Protonation site and hydrogen bonding in anhydrous and hydrated crystalline forms of doxazosin mesylate from powder data

The three-dimensional solid-state structures of two modifications of doxazosin mesylate C₂₃H₂₆N₅O·CH₃SO, 4-amino-2-[4-[(2,3-dihydro-1,4-benzodioxin-2-yl)carbonyl]piperazin-1-yl]-6,7-dimethoxyquinazoline methanesulfonate, a commonly used antihypertensive agent, have been determined by synchrotron X-ray powder diffraction. An anhydrous form (A) and a dihydrate form (dG) crystallize in monoclinic space groups. In both forms the doxazosin molecule is protonated at the N1 atom of the quinazoline bicycle. The N1 atom, and the amino H atoms and O atoms of the mesylate moieties are involved in three-dimensional hydrogen-bonding networks, while solvent water molecules and carboxamide O atoms are also incorporated in a hydrogen-bonding network in dG.

Computing details

For both compounds, cell refinement: LSPAID (Visser et al., 1986); data reduction: MRIA (Zlokazov et al., 1992); program(s) used to solve structure: MRIA; program(s) used to refine structure: MRIA; molecular graphics: PLUTON92 (Spek, 1992); software used to prepare material for publication: MRIA.

(doxA) 4-Amino-2-[4-[(2,3-dihydro-1,4-benzodioxin-2-yl)carbonyl]piperazin-1-yl]- 6,7-dimethoxyquinazoline methanesulfonate

Crystal data

C23H26N5O5^+·CH3SO3^−	F(000) = 2304
Mr = 547.58	Dx = 1.447 Mg m^−3
Monoclinic, C2/c	Synchrotron radiation, λ = 0.79985(1) Å
a = 35.259 (2) Å	µ = 0.19 mm^−1
b = 7.7634 (5) Å	T = 295 K
c = 20.9373 (12) Å	Particle morphology: no specific habit
β = 118.715 (7)°	white
V = 5026.4 (5) Å^3	cylinder, 15 × 1 mm
Z = 8

Data collection

ESRF powder diffractometer	Data collection mode: transmission
Radiation source: BM1B bending magnet at ESRF, synchrotron radiation	Scan method: continuous
Si 111 double crystal monochromator	2θmin = 2.030°, 2θmax = 35.525°, 2θstep = 0.005°
Specimen mounting: specimen was sealed in a 1 mm diameter borosilicate glass capillary

Refinement

Refinement on Inet	112 restraints
Least-squares matrix: full with fixed elements per cycle	35 constraints
Rp = 0.040	H-atom parameters not refined
Rwp = 0.056	Weighting scheme based on measured s.u.'s
Rexp = 0.025	(Δ/σ)max = 0.03
6700 data points	Background function: Chebyshev polynomial up to the 5th order
Profile function: split-type pseudo-Voigt (Toraya, 1986)	Preferred orientation correction: Symmetrized harmonics expansion up to the 4th order (Ahtee et al., 1989, (Jarvinen, 1993)
177 parameters

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

	x	y	z	Uiso*/Ueq
N1	0.0801 (3)	0.3585 (11)	0.0891 (5)	0.032 (3)*
C2	0.1002 (3)	0.4240 (14)	0.0535 (6)	0.032 (3)*
N3	0.0801 (3)	0.4358 (13)	−0.0190 (5)	0.032 (3)*
C4	0.0405 (3)	0.3776 (15)	−0.0591 (6)	0.032 (3)*
C5	−0.0259 (4)	0.2380 (15)	−0.0618 (6)	0.032 (3)*
C6	−0.0452 (3)	0.1710 (11)	−0.0250 (5)	0.032 (3)*
C7	−0.0223 (3)	0.1622 (15)	0.0525 (7)	0.032 (3)*
C8	0.0198 (3)	0.2229 (11)	0.0893 (5)	0.032 (3)*
C9	0.0384 (3)	0.2956 (18)	0.0504 (8)	0.032 (3)*
C10	0.0170 (3)	0.3013 (11)	−0.0253 (5)	0.032 (3)*
O11	−0.0856 (2)	0.0990 (10)	−0.0561 (4)	0.032 (3)*
C12	−0.1092 (3)	0.1009 (11)	−0.1344 (5)	0.032 (3)*
O13	−0.0441 (2)	0.0965 (11)	0.0843 (4)	0.032 (3)*
C14	−0.0180 (3)	0.0856 (12)	0.1590 (5)	0.032 (3)*
N15	0.0230 (3)	0.3871 (12)	−0.1329 (5)	0.032 (3)*
N16	0.1409 (3)	0.4881 (13)	0.0922 (5)	0.032 (3)*
C17	0.1641 (3)	0.5576 (12)	0.0563 (5)	0.032 (3)*
C18	0.1989 (3)	0.6796 (11)	0.1001 (4)	0.032 (3)*
N19	0.2269 (4)	0.6005 (12)	0.1717 (5)	0.032 (3)*
C20	0.2040 (2)	0.5578 (10)	0.2116 (4)	0.032 (3)*
C21	0.1647 (3)	0.4653 (11)	0.1705 (4)	0.032 (3)*
C22	0.2697 (4)	0.5649 (17)	0.1984 (6)	0.032 (3)*
O23	0.2923 (3)	0.5111 (13)	0.2603 (5)	0.032 (3)*
C24	0.2897 (4)	0.6108 (15)	0.1493 (6)	0.032 (3)*
O25	0.2640 (2)	0.5319 (8)	0.0808 (3)	0.064 (4)*
C26	0.2855 (3)	0.4970 (16)	0.0413 (6)	0.064 (4)*
C27	0.2610 (3)	0.4320 (15)	−0.0293 (6)	0.064 (4)*
C28	0.2811 (3)	0.3913 (12)	−0.0700 (4)	0.064 (4)*
C29	0.3262 (4)	0.4154 (16)	−0.0406 (6)	0.064 (4)*
C30	0.3497 (3)	0.5026 (12)	0.0255 (4)	0.064 (4)*
C31	0.3307 (4)	0.5092 (18)	0.0722 (7)	0.064 (4)*
O32	0.3547 (2)	0.5989 (9)	0.1387 (4)	0.064 (4)*
C33	0.3368 (4)	0.5517 (15)	0.1869 (6)	0.064 (4)*
S34	0.4102 (1)	0.0399 (6)	0.2299 (2)	0.052 (4)*
O35	0.4453 (2)	−0.0298 (10)	0.2204 (4)	0.052 (4)*
C36	0.3653 (3)	0.0747 (11)	0.1425 (5)	0.052 (4)*
O37	0.4247 (4)	0.2072 (14)	0.2693 (6)	0.052 (4)*
O38	0.3978 (2)	−0.0839 (10)	0.2670 (4)	0.052 (4)*
H1	0.0933	0.3559	0.1359	0.05*
H5	−0.0412	0.2426	−0.1124	0.05*
H8	0.0355	0.2150	0.1398	0.05*
H12A	−0.1369	0.0478	−0.1507	0.05*
H12B	−0.0933	0.0384	−0.1534	0.05*
H12C	−0.1131	0.2178	−0.1514	0.05*
H14A	−0.0343	0.0382	0.1807	0.05*
H14B	−0.0079	0.1985	0.1785	0.05*
H14C	0.0063	0.0126	0.1697	0.05*
H15A	0.0378	0.4301	−0.1519	0.05*
H15B	−0.0028	0.3501	−0.1605	0.05*
H17A	0.1435	0.6151	0.0120	0.05*
H17B	0.1764	0.4625	0.0424	0.05*
H18A	0.1867	0.7862	0.1063	0.05*
H18B	0.2157	0.7056	0.0757	0.05*
H20A	0.2229	0.4896	0.2538	0.05*
H20B	0.1976	0.6637	0.2291	0.05*
H21A	0.1454	0.4950	0.1898	0.05*
H21B	0.1712	0.3436	0.1799	0.05*
H24	0.2888	0.7360	0.1428	0.05*
H27	0.2314	0.4163	−0.0487	0.05*
H28	0.2649	0.3479	−0.1169	0.05*
H29	0.3403	0.3732	−0.0653	0.05*
H30	0.3763	0.5535	0.0383	0.05*
H33A	0.3529	0.6080	0.2338	0.05*
H33B	0.3385	0.4281	0.1946	0.05*
H36A	0.3729	0.1576	0.1165	0.05*
H36B	0.3414	0.1172	0.1477	0.05*
H36C	0.3574	−0.0319	0.1160	0.05*

Geometric parameters (Å, º)

N1—C2	1.35 (2)	C18—H18B	0.97
N1—C9	1.38 (1)	N19—C20	1.45 (2)
N1—H1	0.86	N19—C22	1.36 (2)
C2—N3	1.33 (1)	C20—C21	1.43 (1)
C2—N16	1.36 (1)	C20—H20A	0.97
N3—C4	1.32 (1)	C20—H20B	0.97
C4—C10	1.45 (2)	C21—H21A	0.97
C4—N15	1.36 (2)	C21—H21B	0.97
C5—C6	1.35 (2)	C22—O23	1.22 (1)
C5—C10	1.42 (2)	C22—C24	1.54 (2)
C5—H5	0.93	C24—O25	1.42 (1)
C6—C7	1.43 (2)	C24—C33	1.53 (2)
C6—O11	1.37 (1)	C24—H24	0.98
C7—C8	1.39 (1)	O25—C26	1.39 (2)
C7—O13	1.34 (2)	C26—C27	1.40 (1)
C8—C9	1.39 (2)	C26—C31	1.41 (2)
C8—H8	0.93	C27—C28	1.38 (2)
C9—C10	1.39 (2)	C27—H27	0.93
O11—C12	1.44 (1)	C28—C29	1.41 (2)
C12—H12A	0.96	C28—H28	0.93
C12—H12B	0.96	C29—C30	1.40 (1)
C12—H12C	0.96	C29—H29	0.93
O13—C14	1.38 (1)	C30—C31	1.43 (2)
C14—H14A	0.96	C30—H30	0.93
C14—H14B	0.96	C31—O32	1.42 (1)
C14—H14C	0.96	O32—C33	1.47 (2)
N15—H15A	0.86	C33—H33A	0.97
N15—H15B	0.86	C33—H33B	0.97
N16—C17	1.45 (2)	S34—O35	1.45 (1)
N16—C21	1.45 (1)	S34—C36	1.773 (8)
C17—C18	1.47 (1)	S34—O37	1.49 (1)
C17—H17A	0.97	S34—O38	1.43 (1)
C17—H17B	0.97	C36—H36A	0.96
C18—N19	1.48 (1)	C36—H36B	0.96
C18—H18A	0.97	C36—H36C	0.96
C9—N1—H1	120	C18—N19—C20	113.2 (8)
C2—N1—H1	120	C20—N19—C22	122 (1)
C2—N1—C9	120 (1)	N19—C20—H20B	109
N1—C2—N16	120 (1)	N19—C20—H20A	109
N1—C2—N3	121 (1)	N19—C20—C21	114.6 (8)
N3—C2—N16	119 (1)	H20A—C20—H20B	108
C2—N3—C4	122 (1)	C21—C20—H20B	109
N3—C4—N15	118 (1)	C21—C20—H20A	109
N3—C4—C10	121 (1)	N16—C21—C20	119.2 (7)
C10—C4—N15	121 (1)	C20—C21—H21B	108
C10—C5—H5	119	C20—C21—H21A	108
C6—C5—H5	119	N16—C21—H21B	107
C6—C5—C10	122 (1)	N16—C21—H21A	108
C5—C6—O11	125 (1)	H21A—C21—H21B	107
C5—C6—C7	120 (1)	N19—C22—C24	117 (1)
C7—C6—O11	114.4 (9)	N19—C22—O23	122 (1)
C6—C7—O13	116 (1)	O23—C22—C24	121 (1)
C6—C7—C8	119 (1)	C22—C24—H24	109
C8—C7—O13	125 (1)	C22—C24—C33	109 (1)
C7—C8—H8	120	C22—C24—O25	107.5 (9)
C7—C8—C9	120 (1)	C33—C24—H24	109
C9—C8—H8	120	O25—C24—H24	109
N1—C9—C8	118 (1)	O25—C24—C33	113.6 (9)
C8—C9—C10	122 (1)	C24—O25—C26	114.9 (8)
N1—C9—C10	120 (1)	O25—C26—C31	122 (1)
C5—C10—C9	117 (1)	O25—C26—C27	118 (1)
C4—C10—C9	116 (1)	C27—C26—C31	120 (1)
C4—C10—C5	126 (1)	C26—C27—H27	120
C6—O11—C12	116.0 (8)	C26—C27—C28	120 (1)
O11—C12—H12C	109	C28—C27—H27	120
O11—C12—H12B	109	C27—C28—H28	120
O11—C12—H12A	109	C27—C28—C29	120 (1)
H12B—C12—H12C	109	C29—C28—H28	120
H12A—C12—H12C	109	C28—C29—H29	120
H12A—C12—H12B	109	C28—C29—C30	120 (1)
C7—O13—C14	110.9 (9)	C30—C29—H29	120
O13—C14—H14C	110	C29—C30—H30	122
O13—C14—H14B	110	C29—C30—C31	116.4 (9)
O13—C14—H14A	109	C31—C30—H30	122
H14B—C14—H14C	109	C26—C31—C30	119 (1)
H14A—C14—H14C	109	C30—C31—O32	116 (1)
H14A—C14—H14B	109	C26—C31—O32	120 (1)
C4—N15—H15B	120	C31—O32—C33	107.5 (9)
C4—N15—H15A	120	C24—C33—O32	107 (1)
H15A—N15—H15B	120	O32—C33—H33B	110
C2—N16—C21	120.1 (9)	O32—C33—H33A	110
C2—N16—C17	122 (1)	C24—C33—H33B	110
C17—N16—C21	117.8 (8)	C24—C33—H33A	110
N16—C17—H17B	108	H33A—C33—H33B	109
N16—C17—H17A	108	O37—S34—O38	113.5 (6)
N16—C17—C18	115.1 (9)	C36—S34—O38	108.0 (5)
H17A—C17—H17B	108	C36—S34—O37	109.7 (6)
C18—C17—H17B	109	O35—S34—O38	109.1 (5)
C18—C17—H17A	108	O35—S34—O37	108.2 (7)
C17—C18—H18B	110	O35—S34—C36	108.3 (5)
C17—C18—H18A	110	S34—C36—H36C	109
C17—C18—N19	108.4 (7)	S34—C36—H36B	109
H18A—C18—H18B	108	S34—C36—H36A	109
N19—C18—H18B	110	H36B—C36—H36C	110
N19—C18—H18A	110	H36A—C36—H36C	109
C18—N19—C22	125 (1)	H36A—C36—H36B	109

(doxG) 4-Amino-2-[4-[(2,3-dihydro-1,4-benzodioxin-2-yl)carbonyl]piperazin-1-yl]- 6,7-dimethoxyquinazoline methanesulfonate dihydrate

Crystal data

C23H26N5O5^+·CH3SO3^−·2(H2O)	F(000) = 1232
Mr = 583.61	Dx = 1.430 Mg m^−3
Monoclinic, P21/c	Synchrotron radiation, λ = 0.69999(1) Å
a = 8.2956 (6) Å	µ = 0.19 mm^−1
b = 32.1542 (15) Å	T = 295 K
c = 10.6473 (8) Å	Particle morphology: no specific habit
β = 107.372 (7)°	white
V = 2710.5 (3) Å^3	cylinder, 15 × 1 mm
Z = 4

Data collection

ESRF powder diffractometer	Data collection mode: transmission
Radiation source: ID31 bending magnet at ESRF, synchrotron radiation	Scan method: continuous
Si 111 double crystal monochromator	2θmin = 2.049°, 2θmax = 30.999°, 2θstep = 0.003°
Specimen mounting: specimen was sealed in a 1 mm diameter borosilicate glass capillary

Refinement

Refinement on Inet	112 restraints
Least-squares matrix: full with fixed elements per cycle	35 constraints
Rp = 0.049	H-atom parameters not refined
Rwp = 0.072	Weighting scheme based on measured s.u.'s
Rexp = 0.026	(Δ/σ)max = 0.03
9651 data points	Background function: Chebyshev polynomial up to the 5th order
Profile function: split-type pseudo-Voigt (Toraya, 1986)	Preferred orientation correction: Symmetrized harmonics expansion up to the 4th order (Ahtee et al., 1989, (Jarvinen, 1993)
185 parameters

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

	x	y	z	Uiso*/Ueq
N1	0.0910 (11)	0.0575 (2)	0.4854 (8)	0.041 (3)*
C2	0.1022 (18)	0.0745 (5)	0.6039 (17)	0.041 (3)*
N3	0.1948 (12)	0.0580 (2)	0.7157 (10)	0.041 (3)*
C4	0.2761 (14)	0.0219 (4)	0.7189 (11)	0.041 (3)*
C5	0.3665 (15)	−0.0345 (5)	0.5820 (14)	0.041 (3)*
C6	0.3546 (14)	−0.0496 (4)	0.4607 (12)	0.041 (3)*
C7	0.2540 (14)	−0.0306 (4)	0.3454 (11)	0.041 (3)*
C8	0.1647 (13)	0.0050 (4)	0.3550 (12)	0.041 (3)*
C9	0.1817 (19)	0.0213 (5)	0.4811 (17)	0.041 (3)*
C10	0.2771 (13)	0.0023 (4)	0.5955 (13)	0.041 (3)*
O11	0.4486 (8)	−0.0831 (2)	0.4403 (6)	0.041 (3)*
C12	0.5389 (11)	−0.1062 (3)	0.5536 (9)	0.041 (3)*
O13	0.2516 (11)	−0.0489 (2)	0.2305 (9)	0.041 (3)*
C14	0.1442 (12)	−0.0303 (3)	0.1114 (11)	0.041 (3)*
N15	0.3574 (10)	0.0077 (3)	0.8390 (9)	0.041 (3)*
N16	0.0017 (12)	0.1070 (4)	0.6088 (10)	0.041 (3)*
C17	−0.0873 (16)	0.1307 (4)	0.4905 (13)	0.041 (3)*
C18	0.0112 (14)	0.1702 (4)	0.4871 (12)	0.041 (3)*
N19	0.0327 (12)	0.1936 (4)	0.6098 (10)	0.041 (3)*
C20	0.1083 (11)	0.1710 (3)	0.7281 (10)	0.041 (3)*
C21	0.0149 (11)	0.1299 (3)	0.7290 (11)	0.041 (3)*
C22	−0.0182 (19)	0.2351 (5)	0.6091 (16)	0.041 (3)*
O23	0.0111 (7)	0.2554 (2)	0.7107 (6)	0.041 (3)*
C24	−0.1082 (16)	0.2539 (5)	0.4736 (14)	0.041 (3)*
O25	−0.2535 (11)	0.2279 (2)	0.4144 (8)	0.073 (5)*
C26	−0.3668 (12)	0.2453 (4)	0.3041 (10)	0.073 (5)*
C27	−0.4877 (14)	0.2194 (4)	0.2210 (11)	0.073 (5)*
C28	−0.5994 (13)	0.2358 (4)	0.1065 (11)	0.073 (5)*
C29	−0.5835 (15)	0.2774 (4)	0.0715 (12)	0.073 (5)*
C30	−0.4675 (13)	0.3036 (4)	0.1554 (11)	0.073 (5)*
C31	−0.3539 (11)	0.2873 (3)	0.2715 (9)	0.073 (5)*
O32	−0.2490 (11)	0.3144 (2)	0.3579 (9)	0.073 (5)*
C33	−0.1667 (14)	0.2981 (4)	0.4857 (11)	0.073 (5)*
S34	0.4611 (5)	0.1034 (2)	0.0695 (4)	0.069 (4)*
O35	0.6075 (10)	0.1129 (3)	0.1737 (8)	0.069 (4)*
C36	0.5030 (12)	0.1078 (4)	−0.0830 (11)	0.069 (4)*
O37	0.3235 (11)	0.1319 (2)	0.0721 (10)	0.069 (4)*
O38	0.4095 (10)	0.0605 (2)	0.0812 (9)	0.069 (4)*
O39	−0.0714 (9)	0.0872 (2)	0.2223 (6)	0.038 (5)*
O40	0.1446 (9)	0.1568 (2)	0.2353 (7)	0.046 (6)*
H1	0.0291	0.0688	0.4141	0.05*
H5	0.4330	−0.0482	0.6565	0.05*
H8	0.0952	0.0178	0.2801	0.05*
H12A	0.5990	−0.1285	0.5277	0.05*
H12B	0.4609	−0.1174	0.5956	0.05*
H12C	0.6176	−0.0882	0.6139	0.05*
H14A	0.1528	−0.0458	0.0367	0.05*
H14B	0.1792	−0.0021	0.1050	0.05*
H14C	0.0293	−0.0306	0.1134	0.05*
H15A	0.3550	0.0216	0.9074	0.05*
H16A	0.4122	−0.0154	0.8480	0.05*
H17A	−0.2004	0.1376	0.4924	0.05*
H17B	−0.0963	0.1142	0.4124	0.05*
H18A	0.1209	0.1633	0.4778	0.05*
H18B	−0.0490	0.1871	0.4123	0.05*
H20A	0.1052	0.1877	0.8033	0.05*
H20B	0.2256	0.1653	0.7355	0.05*
H21A	0.0757	0.1134	0.8046	0.05*
H21B	−0.0971	0.1355	0.7358	0.05*
H24	−0.0320	0.2537	0.4188	0.05*
H27	−0.4937	0.1915	0.2418	0.05*
H28	−0.6844	0.2192	0.0533	0.05*
H29	−0.6515	0.2875	−0.0088	0.05*
H30	−0.4645	0.3317	0.1354	0.05*
H33A	−0.2441	0.2983	0.5383	0.05*
H33B	−0.0704	0.3154	0.5294	0.05*
H36A	0.4027	0.1013	−0.1530	0.05*
H36B	0.5914	0.0888	−0.0852	0.05*
H36C	0.5378	0.1357	−0.0938	0.05*
H39A	−0.1789	0.0958	0.2060	0.05*
H39B	−0.0030	0.1092	0.2264	0.05*
H40A	0.2046	0.1525	0.1788	0.05*
H40B	0.1048	0.1830	0.2280	0.05*

Geometric parameters (Å, º)

N1—C2	1.35 (2)	N19—C22	1.40 (2)
N1—C9	1.39 (2)	C20—C21	1.53 (1)
N1—H1	0.86	C20—H20A	0.97
C2—N3	1.32 (2)	C20—H20B	0.97
C2—N16	1.35 (2)	C21—H21A	0.97
N3—C4	1.34 (1)	C21—H21B	0.97
C4—C10	1.46 (2)	C22—O23	1.22 (2)
C4—N15	1.34 (1)	C22—C24	1.54 (2)
C5—C6	1.36 (2)	C24—O25	1.45 (2)
C5—C10	1.43 (2)	C24—C33	1.52 (2)
C5—H5	0.93	C24—H24	0.98
C6—C7	1.40 (2)	O25—C26	1.38 (1)
C6—O11	1.38 (1)	C26—C27	1.40 (2)
C7—C8	1.38 (2)	C26—C31	1.41 (2)
C7—O13	1.35 (2)	C27—C28	1.40 (1)
C8—C9	1.41 (2)	C27—H27	0.93
C8—H8	0.93	C28—C29	1.41 (2)
C9—C10	1.38 (2)	C28—H28	0.93
O11—C12	1.42 (1)	C29—C30	1.39 (2)
C12—H12A	0.96	C29—H29	0.93
C12—H12B	0.96	C30—C31	1.41 (1)
C12—H12C	0.96	C30—H30	0.93
O13—C14	1.44 (1)	C31—O32	1.37 (1)
C14—H14A	0.96	O32—C33	1.43 (1)
C14—H14B	0.96	C33—H33A	0.97
C14—H14C	0.96	C33—H33B	0.97
N15—H15A	0.86	S34—O35	1.412 (8)
N15—H16A	0.86	S34—C36	1.76 (1)
N16—C17	1.47 (2)	S34—O37	1.47 (1)
N16—C21	1.45 (2)	S34—O38	1.461 (9)
C17—C18	1.52 (2)	C36—H36A	0.96
C17—H17A	0.97	C36—H36B	0.96
C17—H17B	0.97	C36—H36C	0.96
C18—N19	1.47 (2)	O39—H39A	0.90
C18—H18A	0.97	O39—H39B	0.90
C18—H18B	0.97	O40—H40A	0.90
N19—C20	1.43 (1)	O40—H40B	0.90
C9—N1—H1	121	C20—N19—C22	123 (1)
C2—N1—H1	121	N19—C20—H20B	110
C2—N1—C9	119 (1)	N19—C20—H20A	109
N1—C2—N16	119 (1)	N19—C20—C21	110.8 (9)
N1—C2—N3	123 (1)	H20A—C20—H20B	108
N3—C2—N16	118 (1)	C21—C20—H20B	109
C2—N3—C4	122 (1)	C21—C20—H20A	109
N3—C4—N15	115 (1)	N16—C21—C20	109.7 (9)
N3—C4—C10	119 (1)	C20—C21—H21B	110
C10—C4—N15	125 (1)	C20—C21—H21A	110
C10—C5—H5	120	N16—C21—H21B	110
C6—C5—H5	119	N16—C21—H21A	110
C6—C5—C10	120 (1)	H21A—C21—H21B	108
C5—C6—O11	123 (1)	N19—C22—C24	116 (1)
C5—C6—C7	122 (1)	N19—C22—O23	122 (1)
C7—C6—O11	115 (1)	O23—C22—C24	122 (1)
C6—C7—O13	117 (1)	C22—C24—H24	110
C6—C7—C8	119 (1)	C22—C24—C33	111 (1)
C8—C7—O13	124 (1)	C22—C24—O25	107 (1)
C7—C8—H8	121	C33—C24—H24	110
C7—C8—C9	118 (1)	O25—C24—H24	110
C9—C8—H8	121	O25—C24—C33	109 (1)
N1—C9—C8	116 (1)	C24—O25—C26	113.7 (9)
C8—C9—C10	123 (1)	O25—C26—C31	121 (1)
N1—C9—C10	121 (1)	O25—C26—C27	118.3 (9)
C5—C10—C9	117 (1)	C27—C26—C31	121 (1)
C4—C10—C9	117 (1)	C26—C27—H27	120
C4—C10—C5	126 (1)	C26—C27—C28	119 (1)
C6—O11—C12	116.8 (8)	C28—C27—H27	120
O11—C12—H12C	109	C27—C28—H28	120
O11—C12—H12B	109	C27—C28—C29	120 (1)
O11—C12—H12A	109	C29—C28—H28	120
H12B—C12—H12C	109	C28—C29—H29	120
H12A—C12—H12C	110	C28—C29—C30	121 (1)
H12A—C12—H12B	110	C30—C29—H29	120
C7—O13—C14	116.9 (9)	C29—C30—H30	120
O13—C14—H14C	109	C29—C30—C31	119 (1)
O13—C14—H14B	109	C31—C30—H30	120
O13—C14—H14A	110	C26—C31—C30	119 (1)
H14B—C14—H14C	110	C30—C31—O32	118.3 (9)
H14A—C14—H14C	109	C26—C31—O32	121.6 (9)
H14A—C14—H14B	109	C31—O32—C33	115.6 (9)
C4—N15—H16A	120	C24—C33—O32	110 (1)
C4—N15—H15A	120	O32—C33—H33B	110
H15A—N15—H16A	120	O32—C33—H33A	110
C2—N16—C21	123 (1)	C24—C33—H33B	110
C2—N16—C17	122 (1)	C24—C33—H33A	110
C17—N16—C21	112.2 (9)	H33A—C33—H33B	108
N16—C17—H17B	110	O37—S34—O38	109.8 (5)
N16—C17—H17A	110	C36—S34—O38	107.3 (6)
N16—C17—C18	109 (1)	C36—S34—O37	109.6 (6)
H17A—C17—H17B	108	O35—S34—O38	110.0 (6)
C18—C17—H17B	110	O35—S34—O37	109.9 (6)
C18—C17—H17A	110	O35—S34—C36	110.3 (6)
C17—C18—H18B	110	S34—C36—H36C	110
C17—C18—H18A	110	S34—C36—H36B	109
C17—C18—N19	109 (1)	S34—C36—H36A	110
H18A—C18—H18B	108	H36B—C36—H36C	109
N19—C18—H18B	110	H36A—C36—H36C	109
N19—C18—H18A	110	H36A—C36—H36B	110
C18—N19—C22	122 (1)	H39A—O39—H39B	110
C18—N19—C20	115.3 (9)	H40A—O40—H40B	110