Using crystal structure prediction to rationalize the hydration propensities of substituted adamantane hydro­chloride salts

The crystal energy landscapes of the salts of two rigid pharmaceutically active molecules reveal that the experimental structure of amantadine hydrochloride is the most stable structure with the majority of low-energy structures adopting a chain hydrogen-bond motif and packings that do not have solvent accessible voids. By contrast, memantine hydrochloride which differs in the substitution of two methyl groups on the adamantane ring has a crystal energy landscape where all structures within 10 kJ mol⁻¹ of the global minimum have solvent-accessible voids ranging from 3 to 14% of the unit-cell volume including the lattice energy minimum that was calculated after removing water from the hydrated memantine hydrochloride salt structure. The success in using crystal structure prediction (CSP) to rationalize the different hydration propensities of these substituted adamantane hydrochloride salts allowed us to extend the model to predict under blind test conditions the experimental crystal structures of the previously uncharacterized 1-(methylamino)adamantane base and its corresponding hydrochloride salt. Although the crystal structure of 1-(methylamino)adamantane was correctly predicted as the second ranked structure on the static lattice energy landscape, the crystallization of a Z′ = 3 structure of 1-(methylamino)adamantane hydrochloride reveals the limits of applying CSP when the contents of the crystallographic asymmetric unit are unknown.

Computing details

For both compounds, program(s) used to refine structure: SHELXL2014/7 (Sheldrick, 2014).

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Crystal data

C11H19N	F(000) = 184
Mr = 165.27	Dx = 1.165 Mg m^−3
Monoclinic, P21/m	Mo Kα radiation, λ = 0.71073 Å
a = 8.2451 (8) Å	Cell parameters from 13304 reflections
b = 6.5202 (6) Å	θ = 2.3–26.0°
c = 8.8214 (8) Å	µ = 0.07 mm^−1
β = 96.509 (3)°	T = 100 K
V = 471.18 (8) Å^3	BLOCK, colorless
Z = 2	0.30 × 0.20 × 0.20 mm

Data collection

Bruker APEX-II CCD diffractometer	913 reflections with I > 2σ(I)
φ and ω scans	Rint = 0.039
Absorption correction: multi-scan sadabs	θmax = 26.0°, θmin = 2.3°
Tmin = 0.627, Tmax = 0.746	h = −10→10
13304 measured reflections	k = −8→8
1000 independent reflections	l = −10→10

Refinement

Refinement on F^2	0 restraints
Least-squares matrix: full	Hydrogen site location: mixed
R[F^2 > 2σ(F^2)] = 0.076	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.148	w = 1/[σ^2(Fo^2) + (0.029P)^2 + 0.7802P] where P = (Fo^2 + 2Fc^2)/3
S = 1.04	(Δ/σ)max < 0.001
1000 reflections	Δρmax = 0.27 e Å^−3
68 parameters	Δρmin = −0.22 e Å^−3

Special details

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

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

	x	y	z	Uiso*/Ueq	Occ. (<1)
C1	0.8170 (3)	0.7500	0.6373 (3)	0.0174 (6)
N1	0.9161 (3)	0.7500	0.5081 (3)	0.0294 (7)
H1	0.978 (6)	0.873 (7)	0.515 (6)	0.035*	0.5
C2	0.7096 (3)	0.5601 (3)	0.6384 (3)	0.0300 (5)
H2A	0.7783	0.4354	0.6390	0.036*
H2B	0.6309	0.5575	0.5449	0.036*
C6	0.9379 (3)	0.7500	0.7826 (3)	0.0354 (9)
H6A	1.0085	0.6270	0.7840	0.043*	0.5
H6B	1.0085	0.8730	0.7840	0.043*	0.5
C3	0.6169 (3)	0.5609 (4)	0.7793 (3)	0.0409 (7)
H3	0.5472	0.4352	0.7787	0.049*
C5	0.8452 (4)	0.7500	0.9237 (3)	0.0551 (14)
H5	0.9251	0.7500	1.0178	0.066*
C7	0.5094 (4)	0.7500	0.7764 (4)	0.0381 (9)
H7A	0.4471	0.7500	0.8660	0.046*
H7B	0.4306	0.7500	0.6830	0.046*
C8	0.8244 (4)	0.7500	0.3558 (3)	0.0404 (10)
H8A	0.7416	0.8584	0.3498	0.061*	0.5
H8B	0.7710	0.6168	0.3366	0.061*	0.5
H8C	0.8993	0.7748	0.2791	0.061*	0.5
C4	0.7388 (3)	0.5618 (6)	0.9229 (3)	0.0666 (11)
H4A	0.6796	0.5616	1.0145	0.080*
H4B	0.8074	0.4370	0.9256	0.080*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.0145 (12)	0.0237 (15)	0.0142 (12)	0.000	0.0021 (10)	0.000
N1	0.0181 (12)	0.055 (2)	0.0157 (12)	0.000	0.0037 (9)	0.000
C2	0.0353 (12)	0.0141 (11)	0.0410 (13)	0.0001 (9)	0.0058 (9)	−0.0041 (9)
C6	0.0141 (13)	0.074 (3)	0.0177 (15)	0.000	0.0009 (11)	0.000
C3	0.0355 (12)	0.0409 (16)	0.0475 (14)	−0.0148 (12)	0.0097 (10)	0.0193 (12)
C5	0.0194 (15)	0.134 (4)	0.0115 (14)	0.000	0.0006 (12)	0.000
C7	0.0153 (14)	0.073 (3)	0.0277 (16)	0.000	0.0075 (12)	0.000
C8	0.0314 (17)	0.077 (3)	0.0140 (14)	0.000	0.0054 (12)	0.000
C4	0.0428 (14)	0.115 (3)	0.0437 (15)	0.0107 (18)	0.0132 (12)	0.0525 (18)

Geometric parameters (Å, º)

C1—N1	1.476 (3)	C6—C5	1.532 (4)
C1—C2^i	1.523 (2)	C3—C7	1.517 (3)
C1—C2	1.523 (2)	C3—C4	1.525 (4)
C1—C6	1.533 (4)	C5—C4^i	1.508 (4)
N1—C8	1.465 (4)	C5—C4	1.508 (4)
C2—C3	1.532 (3)	C7—C3^i	1.517 (3)
N1—C1—C2^i	112.21 (14)	C7—C3—C4	109.9 (3)
N1—C1—C2	112.21 (14)	C7—C3—C2	109.5 (2)
C2^i—C1—C2	108.8 (2)	C4—C3—C2	109.35 (19)
N1—C1—C6	106.3 (2)	C4^i—C5—C4	108.9 (3)
C2^i—C1—C6	108.56 (15)	C4^i—C5—C6	109.87 (19)
C2—C1—C6	108.56 (15)	C4—C5—C6	109.87 (19)
C8—N1—C1	115.8 (2)	C3—C7—C3^i	108.7 (2)
C1—C2—C3	110.26 (19)	C5—C4—C3	109.6 (2)
C5—C6—C1	110.0 (2)
C2^i—C1—N1—C8	−61.46 (16)	C1—C2—C3—C4	−60.1 (3)
C2—C1—N1—C8	61.46 (16)	C1—C6—C5—C4^i	−59.89 (19)
C6—C1—N1—C8	180.000 (1)	C1—C6—C5—C4	59.89 (19)
N1—C1—C2—C3	176.67 (19)	C4—C3—C7—C3^i	59.2 (3)
C2^i—C1—C2—C3	−58.5 (3)	C2—C3—C7—C3^i	−60.8 (3)
C6—C1—C2—C3	59.5 (2)	C4^i—C5—C4—C3	60.6 (4)
N1—C1—C6—C5	180.000 (1)	C6—C5—C4—C3	−59.8 (3)
C2^i—C1—C6—C5	59.08 (14)	C7—C3—C4—C5	−60.5 (3)
C2—C1—C6—C5	−59.08 (14)	C2—C3—C4—C5	59.7 (3)
C1—C2—C3—C7	60.3 (2)

Symmetry code: (i) x, −y+3/2, z.

(III)

Crystal data

C11H20ClN	Dx = 1.207 Mg m^−3
Mr = 201.73	Cu Kα radiation, λ = 1.54178 Å
Orthorhombic, P212121	Cell parameters from 88459 reflections
a = 6.6114 (3) Å	θ = 2.8–66.7°
b = 20.4778 (10) Å	µ = 2.67 mm^−1
c = 24.6057 (12) Å	T = 100 K
V = 3331.3 (3) Å^3	BLOCK, colorless
Z = 12	0.30 × 0.20 × 0.20 mm
F(000) = 1320

Data collection

Bruker APEX-II CCD diffractometer	5475 reflections with I > 2σ(I)
φ and ω scans	Rint = 0.079
Absorption correction: multi-scan sadabs	θmax = 66.7°, θmin = 2.8°
Tmin = 0.559, Tmax = 0.756	h = −7→7
88459 measured reflections	k = −24→24
5796 independent reflections	l = −29→29

Refinement

Refinement on F^2	Hydrogen site location: mixed
Least-squares matrix: full	H atoms treated by a mixture of independent and constrained refinement
R[F^2 > 2σ(F^2)] = 0.048	w = 1/[σ^2(Fo^2) + (0.039P)^2 + 5.052P] where P = (Fo^2 + 2Fc^2)/3
wR(F^2) = 0.116	(Δ/σ)max = 0.001
S = 1.06	Δρmax = 0.46 e Å^−3
5796 reflections	Δρmin = −0.33 e Å^−3
380 parameters	Absolute structure: Refined as an inversion twin.
0 restraints	Absolute structure parameter: 0.06 (2)

Special details

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

Refinement. Refined as a 2-component inversion twin.

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

	x	y	z	Uiso*/Ueq
Cl1	0.20220 (18)	0.51842 (5)	0.60578 (5)	0.0283 (3)
Cl2	0.60770 (18)	0.59671 (6)	0.42060 (5)	0.0307 (3)
Cl3	0.8375 (2)	0.37486 (6)	0.46439 (5)	0.0366 (3)
N3	0.5768 (6)	0.57616 (18)	0.54649 (17)	0.0259 (9)
N2	0.1412 (7)	0.3787 (2)	0.55876 (18)	0.0297 (9)
N1	0.9777 (6)	0.50539 (19)	0.41262 (15)	0.0247 (9)
C30	0.7311 (8)	0.6873 (2)	0.66567 (19)	0.0292 (11)
H30	0.7553	0.6785	0.7043	0.035*
C10	1.0848 (7)	0.5690 (2)	0.33126 (18)	0.0253 (10)
H10A	0.9657	0.5963	0.3353	0.030*
H10B	1.1952	0.5892	0.3511	0.030*
C4	1.1190 (9)	0.4211 (2)	0.2574 (2)	0.0344 (12)
H4A	1.0947	0.3776	0.2716	0.041*
H4B	1.1557	0.4173	0.2193	0.041*
C23	0.6422 (7)	0.6377 (2)	0.57647 (18)	0.0228 (9)
C21	0.0410 (8)	0.2634 (2)	0.5776 (2)	0.0320 (11)
H21A	−0.0591	0.2662	0.5489	0.038*
H21B	0.1659	0.2471	0.5621	0.038*
C31	0.9222 (8)	0.7162 (3)	0.6401 (2)	0.0337 (12)
H31A	1.0336	0.6858	0.6441	0.040*
H31B	0.9580	0.7564	0.6586	0.040*
C33	0.6990 (8)	0.5166 (2)	0.5550 (2)	0.0314 (10)
H33A	0.6786	0.4872	0.5251	0.047*
H33B	0.6584	0.4958	0.5882	0.047*
H33C	0.8395	0.5282	0.5571	0.047*
C1	1.0428 (7)	0.5008 (2)	0.35420 (18)	0.0235 (10)
C7	0.9664 (8)	0.5308 (2)	0.23972 (19)	0.0301 (11)
H7A	0.8452	0.5572	0.2429	0.036*
H7B	1.0015	0.5276	0.2015	0.036*
C19	−0.0332 (9)	0.2171 (2)	0.6222 (2)	0.0371 (13)
H19	−0.0549	0.1736	0.6066	0.045*
C11	1.1200 (8)	0.5345 (2)	0.45193 (19)	0.0334 (11)
H11A	1.2520	0.5159	0.4468	0.050*
H11B	1.0744	0.5256	0.4882	0.050*
H11C	1.1262	0.5808	0.4464	0.050*
C8	1.1402 (7)	0.5630 (2)	0.27120 (19)	0.0281 (10)
H8	1.1657	0.6066	0.2563	0.034*
C20	0.1286 (10)	0.2128 (2)	0.6664 (2)	0.0429 (14)
H20A	0.2542	0.1970	0.6509	0.052*
H20B	0.0860	0.1824	0.6944	0.052*
C5	0.9275 (7)	0.4626 (2)	0.26303 (19)	0.0280 (11)
H5	0.8162	0.4418	0.2432	0.034*
C27	0.5198 (7)	0.7492 (2)	0.5997 (2)	0.0281 (11)
H27	0.4077	0.7802	0.5960	0.034*
C2	1.2353 (7)	0.4589 (2)	0.34926 (19)	0.0270 (10)
H2C	1.3452	0.4790	0.3693	0.032*
H2D	1.2114	0.4158	0.3643	0.032*
C14	0.1616 (9)	0.2811 (3)	0.6914 (2)	0.0390 (13)
H14	0.2636	0.2782	0.7202	0.047*
C9	1.3314 (7)	0.5215 (3)	0.26569 (19)	0.0314 (11)
H9A	1.3694	0.5181	0.2277	0.038*
H9B	1.4420	0.5420	0.2852	0.038*
C32	0.6796 (8)	0.6228 (2)	0.63613 (18)	0.0273 (10)
H32A	0.7909	0.5923	0.6398	0.033*
H32B	0.5599	0.6033	0.6521	0.033*
C25	0.8851 (8)	0.7299 (2)	0.57964 (19)	0.0274 (10)
H25	1.0072	0.7489	0.5635	0.033*
C22	0.3346 (8)	0.3654 (3)	0.5298 (2)	0.0408 (13)
H22A	0.3562	0.3983	0.5026	0.061*
H22B	0.3280	0.3233	0.5128	0.061*
H22C	0.4443	0.3661	0.5554	0.061*
C16	−0.1971 (9)	0.3103 (2)	0.6705 (2)	0.0356 (12)
H16	−0.3242	0.3268	0.6858	0.043*
C13	0.2361 (8)	0.3273 (2)	0.6471 (2)	0.0331 (12)
H13A	0.3625	0.3114	0.6321	0.040*
H13B	0.2594	0.3704	0.6622	0.040*
C3	1.2906 (8)	0.4536 (2)	0.28896 (19)	0.0304 (11)
H3	1.4131	0.4270	0.2853	0.036*
C17	−0.1210 (7)	0.3569 (2)	0.6263 (2)	0.0271 (10)
H17A	−0.2218	0.3607	0.5978	0.033*
H17B	−0.0989	0.4000	0.6417	0.033*
C28	0.4663 (7)	0.6853 (2)	0.57049 (19)	0.0250 (10)
H28A	0.3449	0.6666	0.5862	0.030*
H28B	0.4409	0.6939	0.5323	0.030*
C26	0.7098 (8)	0.7781 (2)	0.5742 (2)	0.0280 (10)
H26A	0.7440	0.8187	0.5921	0.034*
H26B	0.6853	0.7873	0.5361	0.034*
C15	−0.0365 (9)	0.3057 (3)	0.7154 (2)	0.0388 (13)
H15A	−0.0160	0.3483	0.7317	0.047*
H15B	−0.0822	0.2760	0.7436	0.047*
C18	−0.2310 (9)	0.2421 (2)	0.6457 (2)	0.0388 (13)
H18A	−0.2791	0.2123	0.6735	0.047*
H18B	−0.3324	0.2446	0.6173	0.047*
C29	0.5563 (8)	0.7348 (2)	0.65986 (19)	0.0299 (11)
H29A	0.5874	0.7751	0.6789	0.036*
H29B	0.4352	0.7162	0.6759	0.036*
C24	0.8330 (7)	0.6659 (2)	0.55048 (18)	0.0238 (10)
H24A	0.8100	0.6741	0.5121	0.029*
H24B	0.9440	0.6352	0.5539	0.029*
C6	0.8717 (7)	0.4686 (2)	0.32297 (18)	0.0265 (10)
H6A	0.7496	0.4945	0.3267	0.032*
H6B	0.8454	0.4256	0.3379	0.032*
C12	0.0760 (7)	0.3311 (2)	0.6024 (2)	0.0270 (10)
H1A	0.936 (8)	0.465 (3)	0.425 (2)	0.035 (15)*
H3A	0.450 (9)	0.563 (2)	0.557 (2)	0.029 (14)*
H1B	0.841 (10)	0.532 (3)	0.414 (2)	0.056 (18)*
H3B	0.579 (9)	0.585 (3)	0.506 (2)	0.040 (16)*
H2A	0.163 (10)	0.418 (3)	0.578 (3)	0.053 (18)*
H2B	0.055 (11)	0.374 (3)	0.533 (3)	0.06 (2)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
Cl1	0.0283 (6)	0.0243 (5)	0.0324 (6)	−0.0056 (5)	0.0003 (5)	−0.0008 (4)
Cl2	0.0278 (6)	0.0318 (6)	0.0326 (6)	0.0028 (5)	0.0007 (5)	−0.0013 (5)
Cl3	0.0456 (8)	0.0282 (6)	0.0359 (6)	−0.0129 (5)	−0.0085 (5)	0.0037 (5)
N3	0.025 (2)	0.021 (2)	0.032 (2)	−0.0062 (16)	0.0007 (17)	−0.0020 (16)
N2	0.031 (3)	0.025 (2)	0.032 (2)	−0.0021 (18)	−0.0024 (18)	−0.0025 (18)
N1	0.029 (2)	0.019 (2)	0.026 (2)	−0.0054 (16)	−0.0007 (16)	0.0006 (16)
C30	0.033 (3)	0.029 (2)	0.025 (2)	−0.005 (2)	−0.001 (2)	−0.0011 (19)
C10	0.026 (3)	0.018 (2)	0.032 (2)	−0.0030 (19)	0.002 (2)	−0.0009 (19)
C4	0.043 (3)	0.029 (3)	0.032 (3)	0.006 (2)	−0.006 (2)	−0.005 (2)
C23	0.026 (3)	0.019 (2)	0.024 (2)	−0.0054 (18)	0.0015 (19)	−0.0015 (17)
C21	0.030 (3)	0.023 (3)	0.042 (3)	0.000 (2)	−0.004 (2)	−0.005 (2)
C31	0.035 (3)	0.035 (3)	0.032 (3)	−0.008 (2)	−0.006 (2)	−0.004 (2)
C33	0.028 (3)	0.023 (2)	0.042 (3)	0.000 (2)	0.002 (2)	−0.002 (2)
C1	0.028 (3)	0.021 (2)	0.022 (2)	−0.0007 (18)	0.0014 (18)	0.0009 (17)
C7	0.028 (3)	0.034 (3)	0.028 (3)	0.004 (2)	−0.003 (2)	0.006 (2)
C19	0.042 (3)	0.019 (2)	0.051 (3)	−0.003 (2)	−0.007 (2)	0.000 (2)
C11	0.043 (3)	0.031 (3)	0.027 (2)	−0.006 (2)	0.002 (2)	−0.003 (2)
C8	0.029 (3)	0.026 (2)	0.029 (2)	0.000 (2)	−0.001 (2)	0.0050 (19)
C20	0.054 (4)	0.023 (3)	0.052 (3)	0.002 (2)	−0.010 (3)	0.008 (2)
C5	0.026 (3)	0.028 (3)	0.029 (3)	−0.003 (2)	−0.006 (2)	−0.004 (2)
C27	0.027 (3)	0.021 (2)	0.036 (3)	−0.0014 (19)	0.001 (2)	−0.002 (2)
C2	0.027 (3)	0.024 (2)	0.030 (2)	0.0023 (19)	−0.0047 (19)	0.0001 (19)
C14	0.045 (4)	0.032 (3)	0.040 (3)	−0.002 (2)	−0.014 (2)	0.004 (2)
C9	0.026 (3)	0.041 (3)	0.027 (2)	0.003 (2)	0.0007 (19)	0.001 (2)
C32	0.029 (3)	0.023 (2)	0.030 (2)	−0.004 (2)	0.003 (2)	0.0025 (19)
C25	0.027 (3)	0.028 (2)	0.028 (2)	−0.009 (2)	0.001 (2)	−0.001 (2)
C22	0.039 (3)	0.033 (3)	0.051 (3)	−0.002 (2)	0.009 (3)	−0.003 (2)
C16	0.038 (3)	0.030 (3)	0.039 (3)	−0.006 (2)	0.001 (2)	−0.003 (2)
C13	0.031 (3)	0.024 (2)	0.044 (3)	0.002 (2)	−0.009 (2)	−0.001 (2)
C3	0.027 (3)	0.033 (3)	0.032 (3)	0.010 (2)	−0.003 (2)	−0.005 (2)
C17	0.026 (3)	0.020 (2)	0.035 (3)	0.0018 (19)	−0.006 (2)	−0.0014 (19)
C28	0.024 (3)	0.022 (2)	0.029 (3)	−0.0029 (19)	0.0004 (19)	−0.0010 (19)
C26	0.035 (3)	0.018 (2)	0.031 (2)	−0.003 (2)	0.004 (2)	0.0007 (18)
C15	0.049 (4)	0.034 (3)	0.033 (3)	−0.007 (3)	−0.003 (2)	0.004 (2)
C18	0.046 (4)	0.026 (3)	0.045 (3)	−0.009 (2)	−0.003 (3)	0.003 (2)
C29	0.035 (3)	0.025 (2)	0.030 (3)	−0.001 (2)	0.002 (2)	−0.005 (2)
C24	0.022 (3)	0.020 (2)	0.029 (2)	−0.0003 (18)	−0.0008 (19)	−0.0027 (18)
C6	0.024 (3)	0.024 (2)	0.031 (2)	−0.0045 (19)	−0.001 (2)	0.0032 (19)
C12	0.030 (3)	0.018 (2)	0.033 (2)	−0.0030 (18)	−0.005 (2)	−0.0007 (19)

Geometric parameters (Å, º)

N3—C33	1.478 (6)	C7—C5	1.533 (7)
N3—C23	1.523 (5)	C7—C8	1.534 (7)
N2—C22	1.489 (7)	C19—C18	1.519 (8)
N2—C12	1.513 (6)	C19—C20	1.527 (8)
N1—C11	1.475 (6)	C8—C9	1.529 (7)
N1—C1	1.503 (6)	C20—C14	1.543 (7)
C30—C29	1.517 (7)	C5—C6	1.525 (6)
C30—C31	1.530 (7)	C27—C26	1.524 (7)
C30—C32	1.545 (6)	C27—C29	1.528 (7)
C10—C8	1.528 (6)	C27—C28	1.534 (6)
C10—C1	1.533 (6)	C2—C3	1.532 (7)
C4—C3	1.528 (7)	C14—C15	1.522 (8)
C4—C5	1.531 (7)	C14—C13	1.527 (8)
C23—C32	1.520 (6)	C9—C3	1.528 (7)
C23—C28	1.525 (6)	C25—C26	1.527 (7)
C23—C24	1.527 (6)	C25—C24	1.534 (6)
C21—C19	1.532 (7)	C16—C17	1.533 (7)
C21—C12	1.532 (6)	C16—C15	1.535 (7)
C31—C25	1.535 (7)	C16—C18	1.541 (7)
C1—C6	1.518 (6)	C13—C12	1.528 (7)
C1—C2	1.539 (6)	C17—C12	1.524 (7)
C33—N3—C23	117.4 (4)	C26—C27—C29	110.1 (4)
C22—N2—C12	117.8 (4)	C26—C27—C28	109.1 (4)
C11—N1—C1	118.0 (4)	C29—C27—C28	109.1 (4)
C29—C30—C31	110.0 (4)	C3—C2—C1	108.3 (4)
C29—C30—C32	109.7 (4)	C15—C14—C13	110.4 (4)
C31—C30—C32	108.6 (4)	C15—C14—C20	109.5 (5)
C8—C10—C1	109.0 (4)	C13—C14—C20	108.8 (4)
C3—C4—C5	109.0 (4)	C3—C9—C8	109.0 (4)
C32—C23—N3	110.3 (4)	C23—C32—C30	108.6 (4)
C32—C23—C28	110.2 (4)	C26—C25—C24	109.9 (4)
N3—C23—C28	105.4 (4)	C26—C25—C31	109.0 (4)
C32—C23—C24	110.2 (4)	C24—C25—C31	109.5 (4)
N3—C23—C24	110.1 (4)	C17—C16—C15	108.8 (4)
C28—C23—C24	110.4 (4)	C17—C16—C18	109.3 (4)
C19—C21—C12	108.8 (4)	C15—C16—C18	109.2 (4)
C30—C31—C25	109.7 (4)	C14—C13—C12	108.8 (4)
N1—C1—C6	107.4 (4)	C9—C3—C4	109.7 (4)
N1—C1—C10	110.3 (4)	C9—C3—C2	109.9 (4)
C6—C1—C10	110.1 (4)	C4—C3—C2	110.2 (4)
N1—C1—C2	110.3 (4)	C12—C17—C16	109.8 (4)
C6—C1—C2	109.5 (4)	C23—C28—C27	108.9 (4)
C10—C1—C2	109.2 (4)	C27—C26—C25	109.8 (4)
C5—C7—C8	109.1 (4)	C14—C15—C16	109.7 (4)
C18—C19—C20	110.6 (5)	C19—C18—C16	109.3 (4)
C18—C19—C21	109.9 (4)	C30—C29—C27	109.5 (4)
C20—C19—C21	108.8 (4)	C23—C24—C25	108.2 (4)
C10—C8—C9	109.2 (4)	C1—C6—C5	110.1 (4)
C10—C8—C7	110.1 (4)	N2—C12—C17	107.1 (4)
C9—C8—C7	109.7 (4)	N2—C12—C13	110.2 (4)
C19—C20—C14	109.3 (4)	C17—C12—C13	109.4 (4)
C6—C5—C4	109.4 (4)	N2—C12—C21	110.1 (4)
C6—C5—C7	109.2 (4)	C17—C12—C21	109.8 (4)
C4—C5—C7	109.5 (4)	C13—C12—C21	110.2 (4)
C33—N3—C23—C32	−48.6 (5)	C15—C16—C17—C12	60.0 (5)
C33—N3—C23—C28	−167.6 (4)	C18—C16—C17—C12	−59.2 (5)
C33—N3—C23—C24	73.3 (5)	C32—C23—C28—C27	60.9 (5)
C29—C30—C31—C25	−59.7 (5)	N3—C23—C28—C27	−180.0 (4)
C32—C30—C31—C25	60.3 (5)	C24—C23—C28—C27	−61.1 (5)
C11—N1—C1—C6	179.3 (4)	C26—C27—C28—C23	60.0 (5)
C11—N1—C1—C10	−60.7 (5)	C29—C27—C28—C23	−60.3 (5)
C11—N1—C1—C2	60.0 (5)	C29—C27—C26—C25	59.7 (5)
C8—C10—C1—N1	−177.2 (4)	C28—C27—C26—C25	−60.0 (5)
C8—C10—C1—C6	−58.9 (5)	C24—C25—C26—C27	60.3 (5)
C8—C10—C1—C2	61.4 (5)	C31—C25—C26—C27	−59.7 (5)
C12—C21—C19—C18	60.7 (5)	C13—C14—C15—C16	59.5 (5)
C12—C21—C19—C20	−60.5 (5)	C20—C14—C15—C16	−60.2 (6)
C1—C10—C8—C9	−61.1 (5)	C17—C16—C15—C14	−58.9 (5)
C1—C10—C8—C7	59.3 (5)	C18—C16—C15—C14	60.4 (6)
C5—C7—C8—C10	−60.2 (5)	C20—C19—C18—C16	59.6 (5)
C5—C7—C8—C9	60.0 (5)	C21—C19—C18—C16	−60.5 (6)
C18—C19—C20—C14	−59.2 (6)	C17—C16—C18—C19	59.4 (6)
C21—C19—C20—C14	61.5 (6)	C15—C16—C18—C19	−59.5 (6)
C3—C4—C5—C6	−59.3 (5)	C31—C30—C29—C27	59.0 (5)
C3—C4—C5—C7	60.4 (5)	C32—C30—C29—C27	−60.4 (5)
C8—C7—C5—C6	59.8 (5)	C26—C27—C29—C30	−59.1 (5)
C8—C7—C5—C4	−60.0 (5)	C28—C27—C29—C30	60.7 (5)
N1—C1—C2—C3	177.9 (4)	C32—C23—C24—C25	−61.5 (5)
C6—C1—C2—C3	60.0 (5)	N3—C23—C24—C25	176.5 (4)
C10—C1—C2—C3	−60.7 (5)	C28—C23—C24—C25	60.5 (5)
C19—C20—C14—C15	59.2 (6)	C26—C25—C24—C23	−59.6 (5)
C19—C20—C14—C13	−61.6 (6)	C31—C25—C24—C23	60.0 (5)
C10—C8—C9—C3	60.6 (5)	N1—C1—C6—C5	179.8 (4)
C7—C8—C9—C3	−60.1 (5)	C10—C1—C6—C5	59.7 (5)
N3—C23—C32—C30	−176.1 (4)	C2—C1—C6—C5	−60.4 (5)
C28—C23—C32—C30	−60.1 (5)	C4—C5—C6—C1	59.9 (5)
C24—C23—C32—C30	62.0 (5)	C7—C5—C6—C1	−59.9 (5)
C29—C30—C32—C23	59.7 (5)	C22—N2—C12—C17	178.4 (4)
C31—C30—C32—C23	−60.6 (5)	C22—N2—C12—C13	59.5 (6)
C30—C31—C25—C26	59.6 (5)	C22—N2—C12—C21	−62.3 (6)
C30—C31—C25—C24	−60.6 (5)	C16—C17—C12—N2	179.3 (4)
C15—C14—C13—C12	−59.8 (5)	C16—C17—C12—C13	−61.2 (5)
C20—C14—C13—C12	60.4 (6)	C16—C17—C12—C21	59.9 (5)
C8—C9—C3—C4	60.6 (5)	C14—C13—C12—N2	177.8 (4)
C8—C9—C3—C2	−60.8 (5)	C14—C13—C12—C17	60.3 (5)
C5—C4—C3—C9	−60.8 (5)	C14—C13—C12—C21	−60.5 (5)
C5—C4—C3—C2	60.4 (5)	C19—C21—C12—N2	−177.7 (4)
C1—C2—C3—C9	60.6 (5)	C19—C21—C12—C17	−60.1 (5)
C1—C2—C3—C4	−60.4 (5)	C19—C21—C12—C13	60.5 (5)