A silaproline-containing dipeptide

The silaproline-containing dipeptide N-(3,3-di­methyl-1-pivaloyl-1-aza-3-sila-5-cyclo­pentyl­carbonyl)-L-alanine iso­propyl­amide, C₁₇H₃₃N₃O₃Si, has two independent molecules in the asymmetric unit and each adopts a β-II folded conformation, where the amide on the terminal C interacts intramolecularly with the pivaloyl O atom. The five-membered silaproline ring is C^β-puckered, an infrequent conformation for the homol­ogous proline ring.

S1. Comment

Proline analogues are of great interest due to the importance of such a residue in peptide reverse-turn structures. Recently, we reported the synthesis of 4-(dimethylsila)-L-proline or silaproline (Sip) in both optically pure forms (Vivet et al., 2000) by diastereoselective alkylation of a chiral glycine equivalent using Schöllkopf's bis-lactim ether method (Schöllkopf et al., 1981). These Si-containing proline analogues may also be useful as solubilizing building blocks, due to the high lipophilicity of silyl groups. This new proline surrogate has been introduced in model peptides in place of Pro to investigate the structural consequences of this modification. One of the targeted peptides, N-(3,3-dimethyl-1-pivaloyl-1-aza-3-sila-5-cyclopentylcarbonyl)-L-alanine isopropylamide, or Piv-L-Sip-L-Ala-NHⁱPr, (III), gave satisfactory single crystals for X-ray diffraction. We report here the first crystal molecular structure, to our knowledge, of a silaproline-containing peptide. \sch

The dimensions of both independent molecules, A and B, in the monoclinic unit cell of (III) are quite similar. As expected, the Si—C bonds in the five-membered ring of the silaproline are longer by about 0.55 Å than the C—C bonds in proline, and the intracyclic C—Si—C angle is significantly smaller (about 92°) than the homologous C—C—C angle in proline (Table 1; Aubry, Vitoux & Marraud, 1985). The five-membered ring of silaproline assumes a skew conformation of the C^β-endo type (Nair & Vijayan, 1981), which is otherwise only found in the cis-proline residue involved in the 2,5-diketopiperazine ring (Aubry, Cung & Marraud, 1985).

Both independent molecules are folded by an intramolecular hydrogen bond between the amide on the terminal C and the pivaloyl O atom, which closes a ten-membered pseudocycle (Fig. 1). The orientation of the central amide group (Table 1) with reference to the average plane of the molecules is typical of a type II β-turn (Rose et al., 1985). Although this turn type is not frequently found for homochiral dipeptide sequences in solution, it is classically observed in the crystal structures of similar dipeptides due to favorable intermolecular packing forces involving the central amide NH and CO groups (Table 2; Aubry, Cung & Marraud, 1985). In solution, at very low concentration in order to avoid autoassociation, the folded structure turns into a type I β-turn, as already observed in L-Pro-L-Xaa sequences by Aubry, Cung & Marraud (1985).

The crystal structure of (III) is composed of layers containing molecules A and layers containing molecules B, both oriented parallel to (100) (Fig. 2). In each layer the molecules are stabilized by van der Waals interactions and the layers held together by NH···O hydrogen bonds (Table 2). Moreover, the independent molecules are connected by a non-crystallographic twofold screw axis which is in the crystallographic a direction and located at y = 0.26 (near 1/4) and z = 0.38 (near 3/8). The non-crystallographic operator, identified by the program BUNYIP (Hester & Hall, 1996), is (1/2 + x, 1/2 − y, 3/4 − z). Operation of the crystallographic twofold screw symmetry on the non-crystallographic twofold screw axis yields a second non-crystallographic twofold screw axis in the same direction and associated with the operator (1/2 + x, 1/2 − y, 1/4 − z). It is interesting to note that both non-crystallographic axes extend througout the crystal since their self operation yields (x, y, z). Combinations of the non- and the true crystallographic axes result in two more non-crystallographic twofold screw axes, which present the operators (1/2 − x, −y, 1/4 + z) and (1/2 − x, −y, 3/4 + z). These twofold screw axes do not extend througout the crystal because their self operation does not yield (x, y, z) or any other symmetry element.

S2. Experimental

The N-(tert-butyloxycarbonyl)-L-alanine (Boc-L-Ala-OH) and benzotriazole-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (BOP) were purchased from Novabiochem, and the diisopropylethylamine (DIEA), isopropylamine and pivaloyl chloride (PivCl) from Aldrich. Dichloromethane (DCM) was dried overnight over CaCl₂ then distilled on K₂CO₃ and stored away from bright light in a brown bottle. Dimethylformamide (DMF), acetonitrile and trifluoroacetic acid (TFA) were purchased from Merck. Thin layer chromatography was performed on Merck precoated silica gel 60F₂₅₄ plates and spots were visualized by staining with phosphomolybdic acid or ninhydrin. Flash chromatography was performed using Merck silica gel 60 (230–400 mesh). To prepare Boc-L-Ala-NHⁱPr, (I), Boc-L-Ala-OH (350 mg, 1.85 mmol) was dissolved in DMF (5 ml) then BOP (900 mg, 2.40 mmol), isopropylamine (170 µl, 2 mmol) and DIEA (785 µl, 4.62 mmol) were added. After 4 h at room temperature, the reaction mixture was evaporated in vacuo and the resulting residue dissolved in EtOAc (15 ml). The organic phase was washed successively with aqueous 0.1 N KHSO₄ (3 × 5 ml) and saturated NaHCO₃ (3 × 5 ml), dried over MgSO₄ and then concentrated in vacuo. The crude product was purified by chromatography on silica gel in EtOAc/hexane (6:4) to give 360 mg of (I) (85% yield) as an oil; R_f = 0.30 (EtOAc/hexane 6:4); R_f = 0.55 (EtOAc/hexane 7:3). To prepare Boc-L-Sip-L-Ala-NHⁱPr, (II), a solution of (I) (250 mg, 1.08 mmol) in DCM (3 ml) was stirred for 1 h at room temperature with TFA (3 ml). The mixture was evaporated in vacuo and the residue was coevaporated three times with hexane/Et₂O 4:2 (10 ml) to remove excess TFA. The TFA salt (260 mg, 1.06 mmol) was dissolved in DMF (5 ml). DIEA (450 µl, 2.65 mmol), BOP (514 mg, 1.16 mmol) and Boc-L-Sip-OH (Vivet et al., 2000) (275 mg, 1.06 mmol) were then added. After stirring overnight at room temperature, the reaction mixture was evaporated in vacuo and the resulting residue dissolved in EtOAc (15 ml). The organic phase was washed successively with aqueous 0.1 N KHSO₄ (3 × 5 ml) and saturated NaHCO₃ (3 × 5 ml), dried over MgSO₄ and then concentrated in vacuo. The crude product was purified by chromatography on silica gel in EtOAc/hexane 6:4, to give 300 mg of (II) (76% yield) as an oil; R_f = 0.40 (EtOAc/hexane: 6/4). To prepare Piv-L-Sip-L-Ala-NHⁱPr, (III), a solution of (II) (250 mg, 0.67 mmol) in DCM (3 ml) was stirred for 1 h at room temperature with TFA (3 ml). The mixture was evaporated in vacuo and the residue was coevaporated three times with hexane/Et₂O 4:2 (10 ml) to remove excess TFA. The TFA salt (240 mg, 0.62 mmol) was dissolved in DCM (5 ml). DIEA (210 µl, 1.24 mmol) and PivCl (85 µl, 0.68 mmol) were then added. After stirring overnight at room temperature, the reaction mixture was evaporated in vacuo and the resulting residue dissolved in EtOAc (15 ml). The organic phase was washed successively with aqueous 0.1 N KHSO₄ (3 × 5 ml) and saturated NaHCO₃ (3 × 5 ml), dried over MgSO₄ and then concentrated in vacuo. The crude product was purified by chromatography on silica gel in EtOAc/hexane 6:4, to give 154 mg of (III) (70% yield) as a solid; R_f = 0.50 (EtOAc/hexane 6:4). Single crystals of (III) were obtained at room temperature by slow evaporation of a solution in a mixture of diisopropyl ether and ethyl acetate.

S3. Refinement

The atom-numbering chosen for the independent molecules A and B is in the range 1–17 and 21–37, respectively. The absolute stereochemistry of the L-Sip derivative was confirmed on the basis of the L-Ala residue. The positions of H atoms attached to N were located from a difference map and refined with the N—H bond distance restrained to 1.03 (1) Å (Taylor & Kennard, 1983). H atoms connected to C were placed at calculated positions and refined using a riding model (C—H distance?). All H atoms had their isotropic displacement parameters fixed at 1.3 times that of the parent atom.

Computing details

Data collection: COLLECT (Nonius, 1998); cell refinement: COLLECT (Nonius, 1998); data reduction: HKL suite (Otwinoski & Minor, 1997); program(s) used to solve structure: SIR92 (Altomare et al., 1994); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: maXus (Mackay et al., 1999) and WebLab ViewerPro 3.5 (MSI, 1999).

Figures

	Fig. 1. The molecular structure of the independent molecule A in (III) with the atom-numbering scheme and 25% probability displacement ellipsoids. H atoms, except those of the NH groups, are omitted for clarity. The intramolecular hydrogen bond is marked as a dashed line.
	Fig. 2. A stereoview of the crystal structure of (III), which is composed of alternating layers of molecules A (stick representation) and molecules B (ball and stick representation), oriented parallel to (100). The intermolecular hydrogen bonds are marked as dashed lines. H atoms, except those of the NH groups involved in the intermolecular interactions, are omitted for clarity.

N-(3,3-dimethyl-1-pivaloyl-1-aza-3-sila-5-cyclopentylcarbonyl)-L-alanine isopropylamide

Crystal data

C17H33N3O3Si	F(000) = 776
Mr = 355.55	Dx = 1.117 Mg m^−3
Monoclinic, P21	Mo Kα radiation, λ = 0.71070 Å
a = 9.6650 (5) Å	Cell parameters from 9566 reflections
b = 19.6620 (9) Å	θ = 2.1–25.0°
c = 11.123 (2) Å	µ = 0.13 mm^−1
β = 89.602 (5)°	T = 293 K
V = 2113.7 (4) Å^3	Prismatic, colourless
Z = 4	0.3 × 0.2 × 0.2 mm

Data collection

Nonius KAPPA CCD diffractometer	3090 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.055
Graphite monochromator	θmax = 25.0°, θmin = 2.1°
oscillation scans	h = −10→10
9566 measured reflections	k = −23→23
3659 independent reflections	l = −13→13

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)] = 0.055	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.143	H atoms treated by a mixture of independent and constrained refinement
S = 1.07	w = 1/[σ^2(Fo^2) + (0.0749P)^2 + 0.8441P] where P = (Fo^2 + 2Fc^2)/3
3659 reflections	(Δ/σ)max = 0.001
445 parameters	Δρmax = 0.23 e Å^−3
5 restraints	Δρmin = −0.22 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 of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) 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
C1	0.0153 (6)	0.0826 (3)	0.6235 (5)	0.0520 (14)
C2	0.1723 (8)	0.0820 (4)	0.6431 (9)	0.106 (3)
H2A	0.2190	0.0889	0.5677	0.138*
H2B	0.1993	0.0390	0.6763	0.138*
H2C	0.1968	0.1178	0.6978	0.138*
C3	−0.0555 (12)	0.0714 (4)	0.7429 (8)	0.121 (4)
H3A	−0.0366	0.1091	0.7952	0.157*
H3B	−0.0215	0.0303	0.7786	0.157*
H3C	−0.1535	0.0677	0.7312	0.157*
C4	−0.0184 (10)	0.0239 (4)	0.5410 (8)	0.093 (3)
H4A	0.0268	0.0305	0.4647	0.120*
H4B	−0.1166	0.0216	0.5295	0.120*
H4C	0.0133	−0.0178	0.5763	0.120*
C5	−0.0262 (5)	0.1492 (3)	0.5626 (5)	0.0421 (12)
O1	−0.0838 (4)	0.14747 (19)	0.4631 (3)	0.0538 (10)
N1	0.0031 (4)	0.2112 (2)	0.6098 (3)	0.0410 (10)
C6	−0.0383 (5)	0.2713 (2)	0.5416 (4)	0.0384 (11)
H6A	−0.1393	0.2754	0.5445	0.050*
C7	0.0254 (6)	0.3357 (3)	0.5939 (5)	0.0503 (14)
H7A	−0.0320	0.3751	0.5773	0.065*
H7B	0.1171	0.3435	0.5607	0.065*
Si1	0.03382 (14)	0.31900 (8)	0.75980 (13)	0.0420 (3)
C8	0.0376 (6)	0.2246 (3)	0.7387 (5)	0.0523 (14)
H8A	0.1286	0.2068	0.7572	0.068*
H8B	−0.0297	0.2029	0.7912	0.068*
C9	−0.1237 (6)	0.3492 (4)	0.8421 (6)	0.0622 (16)
H9A	−0.1205	0.3978	0.8496	0.081*
H9B	−0.1266	0.3290	0.9207	0.081*
H9C	−0.2048	0.3363	0.7983	0.081*
C10	0.1928 (6)	0.3524 (3)	0.8310 (5)	0.0539 (14)
H10A	0.1860	0.4009	0.8387	0.070*
H10B	0.2717	0.3412	0.7820	0.070*
H10C	0.2032	0.3324	0.9092	0.070*
C11	0.0085 (4)	0.2663 (2)	0.4097 (4)	0.0355 (11)
O2	0.1289 (3)	0.2523 (2)	0.3825 (3)	0.0467 (9)
N2	−0.0848 (4)	0.2853 (2)	0.3289 (3)	0.0403 (10)
H2	−0.1874 (18)	0.287 (3)	0.353 (5)	0.052*
C12	−0.0519 (5)	0.2946 (3)	0.2016 (4)	0.0438 (12)
H12	−0.1391	0.3075	0.1635	0.057*
C13	0.0460 (7)	0.3543 (3)	0.1809 (5)	0.0631 (17)
H13A	0.0107	0.3938	0.2215	0.082*
H13B	0.0534	0.3634	0.0963	0.082*
H13C	0.1357	0.3432	0.2119	0.082*
C14	−0.0052 (5)	0.2300 (3)	0.1378 (5)	0.0471 (13)
O3	0.0504 (5)	0.2343 (2)	0.0387 (4)	0.0697 (13)
N3	−0.0381 (5)	0.1706 (2)	0.1884 (4)	0.0530 (12)
H3	−0.054 (6)	0.174 (3)	0.2795 (13)	0.069*
C15	0.0061 (8)	0.1053 (4)	0.1377 (6)	0.077 (2)
H15	0.0124	0.1103	0.0502	0.100*
C16	0.1479 (9)	0.0856 (5)	0.1836 (9)	0.108 (3)
H16A	0.2143	0.1193	0.1592	0.140*
H16B	0.1738	0.0422	0.1510	0.140*
H16C	0.1453	0.0829	0.2698	0.140*
C17	−0.1022 (11)	0.0529 (5)	0.1654 (10)	0.115 (3)
H17A	−0.1897	0.0677	0.1346	0.149*
H17B	−0.1094	0.0469	0.2509	0.149*
H17C	−0.0769	0.0105	0.1286	0.149*
C21	0.5124 (6)	0.4464 (3)	0.1441 (5)	0.0509 (14)
C22	0.4844 (7)	0.5041 (3)	0.2338 (6)	0.0679 (17)
H22A	0.5404	0.4977	0.3038	0.088*
H22B	0.3885	0.5038	0.2566	0.088*
H22C	0.5070	0.5469	0.1971	0.088*
C23	0.6683 (8)	0.4473 (4)	0.1157 (8)	0.093 (3)
H23A	0.7192	0.4386	0.1879	0.120*
H23B	0.6937	0.4911	0.0842	0.120*
H23C	0.6893	0.4128	0.0573	0.120*
C24	0.4275 (11)	0.4591 (4)	0.0320 (7)	0.112 (3)
H24A	0.3308	0.4573	0.0521	0.145*
H24B	0.4484	0.4248	−0.0269	0.145*
H24C	0.4497	0.5031	−0.0001	0.145*
C25	0.4715 (5)	0.3796 (3)	0.2058 (5)	0.0403 (12)
O21	0.4120 (4)	0.3812 (2)	0.3043 (3)	0.0539 (10)
N21	0.5030 (4)	0.3175 (2)	0.1564 (4)	0.0413 (9)
C26	0.4597 (5)	0.2579 (3)	0.2292 (4)	0.0402 (11)
H26	0.3587	0.2537	0.2280	0.052*
C27	0.5258 (6)	0.1942 (3)	0.1743 (5)	0.0493 (14)
H27A	0.4705	0.1543	0.1925	0.064*
H27B	0.6181	0.1874	0.2057	0.064*
Si21	0.53255 (15)	0.20964 (8)	0.00767 (13)	0.0433 (4)
C28	0.5437 (6)	0.3048 (3)	0.0291 (5)	0.0516 (14)
H28A	0.6372	0.3208	0.0139	0.067*
H28B	0.4814	0.3281	−0.0251	0.067*
C29	0.6898 (6)	0.1752 (3)	−0.0664 (5)	0.0570 (14)
H29A	0.6810	0.1268	−0.0750	0.074*
H29B	0.7693	0.1854	−0.0184	0.074*
H29C	0.7006	0.1956	−0.1444	0.074*
C30	0.3735 (6)	0.1838 (4)	−0.0714 (5)	0.0598 (16)
H30A	0.3718	0.1352	−0.0796	0.078*
H30B	0.3721	0.2044	−0.1497	0.078*
H30C	0.2940	0.1984	−0.0261	0.078*
C31	0.5084 (4)	0.2631 (3)	0.3570 (4)	0.0386 (12)
O22	0.6292 (3)	0.2778 (2)	0.3837 (3)	0.0477 (9)
N22	0.4148 (4)	0.2442 (2)	0.4409 (3)	0.0402 (10)
H22	0.3128 (18)	0.241 (3)	0.417 (4)	0.052*
C32	0.4493 (5)	0.2353 (3)	0.5663 (4)	0.0444 (13)
H32	0.3629	0.2220	0.6065	0.058*
C33	0.5484 (7)	0.1753 (4)	0.5832 (6)	0.0632 (17)
H33A	0.5130	0.1361	0.5421	0.082*
H33B	0.5567	0.1654	0.6674	0.082*
H33C	0.6377	0.1868	0.5508	0.082*
C34	0.4978 (5)	0.3002 (3)	0.6304 (5)	0.0499 (14)
O23	0.5543 (5)	0.2957 (3)	0.7277 (4)	0.0731 (13)
N23	0.4608 (5)	0.3591 (3)	0.5786 (4)	0.0507 (11)
H23	0.449 (6)	0.358 (3)	0.4870 (12)	0.066*
C35	0.5047 (8)	0.4239 (4)	0.6288 (6)	0.0695 (18)
H35	0.5084	0.4196	0.7165	0.090*
C36	0.6459 (9)	0.4439 (5)	0.5834 (8)	0.106 (3)
H36A	0.7121	0.4100	0.6065	0.137*
H36B	0.6714	0.4870	0.6173	0.137*
H36C	0.6443	0.4475	0.4973	0.137*
C37	0.3967 (9)	0.4768 (4)	0.5973 (8)	0.100 (3)
H37A	0.3085	0.4631	0.6292	0.130*
H37B	0.3910	0.4811	0.5115	0.130*
H37C	0.4224	0.5199	0.6314	0.130*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.064 (4)	0.043 (3)	0.048 (3)	0.003 (3)	0.007 (3)	0.000 (3)
C2	0.082 (5)	0.064 (5)	0.172 (9)	0.027 (4)	−0.046 (5)	−0.016 (5)
C3	0.210 (11)	0.045 (4)	0.107 (7)	0.008 (5)	0.072 (7)	0.014 (4)
C4	0.131 (7)	0.048 (4)	0.099 (6)	0.000 (4)	−0.032 (5)	−0.005 (4)
C5	0.030 (3)	0.053 (3)	0.043 (3)	0.000 (2)	0.002 (2)	0.003 (3)
O1	0.057 (2)	0.052 (2)	0.053 (2)	−0.0051 (17)	−0.0137 (18)	−0.0011 (18)
N1	0.044 (2)	0.044 (2)	0.035 (2)	−0.007 (2)	−0.0017 (16)	−0.001 (2)
C6	0.033 (3)	0.042 (3)	0.040 (3)	−0.002 (2)	0.0016 (19)	0.005 (2)
C7	0.063 (4)	0.050 (4)	0.038 (3)	−0.004 (2)	0.003 (2)	0.005 (2)
Si1	0.0443 (8)	0.0447 (8)	0.0369 (8)	−0.0019 (6)	0.0019 (5)	−0.0027 (7)
C8	0.067 (4)	0.055 (4)	0.035 (3)	−0.003 (3)	−0.010 (2)	0.004 (3)
C9	0.050 (4)	0.082 (5)	0.055 (4)	0.005 (3)	0.001 (3)	0.001 (3)
C10	0.046 (3)	0.062 (4)	0.054 (3)	−0.007 (3)	−0.001 (2)	−0.007 (3)
C11	0.025 (3)	0.041 (3)	0.040 (3)	−0.0020 (19)	−0.0048 (19)	0.003 (2)
O2	0.0273 (19)	0.068 (2)	0.0444 (19)	0.0029 (16)	−0.0026 (14)	−0.0005 (18)
N2	0.028 (2)	0.056 (3)	0.037 (2)	0.0077 (18)	0.0008 (16)	0.003 (2)
C12	0.038 (3)	0.058 (3)	0.036 (3)	0.004 (2)	−0.005 (2)	0.005 (2)
C13	0.079 (4)	0.060 (4)	0.050 (4)	−0.010 (3)	0.007 (3)	0.002 (3)
C14	0.040 (3)	0.063 (4)	0.039 (3)	0.001 (2)	−0.007 (2)	0.003 (3)
O3	0.090 (3)	0.074 (3)	0.044 (2)	0.008 (2)	0.025 (2)	0.004 (2)
N3	0.061 (3)	0.052 (3)	0.045 (3)	−0.007 (2)	−0.004 (2)	−0.001 (2)
C15	0.115 (6)	0.055 (4)	0.060 (4)	−0.001 (4)	0.003 (4)	−0.007 (3)
C16	0.091 (6)	0.089 (6)	0.143 (8)	0.023 (5)	0.031 (5)	0.014 (6)
C17	0.142 (8)	0.069 (5)	0.134 (8)	−0.023 (5)	−0.034 (6)	0.001 (5)
C21	0.061 (4)	0.049 (4)	0.042 (3)	0.000 (3)	−0.005 (2)	0.003 (3)
C22	0.076 (4)	0.045 (3)	0.083 (5)	0.003 (3)	0.000 (3)	−0.003 (3)
C23	0.082 (5)	0.067 (5)	0.128 (7)	−0.025 (4)	0.045 (5)	−0.019 (4)
C24	0.189 (10)	0.061 (5)	0.086 (6)	0.000 (6)	−0.070 (6)	0.016 (4)
C25	0.030 (3)	0.044 (3)	0.047 (3)	0.000 (2)	−0.010 (2)	0.001 (2)
O21	0.065 (2)	0.052 (2)	0.045 (2)	0.0067 (18)	0.0072 (18)	−0.0022 (18)
N21	0.047 (2)	0.041 (2)	0.036 (2)	0.000 (2)	0.0004 (17)	0.002 (2)
C26	0.038 (3)	0.047 (3)	0.036 (3)	−0.001 (2)	−0.003 (2)	0.005 (2)
C27	0.063 (4)	0.039 (3)	0.046 (3)	0.004 (2)	−0.001 (3)	−0.004 (2)
Si21	0.0458 (8)	0.0481 (8)	0.0360 (7)	0.0009 (7)	−0.0009 (6)	−0.0061 (6)
C28	0.072 (4)	0.046 (4)	0.036 (3)	−0.004 (3)	0.013 (2)	0.002 (2)
C29	0.052 (3)	0.066 (4)	0.053 (3)	0.002 (3)	0.008 (3)	−0.010 (3)
C30	0.047 (3)	0.075 (4)	0.058 (4)	0.002 (3)	−0.006 (3)	−0.008 (3)
C31	0.021 (3)	0.053 (3)	0.041 (3)	−0.001 (2)	0.002 (2)	0.003 (2)
O22	0.0263 (19)	0.072 (3)	0.045 (2)	−0.0050 (16)	0.0009 (14)	0.0007 (18)
N22	0.029 (2)	0.055 (3)	0.036 (2)	−0.0037 (18)	0.0001 (16)	0.0060 (19)
C32	0.040 (3)	0.061 (4)	0.032 (3)	−0.001 (2)	0.001 (2)	0.005 (2)
C33	0.071 (4)	0.067 (4)	0.052 (4)	0.014 (3)	−0.006 (3)	0.009 (3)
C34	0.039 (3)	0.066 (4)	0.045 (3)	−0.001 (3)	0.005 (2)	0.006 (3)
O23	0.087 (3)	0.085 (4)	0.048 (2)	−0.007 (2)	−0.027 (2)	0.005 (2)
N23	0.055 (3)	0.061 (3)	0.037 (2)	0.000 (2)	0.005 (2)	0.001 (2)
C35	0.100 (5)	0.061 (4)	0.047 (4)	−0.008 (4)	−0.008 (3)	−0.005 (3)
C36	0.089 (6)	0.115 (8)	0.113 (7)	−0.041 (5)	−0.024 (5)	0.021 (6)
C37	0.115 (7)	0.072 (6)	0.112 (7)	0.008 (5)	0.014 (5)	−0.002 (5)

Geometric parameters (Å, º)

N1—C6	1.462 (7)	N21—C26	1.483 (6)
N1—C8	1.497 (6)	N21—C28	1.488 (6)
C6—C7	1.525 (7)	C26—C27	1.532 (7)
Si1—C7	1.877 (6)	Si21—C27	1.879 (6)
Si1—C8	1.872 (6)	Si21—C28	1.890 (6)
Si1—C9	1.868 (6)	Si21—C29	1.852 (5)
Si1—C10	1.854 (5)	Si21—C30	1.848 (6)
C1—C3	1.507 (10)	C21—C24	1.518 (9)
C1—C4	1.512 (9)	C21—C22	1.533 (8)
C1—C5	1.529 (8)	C21—C25	1.533 (8)
C1—C2	1.534 (10)	C21—C23	1.538 (9)
C2—H2A	0.9600	C22—H22A	0.9600
C2—H2B	0.9600	C22—H22B	0.9600
C2—H2C	0.9600	C22—H22C	0.9600
C3—H3A	0.9600	C23—H23A	0.9600
C3—H3B	0.9600	C23—H23B	0.9600
C3—H3C	0.9600	C23—H23C	0.9600
C4—H4A	0.9600	C24—H24A	0.9600
C4—H4B	0.9600	C24—H24B	0.9600
C4—H4C	0.9600	C24—H24C	0.9600
C5—O1	1.242 (6)	C25—O21	1.234 (6)
C5—N1	1.358 (7)	C25—N21	1.371 (7)
C6—C11	1.535 (7)	C26—C31	1.504 (7)
C6—H6A	0.9800	C26—H26	0.9800
C7—H7A	0.9700	C27—H27A	0.9700
C7—H7B	0.9700	C27—H27B	0.9700
C8—H8A	0.9700	C28—H28A	0.9700
C8—H8B	0.9700	C28—H28B	0.9700
C9—H9A	0.9600	C29—H29A	0.9600
C9—H9B	0.9600	C29—H29B	0.9600
C9—H9C	0.9600	C29—H29C	0.9600
C10—H10A	0.9600	C30—H30A	0.9600
C10—H10B	0.9600	C30—H30B	0.9600
C10—H10C	0.9600	C30—H30C	0.9600
C11—O2	1.232 (6)	C31—O22	1.241 (6)
C11—N2	1.331 (6)	C31—N22	1.347 (6)
N2—C12	1.461 (6)	N22—C32	1.447 (6)
N2—H2	1.025 (11)	N22—H22	1.025 (11)
C12—C14	1.522 (8)	C32—C33	1.531 (8)
C12—C13	1.524 (8)	C32—C34	1.537 (8)
C12—H12	0.9800	C32—H32	0.9800
C13—H13A	0.9600	C33—H33A	0.9600
C13—H13B	0.9600	C33—H33B	0.9600
C13—H13C	0.9600	C33—H33C	0.9600
C14—O3	1.226 (6)	C34—O23	1.219 (7)
C14—N3	1.332 (7)	C34—N23	1.343 (8)
N3—C15	1.465 (8)	N23—C35	1.456 (8)
N3—H3	1.025 (11)	N23—H23	1.027 (11)
C15—C17	1.500 (12)	C35—C36	1.504 (10)
C15—C16	1.516 (11)	C35—C37	1.517 (11)
C15—H15	0.9800	C35—H35	0.9800
C16—H16A	0.9600	C36—H36A	0.9600
C16—H16B	0.9600	C36—H36B	0.9600
C16—H16C	0.9600	C36—H36C	0.9600
C17—H17A	0.9600	C37—H37A	0.9600
C17—H17B	0.9600	C37—H37B	0.9600
C17—H17C	0.9600	C37—H37C	0.9600
C3—C1—C4	109.0 (6)	C24—C21—C22	108.6 (6)
C3—C1—C5	113.4 (5)	C24—C21—C25	111.7 (5)
C4—C1—C5	109.1 (5)	C22—C21—C25	107.4 (5)
C3—C1—C2	108.4 (7)	C24—C21—C23	111.3 (7)
C4—C1—C2	107.3 (6)	C22—C21—C23	107.0 (5)
C5—C1—C2	109.4 (5)	C25—C21—C23	110.5 (5)
C1—C2—H2A	109.5	C21—C22—H22A	109.5
C1—C2—H2B	109.5	C21—C22—H22B	109.5
H2A—C2—H2B	109.5	H22A—C22—H22B	109.5
C1—C2—H2C	109.5	C21—C22—H22C	109.5
H2A—C2—H2C	109.5	H22A—C22—H22C	109.5
H2B—C2—H2C	109.5	H22B—C22—H22C	109.5
C1—C3—H3A	109.5	C21—C23—H23A	109.5
C1—C3—H3B	109.5	C21—C23—H23B	109.5
H3A—C3—H3B	109.5	H23A—C23—H23B	109.5
C1—C3—H3C	109.5	C21—C23—H23C	109.5
H3A—C3—H3C	109.5	H23A—C23—H23C	109.5
H3B—C3—H3C	109.5	H23B—C23—H23C	109.5
C1—C4—H4A	109.5	C21—C24—H24A	109.5
C1—C4—H4B	109.5	C21—C24—H24B	109.5
H4A—C4—H4B	109.5	H24A—C24—H24B	109.5
C1—C4—H4C	109.5	C21—C24—H24C	109.5
H4A—C4—H4C	109.5	H24A—C24—H24C	109.5
H4B—C4—H4C	109.5	H24B—C24—H24C	109.5
O1—C5—N1	117.7 (5)	O21—C25—N21	118.6 (5)
O1—C5—C1	119.4 (5)	O21—C25—C21	119.5 (5)
N1—C5—C1	122.8 (5)	N21—C25—C21	121.9 (5)
C5—N1—C6	117.8 (4)	C25—N21—C26	115.0 (4)
C5—N1—C8	125.1 (4)	C25—N21—C28	125.9 (4)
C6—N1—C8	114.8 (4)	N21—C26—C31	112.0 (4)
N1—C6—C7	111.1 (4)	C26—N21—C28	117.3 (4)
C6—C7—Si1	104.5 (3)	N21—C26—C27	108.3 (4)
N1—C8—Si1	106.8 (4)	C26—C27—Si21	105.8 (3)
C7—Si1—C8	92.9 (2)	N21—C28—Si21	105.7 (3)
C7—Si1—C9	112.7 (3)	C27—Si21—C28	92.1 (2)
C7—Si1—C10	113.6 (3)	C27—Si21—C29	113.8 (3)
C8—Si1—C9	113.1 (3)	C27—Si21—C30	113.7 (3)
C8—Si1—C10	112.9 (3)	C28—Si21—C29	111.8 (3)
C9—Si1—C10	110.7 (3)	C28—Si21—C30	112.4 (3)
N1—C6—C11	111.3 (4)	C29—Si21—C30	111.7 (3)
C7—C6—C11	107.5 (4)	C31—C26—C27	107.4 (4)
N1—C6—H6A	108.9	N21—C26—H26	109.7
C7—C6—H6A	108.9	C31—C26—H26	109.7
C11—C6—H6A	108.9	C27—C26—H26	109.7
C6—C7—H7A	110.9	C26—C27—H27A	110.6
Si1—C7—H7A	110.9	Si21—C27—H27A	110.6
C6—C7—H7B	110.9	C26—C27—H27B	110.6
Si1—C7—H7B	110.9	Si21—C27—H27B	110.6
H7A—C7—H7B	108.9	H27A—C27—H27B	108.7
N1—C8—H8A	110.4	N21—C28—H28A	110.6
Si1—C8—H8A	110.4	Si21—C28—H28A	110.6
N1—C8—H8B	110.4	N21—C28—H28B	110.6
Si1—C8—H8B	110.4	Si21—C28—H28B	110.6
H8A—C8—H8B	108.6	H28A—C28—H28B	108.7
Si1—C9—H9A	109.5	Si21—C29—H29A	109.5
Si1—C9—H9B	109.5	Si21—C29—H29B	109.5
H9A—C9—H9B	109.5	H29A—C29—H29B	109.5
Si1—C9—H9C	109.5	Si21—C29—H29C	109.5
H9A—C9—H9C	109.5	H29A—C29—H29C	109.5
H9B—C9—H9C	109.5	H29B—C29—H29C	109.5
Si1—C10—H10A	109.5	Si21—C30—H30A	109.5
Si1—C10—H10B	109.5	Si21—C30—H30B	109.5
H10A—C10—H10B	109.5	H30A—C30—H30B	109.5
Si1—C10—H10C	109.5	Si21—C30—H30C	109.5
H10A—C10—H10C	109.5	H30A—C30—H30C	109.5
H10B—C10—H10C	109.5	H30B—C30—H30C	109.5
O2—C11—N2	122.7 (4)	O22—C31—N22	121.8 (4)
O2—C11—C6	121.4 (4)	O22—C31—C26	122.9 (4)
N2—C11—C6	115.5 (4)	N22—C31—C26	115.0 (4)
C11—N2—C12	123.1 (4)	C31—N22—C32	122.9 (4)
C11—N2—H2	119 (3)	C31—N22—H22	119 (3)
C12—N2—H2	117 (3)	C32—N22—H22	118 (3)
N2—C12—C14	114.2 (4)	N22—C32—C33	111.1 (4)
N2—C12—C13	111.9 (4)	N22—C32—C34	114.8 (4)
C14—C12—C13	113.0 (5)	C33—C32—C34	112.9 (4)
N2—C12—H12	105.6	N22—C32—H32	105.7
C14—C12—H12	105.6	C33—C32—H32	105.7
C13—C12—H12	105.6	C34—C32—H32	105.7
C12—C13—H13A	109.5	C32—C33—H33A	109.5
C12—C13—H13B	109.5	C32—C33—H33B	109.5
H13A—C13—H13B	109.5	H33A—C33—H33B	109.5
C12—C13—H13C	109.5	C32—C33—H33C	109.5
H13A—C13—H13C	109.5	H33A—C33—H33C	109.5
H13B—C13—H13C	109.5	H33B—C33—H33C	109.5
O3—C14—N3	122.9 (5)	O23—C34—N23	124.4 (6)
O3—C14—C12	119.1 (5)	O23—C34—C32	119.5 (5)
N3—C14—C12	117.7 (5)	N23—C34—C32	115.8 (5)
C14—N3—C15	122.5 (5)	C34—N23—C35	120.8 (5)
C14—N3—H3	114 (4)	C34—N23—H23	116 (4)
C15—N3—H3	118 (4)	C35—N23—H23	116 (4)
N3—C15—C17	108.8 (7)	N23—C35—C36	111.5 (6)
N3—C15—C16	110.8 (6)	N23—C35—C37	108.0 (6)
C17—C15—C16	112.7 (7)	C36—C35—C37	111.5 (7)
N3—C15—H15	108.1	N23—C35—H35	108.6
C17—C15—H15	108.1	C36—C35—H35	108.6
C16—C15—H15	108.1	C37—C35—H35	108.6
C15—C16—H16A	109.5	C35—C36—H36A	109.5
C15—C16—H16B	109.5	C35—C36—H36B	109.5
H16A—C16—H16B	109.5	H36A—C36—H36B	109.5
C15—C16—H16C	109.5	C35—C36—H36C	109.5
H16A—C16—H16C	109.5	H36A—C36—H36C	109.5
H16B—C16—H16C	109.5	H36B—C36—H36C	109.5
C15—C17—H17A	109.5	C35—C37—H37A	109.5
C15—C17—H17B	109.5	C35—C37—H37B	109.5
H17A—C17—H17B	109.5	H37A—C37—H37B	109.5
C15—C17—H17C	109.5	C35—C37—H37C	109.5
H17A—C17—H17C	109.5	H37A—C37—H37C	109.5
H17B—C17—H17C	109.5	H37B—C37—H37C	109.5
C3—C1—C5—O1	−118.7 (7)	C24—C21—C25—O21	−111.2 (7)
C4—C1—C5—O1	3.0 (8)	C22—C21—C25—O21	7.9 (7)
C2—C1—C5—O1	120.1 (6)	C23—C21—C25—O21	124.3 (6)
C3—C1—C5—N1	64.7 (8)	C24—C21—C25—N21	70.9 (7)
C4—C1—C5—N1	−173.6 (6)	C22—C21—C25—N21	−170.1 (5)
C2—C1—C5—N1	−56.5 (7)	C23—C21—C25—N21	−53.6 (7)
O1—C5—N1—C6	1.6 (7)	O21—C25—N21—C26	0.4 (6)
C1—C5—N1—C6	178.2 (4)	C21—C25—N21—C26	178.3 (4)
O1—C5—N1—C8	163.5 (5)	O21—C25—N21—C28	164.9 (5)
C1—C5—N1—C8	−19.9 (7)	C21—C25—N21—C28	−17.1 (7)
C5—N1—C6—C7	−169.3 (4)	C25—N21—C26—C31	−51.2 (5)
C8—N1—C6—C7	27.0 (6)	N21—C26—C31—N22	137.9 (5)
C5—N1—C6—C11	−49.5 (6)	C31—N22—C32—C34	63.5 (6)
N1—C6—C11—N2	136.5 (4)	N22—C32—C34—N23	20.9 (6)
C11—N2—C12—C14	63.3 (6)	N21—C26—C27—Si21	−33.8 (5)
N2—C12—C14—N3	20.1 (6)	C26—C27—Si21—C28	28.3 (4)
N1—C6—C7—Si1	−33.1 (5)	C27—Si21—C28—N21	−15.0 (4)
C6—C7—Si1—C8	24.9 (4)	Si21—C28—N21—C26	−2.9 (5)
C7—Si1—C8—N1	−11.3 (4)	C28—N21—C26—C31	142.8 (5)
Si1—C8—N1—C6	−6.6 (5)	C25—N21—C26—C27	−169.4 (4)
C8—N1—C6—C11	146.8 (4)	C28—N21—C26—C27	24.6 (6)
C11—C6—C7—Si1	−155.2 (3)	C31—C26—C27—Si21	−154.9 (3)
C6—C7—Si1—C10	141.5 (4)	C26—C27—Si21—C30	−87.3 (4)
C6—C7—Si1—C9	−91.6 (4)	C26—C27—Si21—C29	143.2 (4)
C5—N1—C8—Si1	−169.0 (4)	C25—N21—C28—Si21	−167.1 (4)
C10—Si1—C8—N1	−128.5 (4)	C30—Si21—C28—N21	101.7 (4)
C9—Si1—C8—N1	104.8 (4)	C29—Si21—C28—N21	−131.7 (4)
N1—C6—C11—O2	−50.5 (6)	N21—C26—C31—O22	−48.1 (7)
C7—C6—C11—O2	71.4 (6)	C27—C26—C31—O22	70.6 (6)
C7—C6—C11—N2	−101.5 (5)	C27—C26—C31—N22	−103.4 (5)
O2—C11—N2—C12	−3.1 (8)	O22—C31—N22—C32	−4.3 (8)
C6—C11—N2—C12	169.7 (4)	C26—C31—N22—C32	169.8 (5)
C11—N2—C12—C13	−66.6 (7)	C31—N22—C32—C33	−66.2 (7)
N2—C12—C14—O3	−165.7 (5)	N22—C32—C34—O23	−165.8 (5)
C13—C12—C14—O3	−36.4 (7)	C33—C32—C34—O23	−37.0 (7)
C13—C12—C14—N3	149.5 (5)	C33—C32—C34—N23	149.7 (5)
O3—C14—N3—C15	8.6 (9)	O23—C34—N23—C35	9.2 (9)
C12—C14—N3—C15	−177.5 (5)	C32—C34—N23—C35	−177.9 (5)
C14—N3—C15—C17	−148.3 (6)	C34—N23—C35—C36	85.6 (7)
C14—N3—C15—C16	87.2 (8)	C34—N23—C35—C37	−151.5 (6)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2···O22^i	1.03 (2)	1.81 (2)	2.831 (5)	172 (5)
N23—H23···O21	1.03 (2)	2.13 (2)	3.122 (6)	166 (5)
N3—H3···O1	1.03 (2)	2.13 (2)	3.118 (6)	163 (5)
N22—H22···O2	1.02 (2)	1.83 (2)	2.847 (5)	169 (5)

Symmetry code: (i) x−1, y, z.