N-(L-2-Aminobutyryl)-L-alanine and 2-(L-alanylamino)-L-butyric acid 0.33-hydrate

The crystal structure of N-(L-2-amino­butyryl)-L-alanine, C₇H₁₄N₂O₃, is closely related to the structure of L-alanyl-L-alanine, both being tetragonal, while the retro-analogue 2-(L-alanyl­amino)-L-butyric acid 0.33-hydrate, C₇H₁₄N₂O₃·­0.33H₂O, forms a new type of molecular columnar structure with three peptide mol­ecules in the asymmetric unit.

S1. Comment

Recent investigations into the structures of dipeptides with two hydrophobic residues (Ala, Val, Leu, Ile or Phe; the stereochemical indicator L is common to all residues discussed in this paper and so is omitted) have revealed a diverse set of hydrogen-bond and crystal-packing arrangements [see Görbitz (2002a) for an overview and a complete set of references]. Some patterns, however, recur in two or more structures. One example is the hexagonally symmetric hydrophobic columns with empty central channels first observed for Val-Ala (Görbitz & Gundersen, 1996), which were subsequently found not only for the retroanalogue Ala-Val (Görbitz, 2002b), but also for a series of other dipeptides containing Ala, Val and Ile residues (Görbitz, 2003). Finding such stable motifs is a key element in establishing peptides as useful model molecules for the design of materials by crystal engineering (Desiraju, 2001).

The size of the pores in a Val-Ala class structure is inversely related to the bulk of the two side chains. Val-Ala (Görbitz & Gundersen, 1996) and Ala-Val (Görbitz, 2002b) possess the largest known pores, with diameters of around 5 Å. Both these dipeptides have a total of four side-chain C atoms. In order to see if still larger pores could be attained by reducing the number of side-chain C atoms to three, a crystal structure investigation was undertaken for the two title compounds, N-(L-2-aminobutyryl)-L-alanine or Abu-Ala, (I) (Fig. 1), and 2-(L-alanylamino)-L-butyric acid 0.33-hydrate or Ala-Abu, (II) (Fig. 2). As for a further reduction of the number of side-chain C atoms to two, the structure of Ala-Ala (Fletterick et al., 1971) is the only peptide structure in the Cambridge Structural Database (Version?; Allen & Kennard, 1993) with tetragonal symmetry, and is not a member of the Val-Ala class. \sch

The crystal packing of (I) is shown together with that of Ala-Ala (Fletterick et al., 1971) in Fig. 3. The two structures are almost indistinguishable, except that the empty central channels of the Ala₁ hydrophobic columns in Ala-Ala are filled by Abu₂ C^γ methyl groups in (I). The calculated density for (I) (1.379 Mg m^-3) is well above the value of 1.276 Mg m^-3 for Ala-Ala (Fletterick et al., 1971), which used to be the highest value observed for a hydrophobic dipeptide.

The peptide main chain of (I) is in an extended conformation (Fig. 1) and the bond lengths and angles are normal. To avoid steric conflict, there is a 1:1 disorder for the Abu side chain (Fig. 4). The somewhat unusual torsion angles associated with the two alternative orientations, -81.8 (7) and 79.1 (8)° (Table 1), have the curious effect of putting the two C^γ methyl positions on top of each other when viewed along the c axis, as in Fig. 3. The shortest intermolecular H···H contacts between the four molecules related by fourfold symmetry is 2.44 Å, while H···H contacts between quartets related by translation along the c axis start at 2.80 Å. As for Ala-Ala, the tetragonal symmetry renders possible the formation of three strong –NH₃⁺···^-OOC– hydrogen bonds (Table 2), which set these two structures apart from all other structures of hydrophobic dipeptides.

As is evident from Fig. 3, the columns formed by Ala₂ in the Ala-Ala structure (Fletterick et al., 1971) are more densely packed than the Ala₁ columns. Compared with (I), it thus seemed less likely that (II) would retain an Ala-Ala class structure. Indeed, Fig. 5 shows a completely new type of packing pattern that combines elements from the Ala-Ala class, such as the separation of residue 1 and residue 2 side chains into independent columns, with elements from the Val-Ala class, such as the pseudohexagonal arrangement of Ala₁ columns around Abu₂ columns. A unique feature of (II) is a co-crystallized water molecule that is essential for completing the hydrogen-bond network in the crystal. The result is a well defined structure with D_x = 1.282 Mg m^-3.

The three peptide molecules in the asymmetric unit of (II) are in extended conformations with normal bond lengths and angles, and are not related by pseudosymmetry. They differ mainly in the orientation of the Abu side chain, which is trans for molecule B but gauche for A and C (Fig. 2 and Table 4). The observation of Z' = 3 is actually quite rare for peptides, and only eight other examples were found in the Cambridge Structural Database (Version?; Allen & Kennard, 1993).

In conclusion, since neither (I) nor (II) form Val-Ala class structures, the largest known hydrophobic pores still occur in the structures of Val-Ala (Görbitz & Gundersen, 1996) and Ala-Val (Görbitz, 2002b).

S2. Experimental

Both title compounds were obtained from Bachem and used as received. Crystals were grown by fast evaporation of aqueous solutions at ambient temperature. The crystals of (II) were of high quality, but the crystals of (I) were usually twinned and/or displayed obvious orientational disorder for layers along the c axis. The specimen selected for data collection was fairly small, but not twinned.

S3. Refinement

Due to problems with the crystal quality for (I), the refinement converged at a considerably higher R-factor than for (II), with higher s.u.s for the geometric parameters. Isotropic refinement of H atoms was thus limited to those bonded to N and O in (II); other H atoms were placed geometrically and refined with C—H = 0.92–1.01 Å and N—H 0.86–0.92 Å. Are these the correct constraints? Free rotation of amino and methyl groups (without disorder) was permitted. U_iso values were 1.2U_eq of the carrier atom, or 1.5U_eq for methyl and amino groups. Friedel pairs were merged in the final refinement of (I). The Flack parameter [-0.6 (4); Flack, 1983] for (II) did not allow the absolute structure, which was known for the purchased material, to be determined from the refinement (Flack & Bernadinelli, 2000).

Computing details

For both compounds, data collection: SMART (Bruker, 1998); cell refinement: SAINT (Bruker, 1998); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Bruker, 2000); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL.

Figures

	Fig. 1. A view of the molecule of (I) with the atomic numbering scheme. Displacement ellipsoids are shown at the 50% probability level and H atoms are shown as small spheres of arbitrary radii. Two alternative Abu side chain orientations, each with occupancy 1/2, are shown. The H atoms bonded to C2 have been omitted for clarity.
	Fig. 2. A view of the three independent molecules of (II) with the atomic numbering scheme. Displacement ellipsoids are shown at the 50% probability level and H atoms are shown as small spheres of arbitrary radii.
	Fig. 3. The molecular packing and unit cells of (a) Ala-Ala (Fletterick et al., 1971) and (b) (I), both viewed along the c axis. A volume contour surface surrounds selected molecules in each structure to illustrate the presence of two types of hydrophobic columns. Atoms in the side chain of residue 2 are shown in a darker tone than atoms in the side chain of residue 1.
	Fig. 4. A stereo drawing of the hydrophobic interactions of an Abu column in the structure of (I). Alternative side-chain positions prohibited by steric conflict are shown by fine lines. Directly opposing mutually exclusive methyl positions have H···H separations as short as 1.09 Å.
	Fig. 5. The molecular packing and unit cell of (II) viewed along the b axis. Atoms in the Abu side chain are shown in a darker tone than those in the Ala side chain. The three peptide molecules in the asymmetric unit are labelled A, B and C.

(I) N-(L-2-aminobutyryl)-L-alanine

Crystal data

C7H14N2O3	Dx = 1.379 Mg m^−3
Mr = 174.20	Mo Kα radiation, λ = 0.71073 Å
Tetragonal, I4	Cell parameters from 3540 reflections
Hall symbol: I 4	θ = 1.6–27.1°
a = 17.9290 (12) Å	µ = 0.11 mm^−1
c = 5.2196 (5) Å	T = 105 K
V = 1677.8 (2) Å^3	Needle, colourless
Z = 8	0.65 × 0.12 × 0.05 mm
F(000) = 752

Data collection

Bruker SMART CCD area-detector diffractometer	1029 independent reflections
Radiation source: fine-focus sealed tube	1001 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.041
Detector resolution: 8.3 pixels mm^-1	θmax = 27.1°, θmin = 1.6°
Sets of exposures each taken over 0.3° ω rotation scans	h = −22→16
Absorption correction: empirical (using intensity measurements) (SADABS; Sheldrick, 1996)	k = −22→22
Tmin = 0.932, Tmax = 0.995	l = −6→6
5085 measured reflections

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)] = 0.079	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.180	H-atom parameters constrained
S = 1.27	w = 1/[σ^2(Fo^2) + (0.0203P)^2 + 13.6465P] where P = (Fo^2 + 2Fc^2)/3
1029 reflections	(Δ/σ)max = 0.003
121 parameters	Δρmax = 0.36 e Å^−3
13 restraints	Δρmin = −0.39 e Å^−3

Special details

Experimental. Data were collected by measuring three sets (I) and five sets (II) of exposures with the detector set at 2θ = 29°, crystal-to-detector distance 4.98 cm.

Refinement. Refinement of F² against ALL reflections.

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

	x	y	z	Uiso*/Ueq	Occ. (<1)
O1	0.7237 (2)	−0.1241 (2)	0.2407 (8)	0.0183 (9)
O2	0.7414 (2)	0.1470 (2)	0.2108 (10)	0.0191 (9)
O3	0.7550 (3)	0.0763 (3)	−0.1333 (9)	0.0250 (11)
N1	0.7920 (3)	−0.1870 (3)	0.6360 (12)	0.0168 (11)
H1	0.827 (3)	−0.2019 (7)	0.755 (8)	0.025*
H2	0.808 (3)	−0.2014 (7)	0.476 (8)	0.025*
H3	0.747 (2)	−0.2088 (10)	0.672 (10)	0.025*
N2	0.7187 (3)	−0.0067 (3)	0.4167 (11)	0.0162 (11)
H4	0.7306	0.0196	0.5483	0.019*
C1	0.7841 (3)	−0.1040 (3)	0.6442 (12)	0.0122 (11)
H11	0.7567	−0.0905	0.8000	0.015*
C2	0.8606 (3)	−0.0666 (3)	0.6536 (13)	0.0173 (12)
H21	0.8930	−0.0939	0.7692	0.021*	0.50
H22	0.8555	−0.0161	0.7179	0.021*	0.50
H23	0.8563	−0.0159	0.5905	0.021*	0.50
H24	0.8946	−0.0933	0.5419	0.021*	0.50
C31	0.8967 (7)	−0.0648 (8)	0.374 (3)	0.021 (3)	0.50
H31	0.9445	−0.0408	0.3819	0.032*	0.50
H32	0.8646	−0.0377	0.2603	0.032*	0.50
H33	0.9027	−0.1149	0.3126	0.032*	0.50
C32	0.8943 (8)	−0.0652 (7)	0.941 (3)	0.019 (3)	0.50
H34	0.9421	−0.0411	0.9400	0.028*	0.50
H35	0.8998	−0.1154	1.0027	0.028*	0.50
H36	0.8610	−0.0384	1.0520	0.028*	0.50
C4	0.7382 (3)	−0.0795 (3)	0.4127 (12)	0.0137 (11)
C5	0.6781 (3)	0.0294 (3)	0.2067 (13)	0.0184 (13)
H51	0.6656	−0.0084	0.0781	0.022*
C6	0.6060 (4)	0.0644 (4)	0.3054 (15)	0.0280 (16)
H61	0.5730	0.0258	0.3638	0.042*
H62	0.5825	0.0918	0.1697	0.042*
H63	0.6171	0.0975	0.4448	0.042*
C7	0.7291 (3)	0.0887 (3)	0.0812 (13)	0.0153 (12)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.027 (2)	0.019 (2)	0.0091 (19)	−0.0028 (17)	−0.005 (2)	−0.0056 (19)
O2	0.025 (2)	0.0136 (19)	0.019 (2)	−0.0019 (16)	−0.005 (2)	−0.0054 (18)
O3	0.038 (3)	0.022 (2)	0.015 (2)	−0.0038 (19)	−0.002 (2)	0.000 (2)
N1	0.011 (2)	0.015 (2)	0.024 (3)	0.0020 (18)	−0.003 (2)	0.009 (2)
N2	0.024 (3)	0.010 (2)	0.015 (3)	−0.0022 (18)	−0.008 (2)	0.005 (2)
C1	0.016 (3)	0.012 (2)	0.009 (2)	0.0014 (19)	0.002 (2)	0.000 (2)
C2	0.015 (3)	0.018 (3)	0.019 (3)	−0.003 (2)	0.002 (3)	−0.004 (3)
C31	0.012 (5)	0.032 (6)	0.020 (6)	−0.008 (5)	0.002 (5)	−0.001 (5)
C32	0.023 (5)	0.013 (5)	0.021 (6)	0.003 (4)	−0.009 (5)	−0.006 (5)
C4	0.013 (3)	0.017 (3)	0.011 (3)	−0.004 (2)	0.001 (2)	0.002 (2)
C5	0.022 (3)	0.013 (3)	0.020 (3)	−0.004 (2)	−0.008 (3)	0.009 (3)
C6	0.017 (3)	0.033 (4)	0.035 (4)	0.001 (3)	−0.001 (3)	0.015 (3)
C7	0.014 (3)	0.014 (3)	0.017 (3)	0.002 (2)	−0.005 (2)	0.002 (2)

Geometric parameters (Å, º)

O1—C4	1.230 (7)	C2—H22	0.9700
O2—C7	1.265 (7)	C2—H23	0.9700
O3—C7	1.233 (8)	C2—H24	0.9700
N1—C1	1.497 (7)	C31—H31	0.9600
N1—H1	0.9184	C31—H32	0.9600
N1—H2	0.9184	C31—H33	0.9600
N1—H3	0.9184	C32—H34	0.9600
N2—C4	1.351 (7)	C32—H35	0.9600
N2—C5	1.467 (7)	C32—H36	0.9600
N2—H4	0.8600	C5—C6	1.527 (9)
C1—C4	1.526 (8)	C5—C7	1.546 (8)
C1—C2	1.526 (7)	C5—H51	0.9800
C1—H11	0.9800	C6—H61	0.9600
C2—C31	1.595 (14)	C6—H62	0.9600
C2—C32	1.620 (14)	C6—H63	0.9600
C2—H21	0.9700
C1—N1—H1	109.5	C2—C31—H32	109.5
C1—N1—H2	109.5	H31—C31—H32	109.5
H1—N1—H2	109.5	C2—C31—H33	109.5
C1—N1—H3	109.5	H31—C31—H33	109.5
H1—N1—H3	109.5	H32—C31—H33	109.5
H2—N1—H3	109.5	C2—C32—H34	109.5
C4—N2—C5	122.9 (5)	C2—C32—H35	109.5
C4—N2—H4	118.5	H34—C32—H35	109.5
C5—N2—H4	118.5	C2—C32—H36	109.5
N1—C1—C4	108.3 (5)	H34—C32—H36	109.5
N1—C1—C2	110.6 (4)	H35—C32—H36	109.5
C4—C1—C2	112.5 (5)	O1—C4—N2	125.7 (6)
N1—C1—H11	108.4	O1—C4—C1	120.4 (5)
C4—C1—H11	108.4	N2—C4—C1	113.9 (5)
C2—C1—H11	108.4	N2—C5—C6	110.5 (6)
C1—C2—C31	110.1 (7)	N2—C5—C7	109.1 (5)
C1—C2—C32	111.8 (7)	C6—C5—C7	111.2 (5)
C31—C2—C32	134.1 (6)	N2—C5—H51	108.7
C1—C2—H21	109.6	C6—C5—H51	108.7
C31—C2—H21	109.6	C7—C5—H51	108.7
C1—C2—H22	109.6	C5—C6—H61	109.5
C31—C2—H22	109.6	C5—C6—H62	109.5
H21—C2—H22	108.2	H61—C6—H62	109.5
C1—C2—H23	109.3	C5—C6—H63	109.5
C32—C2—H23	109.3	H61—C6—H63	109.5
C1—C2—H24	109.3	H62—C6—H63	109.5
C32—C2—H24	109.3	O3—C7—O2	124.6 (6)
H23—C2—H24	107.9	O3—C7—C5	119.0 (6)
C2—C31—H31	109.5	O2—C7—C5	116.4 (6)
N1—C1—C4—N2	171.6 (5)	C5—N2—C4—O1	−1.6 (9)
C1—C4—N2—C5	176.5 (5)	N1—C1—C4—O1	−10.1 (7)
C4—N2—C5—C7	−114.3 (6)	C2—C1—C4—O1	112.5 (6)
N2—C5—C7—O2	−71.7 (7)	C2—C1—C4—N2	−65.8 (6)
N1—C1—C2—C31	79.1 (8)	C4—N2—C5—C6	123.2 (6)
N1—C1—C2—C32	−81.8 (7)	N2—C5—C7—O3	107.9 (6)
C4—C1—C2—C31	−42.2 (8)	C6—C5—C7—O3	−130.1 (6)
C4—C1—C2—C32	156.9 (6)	C6—C5—C7—O2	50.4 (7)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O3^i	0.92	1.99	2.846 (7)	154
N1—H2···O2^ii	0.92	1.90	2.787 (7)	160
N1—H3···O2^iii	0.92	1.89	2.804 (6)	170
N2—H4···O3^iv	0.86	2.00	2.856 (7)	177
C1—H11···O1^iv	0.98	2.45	3.316 (7)	147

Symmetry codes: (i) −y+1, x−1, z+1; (ii) −y+1, x−1, z; (iii) y+1/2, −x+1/2, z+1/2; (iv) x, y, z+1.

(II) 2-(L-alanylamino)-L-butyric acid

Crystal data

C7H14N2O3·0.33H2O	F(000) = 584
Mr = 180.21	Dx = 1.282 Mg m^−3
Monoclinic, P21	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2yb	Cell parameters from 7806 reflections
a = 15.4292 (5) Å	θ = 2.2–35.0°
b = 5.4602 (2) Å	µ = 0.10 mm^−1
c = 18.1320 (6) Å	T = 105 K
β = 113.505 (1)°	Needle, colourless
V = 1400.81 (8) Å^3	1.30 × 0.12 × 0.08 mm
Z = 6

Data collection

Siemens SMART CCD area-detector diffractometer	10606 independent reflections
Radiation source: fine-focus sealed tube	7926 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.030
Detector resolution: 8.3 pixels mm^-1	θmax = 35.0°, θmin = 2.2°
Sets of exposures each taken over 0.3° ω rotation scans	h = −24→19
Absorption correction: empirical (using intensity measurements) (SADABS; Sheldrick, 1996)	k = −8→8
Tmin = 0.876, Tmax = 0.992	l = −29→28
19775 measured reflections

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.037	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.074	w = 1/[σ^2(Fo^2) + (0.0371P)^2] where P = (Fo^2 + 2Fc^2)/3
S = 0.94	(Δ/σ)max = 0.002
10606 reflections	Δρmax = 0.33 e Å^−3
406 parameters	Δρmin = −0.27 e Å^−3
1 restraint	Absolute structure: Flack (1983), with 3916 Friedel pairs
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: −0.6 (4)

Special details

Experimental. Data were collected by measuring three sets (I) and five sets (II) of exposures with the detector set at 2θ = 29°, crystal-to-detector distance 4.98 cm.

Refinement. Refinement of F² against ALL reflections.

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

	x	y	z	Uiso*/Ueq
O1A	0.66764 (6)	−0.23626 (15)	0.07991 (5)	0.02516 (18)
O2A	0.87241 (6)	−0.25972 (16)	0.27773 (5)	0.02757 (19)
O3A	0.90727 (6)	−0.57948 (15)	0.21725 (5)	0.02571 (18)
N1A	0.54763 (7)	0.11879 (18)	0.07177 (5)	0.01675 (18)
H1A	0.5072 (10)	0.220 (3)	0.0868 (8)	0.027 (2)*
H2A	0.5331 (9)	0.125 (3)	0.0191 (9)	0.027 (2)*
H3A	0.5355 (9)	−0.033 (3)	0.0860 (8)	0.027 (2)*
N2A	0.80056 (7)	−0.00452 (17)	0.13449 (5)	0.01690 (18)
H4A	0.8261 (9)	0.126 (3)	0.1563 (8)	0.020*
C1A	0.64989 (7)	0.1791 (2)	0.11520 (6)	0.0161 (2)
H11A	0.6646 (2)	0.315 (2)	0.0912 (4)	0.019*
C2A	0.67105 (9)	0.2368 (3)	0.20291 (7)	0.0290 (3)
H21A	0.6325 (6)	0.3796 (16)	0.20578 (8)	0.035 (2)*
H22A	0.7393 (6)	0.2761 (17)	0.2317 (3)	0.035 (2)*
H23A	0.6551 (6)	0.0925 (14)	0.2285 (3)	0.035 (2)*
C3A	0.70650 (7)	−0.0416 (2)	0.10763 (6)	0.0160 (2)
C4A	0.86442 (7)	−0.2082 (2)	0.14295 (6)	0.0175 (2)
H41A	0.8358 (4)	−0.3157 (15)	0.0951 (6)	0.021*
C5A	0.95980 (8)	−0.1159 (2)	0.14623 (7)	0.0234 (2)
H51A	0.9921 (3)	−0.0190 (10)	0.1974 (5)	0.028*
H52A	1.0011 (4)	−0.2616 (15)	0.14851 (7)	0.028*
C6A	0.95190 (9)	0.0441 (3)	0.07488 (8)	0.0303 (3)
H61A	1.0146 (6)	0.0880 (15)	0.0792 (3)	0.041 (2)*
H62A	0.9168 (6)	0.1915 (16)	0.0748 (3)	0.041 (2)*
H63A	0.9192 (6)	−0.0455 (10)	0.0253 (5)	0.041 (2)*
C7A	0.88194 (8)	−0.3631 (2)	0.21884 (6)	0.0191 (2)
O1B	0.89076 (6)	0.11117 (14)	0.49263 (5)	0.02087 (16)
O2B	0.62797 (5)	0.08467 (14)	0.53299 (4)	0.01756 (15)
O3B	0.69540 (5)	−0.28414 (14)	0.56143 (5)	0.02018 (16)
N1B	0.91399 (7)	0.51356 (19)	0.42298 (6)	0.01827 (18)
H1B	0.9720 (10)	0.562 (3)	0.4563 (8)	0.025 (2)*
H2B	0.9194 (10)	0.360 (3)	0.4080 (8)	0.025 (2)*
H3B	0.8906 (9)	0.608 (3)	0.3749 (8)	0.025 (2)*
N2B	0.80086 (6)	0.28465 (17)	0.55201 (5)	0.01624 (18)
H4B	0.7730 (9)	0.416 (3)	0.5563 (8)	0.019*
C1B	0.84414 (7)	0.53200 (19)	0.46086 (6)	0.0161 (2)
H11B	0.8627 (3)	0.6636 (18)	0.4998 (5)	0.019*
C2B	0.74622 (8)	0.5856 (2)	0.39696 (7)	0.0244 (2)
H21B	0.74776 (15)	0.7349 (14)	0.3702 (4)	0.0222 (18)*
H22B	0.7024 (4)	0.6005 (14)	0.4218 (2)	0.0222 (18)*
H23B	0.7272 (3)	0.4551 (12)	0.3589 (4)	0.0222 (18)*
C3B	0.84762 (7)	0.28960 (19)	0.50425 (6)	0.0153 (2)
C4B	0.79675 (7)	0.06676 (19)	0.59754 (6)	0.01534 (19)
H41B	0.8430 (7)	−0.0484 (16)	0.59611 (6)	0.018*
C5B	0.82108 (8)	0.1379 (2)	0.68550 (6)	0.0218 (2)
H51B	0.8771 (6)	0.2210 (10)	0.7047 (2)	0.026*
H52B	0.7755 (5)	0.2413 (12)	0.68746 (7)	0.026*
C6B	0.82897 (9)	−0.0813 (3)	0.73994 (7)	0.0292 (3)
H61B	0.8474 (6)	−0.0254 (5)	0.7949 (5)	0.044 (3)*
H62B	0.8762 (6)	−0.1941 (13)	0.7373 (4)	0.044 (3)*
H63B	0.7684 (5)	−0.1638 (13)	0.7223 (4)	0.044 (3)*
C7B	0.69873 (7)	−0.0548 (2)	0.56032 (6)	0.01402 (19)
O1C	0.59661 (6)	0.14929 (14)	0.69421 (4)	0.02234 (17)
O2C	0.53247 (6)	0.17473 (15)	0.91328 (5)	0.02070 (16)
O3C	0.57229 (6)	−0.16241 (15)	0.86590 (5)	0.02214 (17)
N1C	0.54905 (7)	0.49187 (17)	0.58420 (5)	0.01371 (17)
H1C	0.5945 (9)	0.577 (3)	0.5714 (8)	0.0211 (19)*
H2C	0.5669 (9)	0.330 (3)	0.5892 (8)	0.0211 (19)*
H3C	0.4941 (10)	0.502 (3)	0.5487 (8)	0.0211 (19)*
N2C	0.60627 (7)	0.39411 (17)	0.79846 (5)	0.01611 (18)
H4C	0.5972 (9)	0.541 (3)	0.8130 (8)	0.019*
C1C	0.55322 (7)	0.57171 (19)	0.66439 (6)	0.01407 (19)
H11C	0.5976 (7)	0.6950 (18)	0.6837 (3)	0.017*
C2C	0.45825 (8)	0.6697 (2)	0.65850 (7)	0.0241 (2)
H21C	0.4381 (3)	0.8017 (15)	0.6196 (5)	0.031 (2)*
H22C	0.46445 (17)	0.7303 (15)	0.7106 (4)	0.031 (2)*
H23C	0.4118 (4)	0.5395 (11)	0.6415 (5)	0.031 (2)*
C3C	0.58710 (7)	0.3500 (2)	0.72085 (6)	0.01440 (19)
C4C	0.65199 (7)	0.2088 (2)	0.86028 (6)	0.0148 (2)
H41C	0.6842 (5)	0.1011 (16)	0.8408 (3)	0.018*
C5C	0.72384 (8)	0.3338 (2)	0.93545 (6)	0.0199 (2)
H51C	0.6921 (3)	0.4525 (12)	0.9543 (2)	0.024*
H52C	0.7508 (3)	0.2143 (12)	0.9768 (4)	0.024*
C6C	0.80285 (9)	0.4594 (3)	0.91912 (7)	0.0298 (3)
H61C	0.8482 (6)	0.5292 (17)	0.9686 (5)	0.045 (3)*
H62C	0.7763 (3)	0.5884 (16)	0.8798 (6)	0.045 (3)*
H63C	0.8342 (5)	0.3404 (12)	0.8986 (6)	0.045 (3)*
C7C	0.57943 (7)	0.06209 (19)	0.88070 (6)	0.01451 (19)
O1W	0.98203 (7)	0.14204 (19)	0.35508 (5)	0.0307 (2)
H1W	0.9521 (12)	0.016 (4)	0.3371 (11)	0.046*
H2W	0.9659 (12)	0.241 (4)	0.3163 (11)	0.046*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1A	0.0225 (4)	0.0170 (4)	0.0394 (5)	−0.0009 (3)	0.0159 (4)	−0.0042 (3)
O2A	0.0443 (5)	0.0202 (4)	0.0221 (4)	0.0007 (4)	0.0174 (4)	0.0017 (3)
O3A	0.0294 (4)	0.0175 (4)	0.0281 (4)	0.0030 (4)	0.0093 (3)	0.0018 (3)
N1A	0.0195 (4)	0.0152 (4)	0.0181 (4)	0.0007 (4)	0.0103 (4)	−0.0001 (3)
N2A	0.0182 (4)	0.0139 (4)	0.0196 (4)	0.0006 (4)	0.0085 (3)	−0.0005 (3)
C1A	0.0185 (5)	0.0133 (5)	0.0197 (5)	−0.0011 (4)	0.0110 (4)	−0.0013 (4)
C2A	0.0244 (6)	0.0422 (8)	0.0218 (5)	0.0025 (6)	0.0107 (5)	−0.0104 (5)
C3A	0.0189 (5)	0.0170 (5)	0.0160 (4)	0.0026 (4)	0.0111 (4)	0.0038 (4)
C4A	0.0174 (5)	0.0175 (5)	0.0184 (5)	0.0033 (4)	0.0080 (4)	−0.0005 (4)
C5A	0.0180 (5)	0.0276 (6)	0.0250 (5)	0.0054 (5)	0.0090 (4)	0.0059 (5)
C6A	0.0260 (6)	0.0378 (8)	0.0331 (6)	0.0063 (6)	0.0181 (5)	0.0112 (6)
C7A	0.0187 (5)	0.0163 (5)	0.0216 (5)	−0.0020 (4)	0.0073 (4)	0.0003 (4)
O1B	0.0249 (4)	0.0158 (4)	0.0269 (4)	0.0021 (3)	0.0157 (3)	0.0015 (3)
O2B	0.0147 (3)	0.0190 (4)	0.0161 (3)	0.0026 (3)	0.0031 (3)	−0.0013 (3)
O3B	0.0202 (4)	0.0147 (4)	0.0292 (4)	−0.0007 (3)	0.0135 (3)	−0.0005 (3)
N1B	0.0196 (5)	0.0160 (5)	0.0222 (4)	−0.0008 (4)	0.0116 (4)	0.0022 (4)
N2B	0.0178 (4)	0.0129 (4)	0.0212 (4)	0.0012 (4)	0.0110 (3)	0.0022 (3)
C1B	0.0190 (5)	0.0140 (5)	0.0174 (5)	0.0003 (4)	0.0095 (4)	0.0002 (4)
C2B	0.0206 (5)	0.0313 (7)	0.0214 (5)	0.0039 (5)	0.0086 (4)	0.0083 (5)
C3B	0.0138 (5)	0.0156 (5)	0.0155 (4)	−0.0024 (4)	0.0049 (4)	−0.0004 (4)
C4B	0.0141 (5)	0.0143 (5)	0.0183 (4)	0.0006 (4)	0.0071 (4)	0.0029 (4)
C5B	0.0196 (5)	0.0265 (6)	0.0167 (5)	−0.0052 (5)	0.0044 (4)	−0.0001 (4)
C6B	0.0282 (6)	0.0375 (7)	0.0184 (5)	−0.0029 (6)	0.0057 (5)	0.0077 (5)
C7B	0.0166 (5)	0.0166 (5)	0.0116 (4)	−0.0016 (4)	0.0086 (4)	−0.0014 (4)
O1C	0.0357 (5)	0.0156 (4)	0.0170 (3)	0.0030 (4)	0.0119 (3)	0.0006 (3)
O2C	0.0237 (4)	0.0199 (4)	0.0255 (4)	0.0040 (3)	0.0172 (3)	0.0020 (3)
O3C	0.0290 (4)	0.0170 (4)	0.0268 (4)	−0.0022 (3)	0.0179 (3)	−0.0017 (3)
N1C	0.0139 (4)	0.0145 (4)	0.0122 (4)	0.0012 (3)	0.0047 (3)	0.0009 (3)
N2C	0.0222 (4)	0.0133 (4)	0.0149 (4)	0.0018 (4)	0.0097 (3)	0.0011 (3)
C1C	0.0151 (5)	0.0139 (5)	0.0131 (4)	0.0000 (4)	0.0056 (4)	0.0000 (4)
C2C	0.0231 (6)	0.0313 (6)	0.0189 (5)	0.0094 (5)	0.0093 (4)	−0.0001 (4)
C3C	0.0148 (5)	0.0147 (5)	0.0152 (4)	−0.0012 (4)	0.0076 (4)	0.0010 (4)
C4C	0.0165 (5)	0.0163 (5)	0.0138 (4)	0.0020 (4)	0.0084 (4)	0.0023 (4)
C5C	0.0186 (5)	0.0245 (6)	0.0162 (5)	−0.0035 (5)	0.0066 (4)	0.0011 (4)
C6C	0.0250 (6)	0.0385 (7)	0.0249 (6)	−0.0125 (6)	0.0089 (5)	0.0006 (5)
C7C	0.0146 (5)	0.0166 (5)	0.0122 (4)	0.0011 (4)	0.0052 (4)	0.0020 (4)
O1W	0.0423 (6)	0.0230 (5)	0.0254 (4)	0.0024 (4)	0.0121 (4)	0.0008 (4)

Geometric parameters (Å, º)

O1A—C3A	1.2255 (14)	C2B—H22B	0.9537
O2A—C7A	1.2672 (14)	C2B—H23B	0.9537
O3A—C7A	1.2482 (14)	C4B—C5B	1.5355 (14)
N1A—C1A	1.4923 (14)	C4B—C7B	1.5392 (15)
N1A—H1A	0.952 (15)	C4B—H41B	0.9595
N1A—H2A	0.890 (14)	C5B—C6B	1.5249 (17)
N1A—H3A	0.910 (16)	C5B—H51B	0.9137
N2A—C3A	1.3492 (14)	C5B—H52B	0.9137
N2A—C4A	1.4530 (14)	C6B—H61B	0.9701
N2A—H4A	0.834 (15)	C6B—H62B	0.9701
C1A—C2A	1.5235 (14)	C6B—H63B	0.9701
C1A—C3A	1.5262 (15)	O1C—C3C	1.2298 (13)
C1A—H11A	0.9331	O2C—C7C	1.2624 (13)
C2A—H21A	0.9942	O3C—C7C	1.2503 (14)
C2A—H22A	0.9942	N1C—C1C	1.4945 (13)
C2A—H23A	0.9942	N1C—H1C	0.944 (14)
C4A—C5A	1.5342 (15)	N1C—H2C	0.918 (15)
C4A—C7A	1.5444 (15)	N1C—H3C	0.837 (14)
C4A—H41A	0.9935	N2C—C3C	1.3394 (13)
C5A—C6A	1.5250 (16)	N2C—C4C	1.4653 (13)
C5A—H51A	1.0095	N2C—H4C	0.874 (15)
C5A—H52A	1.0095	C1C—C2C	1.5232 (15)
C6A—H61A	0.9694	C1C—C3C	1.5362 (14)
C6A—H62A	0.9694	C1C—H11C	0.9237
C6A—H63A	0.9694	C2C—H21C	0.9681
O1B—C3B	1.2444 (13)	C2C—H22C	0.9681
O2B—C7B	1.2592 (13)	C2C—H23C	0.9681
O3B—C7B	1.2539 (13)	C4C—C5C	1.5320 (15)
N1B—C1B	1.4946 (14)	C4C—C7C	1.5372 (14)
N1B—H1B	0.896 (14)	C4C—H41C	0.9265
N1B—H2B	0.898 (16)	C5C—C6C	1.5271 (17)
N1B—H3B	0.950 (14)	C5C—H51C	0.9549
N2B—C3B	1.3301 (13)	C5C—H52C	0.9549
N2B—C4B	1.4638 (13)	C6C—H61C	0.9694
N2B—H4B	0.855 (15)	C6C—H62C	0.9694
C1B—C2B	1.5213 (15)	C6C—H63C	0.9694
C1B—C3B	1.5297 (15)	O1W—H1W	0.82 (2)
C1B—H11B	0.9674	O1W—H2W	0.840 (19)
C2B—H21B	0.9537
C1A—N1A—H1A	113.4 (8)	N2B—C3B—C1B	115.82 (9)
C1A—N1A—H2A	108.6 (8)	N2B—C4B—C5B	109.43 (9)
H1A—N1A—H2A	111.9 (12)	N2B—C4B—C7B	111.05 (8)
C1A—N1A—H3A	110.2 (9)	C5B—C4B—C7B	110.78 (8)
H1A—N1A—H3A	102.5 (12)	N2B—C4B—H41B	108.5
H2A—N1A—H3A	110.1 (13)	C5B—C4B—H41B	108.5
C3A—N2A—C4A	120.65 (9)	C7B—C4B—H41B	108.5
C3A—N2A—H4A	122.5 (9)	C6B—C5B—C4B	113.41 (10)
C4A—N2A—H4A	115.6 (9)	C6B—C5B—H51B	108.9
N1A—C1A—C2A	109.74 (9)	C4B—C5B—H51B	108.9
N1A—C1A—C3A	107.52 (8)	C6B—C5B—H52B	108.9
C2A—C1A—C3A	111.42 (9)	C4B—C5B—H52B	108.9
N1A—C1A—H11A	109.4	H51B—C5B—H52B	107.7
C2A—C1A—H11A	109.4	C5B—C6B—H61B	109.5
C3A—C1A—H11A	109.4	C5B—C6B—H62B	109.5
C1A—C2A—H21A	109.5	H61B—C6B—H62B	109.5
C1A—C2A—H22A	109.5	C5B—C6B—H63B	109.5
H21A—C2A—H22A	109.5	H61B—C6B—H63B	109.5
C1A—C2A—H23A	109.5	H62B—C6B—H63B	109.5
H21A—C2A—H23A	109.5	O3B—C7B—O2B	125.14 (10)
H22A—C2A—H23A	109.5	O2B—C7B—C4B	117.25 (9)
O1A—C3A—N2A	123.92 (10)	O3B—C7B—C4B	117.58 (9)
O1A—C3A—C1A	121.18 (9)	C1C—N1C—H1C	110.4 (8)
N2A—C3A—C1A	114.89 (9)	C1C—N1C—H2C	106.9 (8)
N2A—C4A—C5A	110.61 (9)	H1C—N1C—H2C	105.7 (11)
N2A—C4A—C7A	112.56 (8)	C1C—N1C—H3C	111.4 (9)
C5A—C4A—C7A	108.73 (8)	H1C—N1C—H3C	113.8 (12)
N2A—C4A—H41A	108.3	H2C—N1C—H3C	108.1 (13)
C5A—C4A—H41A	108.3	C3C—N2C—C4C	121.12 (9)
C7A—C4A—H41A	108.3	C3C—N2C—H4C	119.2 (8)
C6A—C5A—C4A	113.86 (9)	C4C—N2C—H4C	119.4 (8)
C6A—C5A—H51A	108.8	N1C—C1C—C2C	111.55 (8)
C4A—C5A—H51A	108.8	N1C—C1C—C3C	106.83 (8)
C6A—C5A—H52A	108.8	C2C—C1C—C3C	112.70 (9)
C4A—C5A—H52A	108.8	N1C—C1C—H11C	108.5
H51A—C5A—H52A	107.7	C2C—C1C—H11C	108.5
C5A—C6A—H61A	109.5	C3C—C1C—H11C	108.5
C5A—C6A—H62A	109.5	C1C—C2C—H21C	109.5
H61A—C6A—H62A	109.5	C1C—C2C—H22C	109.5
C5A—C6A—H63A	109.5	H21C—C2C—H22C	109.5
H61A—C6A—H63A	109.5	C1C—C2C—H23C	109.5
H62A—C6A—H63A	109.5	H21C—C2C—H23C	109.5
O3A—C7A—O2A	125.72 (10)	H22C—C2C—H23C	109.5
O2A—C7A—C4A	117.96 (10)	O1C—C3C—N2C	124.19 (10)
O3A—C7A—C4A	116.28 (9)	O1C—C3C—C1C	120.18 (9)
C1B—N1B—H1B	112.3 (9)	N2C—C3C—C1C	115.62 (9)
C1B—N1B—H2B	111.9 (9)	N2C—C4C—C5C	109.26 (9)
H1B—N1B—H2B	106.9 (13)	N2C—C4C—C7C	111.68 (8)
C1B—N1B—H3B	107.8 (8)	C5C—C4C—C7C	110.85 (8)
H1B—N1B—H3B	111.8 (12)	N2C—C4C—H41C	108.3
H2B—N1B—H3B	106.0 (12)	C5C—C4C—H41C	108.3
C3B—N2B—C4B	122.71 (9)	C7C—C4C—H41C	108.3
C3B—N2B—H4B	117.7 (9)	C6C—C5C—C4C	112.20 (9)
C4B—N2B—H4B	119.6 (9)	C6C—C5C—H51C	109.2
N1B—C1B—C2B	110.00 (9)	C4C—C5C—H51C	109.2
N1B—C1B—C3B	107.11 (9)	C6C—C5C—H52C	109.2
C2B—C1B—C3B	112.25 (9)	C4C—C5C—H52C	109.2
N1B—C1B—H11B	109.1	H51C—C5C—H52C	107.9
C2B—C1B—H11B	109.1	C5C—C6C—H61C	109.5
C3B—C1B—H11B	109.1	C5C—C6C—H62C	109.5
C1B—C2B—H21B	109.5	H61C—C6C—H62C	109.5
C1B—C2B—H22B	109.5	C5C—C6C—H63C	109.5
H21B—C2B—H22B	109.5	H61C—C6C—H63C	109.5
C1B—C2B—H23B	109.5	H62C—C6C—H63C	109.5
H21B—C2B—H23B	109.5	O3C—C7C—O2C	124.07 (10)
H22B—C2B—H23B	109.5	O2C—C7C—C4C	117.90 (9)
O1B—C3B—N2B	124.06 (10)	O3C—C7C—C4C	118.00 (9)
O1B—C3B—C1B	120.11 (9)	H1W—O1W—H2W	105.8 (17)
N1A—C1A—C3A—N2A	171.50 (8)	C2B—C1B—C3B—O1B	109.52 (11)
C1A—C3A—N2A—C4A	170.07 (9)	C2B—C1B—C3B—N2B	−69.12 (12)
C3A—N2A—C4A—C7A	−77.26 (12)	C3B—N2B—C4B—C5B	130.93 (10)
N2A—C4A—C7A—O2A	−25.90 (14)	C7B—C4B—C5B—C6B	63.36 (12)
N2A—C4A—C5A—C6A	−54.93 (13)	N2B—C4B—C7B—O3B	143.59 (9)
C4A—N2A—C3A—O1A	−9.05 (15)	C5B—C4B—C7B—O3B	−94.58 (11)
N1A—C1A—C3A—O1A	−9.35 (13)	C5B—C4B—C7B—O2B	83.64 (11)
C2A—C1A—C3A—O1A	110.94 (12)	N1C—C1C—C3C—N2C	172.27 (9)
C2A—C1A—C3A—N2A	−68.21 (12)	C1C—C3C—N2C—C4C	−171.04 (9)
C3A—N2A—C4A—C5A	160.88 (9)	C3C—N2C—C4C—C7C	−96.62 (11)
C7A—C4A—C5A—C6A	−179.00 (10)	N2C—C4C—C7C—O2C	−65.36 (11)
N2A—C4A—C7A—O3A	156.20 (10)	N2C—C4C—C5C—C6C	−62.38 (12)
C5A—C4A—C7A—O3A	−80.88 (12)	C4C—N2C—C3C—O1C	7.70 (16)
C5A—C4A—C7A—O2A	97.02 (12)	N1C—C1C—C3C—O1C	−6.53 (13)
N1B—C1B—C3B—N2B	170.04 (9)	C2C—C1C—C3C—O1C	116.33 (11)
C1B—C3B—N2B—C4B	179.71 (9)	C2C—C1C—C3C—N2C	−64.88 (12)
C3B—N2B—C4B—C7B	−106.46 (11)	C3C—N2C—C4C—C5C	140.39 (10)
N2B—C4B—C7B—O2B	−38.19 (12)	C7C—C4C—C5C—C6C	174.13 (10)
N2B—C4B—C5B—C6B	−173.87 (9)	N2C—C4C—C7C—O3C	116.42 (10)
C4B—N2B—C3B—O1B	1.13 (16)	C5C—C4C—C7C—O3C	−121.50 (11)
N1B—C1B—C3B—O1B	−11.32 (13)	C5C—C4C—C7C—O2C	56.72 (12)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1A—H1A···O3C^i	0.952 (15)	1.868 (15)	2.7921 (12)	163.0 (13)
N1A—H2A···O2C^ii	0.890 (14)	1.934 (15)	2.8054 (12)	165.6 (12)
N1A—H3A···O2C^iii	0.910 (16)	1.912 (16)	2.7834 (13)	159.7 (13)
N2A—H4A···O3A^iv	0.834 (15)	2.067 (15)	2.8945 (13)	171.8 (13)
N1B—H1B···O1B^v	0.896 (14)	1.963 (15)	2.8327 (13)	163.3 (13)
N1B—H2B···O1W	0.898 (16)	2.001 (15)	2.7864 (14)	145.3 (12)
N1B—H3B···O2A^iv	0.950 (14)	1.820 (14)	2.7446 (12)	163.4 (12)
N2B—H4B···O3B^iv	0.855 (15)	2.053 (15)	2.9056 (12)	175.2 (13)
N1C—H1C···O3B^iv	0.944 (14)	1.805 (14)	2.7403 (12)	170.7 (12)
N1C—H2C···O2B	0.918 (16)	2.119 (14)	2.8619 (12)	137.3 (11)
N1C—H3C···O2B^i	0.837 (14)	1.929 (14)	2.7573 (12)	170.1 (14)
N2C—H4C···O3C^iv	0.874 (15)	1.995 (15)	2.8539 (12)	167.2 (12)
O1W—H1W···O2A	0.82 (2)	1.97 (2)	2.7835 (14)	171.1 (18)
O1W—H2W···O3A^iv	0.84 (2)	1.93 (2)	2.7548 (12)	168.1 (17)

Symmetry codes: (i) −x+1, y+1/2, −z+1; (ii) x, y, z−1; (iii) −x+1, y−1/2, −z+1; (iv) x, y+1, z; (v) −x+2, y+1/2, −z+1.