Transferability and reproducibility in electron-density studies - bond-topological and atomic properties of tripeptides of the type L-alanyl-X-L-alanine

In the last decade three different data bank approaches have been developed that are intended to make electron-density examinations of large biologically important molecules possible. They rely on Bader's concept of transferability of submolecular fragments with retention of their electronic properties. Therefore, elaborate studies on the quantification of transferability in experiment and theory are still very important. Tripeptides of the type L-alanyl-X-L-alanine (X being any of the 20 naturally encoded amino acids) serve as a model case between amino acids and proteins. The two experimental electron-density determinations (L-alanyl-L-histidinyl-L-alanine and L-alanyl-L-phenylalanyl-L-alanine, highly resolved synchrotron X-ray diffraction data sets) performed in this study and theoretical calculations on all 20 different L-alanyl-X-L-alanine molecules contribute to a better estimation of transferability in the peptide case. As a measure of reproducibility and transferability, standard deviations from averaging over bond-topological and atomic properties of atoms or bonds that are considered equal in their chemical environments were calculated. This way, transferability and reproducibility indices were introduced. It can be shown that experimental transferability indices generally slightly exceed experimental reproducibility indices and that these larger deviations can be attributed to chemical effects such as changes in the geometry (bond lengths and angles), the polarization pattern and the neighboring sphere due to crystal packing. These effects can partly be separated from each other and quantified with the help of gas-phase calculations at optimized and experimental geometries. Thus, the degree of transferability can be quantified in very narrow limits taking into account experimental errors and chemical effects.

Computing details

For both compounds, data collection: XDS Kabsch, W. J. Appl. Cryst. 26, 795 (1993); cell refinement: XDS Kabsch, W. J. Appl. Cryst. 26, 795 (1993); data reduction: XDS Kabsch, W. J. Appl. Cryst. 26, 795 (1993); program(s) used to solve structure: SHELXS97 (Sheldrick, 1990); program(s) used to refine structure: Volkov et al., (2006); molecular graphics: Volkov et al., (2006); software used to prepare material for publication: Volkov et al., (2006).

(AHA)

Crystal data

C12H19N5O4·C3H8O·H2O	F(000) = 404
Mr = 375.43	Dx = 1.269 Mg m^−3
Monoclinic, P21	Synchrotron radiation, λ = 0.56000 Å
Hall symbol: P 2yb	Cell parameters from 43348 reflections
a = 8.7410 (17) Å	θ = 2.2–40.6°
b = 9.4200 (19) Å	µ = 0.06 mm^−1
c = 11.989 (2) Å	T = 100 K
β = 95.49 (3)°	Block, colourless
V = 982.7 (3) Å^3	0.4 × 0.35 × 0.25 mm
Z = 2

Data collection

MarCCD 165 detector diffractometer	Rint = 0.027
phi scans	θmax = 40.6°, θmin = 2.2°
152583 measured reflections	h = −20→20
13235 independent reflections	k = 0→21
11918 reflections with > 3σ(I)	l = 0→27

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)] = 0.020	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.035	Only H-atom displacement parameters refined
S = 1.96	w2 = 1/[s^2(Fo^2)]
11918 reflections	(Δ/σ)max < 0.001
783 parameters	Δρmax = 0.14 e Å^−3
0 restraints	Δρmin = −0.22 e Å^−3

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

	x	y	z	Uiso*/Ueq
O1	0.93272 (6)	−0.19177 (5)	0.50612 (3)	0.018
O2	1.04547 (7)	0.16971 (6)	0.23879 (3)	0.021
O3	0.91839 (5)	0.05960 (6)	−0.08500 (3)	0.018
O4	1.11847 (6)	0.20542 (5)	−0.09695 (3)	0.018
O5	0.62491 (3)	0.06583 (5)	0.58438 (3)	0.017
O6	0.68186 (6)	−0.11637 (6)	−0.03402 (4)	0.020
N1	0.89037 (4)	−0.04533 (4)	0.69941 (2)	0.013
N2	0.96416 (3)	0.01900 (5)	0.41694 (2)	0.012
N3	1.04651 (4)	−0.02934 (5)	0.13043 (2)	0.013
N4	0.61009 (4)	0.13679 (5)	0.35754 (3)	0.016
N5	0.50568 (4)	0.24206 (6)	0.20176 (3)	0.019
C1	0.99961 (4)	0.01262 (5)	0.62189 (2)	0.013
C2	0.96204 (3)	−0.06221 (5)	0.50893 (2)	0.012
C3	0.93079 (4)	−0.04494 (1)	0.30621 (2)	0.011
C4	1.01201 (3)	0.04299 (4)	0.22128 (2)	0.012
C5	1.14237 (4)	0.03211 (5)	0.04935 (2)	0.014
C6	1.05053 (4)	0.10631 (5)	−0.05039 (2)	0.013
C7	1.16624 (4)	−0.01533 (6)	0.66851 (3)	0.022
C8	1.24118 (5)	−0.08525 (6)	0.00243 (3)	0.027
C9	0.75553 (4)	−0.06534 (5)	0.27437 (2)	0.013
C10	0.65792 (4)	0.06595 (5)	0.26470 (2)	0.014
C11	0.51869 (4)	0.24150 (5)	0.31573 (3)	0.019
C12	0.59320 (4)	0.13039 (5)	0.16797 (3)	0.018
C13	0.54317 (5)	0.14881 (7)	0.75869 (3)	0.022
C14	0.55861 (4)	0.18693 (5)	0.63619 (3)	0.016
C15	0.65668 (7)	0.31977 (7)	0.62597 (5)	0.028
H1	0.976938	0.127002	0.612904	0.025
H3	0.982426	−0.151328	0.306389	0.027
H5	1.215996	0.112432	0.094048	0.032
H7A	1.190659	0.041462	0.744358	0.044
H7B	1.241447	0.018591	0.609624	0.045
H7C	1.18175	−0.125315	0.68389	0.041
H8A	1.311567	−0.13261	0.069051	0.058
H8B	1.311165	−0.040358	−0.055775	0.046
H8C	1.16844	−0.16324	−0.038072	0.049
H9A	0.714423	−0.134593	0.338169	0.029
H9B	0.743389	−0.114375	0.206685	0.038
H11	0.465693	0.320938	0.363956	0.039
H12	0.601981	0.104345	0.081346	0.038
H1NA	0.906127	−0.153624	0.707812	0.026
H1NB	0.778768	−0.02497	0.666967	0.022
H1NC	0.910707	0.002481	0.776953	0.024
H2N	0.990045	0.123321	0.422018	0.019
H3N	1.008132	−0.130195	0.122447	0.022
H5N	0.438201	0.302693	0.147906	0.039
H13A	0.480651	0.052884	0.762236	0.040
H13B	0.483984	0.23104	0.796789	0.042
H13C	0.653792	0.135897	0.801795	0.042
H14	0.444371	0.203449	0.591343	0.032
H15A	0.762501	0.307875	0.675982	0.064
H15B	0.597583	0.409304	0.653698	0.056
H15C	0.677793	0.334468	0.541228	0.061
H5O	0.625723	0.087045	0.505525	0.022
H6OA	0.738167	−0.187592	0.0097	0.041
H6OB	0.76287	−0.052805	−0.049176	0.025

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.03078 (17)	0.00989 (10)	0.01166 (9)	−0.00084 (12)	0.00057 (10)	0.00064 (8)
O2	0.0356 (2)	0.01159 (11)	0.01757 (12)	−0.00638 (14)	0.00966 (13)	−0.00345 (10)
O3	0.01833 (14)	0.02400 (16)	0.01254 (10)	−0.00260 (14)	−0.00074 (9)	0.00078 (10)
O4	0.02296 (16)	0.01458 (12)	0.01618 (11)	−0.00018 (13)	0.00242 (11)	0.00542 (9)
O5	0.01968 (12)	0.01824 (11)	0.01398 (10)	0.00465 (10)	0.00020 (7)	−0.00019 (9)
O6	0.01970 (15)	0.02045 (15)	0.01999 (13)	−0.00232 (14)	−0.00244 (12)	−0.00213 (12)
N1	0.01603 (9)	0.01282 (8)	0.01063 (6)	0.00125 (8)	0.00158 (7)	0.00025 (6)
N2	0.01724 (11)	0.01000 (8)	0.00880 (7)	−0.00075 (7)	0.00120 (6)	−0.00001 (6)
N3	0.01985 (11)	0.01200 (9)	0.00884 (6)	−0.00195 (9)	0.00305 (7)	−0.00064 (6)
N4	0.01846 (11)	0.01795 (10)	0.01269 (9)	0.00440 (12)	0.00126 (8)	−0.00042 (8)
N5	0.01873 (12)	0.02024 (12)	0.01737 (12)	0.00426 (13)	−0.00204 (9)	0.00257 (10)
C1	0.01745 (12)	0.01211 (10)	0.00959 (7)	−0.00080 (9)	0.00121 (7)	−0.00058 (7)
C2	0.01792 (11)	0.00967 (9)	0.00908 (7)	0.00020 (8)	0.00086 (6)	0.00010 (6)
C3	0.01499 (10)	0.00998 (9)	0.00926 (7)	−0.00023 (9)	0.00169 (7)	−0.00011 (6)
C4	0.01696 (10)	0.01007 (9)	0.00945 (7)	−0.00112 (8)	0.00213 (7)	−0.00030 (6)
C5	0.01612 (11)	0.01556 (11)	0.01018 (8)	0.00040 (10)	0.00202 (8)	0.00221 (8)
C6	0.01704 (12)	0.01223 (10)	0.00946 (8)	0.00067 (10)	0.00145 (8)	0.00080 (7)
C7	0.01564 (12)	0.03430 (18)	0.01520 (10)	−0.00253 (12)	0.00064 (8)	−0.00392 (10)
C8	0.03115 (17)	0.02823 (17)	0.02364 (14)	0.01538 (15)	0.01357 (13)	0.01074 (12)
C9	0.01541 (11)	0.01222 (10)	0.01279 (9)	−0.00100 (9)	0.00119 (7)	−0.00146 (7)
C10	0.01486 (10)	0.01476 (10)	0.01151 (9)	0.00066 (10)	0.00048 (7)	−0.00022 (7)
C11	0.01872 (13)	0.01963 (13)	0.01752 (12)	0.00556 (13)	0.00065 (9)	−0.00034 (10)
C12	0.01988 (12)	0.02049 (13)	0.01269 (10)	0.00302 (13)	−0.00082 (8)	0.00101 (9)
C13	0.02067 (15)	0.02831 (18)	0.01582 (12)	0.00543 (15)	0.00182 (11)	−0.00132 (12)
C14	0.01461 (11)	0.01798 (12)	0.01618 (10)	0.00250 (10)	0.00023 (9)	−0.00092 (9)
C15	0.0293 (2)	0.02092 (18)	0.0335 (2)	−0.00416 (18)	0.00597 (18)	−0.00419 (16)

Geometric parameters (Å, º)

O1—C2	1.2468 (5)	C3—C9	1.5549 (5)
O2—C4	1.2421 (5)	C3—H3	1.0989
O3—C6	1.2682 (5)	C5—C6	1.5425 (4)
O4—C6	1.2646 (5)	C5—C8	1.5419 (6)
O5—C14	1.4463 (6)	C5—H5	1.0990
O5—H5O	0.9670	C7—H7A	1.0590
O6—H6OA	0.9580	C7—H7B	1.0589
O6—H6OB	0.9579	C7—H7C	1.0588
N1—C1	1.4978 (5)	C8—H8A	1.0591
N1—H1NA	1.0330	C8—H8B	1.0591
N1—H1NB	1.0330	C8—H8C	1.0587
N1—H1NC	1.0330	C9—C10	1.5007 (5)
N2—C2	1.3438 (4)	C9—H9A	1.0919
N2—C3	1.4615 (4)	C9—H9B	0.9309
N2—H2N	1.0090	C10—C12	1.3813 (5)
N3—C4	1.3432 (3)	C11—H11	1.0770
N3—C5	1.4622 (5)	C12—H12	1.0770
N3—H3N	1.0090	C13—C14	1.5304 (5)
N4—C10	1.3957 (5)	C13—H13A	1.0590
N4—C11	1.3364 (5)	C13—H13B	1.0590
N5—C11	1.3603 (6)	C13—H13C	1.0590
N5—C12	1.3839 (6)	C14—C15	1.5284 (6)
N5—H5N	1.0090	C14—H14	1.0990
C1—C2	1.5343 (4)	C15—H15A	1.0591
C1—C7	1.5322 (5)	C15—H15B	1.0590
C1—H1	1.0989	C15—H15C	1.0589
C3—C4	1.5380 (3)
C14—O5—H5O	107.31	C1—C7—H7A	109.44
H6OA—O6—H6OB	101.02	C1—C7—H7B	109.52
C1—N1—H1NA	109.48	C1—C7—H7C	109.46
C1—N1—H1NB	109.50	H7A—C7—H7B	109.45
C1—N1—H1NC	109.54	H7A—C7—H7C	109.44
H1NA—N1—H1NB	109.42	H7B—C7—H7C	109.52
H1NA—N1—H1NC	109.45	C5—C8—H8A	109.40
H1NB—N1—H1NC	109.45	C5—C8—H8B	109.46
C2—N2—C3	119.58 (3)	C5—C8—H8C	109.40
C2—N2—H2N	121.71	H8A—C8—H8B	109.55
C3—N2—H2N	118.71	H8A—C8—H8C	109.49
C4—N3—C5	121.71 (5)	H8B—C8—H8C	109.53
C4—N3—H3N	117.14	C3—C9—C10	117.17 (3)
C5—N3—H3N	121.07	C3—C9—H9A	106.52
C10—N4—C11	105.53 (3)	C3—C9—H9B	107.63
C11—N5—C12	107.19 (4)	C10—C9—H9A	108.89
C11—N5—H5N	129.24	C10—C9—H9B	108.96
C12—N5—H5N	123.27	H9A—C9—H9B	107.24
N1—C1—C2	106.55 (2)	N4—C10—C9	122.95 (3)
N1—C1—C7	110.57 (2)	N4—C10—C12	109.24 (3)
N1—C1—H1	107.37	C9—C10—C12	127.68 (3)
C2—C1—C7	111.03 (3)	N4—C11—N5	111.67 (4)
C2—C1—H1	110.03	N4—C11—H11	125.72
C7—C1—H1	111.13	N5—C11—H11	122.52
O1—C2—N2	123.64 (3)	N5—C12—C10	106.37 (3)
O1—C2—C1	119.98 (3)	N5—C12—H12	123.22
N2—C2—C1	116.38 (3)	C10—C12—H12	130.41
N2—C3—C4	108.34 (2)	C14—C13—H13A	109.39
N2—C3—C9	112.35 (2)	C14—C13—H13B	109.51
N2—C3—H3	109.14	C14—C13—H13C	109.58
C4—C3—C9	114.22 (2)	H13A—C13—H13B	109.37
C4—C3—H3	106.08	H13A—C13—H13C	109.45
C9—C3—H3	106.42	H13B—C13—H13C	109.54
O2—C4—N3	123.85 (3)	O5—C14—C13	107.62 (3)
O2—C4—C3	121.46 (3)	O5—C14—C15	111.13 (3)
N3—C4—C3	114.66 (3)	O5—C14—H14	106.51
N3—C5—C6	113.95 (3)	C13—C14—C15	111.76 (4)
N3—C5—C8	109.59 (3)	C13—C14—H14	110.08
N3—C5—H5	107.13	C15—C14—H14	109.59
C6—C5—C8	108.07 (3)	C14—C15—H15A	109.52
C6—C5—H5	107.65	C14—C15—H15B	109.43
C8—C5—H5	110.44	C14—C15—H15C	109.54
O3—C6—O4	124.28 (4)	H15A—C15—H15B	109.41
O3—C6—C5	119.12 (4)	H15A—C15—H15C	109.52
O4—C6—C5	116.43 (4)	H15B—C15—H15C	109.39
H5O—O5—C14—C13	174.85	N2—C3—C4—O2	−24.43 (4)
H5O—O5—C14—C15	−62.48	N2—C3—C4—N3	153.72 (4)
H5O—O5—C14—H14	56.82	N2—C3—C9—C10	62.45 (3)
H1NA—N1—C1—C2	60.33	N2—C3—C9—H9A	−59.68
H1NA—N1—C1—C7	−60.42	N2—C3—C9—H9B	−174.43
H1NA—N1—C1—H1	178.19	C9—C3—C4—O2	101.62 (4)
H1NB—N1—C1—C2	−59.63	C9—C3—C4—N3	−80.23 (3)
H1NB—N1—C1—C7	179.62	C4—C3—C9—C10	−61.48 (3)
H1NB—N1—C1—H1	58.24	C4—C3—C9—H9A	176.40
H1NC—N1—C1—C2	−179.66	C4—C3—C9—H9B	61.65
H1NC—N1—C1—C7	59.59	H3—C3—C4—O2	−141.50
H1NC—N1—C1—H1	−61.79	H3—C3—C4—N3	36.66
C3—N2—C2—O1	−0.03 (4)	H3—C3—C9—C10	−178.17
C3—N2—C2—C1	179.50 (5)	H3—C3—C9—H9A	59.71
C2—N2—C3—C4	−153.40 (4)	H3—C3—C9—H9B	−55.04
C2—N2—C3—C9	79.46 (3)	N3—C5—C6—O3	−31.70 (4)
C2—N2—C3—H3	−38.32	N3—C5—C6—O4	152.85 (5)
H2N—N2—C2—O1	−178.98	N3—C5—C8—H8A	−59.50
H2N—N2—C2—C1	0.55	N3—C5—C8—H8B	−179.54
H2N—N2—C3—C4	25.58	N3—C5—C8—H8C	60.44
H2N—N2—C3—C9	−101.55	C8—C5—C6—O3	90.36 (5)
H2N—N2—C3—H3	140.66	C8—C5—C6—O4	−85.09 (4)
C5—N3—C4—O2	6.80 (4)	C6—C5—C8—H8A	175.80
C5—N3—C4—C3	−171.31 (5)	C6—C5—C8—H8B	55.75
C4—N3—C5—C6	−93.31 (4)	C6—C5—C8—H8C	−64.26
C4—N3—C5—C8	145.47 (5)	H5—C5—C6—O3	−150.35
C4—N3—C5—H5	25.64	H5—C5—C6—O4	34.20
H3N—N3—C4—O2	−176.38	H5—C5—C8—H8A	58.29
H3N—N3—C4—C3	5.51	H5—C5—C8—H8B	−61.76
H3N—N3—C5—C6	90.00	H5—C5—C8—H8C	178.23
H3N—N3—C5—C8	−31.23	C3—C9—C10—N4	−79.19 (4)
H3N—N3—C5—H5	−151.06	C3—C9—C10—C12	105.45 (5)
C10—N4—C11—N5	−0.19 (4)	H9A—C9—C10—N4	41.70
C11—N4—C10—C9	−176.20 (5)	H9A—C9—C10—C12	−133.66
C11—N4—C10—C12	−0.09 (4)	H9B—C9—C10—N4	158.37
C10—N4—C11—H11	−176.77	H9B—C9—C10—C12	−16.99
C12—N5—C11—N4	0.39 (4)	N4—C10—C12—N5	0.32 (3)
C11—N5—C12—C10	−0.43 (4)	N4—C10—C12—H12	−178.71
C12—N5—C11—H11	177.10	C9—C10—C12—N5	176.20 (6)
C11—N5—C12—H12	178.69	C9—C10—C12—H12	−2.83
H5N—N5—C11—N4	174.25	H13A—C13—C14—O5	−54.13
H5N—N5—C11—H11	−9.04	H13A—C13—C14—C15	−176.41
H5N—N5—C12—C10	−174.74	H13A—C13—C14—H14	61.58
H5N—N5—C12—H12	4.38	H13B—C13—C14—O5	−173.97
N1—C1—C2—O1	−41.28 (4)	H13B—C13—C14—C15	63.75
N1—C1—C2—N2	139.17 (4)	H13B—C13—C14—H14	−58.27
N1—C1—C7—H7A	−64.68	H13C—C13—C14—O5	65.86
N1—C1—C7—H7B	175.33	H13C—C13—C14—C15	−56.42
N1—C1—C7—H7C	55.25	H13C—C13—C14—H14	−178.44
C7—C1—C2—O1	79.18 (4)	O5—C14—C15—H15A	−68.31
C7—C1—C2—N2	−100.37 (4)	O5—C14—C15—H15B	171.76
C2—C1—C7—H7A	177.27	O5—C14—C15—H15C	51.83
C2—C1—C7—H7B	57.28	C13—C14—C15—H15A	51.94
C2—C1—C7—H7C	−62.80	C13—C14—C15—H15B	−68.00
H1—C1—C2—O1	−157.37	C13—C14—C15—H15C	172.08
H1—C1—C2—N2	23.08	H14—C14—C15—H15A	174.24
H1—C1—C7—H7A	54.45	H14—C14—C15—H15B	54.30
H1—C1—C7—H7B	−65.54	H14—C14—C15—H15C	−65.62
H1—C1—C7—H7C	174.38

(AFA)

Crystal data

C15H21N3O4·C3H7NO	F(000) = 408
Mr = 380.44	Dx = 1.278 Mg m^−3
Monoclinic, P21	Synchrotron radiation, λ = 0.56000 Å
Hall symbol: P 2yb	Cell parameters from 53159 reflections
a = 9.598 (2) Å	θ = 1.4–40.6°
b = 8.9390 (5) Å	µ = 0.06 mm^−1
c = 12.170 (1) Å	T = 100 K
β = 108.754 (13)°	Block, colourless
V = 988.7 (2) Å^3	0.45 × 0.25 × 0.15 mm
Z = 2

Data collection

MarCCD 165 detector diffractometer	Rint = 0.059
phi scans	θmax = 40.6°, θmin = 1.4°
180324 measured reflections	h = −22→21
13499 independent reflections	k = 0→20
12060 reflections with > 3σ(I)	l = 0→28

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)] = 0.022	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.033	Only H-atom displacement parameters refined
S = 1.95	w2 = 1/[s^2(Fo^2)]
12060 reflections	(Δ/σ)max < 0.001
733 parameters	Δρmax = 0.32 e Å^−3
0 restraints	Δρmin = −0.34 e Å^−3

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

	x	y	z	Uiso*/Ueq
O1	0.41602 (4)	0.03249 (5)	0.98625 (3)	0.013
O2	0.49704 (6)	0.42296 (5)	0.73918 (4)	0.018
O3	0.34281 (5)	0.22011 (6)	0.40702 (4)	0.018
O4	0.46376 (5)	0.40284 (5)	0.35069 (3)	0.015
O5	1.09598 (6)	0.14282 (9)	1.03306 (5)	0.024
N1	0.38701 (3)	0.19428 (4)	1.17191 (2)	0.012
N2	0.44902 (3)	0.24831 (4)	0.89919 (2)	0.010
N3	0.52174 (3)	0.22564 (4)	0.62873 (2)	0.011
N4	0.95075 (5)	0.01790 (5)	0.87476 (4)	0.021
C1	0.47977 (4)	0.25263 (4)	1.10496 (2)	0.011
C2	0.44431 (3)	0.16793 (4)	0.99066 (2)	0.009
C3	0.42384 (3)	0.181506	0.78548 (2)	0.009
C4	0.48717 (3)	0.28776 (4)	0.71546 (2)	0.010
C5	0.56755 (4)	0.31186 (5)	0.54473 (2)	0.012
C6	0.44539 (4)	0.31227 (5)	0.42592 (2)	0.011
C7	0.64202 (4)	0.23458 (5)	1.17559 (2)	0.017
C8	0.70678 (4)	0.24311 (6)	0.53019 (3)	0.021
C9	0.25852 (4)	0.15243 (5)	0.71995 (2)	0.012
C10	0.16414 (3)	0.29129 (4)	0.69258 (2)	0.012
C11	0.10073 (3)	0.34890 (5)	0.77238 (3)	0.017
C12	0.01112 (4)	0.47565 (5)	0.74611 (3)	0.021
C13	−0.01604 (4)	0.54699 (5)	0.63941 (3)	0.022
C14	0.04886 (4)	0.49203 (5)	0.56023 (3)	0.019
C15	0.13818 (3)	0.36516 (5)	0.58644 (3)	0.015
C16	0.82369 (6)	0.10904 (11)	0.86693 (7)	0.040
C17	0.94126 (6)	−0.08887 (8)	0.78187 (5)	0.030
C18	1.07712 (4)	0.04380 (6)	0.95823 (4)	0.019
H1	0.452959	0.37054	1.082231	0.021 (2)
H3	0.480838	0.073433	0.793462	0.018 (2)
H5	0.591231	0.426197	0.578813	0.019 (2)
H7A	0.666899	0.119557	1.191324	0.0311 (18)
H7B	0.664089	0.291744	1.255595	0.0316 (18)
H7C	0.707709	0.280285	1.12869	0.039 (2)
H8A	0.686163	0.130175	0.503673	0.040 (2)
H8B	0.793497	0.247293	0.610224	0.045 (2)
H8C	0.737254	0.30325	0.466481	0.042 (2)
H9A	0.214557	0.078771	0.772422	0.028 (2)
H9B	0.25127	0.094828	0.652297	0.034 (2)
H11	0.121137	0.302586	0.858364	0.037 (2)
H12	−0.043392	0.512746	0.806581	0.038 (2)
H13	−0.094529	0.638143	0.61937	0.043 (3)
H14	0.035583	0.548639	0.478815	0.038 (2)
H15	0.185068	0.318684	0.523982	0.0296 (19)
H1NA	0.27998	0.182269	1.117592	0.019 (3)
H1NB	0.389296	0.268259	1.237675	0.019 (3)
H1NC	0.426805	0.091666	1.207301	0.017 (2)
H2N	0.47864	0.357075	0.908311	0.016 (2)
H3N	0.511838	0.113214	0.626138	0.013 (2)
H16A	0.83443	0.215781	0.831436	0.058 (4)
H16B	0.816037	0.123994	0.951706	0.070 (4)
H16C	0.726345	0.054677	0.814076	0.069 (4)
H17A	1.037629	−0.156827	0.804914	0.064 (4)
H17B	0.932241	−0.029396	0.703958	0.070 (4)
H17C	0.846573	−0.157727	0.768547	0.068 (4)
H18	1.16673	−0.031806	0.956612	0.041 (3)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.02140 (13)	0.00771 (9)	0.00891 (9)	−0.00070 (9)	0.00525 (9)	−0.00034 (8)
O2	0.03392 (19)	0.00955 (11)	0.01571 (13)	−0.00490 (12)	0.01437 (14)	−0.00369 (10)
O3	0.01592 (14)	0.02323 (15)	0.01313 (12)	−0.00700 (13)	0.00124 (11)	0.00187 (12)
O4	0.02457 (15)	0.01287 (11)	0.00828 (10)	−0.00061 (11)	0.00650 (11)	0.00141 (8)
O5	0.01969 (18)	0.0336 (2)	0.01581 (15)	−0.00202 (18)	0.00293 (14)	−0.00233 (17)
N1	0.01707 (9)	0.01300 (8)	0.00733 (7)	0.00220 (7)	0.00504 (7)	0.00032 (6)
N2	0.01698 (11)	0.00854 (8)	0.00611 (7)	−0.00077 (6)	0.00440 (6)	−0.00030 (7)
N3	0.01752 (11)	0.00980 (9)	0.00709 (7)	−0.00075 (6)	0.00592 (8)	−0.00081 (6)
N4	0.01352 (12)	0.02946 (16)	0.01740 (11)	−0.00334 (12)	0.00086 (12)	0.00169 (12)
C1	0.01738 (11)	0.00881 (8)	0.00659 (8)	−0.00051 (8)	0.00357 (8)	−0.00048 (7)
C2	0.01399 (10)	0.00794 (8)	0.00592 (8)	0.00042 (6)	0.00333 (6)	−0.00001 (7)
C3	0.01290 (10)	0.00854 (8)	0.00644 (8)	0.00011 (8)	0.00348 (7)	−0.00034 (7)
C4	0.01423 (10)	0.00855 (8)	0.00623 (7)	−0.00081 (7)	0.00396 (7)	−0.00085 (6)
C5	0.01535 (11)	0.01335 (10)	0.00683 (8)	−0.00302 (9)	0.00414 (8)	−0.00079 (8)
C6	0.01457 (11)	0.01122 (9)	0.00703 (9)	0.00056 (9)	0.00381 (8)	−0.00004 (7)
C7	0.01654 (12)	0.02048 (12)	0.01141 (9)	−0.00407 (9)	0.00138 (8)	0.00012 (8)
C8	0.01347 (10)	0.03531 (17)	0.01513 (11)	0.00102 (11)	0.00583 (8)	0.00309 (11)
C9	0.01292 (10)	0.01116 (9)	0.01108 (9)	−0.00087 (8)	0.00302 (8)	−0.00132 (7)
C10	0.01263 (9)	0.01371 (9)	0.01036 (9)	0.00099 (9)	0.00389 (7)	0.00039 (7)
C11	0.01937 (12)	0.01883 (11)	0.01439 (11)	0.00418 (10)	0.00894 (9)	0.00142 (9)
C12	0.02342 (14)	0.02278 (13)	0.02170 (13)	0.00833 (12)	0.01204 (12)	0.00085 (11)
C13	0.02037 (14)	0.02050 (13)	0.02414 (16)	0.00843 (12)	0.00781 (11)	0.00389 (11)
C14	0.01806 (12)	0.02210 (13)	0.01720 (12)	0.00612 (11)	0.00495 (10)	0.00641 (10)
C15	0.01528 (10)	0.01933 (11)	0.01110 (9)	0.00369 (9)	0.00420 (8)	0.00269 (8)
C16	0.0173 (2)	0.0551 (4)	0.0392 (3)	0.0075 (2)	−0.0016 (2)	−0.0060 (3)
C17	0.0236 (2)	0.0389 (2)	0.0246 (2)	−0.01205 (19)	0.00533 (16)	−0.0076 (2)
C18	0.01327 (13)	0.02680 (15)	0.01575 (12)	−0.00188 (12)	0.00116 (11)	0.00165 (13)

Geometric parameters (Å, º)

O1—C2	1.2382 (4)	C7—H7A	1.0590
O2—C4	1.2391 (4)	C7—H7B	1.0590
O3—C6	1.2471 (5)	C7—H7C	1.0590
O4—C6	1.2762 (4)	C8—H8A	1.0590
O5—C18	1.2407 (7)	C8—H8B	1.0590
N1—C1	1.4815 (4)	C8—H8C	1.0590
N1—H1NA	1.0330	C9—C10	1.5094 (4)
N1—H1NB	1.0330	C9—H9A	1.0920
N1—H1NC	1.0330	C9—H9B	0.9545
N2—C2	1.3378 (4)	C10—C11	1.3996 (4)
N2—C3	1.4543 (4)	C10—C15	1.3999 (4)
N2—H2N	1.0090	C11—C12	1.3961 (5)
N3—C4	1.3258 (4)	C11—H11	1.0830
N3—C5	1.4565 (4)	C12—C13	1.3940 (5)
N3—H3N	1.0090	C12—H12	1.0830
N4—C16	1.4441 (8)	C13—C14	1.3941 (5)
N4—C17	1.4598 (7)	C13—H13	1.0830
N4—C18	1.3284 (6)	C14—C15	1.3954 (4)
C1—C2	1.5231 (4)	C14—H14	1.0830
C1—C7	1.5262 (5)	C15—H15	1.0830
C1—H1	1.0990	C16—H16A	1.0660
C3—C4	1.5267 (4)	C16—H16B	1.0660
C3—C9	1.5517 (4)	C16—H16C	1.0660
C3—H3	1.0990	C17—H17A	1.0660
C5—C6	1.5412 (4)	C17—H17B	1.0660
C5—C8	1.5320 (5)	C17—H17C	1.0660
C5—H5	1.0990	C18—H18	1.0990
C1—N1—H1NA	109.54	H7B—C7—H7C	109.37
C1—N1—H1NB	109.51	C5—C8—H8A	109.46
C1—N1—H1NC	109.57	C5—C8—H8B	109.66
H1NA—N1—H1NB	109.35	C5—C8—H8C	109.72
H1NA—N1—H1NC	109.44	H8A—C8—H8B	109.18
H1NB—N1—H1NC	109.42	H8A—C8—H8C	109.23
C2—N2—C3	122.10 (3)	H8B—C8—H8C	109.58
C2—N2—H2N	120.64	C3—C9—C10	114.68 (2)
C3—N2—H2N	117.07	C3—C9—H9A	108.91
C4—N3—C5	123.13 (3)	C3—C9—H9B	108.21
C4—N3—H3N	113.38	C10—C9—H9A	107.92
C5—N3—H3N	123.49	C10—C9—H9B	112.40
C16—N4—C17	118.47 (5)	H9A—C9—H9B	104.15
C16—N4—C18	119.75 (5)	C9—C10—C11	120.89 (3)
C17—N4—C18	121.36 (4)	C9—C10—C15	120.51 (2)
N1—C1—C2	109.27 (2)	C11—C10—C15	118.60 (3)
N1—C1—C7	109.75 (2)	C10—C11—C12	120.86 (3)
N1—C1—H1	110.04	C10—C11—H11	123.09
C2—C1—C7	110.47 (2)	C12—C11—H11	115.99
C2—C1—H1	106.34	C11—C12—C13	120.10 (3)
C7—C1—H1	110.92	C11—C12—H12	119.31
O1—C2—N2	123.69 (3)	C13—C12—H12	120.43
O1—C2—C1	120.48 (3)	C12—C13—C14	119.43 (4)
N2—C2—C1	115.82 (2)	C12—C13—H13	117.52
N2—C3—C4	107.55 (2)	C14—C13—H13	122.85
N2—C3—C9	112.80 (2)	C13—C14—C15	120.44 (3)
N2—C3—H3	110.56	C13—C14—H14	121.36
C4—C3—C9	110.01 (2)	C15—C14—H14	118.15
C4—C3—H3	108.66	C10—C15—C14	120.55 (3)
C9—C3—H3	107.21	C10—C15—H15	118.41
O2—C4—N3	125.03 (3)	C14—C15—H15	120.98
O2—C4—C3	119.41 (3)	N4—C16—H16A	110.00
N3—C4—C3	115.49 (3)	N4—C16—H16B	109.05
N3—C5—C6	110.45 (3)	N4—C16—H16C	109.90
N3—C5—C8	109.89 (3)	H16A—C16—H16B	109.01
N3—C5—H5	107.44	H16A—C16—H16C	110.10
C6—C5—C8	108.75 (2)	H16B—C16—H16C	108.75
C6—C5—H5	110.77	N4—C17—H17A	109.63
C8—C5—H5	109.53	N4—C17—H17B	109.25
O3—C6—O4	124.73 (4)	N4—C17—H17C	109.46
O3—C6—C5	119.26 (3)	H17A—C17—H17B	109.49
O4—C6—C5	115.83 (3)	H17A—C17—H17C	109.64
C1—C7—H7A	109.54	H17B—C17—H17C	109.34
C1—C7—H7B	109.45	O5—C18—N4	124.58 (5)
C1—C7—H7C	109.40	O5—C18—H18	121.43
H7A—C7—H7B	109.59	N4—C18—H18	113.99
H7A—C7—H7C	109.47
H1NA—N1—C1—C2	−44.85	N2—C3—C4—O2	−25.91 (3)
H1NA—N1—C1—C7	−166.12	N2—C3—C4—N3	157.00 (3)
H1NA—N1—C1—H1	71.55	N2—C3—C9—C10	62.63 (3)
H1NB—N1—C1—C2	−164.77	N2—C3—C9—H9A	−58.39
H1NB—N1—C1—C7	73.96	N2—C3—C9—H9B	−171.02
H1NB—N1—C1—H1	−48.37	C9—C3—C4—O2	97.30 (4)
H1NC—N1—C1—C2	75.21	C9—C3—C4—N3	−79.79 (3)
H1NC—N1—C1—C7	−46.05	C4—C3—C9—C10	−57.45 (3)
H1NC—N1—C1—H1	−168.38	C4—C3—C9—H9A	−178.47
C3—N2—C2—O1	−1.32 (3)	C4—C3—C9—H9B	68.90
C3—N2—C2—C1	177.37 (4)	H3—C3—C4—O2	−145.61
C2—N2—C3—C4	−161.15 (4)	H3—C3—C4—N3	37.30
C2—N2—C3—C9	77.37 (3)	H3—C3—C9—C10	−175.44
C2—N2—C3—H3	−42.66	H3—C3—C9—H9A	63.54
H2N—N2—C2—O1	−176.26	H3—C3—C9—H9B	−49.09
H2N—N2—C2—C1	2.42	N3—C5—C6—O3	−15.02 (4)
H2N—N2—C3—C4	13.97	N3—C5—C6—O4	169.61 (5)
H2N—N2—C3—C9	−107.51	N3—C5—C8—H8A	57.77
H2N—N2—C3—H3	132.46	N3—C5—C8—H8B	−61.98
C5—N3—C4—O2	−4.10 (4)	N3—C5—C8—H8C	177.62
C5—N3—C4—C3	172.80 (4)	C8—C5—C6—O3	105.65 (5)
C4—N3—C5—C6	−108.22 (4)	C8—C5—C6—O4	−69.73 (4)
C4—N3—C5—C8	131.80 (4)	C6—C5—C8—H8A	−63.24
C4—N3—C5—H5	12.70	C6—C5—C8—H8B	177.01
H3N—N3—C4—O2	176.67	C6—C5—C8—H8C	56.60
H3N—N3—C4—C3	−6.42	H5—C5—C6—O3	−133.93
H3N—N3—C5—C6	70.93	H5—C5—C6—O4	50.69
H3N—N3—C5—C8	−49.06	H5—C5—C8—H8A	175.58
H3N—N3—C5—H5	−168.16	H5—C5—C8—H8B	55.83
C17—N4—C16—H16A	−96.84	H5—C5—C8—H8C	−64.58
C17—N4—C16—H16B	143.66	C3—C9—C10—C11	−87.67 (4)
C17—N4—C16—H16C	24.54	C3—C9—C10—C15	92.37 (4)
C16—N4—C17—H17A	−172.88	H9A—C9—C10—C11	33.89
C16—N4—C17—H17B	67.12	H9A—C9—C10—C15	−146.07
C16—N4—C17—H17C	−52.58	H9B—C9—C10—C11	148.17
C16—N4—C18—O5	0.28 (6)	H9B—C9—C10—C15	−31.79
C18—N4—C16—H16A	75.85	C9—C10—C11—C12	−178.74 (5)
C18—N4—C16—H16B	−43.64	C9—C10—C11—H11	4.09
C18—N4—C16—H16C	−162.76	C9—C10—C15—C14	178.87 (5)
C16—N4—C18—H18	179.89	C9—C10—C15—H15	1.52
C17—N4—C18—O5	172.76 (8)	C15—C10—C11—C12	1.22 (3)
C18—N4—C17—H17A	14.55	C11—C10—C15—C14	−1.09 (3)
C18—N4—C17—H17B	−105.45	C15—C10—C11—H11	−175.95
C18—N4—C17—H17C	134.85	C11—C10—C15—H15	−178.44
C17—N4—C18—H18	−7.63	C10—C11—C12—C13	−0.18 (4)
N1—C1—C2—O1	−36.98 (3)	C10—C11—C12—H12	175.24
N1—C1—C2—N2	144.29 (4)	H11—C11—C12—C13	177.18
N1—C1—C7—H7A	62.19	H11—C11—C12—H12	−7.40
N1—C1—C7—H7B	−57.99	C11—C12—C13—C14	−1.00 (4)
N1—C1—C7—H7C	−177.81	C11—C12—C13—H13	174.14
C7—C1—C2—O1	83.85 (4)	H12—C12—C13—C14	−176.37
C7—C1—C2—N2	−94.88 (3)	H12—C12—C13—H13	−1.23
C2—C1—C7—H7A	−58.35	C12—C13—C14—C15	1.13 (4)
C2—C1—C7—H7B	−178.53	C12—C13—C14—H14	−176.18
C2—C1—C7—H7C	61.65	H13—C13—C14—C15	−173.74
H1—C1—C2—O1	−155.71	H13—C13—C14—H14	8.95
H1—C1—C2—N2	25.56	C13—C14—C15—C10	−0.08 (3)
H1—C1—C7—H7A	−176.02	C13—C14—C15—H15	177.20
H1—C1—C7—H7B	63.80	H14—C14—C15—C10	177.32
H1—C1—C7—H7C	−56.02	H14—C14—C15—H15	−5.40