Supplementary Materials
pH-sensitive morphological transition from nanowire to nanovesicle
of a single amino acid based water soluble molecule
Pradyot Koley and Animesh Pramanik*
Department of Chemistry, University of Calcutta, 92, A. P. C. Road, Kolkata-700 009, India
Fax: +91 33 2351 9755.
E-mail: animesh_in2001@yahoo.co.in
Table of contents
Contents
Page numbers
Contents
Page numbers
Fig. S1
2
Table S1
6
Fig. S2
2
Table S2
6
Fig. S3
3
Table S3
7
Fig. S4
3
Synthesis and characterization
Fig. S5
4
of the peptides
7-12
Fig. S6
4
References
12
Fig. S7
5
Fig. S8
5
1
(b)
(a)
Figures
100 nm
(a)
100 nm
20 nm
100 nm
(c)
(b)
(c)
(d)
100 nm
100 nm
50 nm
Fig. S1 Transmission electron microscopic images (TEM) showing (a) hollow, multilayer
vesicular structures of peptide I, and without showing distinct and credible vesicular morphology
of (b) peptide III and (c) peptide IV from neutral aqueous solution.
Average horizontal distance ~ 38 nm
Average vertical distance ~ 1.7 nm
Fig. S2 Section analysis showing the horizontal and vertical distance of peptide I vesicular
structure grown from neutral aqueous solution (1mg mL-1).
2
50
a)
50
b)
40
Intensity (%)
Intensity (%)
40
30
20
10
30
20
10
0
0.1
1
10
100
1000
0
0.1
10000
1
c)
40
30
Intensity (%)
Intensity (%)
40
20
10
0
0.1
1
10
100
10
100
1000
10000
Diameter (nm)
Diameter (nm)
1000
d)
30
20
10
0
0.1
10000
1
Diameter (nm)
10
100
1000
10000
Diameter (nm)
Fig. S3 DLS results show the well equilibrated nanostructures of (a) peptide I, (b) peptide II, (c)
peptide III, and (d) peptide IV from their aqueous solution (1mg mL-1).
200 nm
Fig. S4 TEM image showing the rupture of the nanovesicles of peptide I in presence of KCl salt.
Arrows indicate the debris of the ruptured vesicles.
3
Fig. S5 ORTEP diagram of peptide I. Thermal ellipsoids are shown at the 50% probability.
Color code: red, oxygen; blue, nitrogen; gray, carbon; light gray, hydrogen; green, fluorine.
O4
O5
O2
N1
N2
O3
Fig. S6 Crystal structure shows that the individual molecules of peptide I are regularly interlinked through four different types of intermolecular hydrogen bonding interactions with
adjacent neighboring peptide molecules and trifluoroacetic acid molecules in an antiparallel
fashion.
4
100 nm
Fig. S7 TEM images showing the resistance of peptide I nanovesicles to enzymatic proteolysis
by proteinase K after 24 hours incubation at physiological temperature 37°C.
0.9
0.8
Initial Curcumin
Unencapsulated Curcumin
Absorbance (a.u)
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0.0
300
325
350
375
400
425
450
475
500
525
Wavelength (nm)
Fig. S8 UV absorption spectra showing the initial concentration of the curcumin (red line) and
the concentration of the unencapsulated curcumin (blue line) in methanol. Corresponding
calibration curve of curcumin in methanol is reported elsewhere [S1].
5
Tables
Table S1 Crystallographic refinement details for peptide I generated from trifluoroacetic acid /
water solvent mixture.
Crystal color
Chemical Formula
Formula Weight (g)
Crystal System
Space group
Z
a (Å)
b (Å)
c (Å)
α (º)
β (º)
γ (º)
V (Å3)
Collected reflections
Unique reflections
Reflections I>2σ(I)
No Parameters
R (int)
GoF
R1 , wR2 [I>2 σ(I)]
R1 , wR2 [all data)]
max, min electron
density e/ Å3
Colorless
C16 H16 N2 O3.CF3COOH
398.34
Triclinic
P-1
2
9.1590 (7)
9.6894 (8)
11.5260 (9)
74.118 (4)
77.024 (4)
71.971 (4)
924.52 (13)
11029
4247
2289
260
0.0405
1.018
0.0791, 0.2487
0.1322, 0.3099
0.809, -0.473
Table S2 Selected backbone torsion angle (°) of peptide I
N1-C1-C2-N2
146.77
C3-C4-C5-C6
C1-C2-N2-C3
-171.97
C4-C5-C6-O1
-12.29
C2-N2-C3-C4
167.87
C4-C5-C6-O2
168.16
N2-C3-C4-C5
-177.20
6
177.16
Table S3 Intermolecular hydrogen bonding parameters of crystals of peptide I grown from
trifluoroacetic acid / water solvent mixture.
Type
H…A(Ǻ)
D...A(Ǻ)
N1-H1...O3a
1.945(3)
2.831(5)
173
N1-H1...O2b
1.986(3)
2.829(4)
157
N1-H1...O5c
1.858(3)
2.748(4)
178
N2-H2…O4b
1.988(4)
2.840(5)
170
D-H...A(o)
Symmetry elements: a1-x, -y, 1-z; b1-x, 1-y, 1-z; c x, y, z.
Synthesis and characterization of the peptides
Synthesis and characterization of terminally protected analogues of these peptides have been
reported elsewhere [S2].
Peptide I (NH2-Phe-m-ABA-OH): At first previously reported terminally protected analogue of
the peptide Boc-Phe-m-ABA-OMe [S2] (2.0 g, 5.02 mmol) was dissolved in methanol (20 ml)
and 2N NaOH (10 ml) was added in the solution drop wise. The reaction mixture was stirred for
1 day at room temperature. The progress of the reaction was monitored by TLC. After
completion of reaction the methanol was evaporated. The residue was diluted with water and
washed with diethyl ether. The aqueous layer was cooled in an ice-bath and then neutralized by
using 2N HCl and extracted with ethyl acetate. The solvent was evaporated in vacuo to give a
waxy colorless solid (compound 1). Yield: (1.75 g, 90.67%).
Now the compound 1 (1.75g, 4.56 mmol) was dissolved in trifluoroacetic acid (8 ml) at 0°C and
stirred at room temperature. The removal of the Boc-group was monitored by TLC. After 8 h the
trifluoroacetic acid was removed under reduced pressure to afford the crude trifluoroacetate salt.
The residue was taken up in water and washed with diethyl ether. The pH of the aqueous solution
was adjusted to pH=8 with sodium bicarbonate and extracted with ethyl acetate. The extracts
were pooled, washed with brine, dried over sodium sulphate, and concentrated to solid materials
7
of peptide I that gave a positive ninhydrin test. The peptide was fully characterised by X-ray
crystallography, FT-IR and NMR studies.
Yield: 1.20 g (4.22 mmol, 93.02%). Mp=228-230 °C; IR (KBr) : 3101, 2644, 1673, 1564 cm-1;
1
H NMR (300 MHz, DMSO-d6, 25C, TMS) ppm 10.58 (s, 1H, m-ABA (2) NH); 8.09 (s, 1H,
m-ABA (2) Ha); 7.71 (d, J = 8.1 Hz, 1H, m-ABA (2) Hd); 7.64 (d, J = 7.8 Hz, 1H, m-ABA (2)
Hb); 7.42 (t, J = 7.8 Hz, 1H, m-ABA (2) Hc); 7.21-7.30 (m, 5H, Phe (1) phenyl ring protons);
4.11-4.15 (m, 1H, Phe (1) Cα Hs); 3.26-3.37 (m, 2H, Phe (1) CβHs).
C NMR (75 MHz, DMSO-d6): ppm 167.23, 167.01, 138.13, 134.90, 131.63, 129.50(2C),
13
129.31, 128.62(2C), 127.29, 125.01, 123.73, 120.41, 54.52, 37.20.
1
H NMR spectra of peptide I in DMSO-d6
8
13
C NMR spectra of peptide I in DMSO-d6
Analogous peptides (peptide II and peptide IV) had been prepared using the same experimental
procedure with reported precursor peptide Boc-Tyr-m-ABA-OMe and Boc-Pro-m-ABA-OMe
respectively [S2], whereas peptide III (NH2-Gly-m-ABA-OH) was synthesized by literature
method [S3].
Peptide II (NH2-Tyr-m-ABA-OH):
Yield: 80.64 %. Mp=216-218 °C; IR (KBr) : 3094, 2649, 1670, 1613, 1565, 1519 cm-1; 1H NMR
(300 MHz, DMSO-d6, 25C, TMS) ppm 10.55 (s, 1H, m-ABA (2) NH); 9.03 (s, 1H, Tyr (1)
phenyl ring OH); 8.12 (s, 1H, m-ABA (2) Ha); 7.72 (d, J = 6.6 Hz, 1H, m-ABA (2) Hd); 7.63 (d,
J = 7.2 Hz, 1H, m-ABA (2) Hb); 7.41 (t, J = 7.8 Hz, 1H, m-ABA (2) Hc); 6.95-7.02 (m, 2H, Tyr
(1) phenyl ring protons); 6.64 (br, 2H, Tyr (1) phenyl ring protons); 4.00 (br, 1H, Tyr (1) Cα Hs);
2.80-2.99 (m, 2H, Tyr (1) CβHs).
C NMR (75 MHz, chloroform-d): ppm 167.96, 167.20, 156.60, 138.30, 130.48(2C), 129.23,
13
127.33, 125.12, 123.60, 121.66, 118.30, 115.42(2C), 55.03, 36.79.
9
1
H NMR spectra of peptide II in DMSO-d6
13
C NMR spectra of peptide II in DMSO-d6
10
Peptide IV (NH2-Pro-m-ABA-OH):
Yield: 87.30 %. Mp=166-168 °C; IR (KBr) : 3086, 2578, 1675, 1595 cm-1; 1H NMR (300 MHz,
DMSO-d6, 25C, TMS) ppm 10.79 (s, 1H, m-ABA (2) NH); 8.21 (s, 1H, m-ABA (2) Ha); 7.77
(d, J = 8.55 Hz, 1H, m-ABA (2) Hd); 7.65 (d, J = 7.5 Hz, 1H, m-ABA (2) Hb); 7.45 (t, J = 7.95
Hz, 1H, m-ABA (2) Hc); 4.33-4.38 (m, 1H, Pro (1) Cα H); 3.21-3.37 (m, 2H, Pro (1) CγHs); 2.322.41 (m, 1H, Pro (1) CβHa); 1.92-2.02 (m, 3H, Pro (1) CβHb and CδHs).
C NMR (75 MHz, DMSO-d6): ppm 167.22, 167.01, 138.40, 131.66, 129.32, 124.98, 123.68,
13
120.40, 59.82, 45.89, 29.61, 23.64.
1
H NMR spectra of peptide IV in DMSO-d6
11
13
C NMR spectra of peptide IV in DMSO-d6
References
S1. Koley P, Pramanik A (2012) Soft Matter 8:5364
S2. Koley P, Pramanik A (2011) Adv Funct Mater 21:4126
S3. Dutta A, Kar S, Frölich R, Koley P, Pramanik A (2009) ARKIVOC (ii):31
CIF files of Peptide I
data_peptideI
_audit_creation_method
SHELXL-97
_chemical_name_systematic
;
?
;
12
_chemical_name_common
_chemical_melting_point
_chemical_formula_moiety
?
?
?
_chemical_formula_sum
'C18 H17 F3 N2 O5'
_chemical_formula_weight
398.34
loop_
_atom_type_symbol
_atom_type_description
_atom_type_scat_dispersion_real
_atom_type_scat_dispersion_imag
_atom_type_scat_source
'C' 'C' 0.0033 0.0016
'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4'
'H' 'H' 0.0000 0.0000
'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4'
'N' 'N' 0.0061 0.0033
'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4'
'O' 'O' 0.0106 0.0060
'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4'
'F' 'F' 0.0171 0.0103
'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4'
_symmetry_cell_setting
'Triclinic'
13
_symmetry_space_group_name_H-M
'P-1'
loop_
_symmetry_equiv_pos_as_xyz
'x, y, z'
'-x, -y, -z'
_cell_length_a
9.1590(7)
_cell_length_b
9.6894(8)
_cell_length_c
11.5260(9)
_cell_angle_alpha
74.118(4)
_cell_angle_beta
77.024(4)
_cell_angle_gamma
_cell_volume
71.971(4)
924.52(13)
_cell_formula_units_Z
2
_cell_measurement_temperature
296(2)
_cell_measurement_reflns_used
1264
_cell_measurement_theta_min
2.60
_cell_measurement_theta_max
21.51
_exptl_crystal_description
_exptl_crystal_colour
needle
white
_exptl_crystal_size_max
0.22
_exptl_crystal_size_mid
0.03
_exptl_crystal_size_min
0.03
14
_exptl_crystal_density_meas
?
_exptl_crystal_density_diffrn
1.435
_exptl_crystal_density_method
_exptl_crystal_F_000
'not measured'
414
_exptl_absorpt_coefficient_mu
0.124
_exptl_absorpt_correction_type
'none'
_exptl_absorpt_correction_T_min 0.973
_exptl_absorpt_correction_T_max 0.996
_exptl_absorpt_process_details ?
_exptl_special_details
;
?
;
_diffrn_ambient_temperature
296(2)
_diffrn_radiation_wavelength
0.71073
_diffrn_radiation_type
MoK\a
_diffrn_radiation_source
'fine-focus sealed wire'
_diffrn_radiation_monochromator graphite
_diffrn_measurement_device_type 'Bruker APEX-II CCD'
_diffrn_measurement_method
'\f and \w scans'
_diffrn_standards_interval_count 'n/a'
_diffrn_standards_interval_time 'n/a'
_diffrn_standards_decay_%
'n/a'
15
_diffrn_detector_area_resol_mean ?
_diffrn_reflns_number
11029
_diffrn_reflns_av_R_equivalents 0.0405
_diffrn_reflns_av_sigmaI/netI
0.0477
_diffrn_reflns_limit_h_min
-11
_diffrn_reflns_limit_h_max
11
_diffrn_reflns_limit_k_min
-12
_diffrn_reflns_limit_k_max
11
_diffrn_reflns_limit_l_min
-14
_diffrn_reflns_limit_l_max
15
_diffrn_reflns_theta_min
1.86
_diffrn_reflns_theta_max
27.70
_reflns_number_total
4247
_reflns_number_gt
2289
_reflns_threshold_expression
>2sigma(I)
_computing_data_collection
'Bruker APEX2'
_computing_cell_refinement
'Bruker SAINT'
_computing_data_reduction
'Bruker SAINT'
_computing_structure_solution
'SHELXS-97 (Sheldrick, 2008)'
_computing_structure_refinement 'SHELXL-97 (Sheldrick, 2008)'
_computing_molecular_graphics
'Bruker SHELXTL'
_computing_publication_material 'Bruker SHELXTL'
_refine_special_details
16
;
Refinement of F^2^ against ALL reflections. The weighted R-factor wR and
goodness of fit S are based on F^2^, conventional R-factors R are based
on F, with F set to zero for negative F^2^. The threshold expression of
F^2^ > 2sigma(F^2^) is used only for calculating R-factors(gt) etc. and is
not relevant to the choice of reflections for refinement. R-factors based
on F^2^ are statistically about twice as large as those based on F, and Rfactors based on ALL data will be even larger.
;
_refine_ls_structure_factor_coef Fsqd
_refine_ls_matrix_type
full
_refine_ls_weighting_scheme
calc
_refine_ls_weighting_details
'calc w=1/[\s^2^(Fo^2^)+(0.2000P)^2^+0.0000P] where P=(Fo^2^+2Fc^2^)/3'
_atom_sites_solution_primary
direct
_atom_sites_solution_secondary difmap
_atom_sites_solution_hydrogens
_refine_ls_hydrogen_treatment
mixed
_refine_ls_extinction_method
_refine_ls_extinction_coef
geom
SHELXL
0.019(10)
_refine_ls_extinction_expression
'Fc^*^=kFc[1+0.001xFc^2^\l^3^/sin(2\q)]^-1/4^'
_refine_ls_number_reflns
_refine_ls_number_parameters
4247
260
17
_refine_ls_number_restraints
0
_refine_ls_R_factor_all
0.1322
_refine_ls_R_factor_gt
0.0791
_refine_ls_wR_factor_ref
0.3099
_refine_ls_wR_factor_gt
0.2487
_refine_ls_goodness_of_fit_ref
1.018
_refine_ls_restrained_S_all
1.018
_refine_ls_shift/su_max
0.000
_refine_ls_shift/su_mean
0.000
loop_
_atom_site_label
_atom_site_type_symbol
_atom_site_fract_x
_atom_site_fract_y
_atom_site_fract_z
_atom_site_U_iso_or_equiv
_atom_site_adp_type
_atom_site_occupancy
_atom_site_symmetry_multiplicity
_atom_site_calc_flag
_atom_site_refinement_flags
_atom_site_disorder_assembly
_atom_site_disorder_group
F1 F 0.6019(7) 0.9274(9) 0.5963(4) 0.265(4) Uani 1 1 d . . .
18
F2 F 0.8348(6) 0.8425(6) 0.5795(3) 0.194(2) Uani 1 1 d . . .
O1 O 0.7504(4) 0.7250(3) 0.8095(3) 0.0962(10) Uani 1 1 d . . .
O2 O 0.6341(4) 0.9509(3) 0.8373(3) 0.0907(9) Uani 1 1 d . . .
O3 O 1.1167(3) -0.4522(3) 1.2352(2) 0.0694(7) Uani 1 1 d . . .
H3 H 1.1340 -0.5419 1.2411 0.104 Uiso 1 1 calc R . .
O4 O 0.9456(3) -0.4424(3) 1.1208(2) 0.0740(7) Uani 1 1 d . . .
O5 O 0.6061(3) 0.3292(3) 1.0448(3) 0.0791(8) Uani 1 1 d . . .
N1 N 0.6900(3) 0.1042(3) 0.9936(2) 0.0540(7) Uani 1 1 d . . .
H1 H 0.6838 0.0586 0.9412 0.065 Uiso 1 1 calc R . .
C16 C 0.8519(3) -0.1276(3) 1.0822(3) 0.0508(7) Uani 1 1 d . . .
C1 C 0.6980(4) 0.8593(4) 0.7753(3) 0.0602(8) Uani 1 1 d . . .
C2 C 0.7138(7) 0.9141(5) 0.6396(4) 0.0949(14) Uani 1 1 d . . .
F3 F 0.7290(11) 1.0460(6) 0.6070(5) 0.257(4) Uani 1 1 d . . .
C4 C 0.1916(6) 0.5613(9) 0.5436(4) 0.115(2) Uani 1 1 d . . .
H4 H 0.1123 0.6016 0.4961 0.138 Uiso 1 1 calc R . .
C5 C 0.2395(6) 0.6511(6) 0.5898(5) 0.1069(17) Uani 1 1 d . . .
H5 H 0.1938 0.7531 0.5737 0.128 Uiso 1 1 calc R . .
C6 C 0.3592(5) 0.5899(5) 0.6627(4) 0.0824(11) Uani 1 1 d . . .
H6 H 0.3933 0.6518 0.6934 0.099 Uiso 1 1 calc R . .
C7 C 0.4251(4) 0.4397(4) 0.6880(3) 0.0628(9) Uani 1 1 d . . .
C8 C 0.5472(4) 0.3716(4) 0.7712(3) 0.0695(9) Uani 1 1 d . . .
H8A H 0.5884 0.4490 0.7790 0.083 Uiso 1 1 calc R . .
H8B H 0.6320 0.3000 0.7348 0.083 Uiso 1 1 calc R . .
C9 C 0.4829(4) 0.2943(3) 0.8977(3) 0.0532(7) Uani 1 1 d . . .
H9 H 0.4536 0.2081 0.8910 0.064 Uiso 1 1 calc R . .
19
C10 C 0.6001(4) 0.2430(3) 0.9861(3) 0.0542(7) Uani 1 1 d . . .
C11 C 0.7947(3) 0.0229(3) 1.0776(3) 0.0504(7) Uani 1 1 d . . .
C12 C 0.9499(3) -0.2182(3) 1.1651(3) 0.0535(7) Uani 1 1 d . . .
C13 C 1.0020(3) -0.3796(4) 1.1703(3) 0.0540(7) Uani 1 1 d . . .
C14 C 0.2574(6) 0.4157(8) 0.5659(4) 0.1016(16) Uani 1 1 d . . .
H14 H 0.2252 0.3556 0.5317 0.122 Uiso 1 1 calc R . .
C15 C 0.3727(5) 0.3512(5) 0.6388(3) 0.0808(11) Uani 1 1 d . . .
H15 H 0.4151 0.2486 0.6549 0.097 Uiso 1 1 calc R . .
N2 N 0.3442(3) 0.3981(3) 0.9511(2) 0.0536(7) Uani 1 1 d . . .
H16A H 0.3674 0.4816 0.9488 0.080 Uiso 1 1 calc R . .
H16B H 0.3147 0.3558 1.0283 0.080 Uiso 1 1 calc R . .
H16C H 0.2672 0.4191 0.9085 0.080 Uiso 1 1 calc R . .
C17 C 0.8404(5) 0.0859(4) 1.1532(3) 0.0692(9) Uani 1 1 d . . .
H17 H 0.8047 0.1877 1.1492 0.083 Uiso 1 1 calc R . .
C18 C 0.9396(5) -0.0042(4) 1.2346(4) 0.0765(11) Uani 1 1 d . . .
H18 H 0.9696 0.0380 1.2858 0.092 Uiso 1 1 calc R . .
C19 C 0.9953(4) -0.1554(4) 1.2414(3) 0.0671(9) Uani 1 1 d . . .
H19 H 1.0623 -0.2145 1.2965 0.081 Uiso 1 1 calc R . .
H11 H 0.830(4) -0.168(4) 1.027(3) 0.070(10) Uiso 1 1 d . . .
loop_
_atom_site_aniso_label
_atom_site_aniso_U_11
_atom_site_aniso_U_22
_atom_site_aniso_U_33
20
_atom_site_aniso_U_23
_atom_site_aniso_U_13
_atom_site_aniso_U_12
F1 0.213(5) 0.487(12) 0.110(3) -0.012(4) -0.107(3) -0.101(6)
F2 0.193(4) 0.236(5) 0.0835(19) -0.040(2) 0.008(2) 0.026(4)
O1 0.110(2) 0.0605(16) 0.0809(16) 0.0036(13) -0.0118(16) 0.0113(15)
O2 0.100(2) 0.094(2) 0.0944(18) -0.0527(17) -0.0231(16) -0.0140(17)
O3 0.0614(14) 0.0570(14) 0.0863(15) -0.0045(12) -0.0391(12) -0.0012(11)
O4 0.0741(16) 0.0594(14) 0.0895(16) -0.0205(12) -0.0392(13) 0.0033(12)
O5 0.100(2) 0.0450(12) 0.1086(19) -0.0203(12) -0.0682(16) -0.0024(12)
N1 0.0610(15) 0.0453(13) 0.0595(14) -0.0116(11) -0.0293(12) -0.0052(11)
C16 0.0489(16) 0.0516(17) 0.0528(15) -0.0097(12) -0.0175(12) -0.0093(13)
C1 0.0651(19) 0.0524(18) 0.0651(18) -0.0102(15) -0.0300(15) -0.0066(15)
C2 0.132(4) 0.068(3) 0.075(2) -0.011(2) -0.039(3) -0.001(3)
F3 0.433(11) 0.124(4) 0.148(4) 0.046(3) -0.005(5) -0.078(5)
C4 0.084(3) 0.177(6) 0.062(2) 0.020(3) -0.032(2) -0.028(4)
C5 0.094(3) 0.096(3) 0.090(3) 0.029(3) -0.025(3) -0.004(3)
C6 0.095(3) 0.067(2) 0.073(2) 0.0069(18) -0.019(2) -0.019(2)
C7 0.0545(18) 0.073(2) 0.0529(16) -0.0017(14) -0.0154(13) -0.0111(16)
C8 0.061(2) 0.076(2) 0.069(2) -0.0049(17) -0.0204(16) -0.0175(17)
C9 0.0556(17) 0.0437(15) 0.0651(17) -0.0095(13) -0.0264(14) -0.0101(13)
C10 0.0576(17) 0.0413(15) 0.0672(17) -0.0052(13) -0.0302(14) -0.0095(13)
C11 0.0459(15) 0.0517(16) 0.0544(15) -0.0106(12) -0.0197(12) -0.0064(12)
C12 0.0443(15) 0.0583(18) 0.0527(15) -0.0059(13) -0.0156(12) -0.0061(13)
C13 0.0476(16) 0.0574(18) 0.0523(15) -0.0064(13) -0.0169(12) -0.0057(13)
21
C14 0.092(3) 0.159(5) 0.066(2) -0.026(3) -0.029(2) -0.038(3)
C15 0.079(2) 0.097(3) 0.072(2) -0.029(2) -0.0203(19) -0.018(2)
N2 0.0605(15) 0.0408(13) 0.0630(14) -0.0091(11) -0.0276(12) -0.0076(11)
C17 0.080(2) 0.0537(19) 0.079(2) -0.0229(16) -0.0379(18) 0.0010(16)
C18 0.087(3) 0.069(2) 0.085(2) -0.0248(18) -0.050(2) -0.0031(19)
C19 0.065(2) 0.070(2) 0.0668(19) -0.0143(16) -0.0341(16) -0.0030(16)
_geom_special_details
;
All esds (except the esd in the dihedral angle between two l.s. planes)
are estimated using the full covariance matrix. The cell esds are taken
into account individually in the estimation of esds in distances, angles
and torsion angles; correlations between esds in cell parameters are only
used when they are defined by crystal symmetry. An approximate (isotropic)
treatment of cell esds is used for estimating esds involving l.s. planes.
;
loop_
_geom_bond_atom_site_label_1
_geom_bond_atom_site_label_2
_geom_bond_distance
_geom_bond_site_symmetry_2
_geom_bond_publ_flag
F1 C2 1.195(6) . ?
F2 C2 1.277(6) . ?
22
O1 C1 1.223(4) . ?
O2 C1 1.216(4) . ?
O3 C13 1.329(3) . ?
O3 H3 0.8200 . ?
O4 C13 1.216(4) . ?
O5 C10 1.229(4) . ?
N1 C10 1.333(4) . ?
N1 C11 1.418(4) . ?
N1 H1 0.8600 . ?
C16 C11 1.379(4) . ?
C16 C12 1.389(4) . ?
C16 H11 0.91(4) . ?
C1 C2 1.498(5) . ?
C2 F3 1.272(7) . ?
C4 C14 1.329(9) . ?
C4 C5 1.353(9) . ?
C4 H4 0.9300 . ?
C5 C6 1.413(7) . ?
C5 H5 0.9300 . ?
C6 C7 1.367(5) . ?
C6 H6 0.9300 . ?
C7 C15 1.389(5) . ?
C7 C8 1.512(5) . ?
C8 C9 1.524(5) . ?
C8 H8A 0.9700 . ?
23
C8 H8B 0.9700 . ?
C9 N2 1.484(4) . ?
C9 C10 1.524(4) . ?
C9 H9 0.9800 . ?
C11 C17 1.385(4) . ?
C12 C19 1.389(5) . ?
C12 C13 1.475(5) . ?
C14 C15 1.384(6) . ?
C14 H14 0.9300 . ?
C15 H15 0.9300 . ?
N2 H16A 0.8900 . ?
N2 H16B 0.8900 . ?
N2 H16C 0.8900 . ?
C17 C18 1.383(5) . ?
C17 H17 0.9300 . ?
C18 C19 1.380(5) . ?
C18 H18 0.9300 . ?
C19 H19 0.9300 . ?
loop_
_geom_angle_atom_site_label_1
_geom_angle_atom_site_label_2
_geom_angle_atom_site_label_3
_geom_angle
_geom_angle_site_symmetry_1
24
_geom_angle_site_symmetry_3
_geom_angle_publ_flag
C13 O3 H3 109.5 . . ?
C10 N1 C11 127.6(3) . . ?
C10 N1 H1 116.2 . . ?
C11 N1 H1 116.2 . . ?
C11 C16 C12 120.8(3) . . ?
C11 C16 H11 120(2) . . ?
C12 C16 H11 119(2) . . ?
O2 C1 O1 128.2(3) . . ?
O2 C1 C2 117.3(3) . . ?
O1 C1 C2 114.4(3) . . ?
F1 C2 F2 109.5(5) . . ?
F1 C2 F3 101.7(6) . . ?
F2 C2 F3 102.4(6) . . ?
F1 C2 C1 115.0(5) . . ?
F2 C2 C1 115.1(4) . . ?
F3 C2 C1 111.6(4) . . ?
C14 C4 C5 120.1(5) . . ?
C14 C4 H4 119.9 . . ?
C5 C4 H4 119.9 . . ?
C4 C5 C6 120.0(5) . . ?
C4 C5 H5 120.0 . . ?
C6 C5 H5 120.0 . . ?
C7 C6 C5 120.1(4) . . ?
25
C7 C6 H6 120.0 . . ?
C5 C6 H6 120.0 . . ?
C6 C7 C15 118.2(4) . . ?
C6 C7 C8 120.7(4) . . ?
C15 C7 C8 121.0(3) . . ?
C7 C8 C9 112.3(3) . . ?
C7 C8 H8A 109.1 . . ?
C9 C8 H8A 109.1 . . ?
C7 C8 H8B 109.1 . . ?
C9 C8 H8B 109.1 . . ?
H8A C8 H8B 107.9 . . ?
N2 C9 C10 106.7(2) . . ?
N2 C9 C8 110.2(3) . . ?
C10 C9 C8 112.2(3) . . ?
N2 C9 H9 109.2 . . ?
C10 C9 H9 109.2 . . ?
C8 C9 H9 109.2 . . ?
O5 C10 N1 124.7(3) . . ?
O5 C10 C9 119.4(3) . . ?
N1 C10 C9 115.9(3) . . ?
C16 C11 C17 119.7(3) . . ?
C16 C11 N1 116.4(3) . . ?
C17 C11 N1 123.9(3) . . ?
C16 C12 C19 119.5(3) . . ?
C16 C12 C13 118.7(3) . . ?
26
C19 C12 C13 121.7(3) . . ?
O4 C13 O3 122.2(3) . . ?
O4 C13 C12 123.8(3) . . ?
O3 C13 C12 114.0(3) . . ?
C4 C14 C15 121.6(5) . . ?
C4 C14 H14 119.2 . . ?
C15 C14 H14 119.2 . . ?
C14 C15 C7 119.9(5) . . ?
C14 C15 H15 120.0 . . ?
C7 C15 H15 120.0 . . ?
C9 N2 H16A 109.5 . . ?
C9 N2 H16B 109.5 . . ?
H16A N2 H16B 109.5 . . ?
C9 N2 H16C 109.5 . . ?
H16A N2 H16C 109.5 . . ?
H16B N2 H16C 109.5 . . ?
C18 C17 C11 119.3(3) . . ?
C18 C17 H17 120.3 . . ?
C11 C17 H17 120.3 . . ?
C19 C18 C17 121.4(3) . . ?
C19 C18 H18 119.3 . . ?
C17 C18 H18 119.3 . . ?
C18 C19 C12 119.1(3) . . ?
C18 C19 H19 120.4 . . ?
C12 C19 H19 120.4 . . ?
27
_diffrn_measured_fraction_theta_max
_diffrn_reflns_theta_full
0.982
27.70
_diffrn_measured_fraction_theta_full 0.982
_refine_diff_density_max
0.809
_refine_diff_density_min -0.473
_refine_diff_density_rms
0.072
28