3-[2,6-Bis­(diethyl­carbamoyl)­pyridin-4-yl]-N-(tert-butoxy­carbonyl)­alanine methyl ester: a chiral tridentate ligand that causes a diastereomeric excess of its lanthanide complexes in solution

L⁴, or 3-[2,6-bis­(diethyl­carbamoyl)­pyridin-4-yl]-N-(tert-but­oxy­car­bonyl)­alanine methyl ester, C₂₄H₃₈N₄O₆, crystallizes in neat [010] laths stabilized by abundant intra- and intermolecular hydrogen bonds. The strongest of these form [010] chains of mol­ecules, thus rationalizing the fastest growth direction, while the slowest direction coincides with the normal to the (110) layers, which are linked by very weak hydrogen bonds. There exist two independent mol­ecules, the distances and bond angles of which differ in a random manner only. The torsion and dihedral angles, however, differ so as to achieve optimal packing. The influence of the chiral group in the 4-position of the pyridine ring on the helical wrapping and on the ensuing diastereomeric induction is briefly discussed.

S1. Comment

Lanthanide coordination chemistry is essentially motivated by applications in biology and medicine, mainly for analysis (Parker, 2000) and diagnosis (Yam & Lo, 1999) but also for therapeutics (Guo & Sadler, 1999). These applications require a precise control of the Ln(III) inner coordination and therefore adequate ligands, which preserve, or preferably enhance, the physicochemical properties of the metal ion.

We have recently turned our attention to mononuclear triple helical lanthanide complexes with chiral tridentate aromatic ligands for the purpose of studying the influence of helical wrapping on diastereomeric induction, thermodynamic properties and energy transfer processes. Related helical induction in the ground state requires diastereomeric resolution, and we have recently synthesized the title compound, (I), bearing a chiral group in the 4-position of the pyridine ring. We have also studied the interaction of (I)? with trivalent lanthanide ions (Muller et al. 2001a). Indeed, interest in synthesizing chiral helices is growing, because they may be incorporated in, for example, biomedical materials and used as probes for chirality sensing of biological substances (Tsukube & Shinoda, 2002; Govenlock et al., 1999).

NMR analysis of L⁴ is consistent with the presence of a single species with a tertendate binding unit in a trans–trans conformation. The absolute configuration of the asymmetric C atom is retained, as demonstrated by the value of the specific optical rotation, [α]²⁵_D = −3.5 (4) ° dm² mol⁻¹ (Muller et al., 2001a). We have determined the crystal structure of L⁴ in order to confirm that the trans–trans conformation observed in solution also prevails in the solid state.

The structure contains two independent molecules, one of which is depicted in Fig. 1. These are roughly equivalent by a translation of 1/2 c. A normal probability plot (NPP) (Abrahams & Keve, 1971) involving 34 distances and 45 angles that are analogous in the two molecules is linear, with a slope of 1.60 and a δm_exp axis intercept of −0.05. The linearity implies that these geometrical quantities differ only in a stochastic way bewteen the two molecules, while the non-unit slope points to an underestimation of the variances. The molecules do, however, distinguish themselves in their torsion and dihedral angles. In each molecule there are seven subsets of atoms, defining planes of which the worst mean deviation is that of the C3a/C16a/C17a/C18a plane (0.06 Å). These planes are the pyridine ring, the C5/C6/C7/C9/N2/O1 and C1/C11/C12/C14/N3/O2 carboxamide groups, the C3/C16/C17/C18 butane skeleton, the C17/C18/C19/N4/O3/O4 amino acetic acid methyl ester group, the C20/C21/O5/O6 aminocarboxylate group, and the C17/C20/N4 azapropane group. The angles between the planes of the last two groups are 16.8 (2) and 12.1 (4)° for the two molecules. Since distances and angles between analogous atoms in the aminocarboxylate and carboxamide groups are very similar and since the latter are perfectly planar, the values of these angles must be due to steric requirements, notwithstanding the intramolecular O···H—C hydrogen bonds (Table 2) that further favour the planar configuration. Furthermore, the C═O and C═N distances (Table 1) indicate some degree of delocalization in the amide groups.

The structure is stabilized by a wealth of intermolecular hydrogen bonds forming a three-dimensional network (Fig. 2 and Table 2). The strongest of these (O···H—N) form [010] chains of molecules, each consecutive pair of? molecules being related by {C_2y|0 1/2 0}. These chains in turn are linked by weak O···H—C hydrogen bonds to form (a,b) layers that are finally connected by even weaker O···H—C bonds to complete the three-dimensional web. The strength of the hydrogen bonds is in perfect accord with the observed growth speeds of the crystal faces, viz. v₀₁₀ >> v₁₀₁ > v₁₀₀ (L⁴ grows as [010] joists). Actually, none of the hydrogen bonds (Table 2) rigorously qualifies according to the Desiraju (1996) criteria 2.0 < d < 2.3 Å and 150 < θ < 180 °, but it seems hard to imagine that these interactions do not determine the packing of this structure. It is surprising that not even the C17—H17···O5 bond succeeds in imposing a planar C17/N4/C20/O5/O6/C21 group, although such a conformation has been observed, for example, in 11-methoxy-15,16-dihydroxycyclopenta(a)phenantrene-17-one (Desiraju et al. 1993). The steric factor warping the azapropane and aminocarboxylate groups is finally demonstrated by the asymmetry of the C22—H22···O5 and C24—H24^···O5 bonds and the C23—C21—O6—C20 torsion angle of −167.88 (18)°.

The average bond lengths fall well within the ranges listed in the International Tables for Crystallography (1992, Vol. C). Following the example of Desiraju (1996), normalized N—H and C—H distances were used for the compilation of Table 2, although the refined distances reached satisfactory values, for example, 1.004 Å for the mean C—H bond. Despite the presence of several O and N atoms and the good quality of the data, the structure does not possess an enantiomorph-discriminating capacity that is high enough to furnish the absolute configuration of atom C17. However, since the synthesis involved no chirality-inverting step, atoms C17a and C17b are likely to be S.

The structure shows that the trans–trans configuration of atoms O1 and O2 prevails in the solid state. This fact is probably due to a minimization of the steric repulsion of the two carbamate groups and the chiral substituent grafted on the 4-position of the pyridine ring. During complexation this configuration changes to cis–cis.

On the other hand, chiro-optical data clearly suggest the helical wrapping of the three ligand strands around the Ln^III ions. This fact is confirmed by the specific rotary dispersion measurements (Muller et al., 2001a) but is contrary to the situation observed when bulky neopentyl subsituents were grafted on to the benzimidazole sidearms of a 2,6-bis(1-S-neopentylbenzimidazol-2-yl)pyridine ligand (Muller et al., 2001b). Moreover, the circularly polarized luminescence of the Eu^III triple helical complex displays a weak effect, pointing to a small diastereomeric excess in solution, similar to that recently observed for the corresponding complex with 2,6-bis[(1-methylbenzimidazol-2-yl)]-4-(neopentylester)pyridine, which also bears a chiral group in the 4-position of the central pyridine (Muller et al., 2002). Therefore, the diastereomeric induction resulting from the influence of the helical wrapping may be modulated by varying the chiral substituent in the 4-position of the pyridine ring, as may? the electronic and photophysical properties. The combination of these properties opens new perspectives for the design of lanthanide triple helical complexes acting as probes for chiral recognition.

S2. Experimental

Ligand L⁴ was synthesized from 4-bromo-N,N,N',N'-tetraethylpyridine-2,6-dicarboxamide via a palladium mediated reaction with Jackson's zinc reagent in a reasonable yield (61%). The details of the preparation have been described elsewhere (G. Muller et al. 2001a). The yellowish solid was recrystallized, by slow diffusion of hexane into a dichloromethane solution, to yield [010] joists. The HABITUS of the measured cut consisted of the {101} prism, the {100} pinacoid and the (010)/(010) cut planes.

S3. Refinement

The χ² value of 2.902 calls for an explanation. Indeed, a δR_exp versus δR_stat NPP displays a slope of 1.9 and a δR_exp axis intercept of 0.09. The line is perfectly straight (except in the tails), suggesting that the experimental s.u. values have been underestimated (a common observation in single-crystal diffraction experiments) rather than that the data are suspicious. All the other usual plots and the small number of inconsistent equivalents (70) confirm the sound nature of this data collection. The number of reflections is 291 short of completeness; these were overloaded reflections that could, unfortunately, not be remeasured because of technical problems. Friedel pairs were averaged. H atoms were placed in calculated positions and then refined using a riding model with variable C—H distances. Anisotropic displacement parameters were preferred for all non-H atoms.

Computing details

Data collection: IPDS (Stoe & Cie, 1997); cell refinement: IPDS; data reduction: IPDS; program(s) used to solve structure: SIR97 (Altomare et al., 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL (Bruker, 1996); software used to prepare material for publication: SHELXTL, PLATON (Spek, 2003).

Figures

Figure 1. The atom-numbering scheme and intramolecular hydrogen bonding (dashed lines) for one of the independant molecules of L^4. Displacement ellipsoids are shown at the 40% probability level. Figure 2. The atom-numbering scheme and intramolecular hydrogen bonding (dashed lines) for one of the independant molecules of L^4 Displacement ellipsoids are shown at the 40% probability level. Figure 3. Hydrogen bonds in one of the (a,b) layers. The layer connecting hydrogen bonds attack at O3?.

L⁴ is 3-[2,6-bis(diethylcarbamoyl)pyridin-4-yl]-N-(tert-butoxycarbonyl)alanine methyl ester

Crystal data

C24H38N4O6	F(000) = 1032
Mr = 478.58	Dx = 1.199 Mg m^−3
Monoclinic, P21	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2yb	Cell parameters from 8000 reflections
a = 11.144 (2) Å	θ = 13.8–28.0°
b = 13.047 (3) Å	µ = 0.09 mm^−1
c = 18.429 (4) Å	T = 115 K
β = 98.19 (3)°	Prismatic, yellow
V = 2652.2 (10) Å^3	0.4 × 0.4 × 0.15 mm
Z = 4

Data collection

Stoe IPDS diffractometer	5570 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.045
Graphite monochromator	θmax = 28.0°, θmin = 2.3°
Detector resolution: 6.7 pixels mm^-1	h = −14→14
ϕ scans	k = −11→15
38694 measured reflections	l = −24→24
6220 independent 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)] = 0.035	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.057	H-atom parameters constrained
S = 2.90	Weighting scheme based on measured s.u.'s
6220 reflections	(Δ/σ)max = 0.001
663 parameters	Δρmax = 0.24 e Å^−3
1 restraint	Δρmin = −0.20 e Å^−3

Special details

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

Refinement. Refinement on F² for ALL reflections except for 0 with very negative F² or flagged by the user for potential systematic errors. Weighted R-factors wR and all goodnesses of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The observed criterion of F² > σ(F²) is used only for calculating _R_factor_obs etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

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

	x	y	z	Uiso*/Ueq
O1	−0.13067 (12)	0.47218 (12)	0.58076 (8)	0.0211 (3)
O2	−0.06780 (13)	−0.01964 (12)	0.62291 (8)	0.0225 (4)
O3	0.36159 (14)	0.20812 (13)	0.36137 (8)	0.0275 (4)
O4	0.39722 (14)	0.37405 (14)	0.38399 (8)	0.0311 (4)
O5	0.34677 (12)	0.34885 (12)	0.59950 (7)	0.0230 (4)
O6	0.23690 (13)	0.49583 (12)	0.57621 (7)	0.0214 (3)
N1	−0.08211 (14)	0.21795 (14)	0.60075 (8)	0.0154 (4)
N2	−0.29051 (14)	0.36279 (14)	0.57196 (9)	0.0189 (4)
N3	0.08920 (14)	0.05260 (15)	0.69720 (8)	0.0182 (4)
N4	0.25076 (14)	0.38857 (14)	0.48523 (9)	0.0171 (4)
H4A	0.2244	0.4329	0.4598	0.021*
C1	−0.00314 (16)	0.14455 (17)	0.58858 (10)	0.0149 (4)
C2	0.06786 (17)	0.14759 (18)	0.53189 (10)	0.0169 (5)
H2A	0.1230	0.0889	0.5243	0.020*
C3	0.06134 (17)	0.23259 (17)	0.48626 (10)	0.0161 (5)
C4	−0.01781 (16)	0.31131 (18)	0.49975 (10)	0.0152 (4)
H4B	−0.0234	0.3737	0.4705	0.018*
C5	−0.08835 (16)	0.29913 (17)	0.55553 (10)	0.0151 (4)
C6	−0.17281 (17)	0.38555 (18)	0.57013 (10)	0.0162 (5)
C7	−0.37071 (18)	0.44674 (19)	0.58929 (12)	0.0234 (5)
H7A	−0.3235	0.4940	0.6275	0.028*
H7B	−0.4417	0.4164	0.6117	0.028*
C8	−0.4199 (2)	0.5094 (2)	0.52201 (12)	0.0298 (6)
H8A	−0.4776	0.5635	0.5361	0.045*
H8B	−0.4646	0.4627	0.4834	0.045*
H8C	−0.3503	0.5439	0.5017	0.045*
C9	−0.34856 (18)	0.26419 (19)	0.55089 (12)	0.0242 (5)
H9A	−0.2954	0.2241	0.5239	0.029*
H9B	−0.4242	0.2766	0.5181	0.029*
C10	−0.3758 (2)	0.2026 (2)	0.61649 (13)	0.0348 (6)
H10A	−0.4201	0.1370	0.5988	0.052*
H10B	−0.4288	0.2448	0.6458	0.052*
H10C	−0.2968	0.1846	0.6488	0.052*
C11	0.00314 (17)	0.05276 (18)	0.63846 (10)	0.0163 (4)
C12	0.17143 (19)	0.13921 (19)	0.71780 (11)	0.0239 (5)
H12A	0.1764	0.1507	0.7692	0.029*
H12B	0.1381	0.1993	0.6933	0.029*
C13	0.2992 (2)	0.1223 (2)	0.69897 (13)	0.0335 (6)
H13A	0.3490	0.1876	0.7098	0.050*
H13B	0.2943	0.1045	0.6447	0.050*
H13C	0.3396	0.0636	0.7299	0.050*
C14	0.1012 (2)	−0.03859 (19)	0.74444 (11)	0.0246 (5)
H14A	0.0198	−0.0649	0.74874	0.029*
H14B	0.1397	−0.0186	0.7937	0.029*
C15	0.1747 (2)	−0.1232 (2)	0.71641 (14)	0.0396 (7)
H15A	0.1766	−0.1859	0.7508	0.059*
H15B	0.2621	−0.0977	0.7150	0.059*
H15C	0.1357	−0.1439	0.6642	0.059*
C16	0.14021 (17)	0.24028 (17)	0.42608 (10)	0.0167 (5)
H16A	0.0994	0.2818	0.3862	0.020*
H16B	0.1526	0.1723	0.4069	0.020*
C17	0.26427 (16)	0.28867 (17)	0.45502 (10)	0.0161 (4)
H17A	0.3023	0.2449	0.4953	0.019*
C18	0.34540 (17)	0.28450 (18)	0.39483 (11)	0.0182 (5)
C19	0.4808 (2)	0.3726 (2)	0.33017 (15)	0.0461 (8)
H19A	0.5181	0.4428	0.3272	0.069*
H19B	0.4355	0.3533	0.2806	0.069*
H19C	0.5469	0.3207	0.3453	0.069*
C20	0.28376 (16)	0.40624 (18)	0.55790 (11)	0.0180 (5)
C21	0.24384 (18)	0.52630 (18)	0.65384 (10)	0.0218 (5)
C22	0.19722 (19)	0.44173 (19)	0.69936 (11)	0.0239 (5)
H22A	0.1163	0.4168	0.6742	0.036*
H22B	0.1878	0.4693	0.7493	0.036*
H22C	0.2567	0.3831	0.7048	0.036*
C23	0.1576 (2)	0.6168 (2)	0.64875 (13)	0.0310 (6)
H23A	0.0726	0.5932	0.6267	0.047*
H23B	0.1869	0.6721	0.6161	0.047*
H23C	0.1551	0.6460	0.7000	0.047*
C24	0.3729 (2)	0.5582 (2)	0.68241 (13)	0.0343 (6)
H24A	0.4290	0.4962	0.6827	0.051*
H24B	0.3766	0.5861	0.7345	0.051*
H24C	0.4000	0.6139	0.6492	0.051*
O1A	−0.14632 (12)	0.53209 (12)	1.06909 (7)	0.0210 (4)
O2A	−0.07864 (12)	0.05176 (12)	1.13155 (7)	0.0218 (3)
O3A	0.34737 (14)	0.25551 (14)	0.85549 (8)	0.0300 (4)
O4A	0.41288 (13)	0.41303 (13)	0.88769 (8)	0.0265 (4)
O5A	0.32735 (13)	0.39567 (13)	1.09555 (7)	0.0239 (4)
O6A	0.25146 (13)	0.55589 (12)	1.06990 (7)	0.0225 (3)
N1A	−0.09261 (14)	0.27904 (14)	1.09255 (9)	0.0161 (4)
N2A	−0.30183 (14)	0.41971 (14)	1.06750 (9)	0.0186 (4)
N3A	0.09569 (14)	0.12164 (14)	1.18945 (8)	0.0169 (4)
N4A	0.25045 (14)	0.44425 (14)	0.97934 (8)	0.0158 (4)
H4AB	0.2298	0.4909	0.9533	0.019*
C1A	−0.01104 (16)	0.20690 (17)	1.08160 (10)	0.0151 (4)
C2A	0.05917 (17)	0.20979 (17)	1.02523 (10)	0.0162 (4)
H2AA	0.1105	0.1567	1.01891	0.019*
C3A	0.05095 (17)	0.29396 (17)	0.97832 (10)	0.0161 (4)
C4A	−0.02947 (16)	0.37137 (18)	0.99065 (10)	0.0154 (4)
H4AA	−0.0362	0.4337	0.9604	0.018*
C5A	−0.10081 (16)	0.35929 (17)	1.04679 (10)	0.0146 (4)
C6A	−0.18630 (17)	0.44422 (18)	1.06129 (10)	0.0163 (4)
C7A	−0.38131 (18)	0.50342 (19)	1.08679 (11)	0.0218 (5)
H7AA	−0.3329	0.5497	1.1258	0.026*
H7AB	−0.4525	0.4723	1.1093	0.026*
C8A	−0.43122 (19)	0.56846 (19)	1.02051 (12)	0.0272 (5)
H8AA	−0.4880	0.6221	1.0358	0.041*
H8AB	−0.4768	0.5231	0.9815	0.041*
H8AC	−0.3619	0.6032	1.0003	0.041*
C9A	−0.35970 (18)	0.32107 (18)	1.04895 (12)	0.0226 (5)
H9AA	−0.3076	0.2804	1.0198	0.027*
H9AB	−0.4390	0.3331	1.0174	0.027*
C10A	−0.3816 (2)	0.2587 (2)	1.11555 (12)	0.0301 (6)
H10D	−0.4274	0.1939	1.0989	0.045*
H10E	−0.4310	0.3006	1.1468	0.045*
H10F	−0.3011	0.2401	1.1453	0.045*
C11A	−0.00069 (17)	0.11984 (17)	1.13646 (10)	0.0159 (4)
C12A	0.18809 (18)	0.20302 (19)	1.19726 (11)	0.0221 (5)
H12C	0.1962	0.2320	1.2497	0.026*
H12D	0.1594	0.2616	1.1616	0.026*
C13A	0.31142 (19)	0.1667 (2)	1.18236 (13)	0.0311 (6)
H13D	0.3659	0.2257	1.1820	0.047*
H13E	0.3031	0.1322	1.1346	0.047*
H13F	0.3452	0.1186	1.2209	0.047*
C14A	0.10670 (18)	0.04140 (18)	1.24616 (10)	0.0204 (5)
H14C	0.0244	0.0274	1.2598	0.025*
H14D	0.1592	0.0677	1.2909	0.025*
C15A	0.1594 (2)	−0.05802 (19)	1.22315 (11)	0.0261 (5)
H15D	0.1634	−0.1087	1.2641	0.039*
H15E	0.2428	−0.0455	1.2111	0.039*
H15F	0.1069	−0.0857	1.1790	0.039*
C17A	0.25682 (16)	0.34268 (16)	0.94937 (10)	0.0150 (4)
H17B	0.2905	0.2955	0.9924	0.018*
C16A	0.13002 (16)	0.30060 (17)	0.91827 (10)	0.0158 (4)
H16C	0.0906	0.3474	0.8778	0.019*
H16D	0.1386	0.2300	0.8965	0.019*
C18A	0.34196 (17)	0.33182 (18)	0.89154 (11)	0.0169 (5)
C19A	0.5049 (2)	0.4009 (2)	0.83960 (13)	0.0365 (7)
H19D	0.5441	0.4671	0.8338	0.055*
H19E	0.4668	0.3762	0.7916	0.055*
H19F	0.5658	0.3512	0.8611	0.055*
C20A	0.28014 (16)	0.45934 (18)	1.05262 (10)	0.0168 (5)
C21A	0.25508 (18)	0.58613 (18)	1.14752 (11)	0.0213 (5)
C22A	0.1744 (2)	0.5151 (2)	1.18468 (13)	0.0357 (7)
H22D	0.0926	0.5088	1.1531	0.054*
H22E	0.1634	0.5443	1.2342	0.054*
H22F	0.2136	0.4451	1.1914	0.054*
C23A	0.2021 (3)	0.6928 (2)	1.14171 (13)	0.0408 (7)
H23D	0.1175	0.6900	1.1152	0.061*
H23E	0.2526	0.7377	1.1142	0.061*
H23F	0.2011	0.7213	1.1920	0.061*
C24A	0.38499 (19)	0.5878 (2)	1.18641 (12)	0.0272 (6)
H24D	0.4192	0.5163	1.1883	0.041*
H24E	0.3863	0.6146	1.2377	0.041*
H24F	0.4354	0.6337	1.1589	0.041*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0197 (7)	0.0141 (11)	0.0304 (8)	−0.0014 (6)	0.0063 (6)	−0.0024 (6)
O2	0.0249 (8)	0.0175 (11)	0.0243 (8)	−0.0058 (6)	0.0004 (6)	0.0013 (6)
O3	0.0323 (9)	0.0230 (12)	0.0308 (8)	0.0010 (7)	0.0166 (7)	−0.0052 (7)
O4	0.0361 (9)	0.0285 (13)	0.0326 (9)	−0.0111 (8)	0.0187 (7)	−0.0041 (7)
O5	0.0219 (7)	0.0247 (11)	0.0214 (7)	0.0072 (6)	−0.0008 (6)	−0.0042 (6)
O6	0.0273 (8)	0.0189 (10)	0.0174 (7)	0.0052 (6)	0.0015 (6)	−0.0034 (6)
N1	0.0158 (8)	0.0127 (12)	0.0176 (8)	−0.0013 (7)	0.0025 (6)	−0.0014 (7)
N2	0.0147 (8)	0.0173 (13)	0.0249 (9)	0.0006 (7)	0.0036 (7)	−0.0002 (8)
N3	0.0214 (8)	0.0138 (12)	0.0188 (8)	0.0011 (7)	0.0006 (7)	−0.0019 (7)
N4	0.0216 (8)	0.0121 (12)	0.0177 (9)	0.0026 (7)	0.0024 (7)	0.0012 (7)
C1	0.0135 (9)	0.0126 (14)	0.0176 (10)	0.0002 (8)	−0.0010 (7)	−0.0021 (8)
C2	0.0141 (9)	0.0161 (15)	0.0203 (10)	0.0005 (8)	0.0019 (8)	−0.0019 (8)
C3	0.0154 (9)	0.0146 (15)	0.0183 (10)	−0.0036 (8)	0.0026 (8)	−0.0040 (8)
C4	0.0172 (10)	0.0114 (14)	0.0166 (9)	−0.0026 (8)	0.0011 (7)	−0.0012 (8)
C5	0.0128 (9)	0.0127 (14)	0.0194 (10)	−0.0015 (8)	0.0016 (7)	−0.0026 (8)
C6	0.0172 (9)	0.0176 (15)	0.0142 (9)	0.0017 (8)	0.0028 (7)	0.0038 (8)
C7	0.0157 (10)	0.0249 (16)	0.0306 (12)	0.0045 (9)	0.0063 (8)	−0.0004 (10)
C8	0.0238 (12)	0.0253 (17)	0.0380 (13)	0.0065 (10)	−0.0035 (10)	−0.0016 (11)
C9	0.0176 (10)	0.0212 (16)	0.0319 (12)	−0.0037 (9)	−0.0034 (9)	0.0000 (9)
C10	0.0259 (12)	0.0296 (19)	0.0490 (16)	−0.0053 (10)	0.0059 (11)	0.0103 (12)
C11	0.0160 (9)	0.0171 (14)	0.0161 (9)	0.0048 (8)	0.0035 (7)	−0.0019 (8)
C12	0.0269 (12)	0.0169 (16)	0.0255 (11)	0.0007 (9)	−0.0044 (9)	−0.0033 (9)
C13	0.0288 (12)	0.0364 (19)	0.0343 (13)	−0.0072 (11)	0.0015 (10)	−0.0018 (11)
C14	0.0327 (12)	0.0214 (16)	0.0182 (10)	0.0016 (10)	−0.0015 (9)	0.0061 (9)
C15	0.0483 (15)	0.0226 (19)	0.0474 (15)	0.0143 (12)	0.0053 (12)	0.0053 (12)
C16	0.0180 (10)	0.0176 (15)	0.0151 (10)	−0.0007 (8)	0.0049 (8)	−0.0036 (8)
C17	0.0165 (10)	0.0163 (15)	0.0158 (9)	0.0014 (8)	0.0031 (7)	0.0002 (8)
C18	0.0131 (9)	0.0225 (16)	0.0183 (10)	−0.0005 (9)	0.0005 (8)	0.0010 (9)
C19	0.0516 (16)	0.047 (2)	0.0474 (16)	−0.0198 (14)	0.0350 (13)	−0.0066 (13)
C20	0.0122 (9)	0.0197 (15)	0.0222 (11)	−0.0017 (8)	0.0033 (8)	−0.0009 (9)
C21	0.0250 (11)	0.0213 (17)	0.0184 (10)	0.0027 (9)	0.0009 (8)	−0.0068 (9)
C22	0.0249 (11)	0.0213 (15)	0.0260 (11)	0.0017 (9)	0.0054 (9)	−0.0014 (9)
C23	0.0428 (14)	0.0227 (17)	0.0281 (12)	0.0085 (11)	0.0070 (10)	−0.0058 (10)
C24	0.0298 (12)	0.0407 (19)	0.0324 (12)	−0.0079 (11)	0.0045 (10)	−0.0126 (12)
O1A	0.0212 (7)	0.0152 (11)	0.0281 (8)	−0.0001 (6)	0.0082 (6)	−0.0003 (6)
O2A	0.0222 (7)	0.0189 (10)	0.0237 (7)	−0.0048 (6)	0.0008 (6)	0.0045 (6)
O3A	0.0321 (8)	0.0275 (12)	0.0342 (9)	−0.0050 (7)	0.0177 (7)	−0.0109 (8)
O4A	0.0236 (8)	0.0262 (12)	0.0329 (9)	−0.0079 (7)	0.0145 (6)	−0.0056 (7)
O5A	0.0300 (8)	0.0209 (11)	0.0193 (7)	0.0072 (7)	−0.0018 (6)	−0.0015 (6)
O6A	0.0307 (8)	0.0183 (11)	0.0176 (7)	0.0051 (7)	0.0003 (6)	−0.0061 (6)
N1A	0.0151 (8)	0.0139 (12)	0.0196 (9)	−0.0002 (7)	0.0035 (6)	−0.0008 (7)
N2A	0.0161 (8)	0.0174 (13)	0.0235 (9)	0.0028 (7)	0.0065 (7)	0.0012 (7)
N3A	0.0180 (8)	0.0156 (12)	0.0170 (8)	−0.0011 (7)	0.0018 (6)	0.0012 (7)
N4A	0.0201 (8)	0.0105 (11)	0.0166 (8)	0.0015 (7)	0.0023 (6)	0.0007 (7)
C1A	0.0142 (9)	0.0135 (14)	0.0169 (9)	−0.0023 (8)	−0.0002 (7)	−0.0005 (8)
C2A	0.0149 (9)	0.0131 (14)	0.0207 (10)	0.0024 (8)	0.0033 (8)	−0.0041 (8)
C3A	0.0143 (9)	0.0179 (14)	0.0160 (9)	−0.0036 (8)	0.0015 (7)	−0.0029 (8)
C4A	0.0155 (9)	0.0144 (14)	0.0162 (10)	−0.0009 (8)	0.0024 (7)	−0.0010 (8)
C5A	0.0123 (9)	0.0129 (13)	0.0181 (10)	−0.0017 (8)	0.0003 (7)	−0.0011 (8)
C6A	0.0177 (9)	0.0182 (15)	0.0136 (9)	0.0020 (9)	0.0037 (7)	0.0035 (8)
C7A	0.0180 (10)	0.0208 (15)	0.0277 (11)	0.0037 (9)	0.0069 (8)	−0.0004 (9)
C8A	0.0226 (11)	0.0268 (17)	0.0307 (12)	0.0049 (9)	−0.0008 (9)	−0.0017 (10)
C9A	0.0165 (10)	0.0224 (16)	0.0282 (11)	−0.0036 (9)	0.0006 (8)	−0.0038 (9)
C10A	0.0272 (12)	0.0265 (18)	0.0371 (13)	−0.0072 (10)	0.0056 (10)	0.0020 (11)
C11A	0.0169 (10)	0.0162 (14)	0.0154 (9)	0.0024 (8)	0.0046 (7)	−0.0022 (8)
C12A	0.0219 (11)	0.0214 (15)	0.0214 (10)	−0.0044 (9)	−0.0022 (8)	−0.0004 (9)
C13A	0.0228 (12)	0.0398 (19)	0.0314 (12)	−0.0083 (10)	0.0058 (10)	−0.0010 (10)
C14A	0.0231 (10)	0.0220 (15)	0.0162 (9)	0.0016 (9)	0.0024 (8)	0.0026 (9)
C15A	0.0342 (12)	0.0208 (16)	0.0218 (11)	0.0038 (10)	−0.0009 (9)	0.0016 (9)
C17A	0.0163 (10)	0.0141 (14)	0.0150 (9)	0.0010 (8)	0.0036 (7)	−0.0008 (8)
C16A	0.0154 (9)	0.0172 (14)	0.0152 (9)	−0.0008 (8)	0.0042 (7)	−0.0026 (8)
C18A	0.0144 (9)	0.0189 (15)	0.0172 (10)	0.0013 (8)	0.0017 (8)	0.0024 (8)
C19A	0.0298 (12)	0.045 (2)	0.0397 (14)	−0.0106 (12)	0.0223 (11)	−0.0033 (12)
C20A	0.0140 (10)	0.0173 (15)	0.0195 (10)	−0.0011 (8)	0.0040 (8)	−0.0030 (9)
C21A	0.0239 (11)	0.0185 (16)	0.0208 (11)	0.0039 (9)	0.0008 (8)	−0.0062 (8)
C22A	0.0298 (12)	0.047 (2)	0.0328 (13)	−0.0123 (11)	0.0138 (10)	−0.0163 (12)
C23A	0.0515 (16)	0.034 (2)	0.0335 (14)	0.0189 (13)	−0.0068 (12)	−0.0126 (11)
C24A	0.0236 (11)	0.0343 (18)	0.0231 (11)	−0.0014 (10)	0.0008 (9)	−0.0099 (10)

Geometric parameters (Å, º)

O1—C6	1.229 (3)	O1A—C6A	1.231 (3)
O2—C11	1.239 (3)	O2A—C11A	1.237 (3)
O3—C18	1.199 (3)	O3A—C18A	1.203 (3)
O4—C18	1.331 (3)	O4A—C18A	1.330 (3)
O4—C19	1.454 (3)	O4A—C19A	1.457 (2)
O5—C20	1.220 (3)	O5A—C20A	1.214 (3)
O6—C20	1.343 (3)	O6A—C20A	1.349 (3)
O6—C21	1.476 (2)	O6A—C21A	1.479 (2)
N1—C1	1.341 (3)	N1A—C5A	1.339 (3)
N1—C5	1.343 (3)	N1A—C1A	1.343 (3)
N2—C6	1.350 (2)	N2A—C6A	1.347 (3)
N2—C9	1.467 (3)	N2A—C9A	1.458 (3)
N2—C7	1.477 (3)	N2A—C7A	1.481 (3)
N3—C11	1.340 (2)	N3A—C11A	1.345 (2)
N3—C14	1.469 (3)	N3A—C12A	1.472 (3)
N3—C12	1.470 (3)	N3A—C14A	1.472 (3)
N4—C20	1.357 (3)	N4A—C20A	1.358 (2)
N4—C17	1.434 (3)	N4A—C17A	1.441 (3)
N4—H4A	0.7751	N4A—H4AB	0.7881
C1—C2	1.398 (3)	C1A—C2A	1.387 (3)
C1—C11	1.505 (3)	C1A—C11A	1.514 (3)
C2—C3	1.387 (3)	C2A—C3A	1.392 (3)
C2—H2A	1.0035	C2A—H2AA	0.9161
C3—C4	1.399 (3)	C3A—C4A	1.390 (3)
C3—C16	1.513 (3)	C3A—C16A	1.512 (3)
C4—C5	1.389 (3)	C4A—C5A	1.401 (3)
C4—H4B	0.9736	C4A—H4AA	0.9832
C5—C6	1.517 (3)	C5A—C6A	1.510 (3)
C7—C8	1.521 (3)	C7A—C8A	1.526 (3)
C7—H7A	1.0233	C7A—H7AA	1.0300
C7—H7B	1.0233	C7A—H7AB	1.0300
C8—H8A	1.0132	C8A—H8AA	1.0106
C8—H8B	1.0132	C8A—H8AB	1.0106
C8—H8C	1.0132	C8A—H8AC	1.0106
C9—C10	1.518 (3)	C9A—C10A	1.521 (3)
C9—H9A	0.9782	C9A—H9AA	0.9985
C9—H9B	0.9782	C9A—H9AB	0.9985
C10—H10A	1.0173	C10A—H10D	1.0122
C10—H10B	1.0173	C10A—H10E	1.0122
C10—H10C	1.0173	C10A—H10F	1.0122
C12—C13	1.529 (3)	C12A—C13A	1.515 (3)
C12—H12A	0.9533	C12A—H12C	1.0288
C12—H12B	0.9533	C12A—H12D	1.0288
C13—H13A	1.0206	C13A—H13D	0.9813
C13—H13B	1.0206	C13A—H13E	0.9813
C13—H13C	1.0206	C13A—H13F	0.9813
C14—C15	1.509 (3)	C14A—C15A	1.509 (3)
C14—H14A	0.9831	C14A—H14C	1.0017
C14—H14B	0.9831	C14A—H14D	1.0017
C15—H15A	1.0335	C15A—H15D	0.9990
C15—H15B	1.0335	C15A—H15E	0.9990
C15—H15C	1.0335	C15A—H15F	0.9990
C16—C17	1.544 (3)	C17A—C18A	1.531 (3)
C16—H16A	0.9718	C17A—C16A	1.548 (3)
C16—H16B	0.9718	C17A—H17B	1.0315
C17—C18	1.529 (3)	C16A—H16C	1.0147
C17—H17A	0.9835	C16A—H16D	1.0147
C19—H19A	1.0099	C19A—H19D	0.9799
C19—H19B	1.0099	C19A—H19E	0.9799
C19—H19C	1.0099	C19A—H19F	0.9799
C21—C23	1.517 (3)	C21A—C23A	1.510 (3)
C21—C24	1.518 (3)	C21A—C22A	1.520 (3)
C21—C22	1.522 (3)	C21A—C24A	1.521 (3)
C22—H22A	1.0079	C22A—H22D	1.0126
C22—H22B	1.0079	C22A—H22E	1.0126
C22—H22C	1.0079	C22A—H22F	1.0126
C23—H23A	1.0229	C23A—H23D	0.9994
C23—H23B	1.0229	C23A—H23E	0.9994
C23—H23C	1.0229	C23A—H23F	0.9994
C24—H24A	1.0219	C24A—H24D	1.0064
C24—H24B	1.0219	C24A—H24E	1.0064
C24—H24C	1.0219	C24A—H24F	1.0064
C18—O4—C19	115.14 (19)	C18A—O4A—C19A	114.90 (18)
C20—O6—C21	120.62 (16)	C20A—O6A—C21A	120.19 (16)
C1—N1—C5	115.89 (17)	C5A—N1A—C1A	116.10 (17)
C6—N2—C9	125.43 (18)	C6A—N2A—C9A	125.85 (18)
C6—N2—C7	117.53 (19)	C6A—N2A—C7A	117.18 (19)
C9—N2—C7	116.73 (16)	C9A—N2A—C7A	116.58 (16)
C11—N3—C14	118.30 (18)	C11A—N3A—C12A	123.98 (17)
C11—N3—C12	123.74 (19)	C11A—N3A—C14A	118.70 (17)
C14—N3—C12	117.95 (17)	C12A—N3A—C14A	117.20 (16)
C20—N4—C17	120.59 (18)	C20A—N4A—C17A	119.74 (18)
C20—N4—H4A	119.7	C20A—N4A—H4AB	120.1
C17—N4—H4A	119.7	C17A—N4A—H4AB	120.1
N1—C1—C2	124.0 (2)	N1A—C1A—C2A	124.01 (19)
N1—C1—C11	116.15 (17)	N1A—C1A—C11A	114.46 (16)
C2—C1—C11	119.80 (18)	C2A—C1A—C11A	121.53 (18)
C3—C2—C1	119.30 (19)	C1A—C2A—C3A	119.48 (19)
C3—C2—H2A	120.4	C1A—C2A—H2AA	120.3
C1—C2—H2A	120.4	C3A—C2A—H2AA	120.3
C2—C3—C4	117.33 (18)	C4A—C3A—C2A	117.29 (18)
C2—C3—C16	120.76 (18)	C4A—C3A—C16A	122.30 (19)
C4—C3—C16	121.9 (2)	C2A—C3A—C16A	120.39 (18)
C5—C4—C3	119.0 (2)	C3A—C4A—C5A	119.1 (2)
C5—C4—H4B	120.5	C3A—C4A—H4AA	120.5
C3—C4—H4B	120.5	C5A—C4A—H4AA	120.5
N1—C5—C4	124.37 (19)	N1A—C5A—C4A	123.92 (19)
N1—C5—C6	117.04 (17)	N1A—C5A—C6A	116.77 (16)
C4—C5—C6	118.47 (19)	C4A—C5A—C6A	119.16 (18)
O1—C6—N2	123.29 (19)	O1A—C6A—N2A	123.06 (19)
O1—C6—C5	118.64 (17)	O1A—C6A—C5A	118.50 (17)
N2—C6—C5	118.1 (2)	N2A—C6A—C5A	118.4 (2)
N2—C7—C8	112.41 (17)	N2A—C7A—C8A	112.34 (17)
N2—C7—H7A	109.1	N2A—C7A—H7AA	109.1
C8—C7—H7A	109.1	C8A—C7A—H7AA	109.1
N2—C7—H7B	109.1	N2A—C7A—H7AB	109.1
C8—C7—H7B	109.1	C8A—C7A—H7AB	109.1
H7A—C7—H7B	107.9	H7AA—C7A—H7AB	107.9
C7—C8—H8A	109.5	C7A—C8A—H8AA	109.5
C7—C8—H8B	109.5	C7A—C8A—H8AB	109.5
H8A—C8—H8B	109.5	H8AA—C8A—H8AB	109.5
C7—C8—H8C	109.5	C7A—C8A—H8AC	109.5
H8A—C8—H8C	109.5	H8AA—C8A—H8AC	109.5
H8B—C8—H8C	109.5	H8AB—C8A—H8AC	109.5
N2—C9—C10	112.59 (19)	N2A—C9A—C10A	113.55 (18)
N2—C9—H9A	109.1	N2A—C9A—H9AA	108.9
C10—C9—H9A	109.1	C10A—C9A—H9AA	108.9
N2—C9—H9B	109.1	N2A—C9A—H9AB	108.9
C10—C9—H9B	109.1	C10A—C9A—H9AB	108.9
H9A—C9—H9B	107.8	H9AA—C9A—H9AB	107.7
C9—C10—H10A	109.5	C9A—C10A—H10D	109.5
C9—C10—H10B	109.5	C9A—C10A—H10E	109.5
H10A—C10—H10B	109.5	H10D—C10A—H10E	109.5
C9—C10—H10C	109.5	C9A—C10A—H10F	109.5
H10A—C10—H10C	109.5	H10D—C10A—H10F	109.5
H10B—C10—H10C	109.5	H10E—C10A—H10F	109.5
O2—C11—N3	123.1 (2)	O2A—C11A—N3A	123.07 (19)
O2—C11—C1	119.52 (17)	O2A—C11A—C1A	120.27 (17)
N3—C11—C1	117.40 (18)	N3A—C11A—C1A	116.66 (17)
N3—C12—C13	113.40 (19)	N3A—C12A—C13A	113.36 (19)
N3—C12—H12A	108.9	N3A—C12A—H12C	108.9
C13—C12—H12A	108.9	C13A—C12A—H12C	108.9
N3—C12—H12B	108.9	N3A—C12A—H12D	108.9
C13—C12—H12B	108.9	C13A—C12A—H12D	108.9
H12A—C12—H12B	107.7	H12C—C12A—H12D	107.7
C12—C13—H13A	109.5	C12A—C13A—H13D	109.5
C12—C13—H13B	109.5	C12A—C13A—H13E	109.5
H13A—C13—H13B	109.5	H13D—C13A—H13E	109.5
C12—C13—H13C	109.5	C12A—C13A—H13F	109.5
H13A—C13—H13C	109.5	H13D—C13A—H13F	109.5
H13B—C13—H13C	109.5	H13E—C13A—H13F	109.5
N3—C14—C15	113.42 (19)	N3A—C14A—C15A	114.08 (16)
N3—C14—H14A	108.9	N3A—C14A—H14C	108.7
C15—C14—H14A	108.9	C15A—C14A—H14C	108.7
N3—C14—H14B	108.9	N3A—C14A—H14D	108.7
C15—C14—H14B	108.9	C15A—C14A—H14D	108.7
H14A—C14—H14B	107.7	H14C—C14A—H14D	107.6
C14—C15—H15A	109.5	C14A—C15A—H15D	109.5
C14—C15—H15B	109.5	C14A—C15A—H15E	109.5
H15A—C15—H15B	109.5	H15D—C15A—H15E	109.5
C14—C15—H15C	109.5	C14A—C15A—H15F	109.5
H15A—C15—H15C	109.5	H15D—C15A—H15F	109.5
H15B—C15—H15C	109.5	H15E—C15A—H15F	109.5
C3—C16—C17	111.03 (16)	N4A—C17A—C18A	114.90 (17)
C3—C16—H16A	109.4	N4A—C17A—C16A	112.08 (16)
C17—C16—H16A	109.4	C18A—C17A—C16A	109.45 (15)
C3—C16—H16B	109.4	N4A—C17A—H17B	106.6
C17—C16—H16B	109.4	C18A—C17A—H17B	106.6
H16A—C16—H16B	108.0	C16A—C17A—H17B	106.6
N4—C17—C18	114.82 (17)	C3A—C16A—C17A	110.23 (15)
N4—C17—C16	111.56 (16)	C3A—C16A—H16C	109.6
C18—C17—C16	109.14 (15)	C17A—C16A—H16C	109.6
N4—C17—H17A	107.0	C3A—C16A—H16D	109.6
C18—C17—H17A	107.0	C17A—C16A—H16D	109.6
C16—C17—H17A	107.0	H16C—C16A—H16D	108.1
O3—C18—O4	123.51 (19)	O3A—C18A—O4A	123.57 (18)
O3—C18—C17	123.4 (2)	O3A—C18A—C17A	123.07 (19)
O4—C18—C17	113.08 (18)	O4A—C18A—C17A	113.28 (18)
O4—C19—H19A	109.5	O4A—C19A—H19D	109.5
O4—C19—H19B	109.5	O4A—C19A—H19E	109.5
H19A—C19—H19B	109.5	H19D—C19A—H19E	109.5
O4—C19—H19C	109.5	O4A—C19A—H19F	109.5
H19A—C19—H19C	109.5	H19D—C19A—H19F	109.5
H19B—C19—H19C	109.5	H19E—C19A—H19F	109.5
O5—C20—O6	125.87 (19)	O5A—C20A—O6A	125.47 (18)
O5—C20—N4	124.5 (2)	O5A—C20A—N4A	124.8 (2)
O6—C20—N4	109.60 (18)	O6A—C20A—N4A	109.74 (18)
O6—C21—C23	101.79 (16)	O6A—C21A—C23A	102.76 (17)
O6—C21—C24	109.04 (16)	O6A—C21A—C22A	109.69 (18)
C23—C21—C24	111.7 (2)	C23A—C21A—C22A	110.1 (2)
O6—C21—C22	111.36 (18)	O6A—C21A—C24A	110.66 (16)
C23—C21—C22	109.59 (18)	C23A—C21A—C24A	110.9 (2)
C24—C21—C22	112.88 (19)	C22A—C21A—C24A	112.37 (19)
C21—C22—H22A	109.5	C21A—C22A—H22D	109.5
C21—C22—H22B	109.5	C21A—C22A—H22E	109.5
H22A—C22—H22B	109.5	H22D—C22A—H22E	109.5
C21—C22—H22C	109.5	C21A—C22A—H22F	109.5
H22A—C22—H22C	109.5	H22D—C22A—H22F	109.5
H22B—C22—H22C	109.5	H22E—C22A—H22F	109.5
C21—C23—H23A	109.5	C21A—C23A—H23D	109.5
C21—C23—H23B	109.5	C21A—C23A—H23E	109.5
H23A—C23—H23B	109.5	H23D—C23A—H23E	109.5
C21—C23—H23C	109.5	C21A—C23A—H23F	109.5
H23A—C23—H23C	109.5	H23D—C23A—H23F	109.5
H23B—C23—H23C	109.5	H23E—C23A—H23F	109.5
C21—C24—H24A	109.5	C21A—C24A—H24D	109.5
C21—C24—H24B	109.5	C21A—C24A—H24E	109.5
H24A—C24—H24B	109.5	H24D—C24A—H24E	109.5
C21—C24—H24C	109.5	C21A—C24A—H24F	109.5
H24A—C24—H24C	109.5	H24D—C24A—H24F	109.5
H24B—C24—H24C	109.5	H24E—C24A—H24F	109.5

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C2—H2a···O1^i	1.08	2.42	3.234 (3)	131
N4—H4a···O2^ii	1.01	2.05	2.899 (2)	140
C4—H4b···O2^ii	1.08	2.45	3.391 (3)	145
C12a—H12c···O3^iii	1.06	2.56	3.350 (3)	131
C8—H8b···O4^iv	1.06	2.46	3.504 (3)	169
C7—H7b···O5^iv	1.06	2.47	3.428 (3)	151
C9—H9a···N1	1.06	2.56	3.041 (3)	107
C17—H17a···O5	1.06	2.32	2.802 (2)	106
C22—H22c···O5	1.06	2.33	2.917 (3)	113
C24—H24a···O5	1.06	2.53	3.123 (3)	114
C2a—H2aa···O1a^v	1.08	2.24	3.131 (3)	138
N4a—H4ab···O2a^vi	1.01	2.10	2.949 (2)	141
C8a—H8ab···O4a^iv	1.06	2.39	3.451 (3)	180
C9a—H9aa···N1a	1.06	2.56	3.021 (3)	106
C17a—H17b···O5a	1.06	2.29	2.784 (2)	107
C22a—H22f···O5a	1.06	2.39	2.971 (3)	113
C24a—H24d···O5a	1.06	2.42	3.032 (3)	116

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