β-Turn structure of a tripeptide N-(tert-butoxy­carbon­yl)-Phe-D-Pro-Gly methyl ester monohydrate

The title peptide, N-(tert-butoxy­carbon­yl)phenyl­alanyl-D-prolylglycine methyl ester monohydrate, C₂₂H₃₁N₃O₆·H₂O, was designed to form a β-turn structure. The crystal structure exhibits a type-II β-turn structure which is stabilized through the inter­molecular hydrogen bond between the Gly–NH group and the tert-butyl­oxycarbonyl O atom. The water mol­ecule further inter­acts with the carbonyl O atoms of the peptide, stabilizing the β-turn structure. The circular dichroism spectra suggest the existence of a stable conformation.

Key indicators

• Single-crystal X-ray study
• T = 296 K
• Mean [sigma](C-C) = 0.006 Å
• R factor = 0.060
• wR factor = 0.177
• Data-to-parameter ratio = 10.4

checkCIF/PLATON results

No syntax errors found



Alert level B
PLAT242_ALERT_2_B Check Low       Ueq as Compared to Neighbors for        C10

Alert level C
STRVA01_ALERT_4_C           Flack parameter is too small
           From the CIF: _refine_ls_abs_structure_Flack   -3.000
           From the CIF: _refine_ls_abs_structure_Flack_su    2.000
PLAT032_ALERT_4_C Std. Uncertainty in Flack Parameter too High ...       2.00
PLAT033_ALERT_2_C Flack Parameter Value Deviates 2 * su from zero.      -3.00
PLAT220_ALERT_2_C Large Non-Solvent    C     Ueq(max)/Ueq(min) ...       2.78 Ratio
PLAT222_ALERT_3_C Large Non-Solvent    H     Ueq(max)/Ueq(min) ...       3.46 Ratio
PLAT241_ALERT_2_C Check High      Ueq as Compared to Neighbors for        O10
PLAT242_ALERT_2_C Check Low       Ueq as Compared to Neighbors for        C41
PLAT340_ALERT_3_C Low Bond Precision on C-C Bonds (x 1000) Ang ...          6

Alert level G
REFLT03_ALERT_4_G Please check that the estimate of the number of Friedel pairs is
            correct. If it is not, please give the correct count in the
            _publ_section_exptl_refinement section of the submitted CIF.
           From the CIF: _diffrn_reflns_theta_max           27.10
           From the CIF: _reflns_number_total               3002
           Count of symmetry unique reflns         3012
           Completeness (_total/calc)             99.67%
           TEST3: Check Friedels for noncentro structure
           Estimate of Friedel pairs measured         0
           Fraction of Friedel pairs measured     0.000
           Are heavy atom types Z>Si present         no
PLAT791_ALERT_1_G Confirm the Absolute Configuration of C20    = .          S
PLAT791_ALERT_1_G Confirm the Absolute Configuration of C30    = .          R

   0 ALERT level A = In general: serious problem
   1 ALERT level B = Potentially serious problem
   8 ALERT level C = Check and explain
   3 ALERT level G = General alerts; check

   2 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   5 ALERT type 2 Indicator that the structure model may be wrong or deficient
   2 ALERT type 3 Indicator that the structure quality may be low
   3 ALERT type 4 Improvement, methodology, query or suggestion
   0 ALERT type 5 Informative message, check

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S1. Comment

The certain motifs have been studied to engineer peptide mimics with well defined conformation and novel functions (Venkatraman et al., 2001). The structural studies of these motifs will provide the important fundamental information for peptide design. A protected tripeptide Boc-Phe-D-Pro-Gly-OMe, that Boc = N-t-butyloxycarbonyl moiety, was designed to form β-turn from motifs of Gramicidin S (Schwyzer & Ludescher, 1968) and analogues (Tamaki et al., 1985) considering a D-Pro-Gly segment of β-hairpin peptide (Espinosa & Gellman, 2000).

The molecular structure of the title compound (I) is shown in Fig.1. A l l peptide bonds are planar with a trans conformation. The distances of the atoms from the best planes of peptide bond are lower than 0.062Å for the C14—N20, C28—N30 and C34—N40 bond planes. The Pro residue shows a ring puckering with amplitude of Q2 = 0.408 (5)Å and phase of ϕ2 = 261.2 (5)° (Cremer & Pople, 1975). The torsion angles, (C14—N20—C20—C28, N20—C20—C28—N30) and (C28—N30—C30—C34, N30—C30—C34—N40), are (-54.6 (4)°, 129.8 (3)°) and (86.9 (4)°, -14.0 (5)°), respectively, and classified as type II β-turn. A N–H···O=C intramolecular hydrogen bond is formed between Gly–NH and Boc=O: N40···O14 = 3.097 (4)Å stabilizing of the β-turn structure. In this crystal, the hydrated water molecule further stabilizes the folded structure by forming O–H···O=C interactions with the carbonyl oxygen atoms (O1···O14 and O1···O41). A N–H···O=C interaction is established between the Gly residue (N20) and Pro residue (O28) translated by (1/2 + x, 3/2 - y, 2 - z). This motif propagates along the a axis (Fig. 2).

The CD spectra of I are measured in acetonitrile solutions changing the trifluoroethanol (TFE) concentration. TFE provides a specific environment conducive to hydrophobic interactions between peptide side chains (Reiersen & Rees, 2000), and is often used to induce structural changes of polypeptides. The isosbestic point around 220 nm indicates the conformational equilibrium, but several concentrations of TFE had little effect on the spectra (Fig.3), indicating that the solution conformations of I are stable with respect to TFE titration. These results indicate that this tripeptide motif forms a stable β-turn structure and could be a candidate to induce β-turn into poplypeptides.

Related literature

For related literature, see: Cremer & Pople (1975); Espinosa & Gellman (2000); Reiersen & Rees (2000); Schwyzer & Ludescher (1968); Tamaki et al., (1985); Venkatraman et al., (2001).

For related literature, see: Flack & Bernardinelli (2000).

S2. Experimental

The title compound was synthesized by a conventional liquid-phase method, and purified by silica-gel column chromatography and re-crystallization, respectively. Crystals were grown from ethylacetate and methanol (3:1) solutions by vapor diffusion method. CD spectra were measured by JASCO J-820 dichrograph at approximate 0.05 mmol dm^-3 peptide concentrations. Spectra were scanned at 5 nm^.min^-1 speed with 0.1 nm interval-uptake to a computer. Data were averaged at each 1 nm and plotted.

S3. Refinement

H atoms were treated as riding atoms with distances C–H = 0.96–0.98Å and N–H = 0.86 Å; U_iso(H) = 1.2U_eq(C), U_iso(H) = 1.5U_eq(C_methyl) and U_iso(H) = 1.2U_eq(N). H atoms of the water molecule were found in a difference Fourier map considering hydrogen-bond networks and refined with U_iso(H) = 1.5U_eq(O). In the absence of any significant anomalous scattering, 2290 Friedel pairs were merged prior to the final refinements, and the absolute structure was set by reference to the known chirality of the amino acid employed.

Computing details

Data collection: SMART (Bruker, 1998); cell refinement: SAINT-Plus (Bruker, 1998); data reduction: SAINT-Plus (Bruker, 1998); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: PLATON (Spek, 2003); software used to prepare material for publication: SHELXL97 (Sheldrick, 1997).

Figures

	Fig. 1. Views of I with the atom numbering scheme. Displacement ellipsoids are drawn at the 50% probability level. H atoms are presented as spheres of arbitrary radius. Dotted lines represent hydrogen bonds.
	Fig. 2. Packing diagram of I. Side chains of amino acids are omitted for clarity. H atoms related to hydrogen bonds are included in drawing. Dotted lines represent hydrogen bonds. Open and closed circles represent non-hydrogen atoms and water molecules - O1.
	Fig. 3. CD spectra of I. Trifluoroethanol was added to acetonitrile solutions to concentrations of 0, 10, 20, 30 and 40%.

Boc-Phe-D-Pro-Gly-OMe monohydrate

Crystal data

C22H31N3O6·H2O	F(000) = 968
Mr = 451.51	Dx = 1.245 Mg m^−3
Orthorhombic, P212121	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 7049 reflections
a = 9.0814 (8) Å	θ = 2.4–22.1°
b = 11.6889 (10) Å	µ = 0.09 mm^−1
c = 22.685 (2) Å	T = 296 K
V = 2408.1 (4) Å^3	Needle, colourless
Z = 4	0.40 × 0.20 × 0.20 mm

Data collection

Bruker SMART APEX CCD area-detector diffractometer	3002 independent reflections
Radiation source: MacScience M18XCE (rotating anode)	2771 reflections with I > 2σ(I)
Confocal multilayer optics monochromator	Rint = 0.031
Detector resolution: 8.366 pixels mm^-1	θmax = 27.1°, θmin = 1.8°
ω–scan	h = −11→11
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)	k = −14→14
Tmin = 0.912, Tmax = 0.982	l = −28→29
28185 measured reflections

Refinement

Refinement on F^2	Primary atom site location: Direct
Least-squares matrix: Full	Secondary atom site location: Difmap
R[F^2 > 2σ(F^2)] = 0.060	Hydrogen site location: Geom
wR(F^2) = 0.177	H-atom parameters constrained
S = 1.11	w = 1/[σ^2(Fo^2) + (0.1079P)^2 + 0.5338P] where P = (Fo^2 + 2Fc^2)/3
3002 reflections	(Δ/σ)max = 0.001
289 parameters	Δρmax = 0.28 e Å^−3
0 restraints	Δρmin = −0.27 e Å^−3

Special details

Geometry. Cremer & Pople Puckering Parameters ———————————– Q(2) = 0.4080 (47) Å, Phi(2) = 261.2 (5)°

The equation of the plane is of the form: P * x + Q * y + R * z - S = 0 where P, Q, R, S are constants and x, y, z are fractional coordinates.

P = 6.063 (7), Q = 5.023 (11), R = -13.79 (2), S = -3.43 (3) Atom Distance x y z X Y Z O10 0.033 (3) 0.9104 1.0015 1.0110 8.2677 11.7064 22.9345 O14 - 0.023 (3) 0.7517 0.9726 0.9348 6.8265 11.3686 21.2050 N20 - 0.007 (3) 0.9224 0.8418 0.9611 8.3767 9.8397 21.8016 C14 - 0.003 (3) 0.8530 0.9413 0.9665 7.7464 11.0028 21.9251 C20 0.032 (3) 0.8853 0.7638 0.9135 8.0398 8.9280 20.7223 H20 - 0.03253 0.9899 0.8235 0.9859 8.9897 9.6258 22.3651

P = -2.027 (10), Q =11.121 (5), R = 4.81 (3), S = 11.14 (3) Atom Distance x y z X Y Z O28 0.008 (2) 0.6619 0.7070 0.9607 6.0110 8.2641 21.7944 N30 max 0.062 (2) 0.6433 0.7499 0.8650 5.8421 8.7655 19.6218 C20 - 0.041 (2) 0.8853 0.7638 0.9135 8.0398 8.9280 20.7223 C28 0.023 (2) 0.7192 0.7387 0.9147 6.5313 8.6346 20.7497 C30 - 0.051 (4) 0.4893 0.7135 0.8609 4.4435 8.3400 19.5297

P = -1.364 (12), Q = -5.598 (12), R = 19.621 (12), S = 12.24 (2) Atom Distance x y z X Y Z O34 0.009 (3) 0.2493 0.7954 0.8686 2.2640 9.2973 19.7040 N40 0.002 (3) 0.4315 0.8956 0.9095 3.9186 10.4686 20.6322 C30 - 0.011 (3) 0.4893 0.7135 0.8609 4.4435 8.3400 19.5297 C34 0.002 (3) 0.3787 0.8057 0.8802 3.4391 9.4177 19.9664 C40 - 0.012 (3) 0.3298 0.9842 0.9270 2.9950 11.5042 21.0288 H40 0.01105 0.5237 0.9006 0.9178 4.7559 10.5270 20.8203

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

	x	y	z	Uiso*/Ueq
C10	0.8478 (4)	1.1109 (3)	1.02972 (16)	0.0502 (8)
O10	0.9104 (4)	1.0015 (2)	1.01100 (14)	0.0718 (9)
C11	0.9449 (6)	1.1437 (4)	1.0808 (3)	0.0986 (19)
H11A	1.0446	1.1518	1.0673	0.148*
H11B	0.9404	1.0853	1.1105	0.148*
H11C	0.9117	1.2150	1.0971	0.148*
C12	0.6942 (6)	1.0963 (5)	1.0481 (3)	0.0984 (18)
H12A	0.6356	1.0749	1.0146	0.148*
H12B	0.6580	1.1669	1.0641	0.148*
H12C	0.6884	1.0375	1.0775	0.148*
C13	0.8604 (8)	1.1983 (4)	0.9807 (3)	0.0990 (19)
H13A	0.9619	1.2070	0.9698	0.149*
H13B	0.8224	1.2704	0.9941	0.149*
H13C	0.8048	1.1728	0.9472	0.149*
C14	0.8530 (4)	0.9413 (3)	0.96650 (14)	0.0468 (7)
O14	0.7517 (3)	0.9726 (2)	0.93476 (12)	0.0571 (7)
N20	0.9224 (3)	0.8418 (2)	0.96106 (12)	0.0442 (6)
H20	0.9899	0.8235	0.9859	0.053*
C20	0.8853 (3)	0.7638 (2)	0.91348 (12)	0.0358 (6)
H20A	0.9126	0.7976	0.8755	0.043*
C21	0.9679 (3)	0.6509 (3)	0.92253 (13)	0.0432 (7)
H21A	1.0725	0.6667	0.9258	0.052*
H21B	0.9360	0.6165	0.9593	0.052*
C22	0.9433 (4)	0.5669 (3)	0.87295 (14)	0.0444 (7)
C23	1.0342 (5)	0.5667 (3)	0.82448 (15)	0.0584 (9)
H23	1.1119	0.6184	0.8223	0.070*
C24	1.0108 (6)	0.4904 (4)	0.77903 (18)	0.0772 (13)
H24	1.0737	0.4909	0.7467	0.093*
C25	0.8975 (7)	0.4143 (4)	0.7808 (2)	0.0861 (16)
H25	0.8818	0.3640	0.7496	0.103*
C26	0.8071 (6)	0.4129 (4)	0.8288 (2)	0.0812 (14)
H26	0.7302	0.3604	0.8306	0.097*
C27	0.8288 (5)	0.4889 (3)	0.87470 (19)	0.0617 (9)
H27	0.7659	0.4876	0.9070	0.074*
C28	0.7192 (3)	0.7387 (2)	0.91469 (12)	0.0356 (6)
O28	0.6619 (2)	0.7070 (2)	0.96074 (9)	0.0492 (5)
N30	0.6433 (3)	0.7499 (2)	0.86497 (10)	0.0401 (5)
C30	0.4893 (4)	0.7135 (3)	0.86091 (15)	0.0480 (7)
H30	0.4743	0.6437	0.8841	0.058*
C31	0.4722 (5)	0.6873 (4)	0.79539 (19)	0.0746 (13)
H31A	0.5092	0.6117	0.7858	0.090*
H31B	0.3702	0.6931	0.7830	0.090*
C32	0.5646 (5)	0.7791 (5)	0.76797 (16)	0.0762 (13)
H32A	0.5131	0.8518	0.7680	0.091*
H32B	0.5904	0.7595	0.7277	0.091*
C33	0.7009 (4)	0.7845 (4)	0.80662 (14)	0.0576 (9)
H33A	0.7761	0.7320	0.7929	0.069*
H33B	0.7413	0.8613	0.8078	0.069*
C34	0.3787 (3)	0.8057 (3)	0.88016 (15)	0.0468 (7)
O34	0.2493 (3)	0.7954 (3)	0.86859 (15)	0.0707 (8)
N40	0.4315 (3)	0.8956 (2)	0.90951 (13)	0.0482 (6)
H40	0.5237	0.9006	0.9178	0.058*
C40	0.3298 (4)	0.9842 (3)	0.92699 (15)	0.0550 (8)
H40A	0.3772	1.0344	0.9553	0.066*
H40B	0.2450	0.9497	0.9460	0.066*
C41	0.2794 (4)	1.0531 (3)	0.87493 (16)	0.0509 (8)
O41	0.3458 (4)	1.0663 (3)	0.83062 (14)	0.0852 (10)
O42	0.1512 (4)	1.1022 (3)	0.88564 (11)	0.0715 (8)
C42	0.0908 (6)	1.1746 (5)	0.8400 (2)	0.0863 (15)
H42A	−0.0019	1.2051	0.8529	0.129*
H42B	0.0764	1.1304	0.8048	0.129*
H42C	0.1578	1.2362	0.8321	0.129*
O1	0.6824 (7)	1.0983 (6)	0.8311 (2)	0.164 (3)
H1	0.5875	1.0888	0.8283	0.246*
H2	0.7008	1.0675	0.8637	0.246*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C10	0.0463 (17)	0.0414 (15)	0.0630 (19)	−0.0005 (14)	0.0013 (16)	−0.0147 (14)
O10	0.0724 (17)	0.0570 (15)	0.0861 (18)	0.0250 (14)	−0.0374 (16)	−0.0325 (14)
C11	0.102 (4)	0.076 (3)	0.118 (4)	0.021 (3)	−0.040 (4)	−0.056 (3)
C12	0.071 (3)	0.107 (4)	0.118 (4)	−0.025 (3)	0.031 (3)	−0.045 (3)
C13	0.142 (5)	0.054 (2)	0.102 (4)	−0.025 (3)	0.013 (4)	0.002 (2)
C14	0.0425 (16)	0.0442 (15)	0.0538 (17)	0.0041 (13)	−0.0115 (14)	−0.0057 (14)
O14	0.0592 (14)	0.0439 (12)	0.0682 (15)	0.0113 (11)	−0.0210 (12)	−0.0070 (11)
N20	0.0409 (13)	0.0408 (12)	0.0508 (14)	0.0078 (11)	−0.0126 (11)	−0.0085 (11)
C20	0.0359 (13)	0.0376 (13)	0.0338 (13)	0.0024 (11)	0.0017 (11)	−0.0030 (11)
C21	0.0406 (15)	0.0422 (15)	0.0469 (16)	0.0069 (13)	−0.0018 (13)	−0.0044 (13)
C22	0.0482 (16)	0.0366 (14)	0.0485 (16)	0.0106 (13)	−0.0047 (14)	−0.0050 (13)
C23	0.066 (2)	0.0539 (19)	0.0554 (19)	0.0128 (18)	0.0079 (17)	−0.0022 (16)
C24	0.098 (3)	0.074 (3)	0.059 (2)	0.030 (3)	0.004 (2)	−0.013 (2)
C25	0.123 (4)	0.065 (3)	0.070 (3)	0.027 (3)	−0.024 (3)	−0.029 (2)
C26	0.080 (3)	0.059 (2)	0.104 (4)	−0.002 (2)	−0.020 (3)	−0.023 (2)
C27	0.061 (2)	0.0507 (19)	0.074 (2)	0.0009 (18)	0.000 (2)	−0.0106 (17)
C28	0.0368 (14)	0.0333 (13)	0.0368 (13)	0.0023 (11)	0.0047 (11)	−0.0060 (11)
O28	0.0439 (11)	0.0626 (13)	0.0410 (11)	0.0012 (11)	0.0082 (10)	0.0063 (10)
N30	0.0385 (12)	0.0438 (13)	0.0381 (12)	0.0012 (11)	−0.0003 (10)	−0.0048 (10)
C30	0.0407 (15)	0.0455 (16)	0.0579 (18)	−0.0008 (14)	−0.0050 (14)	−0.0133 (14)
C31	0.065 (2)	0.092 (3)	0.068 (2)	0.004 (2)	−0.018 (2)	−0.040 (2)
C32	0.077 (3)	0.114 (4)	0.0384 (17)	0.023 (3)	−0.0121 (18)	−0.012 (2)
C33	0.059 (2)	0.078 (2)	0.0359 (15)	0.008 (2)	0.0032 (14)	0.0001 (15)
C34	0.0370 (15)	0.0526 (17)	0.0507 (17)	−0.0009 (14)	−0.0010 (13)	−0.0005 (14)
O34	0.0381 (12)	0.0759 (17)	0.098 (2)	−0.0033 (13)	−0.0020 (13)	−0.0149 (16)
N40	0.0412 (14)	0.0477 (14)	0.0556 (15)	0.0058 (12)	−0.0032 (12)	−0.0073 (12)
C40	0.056 (2)	0.0549 (18)	0.0539 (19)	0.0105 (17)	0.0059 (16)	−0.0049 (15)
C41	0.0487 (18)	0.0490 (17)	0.0550 (19)	0.0046 (15)	−0.0004 (15)	−0.0061 (14)
O41	0.077 (2)	0.103 (2)	0.0761 (19)	0.019 (2)	0.0196 (18)	0.0275 (18)
O42	0.0710 (17)	0.0838 (19)	0.0597 (14)	0.0340 (16)	0.0007 (14)	−0.0016 (14)
C42	0.093 (3)	0.097 (4)	0.069 (3)	0.037 (3)	−0.018 (3)	−0.003 (2)
O1	0.137 (5)	0.208 (6)	0.145 (4)	−0.028 (5)	−0.035 (4)	0.081 (5)

Geometric parameters (Å, º)

C10—O10	1.462 (4)	C26—H26	0.9300
C10—C12	1.466 (6)	C27—H27	0.9300
C10—C11	1.505 (6)	C28—O28	1.224 (3)
C10—C13	1.514 (6)	C28—N30	1.328 (4)
O10—C14	1.336 (4)	N30—C30	1.465 (4)
C11—H11A	0.9600	N30—C33	1.480 (4)
C11—H11B	0.9600	C30—C31	1.526 (5)
C11—H11C	0.9600	C30—C34	1.537 (5)
C12—H12A	0.9600	C30—H30	0.9800
C12—H12B	0.9600	C31—C32	1.498 (7)
C12—H12C	0.9600	C31—H31A	0.9700
C13—H13A	0.9600	C31—H31B	0.9700
C13—H13B	0.9600	C32—C33	1.518 (5)
C13—H13C	0.9600	C32—H32A	0.9700
C14—O14	1.224 (4)	C32—H32B	0.9700
C14—N20	1.329 (4)	C33—H33A	0.9700
N20—C20	1.453 (3)	C33—H33B	0.9700
N20—H20	0.8600	C34—O34	1.210 (4)
C20—C21	1.531 (4)	C34—N40	1.333 (4)
C20—C28	1.537 (4)	N40—C40	1.444 (4)
C20—H20A	0.9800	N40—H40	0.8600
C21—C22	1.510 (4)	C40—C41	1.501 (5)
C21—H21A	0.9700	C40—H40A	0.9700
C21—H21B	0.9700	C40—H40B	0.9700
C22—C23	1.375 (5)	C41—O41	1.182 (5)
C22—C27	1.384 (5)	C41—O42	1.320 (5)
C23—C24	1.380 (6)	O42—C42	1.445 (5)
C23—H23	0.9300	C42—H42A	0.9600
C24—C25	1.361 (8)	C42—H42B	0.9600
C24—H24	0.9300	C42—H42C	0.9600
C25—C26	1.364 (8)	O1—H1	0.872
C25—H25	0.9300	O1—H2	0.838
C26—C27	1.383 (6)
O10—C10—C12	110.5 (4)	C27—C26—H26	119.7
O10—C10—C11	102.6 (3)	C26—C27—C22	120.6 (4)
C12—C10—C11	111.6 (4)	C26—C27—H27	119.7
O10—C10—C13	110.3 (3)	C22—C27—H27	119.7
C12—C10—C13	111.0 (5)	O28—C28—N30	122.3 (3)
C11—C10—C13	110.5 (4)	O28—C28—C20	119.3 (3)
C14—O10—C10	121.9 (3)	N30—C28—C20	118.4 (2)
C10—C11—H11A	109.5	C28—N30—C30	121.3 (3)
C10—C11—H11B	109.5	C28—N30—C33	127.1 (3)
H11A—C11—H11B	109.5	C30—N30—C33	111.1 (3)
C10—C11—H11C	109.5	N30—C30—C31	102.5 (3)
H11A—C11—H11C	109.5	N30—C30—C34	113.7 (3)
H11B—C11—H11C	109.5	C31—C30—C34	110.6 (3)
C10—C12—H12A	109.5	N30—C30—H30	109.9
C10—C12—H12B	109.5	C31—C30—H30	109.9
H12A—C12—H12B	109.5	C34—C30—H30	109.9
C10—C12—H12C	109.5	C32—C31—C30	101.8 (3)
H12A—C12—H12C	109.5	C32—C31—H31A	111.4
H12B—C12—H12C	109.5	C30—C31—H31A	111.4
C10—C13—H13A	109.5	C32—C31—H31B	111.4
C10—C13—H13B	109.5	C30—C31—H31B	111.4
H13A—C13—H13B	109.5	H31A—C31—H31B	109.3
C10—C13—H13C	109.5	C31—C32—C33	104.3 (3)
H13A—C13—H13C	109.5	C31—C32—H32A	110.9
H13B—C13—H13C	109.5	C33—C32—H32A	110.9
O14—C14—N20	124.3 (3)	C31—C32—H32B	110.9
O14—C14—O10	125.5 (3)	C33—C32—H32B	110.9
N20—C14—O10	110.2 (3)	H32A—C32—H32B	108.9
C14—N20—C20	120.6 (2)	N30—C33—C32	102.6 (3)
C14—N20—H20	119.7	N30—C33—H33A	111.3
C20—N20—H20	119.7	C32—C33—H33A	111.3
N20—C20—C21	109.1 (2)	N30—C33—H33B	111.3
N20—C20—C28	109.5 (2)	C32—C33—H33B	111.3
C21—C20—C28	108.3 (2)	H33A—C33—H33B	109.2
N20—C20—H20A	110.0	O34—C34—N40	122.4 (3)
C21—C20—H20A	110.0	O34—C34—C30	120.2 (3)
C28—C20—H20A	110.0	N40—C34—C30	117.4 (3)
C22—C21—C20	112.8 (2)	C34—N40—C40	118.2 (3)
C22—C21—H21A	109.0	C34—N40—H40	120.9
C20—C21—H21A	109.0	C40—N40—H40	120.9
C22—C21—H21B	109.0	N40—C40—C41	111.3 (3)
C20—C21—H21B	109.0	N40—C40—H40A	109.4
H21A—C21—H21B	107.8	C41—C40—H40A	109.4
C23—C22—C27	118.2 (3)	N40—C40—H40B	109.4
C23—C22—C21	120.5 (3)	C41—C40—H40B	109.4
C27—C22—C21	121.2 (3)	H40A—C40—H40B	108.0
C22—C23—C24	120.4 (4)	O41—C41—O42	123.4 (4)
C22—C23—H23	119.8	O41—C41—C40	125.7 (3)
C24—C23—H23	119.8	O42—C41—C40	110.9 (3)
C25—C24—C23	121.1 (4)	C41—O42—C42	117.2 (3)
C25—C24—H24	119.4	O42—C42—H42A	109.5
C23—C24—H24	119.4	O42—C42—H42B	109.5
C24—C25—C26	119.1 (4)	H42A—C42—H42B	109.5
C24—C25—H25	120.5	O42—C42—H42C	109.5
C26—C25—H25	120.5	H42A—C42—H42C	109.5
C25—C26—C27	120.5 (5)	H42B—C42—H42C	109.5
C25—C26—H26	119.7	H1—O1—H2	101.9
C12—C10—O10—C14	59.6 (5)	O28—C28—N30—C30	−6.4 (4)
C11—C10—O10—C14	178.7 (4)	C20—C28—N30—C30	172.1 (3)
C13—C10—O10—C14	−63.6 (5)	O28—C28—N30—C33	−178.4 (3)
C10—O10—C14—O14	5.0 (6)	C20—C28—N30—C33	0.1 (5)
C10—O10—C14—N20	−175.4 (3)	C28—N30—C30—C31	−153.7 (3)
O14—C14—N20—C20	3.1 (5)	C33—N30—C30—C31	19.4 (4)
O10—C14—N20—C20	−176.5 (3)	C28—N30—C30—C34	86.9 (4)
C14—N20—C20—C21	−173.0 (3)	C33—N30—C30—C34	−100.0 (3)
C14—N20—C20—C28	−54.6 (4)	N30—C30—C31—C32	−37.2 (4)
N20—C20—C21—C22	−176.4 (3)	C34—C30—C31—C32	84.4 (4)
C28—C20—C21—C22	64.4 (3)	C30—C31—C32—C33	42.0 (4)
C20—C21—C22—C23	89.4 (4)	C28—N30—C33—C32	178.8 (3)
C20—C21—C22—C27	−90.1 (4)	C30—N30—C33—C32	6.2 (4)
C27—C22—C23—C24	0.0 (5)	C31—C32—C33—N30	−30.0 (4)
C21—C22—C23—C24	−179.5 (3)	N30—C30—C34—O34	165.9 (4)
C22—C23—C24—C25	0.5 (6)	C31—C30—C34—O34	51.2 (5)
C23—C24—C25—C26	−0.9 (7)	N30—C30—C34—N40	−14.0 (5)
C24—C25—C26—C27	1.0 (7)	C31—C30—C34—N40	−128.7 (4)
C25—C26—C27—C22	−0.6 (7)	O34—C34—N40—C40	−1.1 (6)
C23—C22—C27—C26	0.1 (6)	C30—C34—N40—C40	178.8 (3)
C21—C22—C27—C26	179.6 (4)	C34—N40—C40—C41	−72.1 (4)
N20—C20—C28—O28	−51.7 (4)	N40—C40—C41—O41	−26.2 (6)
C21—C20—C28—O28	67.2 (3)	N40—C40—C41—O42	156.3 (3)
N20—C20—C28—N30	129.8 (3)	O41—C41—O42—C42	0.5 (6)
C21—C20—C28—N30	−111.3 (3)	C40—C41—O42—C42	178.0 (4)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N40—H40···O14	0.86	2.27	3.097 (4)	162
O1—H1···O41	0.87	2.21	3.080 (7)	174
O1—H2···O14	0.84	2.01	2.843 (6)	171
N20—H20···O28^i	0.86	2.01	2.864 (3)	174

Symmetry code: (i) x+1/2, −y+3/2, −z+2.