.4 (10)	C6B—C14B—H14B	111.7 (12)
H4A—C5A—H5A	107.2 (15)	H12B—C14B—H14B	105.7 (16)
N1A—C6A—C14A	107.71 (12)	H13B—C14B—H14B	110.5 (17)
N1A—C6A—C5A	110.10 (11)	C6B—C15B—H15B	108.9 (11)
C14A—C6A—C5A	108.81 (12)	C6B—C15B—H16B	110.4 (11)
N1A—C6A—C15A	109.44 (12)	H15B—C15B—H16B	107.0 (16)
C14A—C6A—C15A	109.59 (13)	C6B—C15B—H17B	109.9 (11)
C5A—C6A—C15A	111.12 (12)	H15B—C15B—H17B	110.5 (16)
C2A—C8A—H6A	109.3 (11)	H16B—C15B—H17B	110.1 (15)
C2A—C8A—H7A	111.4 (12)	O7C—N1C—C2C	116.08 (11)
H6A—C8A—H7A	109.9 (16)	O7C—N1C—C6C	115.49 (11)
C2A—C8A—H8A	112.1 (13)	C2C—N1C—C6C	124.39 (11)
H6A—C8A—H8A	106.5 (16)	N1C—C2C—C8C	107.70 (13)
H7A—C8A—H8A	107.5 (17)	N1C—C2C—C9C	109.48 (13)
C2A—C9A—H9A	110.4 (11)	C8C—C2C—C9C	110.00 (14)
C2A—C9A—H10A	113.2 (12)	N1C—C2C—C3C	109.51 (12)
H9A—C9A—H10A	109.3 (16)	C8C—C2C—C3C	108.84 (14)
C2A—C9A—H11A	109.7 (12)	C9C—C2C—C3C	111.23 (13)
H9A—C9A—H11A	106.5 (15)	C4C—C3C—C2C	113.53 (13)
H10A—C9A—H11A	107.5 (17)	C4C—C3C—H1C	107.2 (10)
C11A—N10A—C4A	123.20 (13)	C2C—C3C—H1C	109.2 (10)
C11A—N10A—H18A	117.1 (12)	C4C—C3C—H2C	109.6 (11)
C4A—N10A—H18A	119.4 (12)	C2C—C3C—H2C	107.3 (11)
O12A—C11A—N10A	122.40 (14)	H1C—C3C—H2C	110.0 (15)
O12A—C11A—C13A	121.91 (14)	N10C—C4C—C5C	109.25 (12)
N10A—C11A—C13A	115.68 (14)	N10C—C4C—C3C	110.23 (12)
C11A—C13A—H19A	109.5	C5C—C4C—C3C	108.23 (12)
C11A—C13A—H20A	109.5	N10C—C4C—H3C	107.1 (10)
H19A—C13A—H20A	109.5	C5C—C4C—H3C	111.1 (10)
C11A—C13A—H21A	109.5	C3C—C4C—H3C	111.0 (10)
H19A—C13A—H21A	109.5	C4C—C5C—C6C	114.20 (12)
H20A—C13A—H21A	109.5	C4C—C5C—H4C	112.9 (11)
C6A—C14A—H12A	111.4 (11)	C6C—C5C—H4C	106.0 (11)
C6A—C14A—H13A	109.0 (12)	C4C—C5C—H5C	109.4 (9)
H12A—C14A—H13A	109.4 (16)	C6C—C5C—H5C	107.5 (9)
C6A—C14A—H14A	107.7 (11)	H4C—C5C—H5C	106.4 (14)
H12A—C14A—H14A	109.0 (15)	N1C—C6C—C14C	108.32 (12)
H13A—C14A—H14A	109.2 (16)	N1C—C6C—C5C	109.68 (12)
C6A—C15A—H15A	112.1 (10)	C14C—C6C—C5C	109.06 (12)
C6A—C15A—H16A	111.4 (11)	N1C—C6C—C15C	108.50 (12)
H15A—C15A—H16A	107.5 (15)	C14C—C6C—C15C	109.12 (14)
C6A—C15A—H17A	109.1 (12)	C5C—C6C—C15C	112.08 (13)
H15A—C15A—H17A	107.4 (15)	C2C—C8C—H6C	109.8 (13)
H16A—C15A—H17A	109.3 (16)	C2C—C8C—H7C	110.2 (14)
O7B—N1B—C2B	115.80 (12)	H6C—C8C—H7C	106.8 (19)
O7B—N1B—C6B	115.71 (11)	C2C—C8C—H8C	111.6 (11)
C2B—N1B—C6B	124.61 (12)	H6C—C8C—H8C	109.5 (17)
N1B—C2B—C9B	109.47 (13)	H7C—C8C—H8C	108.8 (17)
N1B—C2B—C8B	107.61 (14)	C2C—C9C—H9C	114.2 (13)
C9B—C2B—C8B	109.45 (15)	C2C—C9C—H10C	110.8 (13)
N1B—C2B—C3B	110.10 (12)	H9C—C9C—H10C	106.7 (18)
C9B—C2B—C3B	111.15 (14)	C2C—C9C—H11C	106.8 (14)
C8B—C2B—C3B	108.99 (13)	H9C—C9C—H11C	110.8 (18)
C4B—C3B—C2B	113.69 (12)	H10C—C9C—H11C	107.3 (18)
C4B—C3B—H1B	106.7 (11)	C11C—N10C—C4C	123.81 (13)
C2B—C3B—H1B	110.3 (11)	C11C—N10C—H18C	119.9 (12)
C4B—C3B—H2B	109.3 (11)	C4C—N10C—H18C	116.2 (12)
C2B—C3B—H2B	107.7 (11)	O12C—C11C—N10C	123.04 (14)
H1B—C3B—H2B	109.1 (15)	O12C—C11C—C13C	121.34 (14)
N10B—C4B—C5B	110.33 (12)	N10C—C11C—C13C	115.62 (14)
N10B—C4B—C3B	110.29 (12)	C11C—C13C—H19C	109.5
C5B—C4B—C3B	107.76 (12)	C11C—C13C—H20C	109.5
N10B—C4B—H3B	106.5 (10)	H19C—C13C—H20C	109.5
C5B—C4B—H3B	112.6 (10)	C11C—C13C—H21C	109.5
C3B—C4B—H3B	109.4 (10)	H19C—C13C—H21C	109.5
C4B—C5B—C6B	113.03 (12)	H20C—C13C—H21C	109.5
C4B—C5B—H4B	109.5 (11)	C6C—C14C—H12C	110.3 (12)
C6B—C5B—H4B	108.0 (11)	C6C—C14C—H13C	111.5 (11)
C4B—C5B—H5B	108.9 (10)	H12C—C14C—H13C	108.5 (16)
C6B—C5B—H5B	109.0 (10)	C6C—C14C—H14C	111.3 (12)
H4B—C5B—H5B	108.2 (15)	H12C—C14C—H14C	107.5 (17)
N1B—C6B—C14B	107.46 (12)	H13C—C14C—H14C	107.7 (16)
N1B—C6B—C5B	110.30 (12)	C6C—C15C—H15C	110.2 (12)
C14B—C6B—C5B	108.53 (12)	C6C—C15C—H16C	108.0 (12)
N1B—C6B—C15B	109.09 (12)	H15C—C15C—H16C	107.5 (17)
C14B—C6B—C15B	109.81 (13)	C6C—C15C—H17C	111.2 (11)
C5B—C6B—C15B	111.57 (12)	H15C—C15C—H17C	109.9 (17)
C2B—C8B—H6B	109.2 (14)	H16C—C15C—H17C	109.9 (16)
C2B—C8B—H7B	107.3 (13)	H1—O1—H2	104 (2)
C4A—N10A—C11A—O12A	−1.6 (2)	C3A—C4A—N10A—C11A	−91.05 (17)
C4B—N10B—C11B—O12B	2.7 (2)	C3B—C4B—N10B—C11B	94.37 (16)
C4C—N10C—C11C—O12C	2.7 (3)	C3C—C4C—N10C—C11C	99.78 (17)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N10A—H18A···O12B^i	0.86 (2)	2.01 (2)	2.865 (2)	173.3 (9)
N10B—H18B···O1	0.83 (2)	2.06 (2)	2.862 (2)	165 (1)
N10C—H18C···O12A	0.89 (2)	1.97 (2)	2.859 (2)	173.3 (9)
O1—H1···O12C	0.84 (3)	1.94 (3)	2.778 (2)	174 (2)
O1—H2···O7C^ii	0.89 (3)	2.00 (3)	2.890 (2)	174 (2)
C13C—H19C···O7C^ii	0.96	2.65	3.562 (2)	158
C13C—H21C···O12A	0.96	2.64	3.474 (2)	146
C8A—H6A···O12B^iii	1.01 (2)	2.57 (2)	3.516 (2)	156 (1)
C9C—H10C···O1^iv	1.02 (2)	2.61 (2)	3.540 (2)	151 (2)

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