Mechanochemical synthesis insights and solid-state characterization of quininium aspirinate, a glass-forming drug–drug salt

Quinine (an anti­malarial) and aspirin (a nonsteroidal anti-inflammatory drug) were combined into a new drug–drug salt, quininium aspirinate, C₂₀H₂₅N₂O₂⁺·C₉H₇O₄⁻, by liquid-assisted grinding using stoichiometric amounts of the reactants in a 1:1 molar ratio, and water, EtOH, toluene, or heptane as additives. A tetra­hydro­furan (THF) solution of the mechanochemical product prepared using EtOH as additive led to a single crystal of the same material obtained by mechanochemistry, which was used for crystal structure determination at 100 K. Powder X-ray diffraction ruled out crystallographic phase transitions in the 100–295 K inter­val. Neat mechanical treatment (in a mortar and pestle, or in a ball mill at 20 or 30 Hz milling frequencies) gave rise to an amorphous phase, as shown by powder X-ray diffraction; however, FT–IR spectroscopy unambiguously indicates that a mechanochemical reaction has occurred. Neat milling the reactants at 10 and 15 Hz led to incom­plete reactions. Thermogravimetry and differential scanning calorimetry indicate that the amorphous and crystalline mechanochemical products form glasses/supercooled liquids before melting, and do not recrystallize upon cooling. However, the amorphous material obtained by neat grinding crystallizes upon storage into the salt reported. The mechanochemical synthesis, crystal structure analysis, Hirshfeld surfaces, powder X-ray diffraction, thermogravimetry, differential scanning calorimetry, FT–IR spectroscopy, and aqueous solubility of quininium aspirinate are herein reported.

Computing details

Data collection: APEX3 (Bruker, 2017); cell refinement: SAINT (Bruker, 2017); data reduction: SAINT (Bruker, 2017); program(s) used to solve structure: SHELXT2014 (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2017 (Sheldrick, 2015b) and OLEX2 (Dolomanov et al., 2009).

(R)-[(2S,4S,5R)-5-Ethenyl-1-azoniabicyclo[2.2.2]octan-2-yl](6-methoxyquinolin-4-yl)methanol 2-acetoxybenzoate

Crystal data

C20H25N2O2^+·C9H7O4^−	Dx = 1.315 Mg m^−3
Mr = 504.56	Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, P212121	Cell parameters from 8326 reflections
a = 8.6256 (12) Å	θ = 2.5–24.7°
b = 9.6680 (13) Å	µ = 0.09 mm^−1
c = 30.557 (4) Å	T = 100 K
V = 2548.2 (6) Å^3	Block, colorless
Z = 4	0.23 × 0.22 × 0.18 mm
F(000) = 1072

Data collection

Bruker Kappa APEXII CCD diffractometer	5223 independent reflections
Radiation source: fine-focus sealed tube	4290 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.067
Detector resolution: 8.3333 pixels mm^-1	θmax = 26.4°, θmin = 2.2°
φ and ω scans	h = −10→10
Absorption correction: multi-scan (SADABS; Bruker, 2017)	k = −12→11
Tmin = 0.91, Tmax = 0.98	l = −38→38
45099 measured reflections

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)] = 0.040	w = 1/[σ^2(Fo^2) + (0.0287P)^2 + 0.6236P] where P = (Fo^2 + 2Fc^2)/3
wR(F^2) = 0.080	(Δ/σ)max < 0.001
S = 1.05	Δρmax = 0.18 e Å^−3
5223 reflections	Δρmin = −0.19 e Å^−3
344 parameters	Absolute structure: Flack x determined using 1588 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013)
1 restraint	Absolute structure parameter: 0.2 (5)
Primary atom site location: dual

Special details

Experimental. Absolute configuration as indicated by the manufacturer (Sigma) for the parent compound quinine, (R)-[(2S,4S,5R)-5-ethenyl-1-azabicyclo[2.2.2]octan-2-yl]- (6-methoxyquinolin-4-yl)methanol): Chirality at N1 S Chirality at C12 R Chirality at C13 S Chirality at C18 S Chirality at C19 R

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
O1	0.5081 (2)	0.3078 (2)	0.29584 (6)	0.0321 (5)
O2	0.4889 (2)	0.43901 (19)	0.35540 (6)	0.0267 (5)
O3	0.1126 (2)	0.4756 (2)	0.35631 (7)	0.0311 (5)
O4	0.2512 (2)	0.37979 (17)	0.41103 (5)	0.0194 (4)
C1	0.2528 (3)	0.2513 (3)	0.38938 (8)	0.0175 (6)
C2	0.1629 (3)	0.1487 (3)	0.40772 (9)	0.0222 (6)
H2	0.100645	0.16807	0.43262	0.027*
C3	0.1636 (3)	0.0172 (3)	0.38974 (10)	0.0265 (7)
H3	0.103143	−0.054156	0.402582	0.032*
C4	0.2519 (3)	−0.0099 (3)	0.35325 (10)	0.0265 (7)
H4	0.251175	−0.09946	0.340462	0.032*
C5	0.3421 (3)	0.0943 (3)	0.33526 (9)	0.0217 (6)
H5A	0.402722	0.07445	0.31008	0.026*
C6	0.3467 (3)	0.2280 (3)	0.35300 (8)	0.0172 (6)
C7	0.1846 (3)	0.4875 (3)	0.38969 (9)	0.0212 (6)
C8	0.2121 (3)	0.6195 (3)	0.41409 (9)	0.0257 (7)
H8A	0.21158	0.600988	0.445621	0.039*
H8B	0.129947	0.685854	0.407009	0.039*
H8C	0.312782	0.658077	0.405614	0.039*
C9	0.4554 (3)	0.3328 (3)	0.33240 (8)	0.0189 (6)
O5	0.6107 (2)	0.82378 (18)	0.39913 (6)	0.0175 (4)
H5	0.564 (4)	0.835 (4)	0.4251 (12)	0.057 (11)*
O6	0.7937 (2)	0.16887 (18)	0.44178 (5)	0.0190 (4)
N1	0.6695 (3)	0.6255 (2)	0.32110 (7)	0.0173 (5)
H1	0.601 (3)	0.552 (3)	0.3294 (10)	0.046 (10)*
N2	0.9686 (3)	0.6636 (2)	0.51756 (7)	0.0184 (5)
C10	1.0919 (4)	0.7137 (3)	0.21791 (10)	0.0314 (7)
H10A	1.034783	0.758586	0.195438	0.038*
H10B	1.198541	0.693001	0.213666	0.038*
C11	1.0230 (3)	0.6801 (3)	0.25515 (9)	0.0248 (6)
H11	1.082835	0.635309	0.277065	0.03*
C12	0.8547 (3)	0.7091 (3)	0.26458 (8)	0.0191 (6)
H12	0.802919	0.73521	0.236487	0.023*
C13	0.8338 (3)	0.8292 (3)	0.29724 (8)	0.0189 (6)
H13	0.899002	0.909627	0.28804	0.023*
C14	0.6631 (3)	0.8712 (3)	0.29764 (9)	0.0202 (6)
H14A	0.634107	0.912154	0.269086	0.024*
H14B	0.644517	0.941007	0.320763	0.024*
C15	0.5655 (3)	0.7411 (3)	0.30648 (9)	0.0204 (6)
H15A	0.487634	0.760842	0.329437	0.024*
H15B	0.509892	0.713667	0.2795	0.024*
C16	0.7706 (3)	0.5819 (3)	0.28346 (8)	0.0205 (6)
H16A	0.706297	0.538331	0.26044	0.025*
H16B	0.847641	0.513133	0.293607	0.025*
C17	0.8795 (3)	0.7837 (3)	0.34354 (8)	0.0180 (6)
H17A	0.869635	0.862794	0.36394	0.022*
H17B	0.988938	0.752766	0.343721	0.022*
C18	0.7738 (3)	0.6648 (3)	0.35864 (8)	0.0145 (5)
H18	0.842507	0.583449	0.364377	0.017*
C19	0.6824 (3)	0.6914 (3)	0.40085 (8)	0.0149 (5)
H19	0.599577	0.619501	0.403486	0.018*
C20	0.7899 (3)	0.6795 (3)	0.44028 (8)	0.0146 (6)
C21	0.8487 (3)	0.7960 (3)	0.46016 (8)	0.0179 (6)
H21	0.828158	0.884935	0.448254	0.021*
C22	0.9391 (3)	0.7829 (3)	0.49805 (9)	0.0196 (6)
H22	0.981692	0.864585	0.510469	0.023*
C23	0.9144 (3)	0.5456 (3)	0.49781 (8)	0.0165 (6)
C24	0.8270 (3)	0.5477 (3)	0.45844 (8)	0.0147 (5)
C25	0.7812 (3)	0.4196 (3)	0.43929 (8)	0.0154 (6)
H25	0.721577	0.41894	0.413156	0.019*
C26	0.8234 (3)	0.2972 (3)	0.45868 (8)	0.0156 (6)
C27	0.9045 (3)	0.2960 (3)	0.49887 (9)	0.0197 (6)
H27	0.928647	0.210497	0.512586	0.024*
C28	0.9482 (3)	0.4170 (3)	0.51794 (8)	0.0198 (6)
H28	1.001878	0.415337	0.545073	0.024*
C29	0.7330 (3)	0.1652 (3)	0.39804 (8)	0.0239 (6)
H29A	0.806913	0.209024	0.378018	0.036*
H29B	0.634213	0.2152	0.397057	0.036*
H29C	0.716423	0.068903	0.389195	0.036*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0346 (12)	0.0418 (13)	0.0198 (10)	−0.0103 (10)	0.0079 (10)	−0.0070 (10)
O2	0.0305 (11)	0.0247 (11)	0.0249 (10)	−0.0099 (9)	0.0048 (9)	−0.0051 (9)
O3	0.0318 (12)	0.0299 (12)	0.0317 (12)	0.0070 (9)	−0.0144 (10)	−0.0062 (10)
O4	0.0215 (10)	0.0187 (10)	0.0180 (9)	0.0014 (8)	−0.0016 (9)	−0.0015 (8)
C1	0.0158 (14)	0.0185 (14)	0.0182 (13)	−0.0001 (12)	−0.0053 (12)	−0.0029 (11)
C2	0.0147 (13)	0.0257 (16)	0.0261 (15)	−0.0008 (12)	0.0004 (12)	0.0015 (12)
C3	0.0168 (15)	0.0220 (15)	0.0408 (18)	−0.0048 (13)	−0.0022 (14)	0.0053 (13)
C4	0.0207 (15)	0.0175 (15)	0.0413 (17)	0.0002 (12)	−0.0067 (14)	−0.0052 (13)
C5	0.0151 (14)	0.0255 (15)	0.0247 (14)	0.0020 (12)	−0.0035 (12)	−0.0052 (12)
C6	0.0121 (12)	0.0208 (14)	0.0188 (13)	0.0003 (11)	−0.0060 (11)	0.0014 (12)
C7	0.0160 (14)	0.0225 (15)	0.0250 (15)	0.0034 (12)	0.0032 (13)	−0.0017 (12)
C8	0.0244 (16)	0.0211 (15)	0.0317 (16)	0.0005 (12)	−0.0021 (14)	−0.0047 (13)
C9	0.0164 (13)	0.0233 (14)	0.0170 (14)	0.0000 (12)	−0.0054 (11)	−0.0011 (12)
O5	0.0202 (10)	0.0167 (9)	0.0154 (9)	0.0064 (8)	0.0030 (8)	−0.0004 (8)
O6	0.0216 (10)	0.0157 (9)	0.0199 (9)	−0.0009 (8)	−0.0017 (8)	0.0008 (8)
N1	0.0184 (12)	0.0193 (12)	0.0140 (11)	−0.0022 (10)	0.0010 (10)	−0.0004 (9)
N2	0.0177 (12)	0.0212 (12)	0.0163 (11)	−0.0015 (10)	−0.0011 (9)	−0.0019 (10)
C10	0.0316 (17)	0.0285 (17)	0.0340 (17)	0.0020 (14)	0.0133 (15)	0.0002 (14)
C11	0.0248 (16)	0.0237 (15)	0.0260 (15)	0.0025 (13)	0.0028 (13)	−0.0029 (13)
C12	0.0213 (14)	0.0212 (15)	0.0147 (13)	0.0013 (12)	0.0020 (11)	0.0000 (11)
C13	0.0225 (14)	0.0173 (13)	0.0169 (13)	−0.0009 (12)	0.0039 (12)	0.0022 (11)
C14	0.0227 (15)	0.0198 (14)	0.0180 (13)	0.0043 (12)	−0.0005 (12)	0.0012 (11)
C15	0.0163 (14)	0.0273 (15)	0.0174 (14)	0.0017 (12)	−0.0019 (11)	0.0017 (12)
C16	0.0253 (15)	0.0217 (14)	0.0146 (13)	−0.0005 (12)	0.0033 (12)	−0.0031 (12)
C17	0.0181 (13)	0.0177 (14)	0.0181 (13)	−0.0028 (11)	0.0028 (11)	−0.0022 (11)
C18	0.0113 (12)	0.0171 (13)	0.0152 (12)	0.0024 (11)	−0.0011 (11)	−0.0015 (11)
C19	0.0151 (13)	0.0145 (13)	0.0152 (12)	0.0016 (11)	0.0020 (11)	0.0004 (11)
C20	0.0119 (13)	0.0189 (14)	0.0129 (12)	0.0000 (11)	0.0026 (10)	−0.0008 (11)
C21	0.0168 (14)	0.0194 (14)	0.0175 (13)	−0.0011 (11)	0.0018 (12)	−0.0014 (11)
C22	0.0204 (14)	0.0203 (15)	0.0180 (14)	−0.0046 (12)	0.0016 (12)	−0.0041 (12)
C23	0.0110 (13)	0.0237 (15)	0.0146 (13)	−0.0014 (11)	−0.0006 (11)	0.0000 (11)
C24	0.0119 (13)	0.0181 (14)	0.0139 (12)	0.0006 (11)	0.0025 (11)	−0.0008 (11)
C25	0.0127 (13)	0.0200 (14)	0.0137 (12)	−0.0013 (11)	−0.0013 (10)	0.0007 (11)
C26	0.0128 (12)	0.0166 (14)	0.0175 (13)	−0.0012 (11)	0.0043 (11)	−0.0005 (11)
C27	0.0180 (14)	0.0193 (15)	0.0219 (14)	0.0026 (12)	−0.0005 (12)	0.0061 (12)
C28	0.0195 (14)	0.0257 (15)	0.0143 (13)	0.0026 (13)	−0.0035 (11)	0.0034 (12)
C29	0.0316 (16)	0.0206 (15)	0.0193 (13)	−0.0021 (13)	−0.0031 (13)	−0.0014 (12)

Geometric parameters (Å, º)

O1—C9	1.230 (3)	C12—C13	1.542 (3)
O2—C9	1.277 (3)	C12—H12	1.0
O3—C7	1.200 (3)	C13—C14	1.527 (4)
O4—C7	1.357 (3)	C13—C17	1.533 (3)
O4—C1	1.407 (3)	C13—H13	1.0
C1—C2	1.379 (4)	C14—C15	1.538 (4)
C1—C6	1.394 (3)	C14—H14A	0.99
C2—C3	1.385 (4)	C14—H14B	0.99
C2—H2	0.95	C15—H15A	0.99
C3—C4	1.376 (4)	C15—H15B	0.99
C3—H3	0.95	C16—H16A	0.99
C4—C5	1.386 (4)	C16—H16B	0.99
C4—H4	0.95	C17—C18	1.538 (3)
C5—C6	1.402 (4)	C17—H17A	0.99
C5—H5A	0.95	C17—H17B	0.99
C6—C9	1.517 (4)	C18—C19	1.534 (3)
C7—C8	1.497 (4)	C18—H18	1.0
C8—H8A	0.98	C19—C20	1.525 (3)
C8—H8B	0.98	C19—H19	1.0
C8—H8C	0.98	C20—C21	1.377 (3)
O5—C19	1.422 (3)	C20—C24	1.427 (4)
O5—H5	0.90 (4)	C21—C22	1.401 (4)
O6—C26	1.368 (3)	C21—H21	0.95
O6—C29	1.436 (3)	C22—H22	0.95
N1—C15	1.501 (3)	C23—C28	1.417 (4)
N1—C16	1.504 (3)	C23—C24	1.419 (3)
N1—C18	1.506 (3)	C24—C25	1.426 (3)
N1—H1	0.96 (2)	C25—C26	1.372 (3)
N2—C22	1.323 (3)	C25—H25	0.95
N2—C23	1.373 (3)	C26—C27	1.413 (4)
C10—C11	1.325 (4)	C27—C28	1.360 (4)
C10—H10A	0.95	C27—H27	0.95
C10—H10B	0.95	C28—H28	0.95
C11—C12	1.506 (4)	C29—H29A	0.98
C11—H11	0.95	C29—H29B	0.98
C12—C16	1.539 (4)	C29—H29C	0.98
C7—O4—C1	117.11 (19)	N1—C15—C14	109.5 (2)
C2—C1—C6	122.3 (2)	N1—C15—H15A	109.8
C2—C1—O4	116.0 (2)	C14—C15—H15A	109.8
C6—C1—O4	121.6 (2)	N1—C15—H15B	109.8
C1—C2—C3	119.8 (3)	C14—C15—H15B	109.8
C1—C2—H2	120.1	H15A—C15—H15B	108.2
C3—C2—H2	120.1	N1—C16—C12	109.6 (2)
C4—C3—C2	119.9 (3)	N1—C16—H16A	109.7
C4—C3—H3	120.0	C12—C16—H16A	109.7
C2—C3—H3	120.0	N1—C16—H16B	109.7
C3—C4—C5	119.6 (3)	C12—C16—H16B	109.7
C3—C4—H4	120.2	H16A—C16—H16B	108.2
C5—C4—H4	120.2	C13—C17—C18	109.8 (2)
C4—C5—C6	122.2 (3)	C13—C17—H17A	109.7
C4—C5—H5A	118.9	C18—C17—H17A	109.7
C6—C5—H5A	118.9	C13—C17—H17B	109.7
C1—C6—C5	116.2 (2)	C18—C17—H17B	109.7
C1—C6—C9	125.6 (2)	H17A—C17—H17B	108.2
C5—C6—C9	118.2 (2)	N1—C18—C19	112.05 (19)
O3—C7—O4	123.7 (2)	N1—C18—C17	108.30 (19)
O3—C7—C8	126.0 (3)	C19—C18—C17	115.6 (2)
O4—C7—C8	110.4 (2)	N1—C18—H18	106.8
C7—C8—H8A	109.5	C19—C18—H18	106.8
C7—C8—H8B	109.5	C17—C18—H18	106.8
H8A—C8—H8B	109.5	O5—C19—C20	111.2 (2)
C7—C8—H8C	109.5	O5—C19—C18	110.1 (2)
H8A—C8—H8C	109.5	C20—C19—C18	109.81 (19)
H8B—C8—H8C	109.5	O5—C19—H19	108.6
O1—C9—O2	125.0 (3)	C20—C19—H19	108.6
O1—C9—C6	118.3 (2)	C18—C19—H19	108.6
O2—C9—C6	116.6 (2)	C21—C20—C24	118.5 (2)
C19—O5—H5	106 (2)	C21—C20—C19	120.8 (2)
C26—O6—C29	116.2 (2)	C24—C20—C19	120.7 (2)
C15—N1—C16	109.1 (2)	C20—C21—C22	119.7 (2)
C15—N1—C18	113.3 (2)	C20—C21—H21	120.1
C16—N1—C18	107.86 (19)	C22—C21—H21	120.1
C15—N1—H1	105 (2)	N2—C22—C21	123.9 (2)
C16—N1—H1	111 (2)	N2—C22—H22	118.0
C18—N1—H1	111 (2)	C21—C22—H22	118.0
C22—N2—C23	117.5 (2)	N2—C23—C28	117.9 (2)
C11—C10—H10A	120.0	N2—C23—C24	122.8 (2)
C11—C10—H10B	120.0	C28—C23—C24	119.3 (2)
H10A—C10—H10B	120.0	C23—C24—C25	118.8 (2)
C10—C11—C12	123.5 (3)	C23—C24—C20	117.5 (2)
C10—C11—H11	118.3	C25—C24—C20	123.7 (2)
C12—C11—H11	118.3	C26—C25—C24	119.9 (2)
C11—C12—C16	112.2 (2)	C26—C25—H25	120.1
C11—C12—C13	112.1 (2)	C24—C25—H25	120.1
C16—C12—C13	107.7 (2)	O6—C26—C25	124.7 (2)
C11—C12—H12	108.2	O6—C26—C27	114.4 (2)
C16—C12—H12	108.2	C25—C26—C27	120.9 (2)
C13—C12—H12	108.2	C28—C27—C26	120.1 (2)
C14—C13—C17	108.5 (2)	C28—C27—H27	119.9
C14—C13—C12	108.6 (2)	C26—C27—H27	119.9
C17—C13—C12	110.6 (2)	C27—C28—C23	120.8 (2)
C14—C13—H13	109.7	C27—C28—H28	119.6
C17—C13—H13	109.7	C23—C28—H28	119.6
C12—C13—H13	109.7	O6—C29—H29A	109.5
C13—C14—C15	108.1 (2)	O6—C29—H29B	109.5
C13—C14—H14A	110.1	H29A—C29—H29B	109.5
C15—C14—H14A	110.1	O6—C29—H29C	109.5
C13—C14—H14B	110.1	H29A—C29—H29C	109.5
C15—C14—H14B	110.1	H29B—C29—H29C	109.5
H14A—C14—H14B	108.4
C7—O4—C1—C2	−112.8 (2)	C15—N1—C18—C17	−61.5 (2)
C7—O4—C1—C6	70.6 (3)	C16—N1—C18—C17	59.4 (2)
C6—C1—C2—C3	−0.3 (4)	C13—C17—C18—N1	4.7 (3)
O4—C1—C2—C3	−176.9 (2)	C13—C17—C18—C19	−122.0 (2)
C1—C2—C3—C4	−1.1 (4)	N1—C18—C19—O5	−77.4 (3)
C2—C3—C4—C5	1.2 (4)	C17—C18—C19—O5	47.3 (3)
C3—C4—C5—C6	−0.1 (4)	N1—C18—C19—C20	159.9 (2)
C2—C1—C6—C5	1.5 (4)	C17—C18—C19—C20	−75.4 (3)
O4—C1—C6—C5	177.8 (2)	O5—C19—C20—C21	−21.7 (3)
C2—C1—C6—C9	−176.5 (2)	C18—C19—C20—C21	100.4 (3)
O4—C1—C6—C9	−0.1 (4)	O5—C19—C20—C24	155.8 (2)
C4—C5—C6—C1	−1.3 (4)	C18—C19—C20—C24	−82.1 (3)
C4—C5—C6—C9	176.8 (2)	C24—C20—C21—C22	−1.8 (4)
C1—O4—C7—O3	8.9 (4)	C19—C20—C21—C22	175.8 (2)
C1—O4—C7—C8	−172.0 (2)	C23—N2—C22—C21	3.9 (4)
C1—C6—C9—O1	−166.1 (3)	C20—C21—C22—N2	−2.5 (4)
C5—C6—C9—O1	16.0 (4)	C22—N2—C23—C28	178.7 (2)
C1—C6—C9—O2	16.1 (4)	C22—N2—C23—C24	−1.2 (4)
C5—C6—C9—O2	−161.8 (2)	N2—C23—C24—C25	177.4 (2)
C10—C11—C12—C16	132.5 (3)	C28—C23—C24—C25	−2.6 (4)
C10—C11—C12—C13	−106.2 (3)	N2—C23—C24—C20	−2.7 (4)
C11—C12—C13—C14	168.3 (2)	C28—C23—C24—C20	177.4 (2)
C16—C12—C13—C14	−67.8 (3)	C21—C20—C24—C23	4.1 (3)
C11—C12—C13—C17	−72.7 (3)	C19—C20—C24—C23	−173.5 (2)
C16—C12—C13—C17	51.1 (3)	C21—C20—C24—C25	−176.0 (2)
C17—C13—C14—C15	−66.8 (3)	C19—C20—C24—C25	6.4 (4)
C12—C13—C14—C15	53.4 (3)	C23—C24—C25—C26	−0.8 (4)
C16—N1—C15—C14	−68.1 (3)	C20—C24—C25—C26	179.3 (2)
C18—N1—C15—C14	52.1 (3)	C29—O6—C26—C25	8.8 (3)
C13—C14—C15—N1	12.1 (3)	C29—O6—C26—C27	−170.8 (2)
C15—N1—C16—C12	53.1 (3)	C24—C25—C26—O6	−176.0 (2)
C18—N1—C16—C12	−70.4 (3)	C24—C25—C26—C27	3.6 (4)
C11—C12—C16—N1	136.3 (2)	O6—C26—C27—C28	176.6 (2)
C13—C12—C16—N1	12.5 (3)	C25—C26—C27—C28	−3.0 (4)
C14—C13—C17—C18	57.3 (3)	C26—C27—C28—C23	−0.5 (4)
C12—C13—C17—C18	−61.6 (3)	N2—C23—C28—C27	−176.7 (3)
C15—N1—C18—C19	67.1 (3)	C24—C23—C28—C27	3.3 (4)
C16—N1—C18—C19	−172.0 (2)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O5—H5···N2^i	0.90 (4)	1.94 (4)	2.828 (3)	173 (3)
N1—H1···O1	0.96 (2)	2.70 (3)	3.460 (3)	137 (3)
N1—H1···O2	0.96 (2)	1.66 (2)	2.603 (3)	167 (3)

Symmetry code: (i) x−1/2, −y+3/2, −z+1.