The crystal structure of the title compound contains four 2,4-diamino-5-methyl-6-[(3,4,5-trimethoxyanilino)methyl]quinazoline molecules, two dimethyl sulfoxide molecules and three water molecules in the asymmetric unit,
i.e. 4C
19H
23N
5O
3·2C
2H
6OS·3H
2O. All four quinazoline molecules adopt
trans,gauche conformations. An extensive hydrogen-bond network involving N
N base-pairing interactions, as well as the dimethyl sulfoxide and water molecules, stabilizes the crystal structure.
Supporting information
CCDC reference: 152606
Trimetrexate (NSC 249008-T) was obtained from the NCI Drug Synthesis and Chemistry Branch (NCI National Service Center). Crystals were obtained as pale yellow prisms by slow solvent evaporation from a water–dimethyl sulfoxide mixture.
The H atoms bound to N atoms and those in the water molecules were found from the difference electron-density calculations and were refined independently [range of distances 0.72 (3)–0.98 (5) Å]. The remaining H atoms were calculated geometrically and were treated as riding atoms (range of distances 0.93–0.98 Å).
Data collection: Nonius KappaCCD Server Software (Nonius, 1997); cell refinement: DENZO-SMN (Otwinowski & Minor, 1997); data reduction: DENZO-SMN; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997); software used to prepare material for publication: SHELXL97.
2,4-diamino-5-methyl-6-[(3,4,5-trimethoxyanilino)methyl]quinazoline
top
Crystal data top
4C19H23N5O3·2C2H6OS·3H2O | Z = 2 |
Mr = 1688.02 | F(000) = 1796 |
Triclinic, P1 | Dx = 1.330 Mg m−3 |
a = 16.124 (2) Å | Mo Kα radiation, λ = 0.71073 Å |
b = 16.371 (2) Å | Cell parameters from all reflections reflections |
c = 17.766 (1) Å | µ = 0.14 mm−1 |
α = 81.676 (3)° | T = 100 K |
β = 66.289 (2)° | Prism, pale yellow |
γ = 80.050 (3)° | 0.50 × 0.40 × 0.37 mm |
V = 4214.4 (8) Å3 | |
Data collection top
Nonius KappaCCD diffractometer | 6946 reflections with I > 2σ(I) |
Radiation source: rotating-anode | Rint = 0.000 |
Graphite monochromator | θmax = 26.4°, θmin = 4.1° |
ω rotation scans | h = 0→20 |
16962 measured reflections | k = −19→20 |
16962 independent reflections | l = −20→22 |
Refinement top
Refinement on F2 | Primary atom site location: structure-invariant direct methods |
Least-squares matrix: full | Secondary atom site location: difference Fourier map |
R[F2 > 2σ(F2)] = 0.065 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.168 | H atoms treated by a mixture of independent and constrained refinement |
S = 0.88 | w = 1/[σ2(Fo2) + (0.0735P)2] where P = (Fo2 + 2Fc2)/3 |
16962 reflections | (Δ/σ)max = 0.001 |
1174 parameters | Δρmax = 0.36 e Å−3 |
0 restraints | Δρmin = −0.47 e Å−3 |
Crystal data top
4C19H23N5O3·2C2H6OS·3H2O | γ = 80.050 (3)° |
Mr = 1688.02 | V = 4214.4 (8) Å3 |
Triclinic, P1 | Z = 2 |
a = 16.124 (2) Å | Mo Kα radiation |
b = 16.371 (2) Å | µ = 0.14 mm−1 |
c = 17.766 (1) Å | T = 100 K |
α = 81.676 (3)° | 0.50 × 0.40 × 0.37 mm |
β = 66.289 (2)° | |
Data collection top
Nonius KappaCCD diffractometer | 6946 reflections with I > 2σ(I) |
16962 measured reflections | Rint = 0.000 |
16962 independent reflections | |
Refinement top
R[F2 > 2σ(F2)] = 0.065 | 0 restraints |
wR(F2) = 0.168 | H atoms treated by a mixture of independent and constrained refinement |
S = 0.88 | Δρmax = 0.36 e Å−3 |
16962 reflections | Δρmin = −0.47 e Å−3 |
1174 parameters | |
Special details top
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 (Å2) top | x | y | z | Uiso*/Ueq | |
C1A | 0.3884 (2) | 0.2290 (2) | 0.5196 (2) | 0.0306 (9) | |
C2A | 0.3911 (2) | 0.1537 (2) | 0.56635 (19) | 0.0315 (9) | |
C3A | 0.4721 (2) | 0.0975 (2) | 0.5452 (2) | 0.0341 (10) | |
H3A | 0.4726 | 0.0468 | 0.5765 | 0.0264 (15)* | |
C4A | 0.5501 (2) | 0.1155 (2) | 0.47994 (19) | 0.0342 (10) | |
H4A | 0.6029 | 0.0776 | 0.4683 | 0.0264 (15)* | |
N5A | 0.63273 (18) | 0.20490 (18) | 0.36555 (15) | 0.0288 (7) | |
C6A | 0.6309 (2) | 0.2746 (2) | 0.31824 (19) | 0.0290 (9) | |
N7A | 0.5562 (2) | 0.33161 (19) | 0.32545 (16) | 0.0302 (7) | |
C8A | 0.4775 (2) | 0.3201 (2) | 0.38924 (19) | 0.0285 (9) | |
C9A | 0.4699 (2) | 0.2479 (2) | 0.44848 (19) | 0.0280 (9) | |
C10A | 0.5513 (2) | 0.1909 (2) | 0.43019 (19) | 0.0291 (9) | |
C11A | 0.3020 (2) | 0.2895 (2) | 0.5455 (2) | 0.0385 (10) | |
H11A | 0.2566 | 0.2659 | 0.5941 | 0.0478 (16)* | |
H11B | 0.2799 | 0.3005 | 0.5019 | 0.0478 (16)* | |
H11C | 0.3144 | 0.3405 | 0.5572 | 0.0478 (16)* | |
N12A | 0.7108 (2) | 0.2920 (2) | 0.25637 (19) | 0.0360 (9) | |
N13A | 0.4065 (2) | 0.3773 (2) | 0.3897 (2) | 0.0404 (9) | |
C14A | 0.3066 (2) | 0.1290 (2) | 0.6414 (2) | 0.0338 (10) | |
H14A | 0.2892 | 0.1693 | 0.6818 | 0.0264 (15)* | |
H14B | 0.2564 | 0.1318 | 0.6238 | 0.0264 (15)* | |
N15A | 0.3196 (2) | 0.0466 (2) | 0.68071 (17) | 0.0335 (8) | |
C16A | 0.3481 (2) | 0.0309 (2) | 0.74604 (19) | 0.0300 (9) | |
C17A | 0.3826 (2) | 0.0909 (2) | 0.7694 (2) | 0.0347 (10) | |
H17A | 0.3894 | 0.1426 | 0.7396 | 0.0264 (15)* | |
C18A | 0.4072 (2) | 0.0734 (3) | 0.8379 (2) | 0.0338 (10) | |
C19A | 0.3979 (2) | −0.0035 (3) | 0.8827 (2) | 0.0309 (9) | |
C20A | 0.3652 (2) | −0.0643 (2) | 0.85776 (19) | 0.0293 (9) | |
C21A | 0.3411 (2) | −0.0478 (2) | 0.78995 (19) | 0.0274 (9) | |
H21A | 0.3203 | −0.0889 | 0.7735 | 0.0264 (15)* | |
O22A | 0.43835 (19) | 0.13345 (19) | 0.86320 (15) | 0.0501 (8) | |
C23A | 0.5237 (3) | 0.1521 (3) | 0.8135 (3) | 0.0738 (16) | |
H23A | 0.5665 | 0.1024 | 0.8071 | 0.0478 (16)* | |
H23B | 0.5404 | 0.1919 | 0.8378 | 0.0478 (16)* | |
H23C | 0.5242 | 0.1752 | 0.7604 | 0.0478 (16)* | |
O24A | 0.41628 (16) | −0.02002 (16) | 0.95432 (13) | 0.0367 (7) | |
C25A | 0.5040 (3) | −0.0685 (3) | 0.9405 (2) | 0.0397 (10) | |
H25A | 0.5111 | −0.1145 | 0.9096 | 0.0478 (16)* | |
H25B | 0.5077 | −0.0890 | 0.9926 | 0.0478 (16)* | |
H25C | 0.5515 | −0.0342 | 0.9101 | 0.0478 (16)* | |
O26A | 0.35833 (16) | −0.13854 (16) | 0.90676 (13) | 0.0361 (7) | |
C27A | 0.3344 (3) | −0.2051 (3) | 0.8794 (2) | 0.0428 (11) | |
H27A | 0.2766 | −0.1885 | 0.8745 | 0.0478 (16)* | |
H27B | 0.3302 | −0.2528 | 0.9185 | 0.0478 (16)* | |
H27C | 0.3803 | −0.2188 | 0.8266 | 0.0478 (16)* | |
C1B | 0.5634 (2) | 0.5593 (2) | 0.02767 (19) | 0.0268 (9) | |
C2B | 0.5550 (2) | 0.6213 (2) | −0.03224 (19) | 0.0296 (9) | |
C3B | 0.4889 (2) | 0.6908 (2) | −0.0102 (2) | 0.0322 (9) | |
H3B | 0.4868 | 0.7330 | −0.0508 | 0.0264 (15)* | |
C4B | 0.4276 (2) | 0.6987 (2) | 0.06890 (19) | 0.0283 (9) | |
H4B | 0.3845 | 0.7457 | 0.0817 | 0.0264 (15)* | |
N5B | 0.36028 (18) | 0.64222 (19) | 0.20859 (16) | 0.0287 (7) | |
C6B | 0.3613 (2) | 0.5785 (2) | 0.2640 (2) | 0.0294 (9) | |
N7B | 0.42905 (19) | 0.5143 (2) | 0.25532 (16) | 0.0317 (8) | |
C8B | 0.5009 (2) | 0.5108 (2) | 0.1822 (2) | 0.0274 (9) | |
C9B | 0.5008 (2) | 0.5685 (2) | 0.1119 (2) | 0.0278 (9) | |
C10B | 0.4297 (2) | 0.6357 (2) | 0.13101 (19) | 0.0271 (9) | |
C11B | 0.6336 (2) | 0.4835 (2) | 0.0015 (2) | 0.0351 (10) | |
H11D | 0.6502 | 0.4783 | −0.0561 | 0.0478 (16)* | |
H11E | 0.6083 | 0.4347 | 0.0332 | 0.0478 (16)* | |
H11F | 0.6869 | 0.4897 | 0.0107 | 0.0478 (16)* | |
N12B | 0.2867 (2) | 0.5757 (2) | 0.33609 (18) | 0.0351 (9) | |
N13B | 0.5685 (2) | 0.4514 (2) | 0.18107 (19) | 0.0390 (10) | |
C14B | 0.6171 (2) | 0.6122 (2) | −0.12352 (19) | 0.0335 (9) | |
H14C | 0.6802 | 0.6080 | −0.1297 | 0.0264 (15)* | |
H14D | 0.6089 | 0.5607 | −0.1391 | 0.0264 (15)* | |
N15B | 0.6001 (2) | 0.6798 (2) | −0.17920 (17) | 0.0372 (9) | |
C16B | 0.6344 (2) | 0.7539 (2) | −0.1919 (2) | 0.0324 (10) | |
C17B | 0.6801 (2) | 0.7709 (2) | −0.1452 (2) | 0.0316 (9) | |
H17B | 0.6855 | 0.7325 | −0.1029 | 0.0264 (15)* | |
C18B | 0.7177 (2) | 0.8448 (2) | −0.1613 (2) | 0.0323 (9) | |
C19B | 0.7115 (3) | 0.9035 (2) | −0.2263 (2) | 0.0337 (9) | |
C20B | 0.6624 (2) | 0.8867 (3) | −0.2702 (2) | 0.0342 (10) | |
C21B | 0.6235 (2) | 0.8142 (2) | −0.25381 (19) | 0.0319 (9) | |
H21B | 0.5902 | 0.8050 | −0.2834 | 0.0264 (15)* | |
O22B | 0.76314 (17) | 0.86766 (17) | −0.11841 (14) | 0.0405 (7) | |
C23B | 0.7498 (3) | 0.8248 (3) | −0.0391 (2) | 0.0493 (12) | |
H23D | 0.6857 | 0.8286 | −0.0055 | 0.0478 (16)* | |
H23E | 0.7802 | 0.8497 | −0.0132 | 0.0478 (16)* | |
H23F | 0.7746 | 0.7674 | −0.0454 | 0.0478 (16)* | |
O24B | 0.74881 (18) | 0.97609 (17) | −0.24214 (14) | 0.0419 (7) | |
C25B | 0.8423 (3) | 0.9684 (3) | −0.3003 (2) | 0.0501 (12) | |
H25D | 0.8788 | 0.9281 | −0.2778 | 0.0478 (16)* | |
H25E | 0.8648 | 1.0213 | −0.3111 | 0.0478 (16)* | |
H25F | 0.8456 | 0.9508 | −0.3508 | 0.0478 (16)* | |
O26B | 0.65810 (17) | 0.94779 (17) | −0.33095 (14) | 0.0416 (7) | |
C27B | 0.6039 (3) | 0.9377 (3) | −0.3747 (2) | 0.0450 (11) | |
H27D | 0.6267 | 0.8869 | −0.4015 | 0.0478 (16)* | |
H27E | 0.6067 | 0.9838 | −0.4154 | 0.0478 (16)* | |
H27F | 0.5417 | 0.9357 | −0.3368 | 0.0478 (16)* | |
C1C | 1.0667 (2) | 0.0677 (2) | 0.01269 (19) | 0.0264 (9) | |
C2C | 1.0541 (2) | 0.1279 (2) | −0.04736 (19) | 0.0282 (9) | |
C3C | 0.9836 (2) | 0.1942 (2) | −0.02490 (19) | 0.0288 (9) | |
H3C | 0.9781 | 0.2352 | −0.0653 | 0.0264 (15)* | |
C4C | 0.9224 (2) | 0.2002 (2) | 0.05537 (19) | 0.0297 (9) | |
H4C | 0.8763 | 0.2449 | 0.0685 | 0.0264 (15)* | |
N5C | 0.86151 (18) | 0.14490 (19) | 0.19564 (15) | 0.0286 (7) | |
C6C | 0.8698 (2) | 0.0860 (2) | 0.25226 (19) | 0.0278 (9) | |
N7C | 0.94177 (19) | 0.02541 (19) | 0.24331 (15) | 0.0274 (7) | |
C8C | 1.0087 (2) | 0.0196 (2) | 0.16872 (19) | 0.0259 (9) | |
C9C | 1.0047 (2) | 0.0739 (2) | 0.09776 (19) | 0.0266 (9) | |
C10C | 0.9293 (2) | 0.1393 (2) | 0.1177 (2) | 0.0280 (9) | |
C11C | 1.1419 (2) | −0.0037 (2) | −0.0129 (2) | 0.0344 (10) | |
H11G | 1.1908 | 0.0043 | 0.0020 | 0.0478 (16)* | |
H11H | 1.1187 | −0.0549 | 0.0144 | 0.0478 (16)* | |
H11I | 1.1643 | −0.0062 | −0.0716 | 0.0478 (16)* | |
N12C | 0.7979 (2) | 0.0818 (2) | 0.32715 (18) | 0.0317 (8) | |
N13C | 1.0767 (2) | −0.0412 (2) | 0.16541 (19) | 0.0343 (9) | |
C14C | 1.1147 (2) | 0.1200 (2) | −0.13932 (19) | 0.0335 (10) | |
H14E | 1.1131 | 0.0653 | −0.1531 | 0.0264 (15)* | |
H14F | 1.1773 | 0.1240 | −0.1477 | 0.0264 (15)* | |
N15C | 1.0887 (2) | 0.1818 (2) | −0.19516 (18) | 0.0354 (9) | |
C16C | 1.1155 (2) | 0.2596 (2) | −0.2177 (2) | 0.0326 (10) | |
C17C | 1.1694 (2) | 0.2881 (2) | −0.1843 (2) | 0.0338 (10) | |
H17C | 1.1858 | 0.2545 | −0.1443 | 0.0264 (15)* | |
C18C | 1.1983 (2) | 0.3659 (3) | −0.2105 (2) | 0.0357 (10) | |
C19C | 1.1751 (2) | 0.4178 (2) | −0.2711 (2) | 0.0338 (10) | |
C20C | 1.1201 (2) | 0.3896 (3) | −0.3031 (2) | 0.0343 (10) | |
C21C | 1.0896 (2) | 0.3125 (3) | −0.2767 (2) | 0.0346 (10) | |
H21C | 1.0519 | 0.2954 | −0.2980 | 0.0264 (15)* | |
O22C | 1.25143 (18) | 0.39887 (17) | −0.18035 (14) | 0.0437 (7) | |
C23C | 1.2730 (3) | 0.3496 (3) | −0.1156 (3) | 0.0570 (13) | |
H23G | 1.3029 | 0.2958 | −0.1336 | 0.0478 (16)* | |
H23H | 1.3129 | 0.3767 | −0.1020 | 0.0478 (16)* | |
H23I | 1.2179 | 0.3434 | −0.0678 | 0.0478 (16)* | |
O24C | 1.21111 (17) | 0.49229 (17) | −0.30187 (14) | 0.0410 (7) | |
C25C | 1.1461 (3) | 0.5658 (3) | −0.2762 (2) | 0.0458 (11) | |
H25G | 1.1203 | 0.5642 | −0.2170 | 0.0478 (16)* | |
H25H | 1.1766 | 0.6146 | −0.2986 | 0.0478 (16)* | |
H25I | 1.0984 | 0.5676 | −0.2958 | 0.0478 (16)* | |
O26C | 1.10361 (17) | 0.44335 (16) | −0.36433 (14) | 0.0385 (7) | |
C27C | 1.0541 (3) | 0.4155 (3) | −0.4050 (2) | 0.0447 (11) | |
H27G | 0.9922 | 0.4122 | −0.3671 | 0.0478 (16)* | |
H27H | 1.0549 | 0.4541 | −0.4513 | 0.0478 (16)* | |
H27I | 1.0822 | 0.3616 | −0.4237 | 0.0478 (16)* | |
C1D | −0.0953 (2) | 0.7583 (2) | 0.52608 (19) | 0.0293 (9) | |
C2D | −0.0941 (2) | 0.6861 (2) | 0.57858 (19) | 0.0308 (9) | |
C3D | −0.0104 (2) | 0.6356 (2) | 0.5665 (2) | 0.0338 (10) | |
H3D | −0.0089 | 0.5903 | 0.6044 | 0.0264 (15)* | |
C4D | 0.0690 (2) | 0.6507 (2) | 0.50095 (19) | 0.0324 (9) | |
H4D | 0.1231 | 0.6160 | 0.4950 | 0.0264 (15)* | |
N5D | 0.14782 (19) | 0.72581 (19) | 0.37412 (15) | 0.0309 (8) | |
C6D | 0.1446 (2) | 0.7865 (2) | 0.3169 (2) | 0.0291 (9) | |
N7D | 0.07076 (19) | 0.84447 (19) | 0.32154 (16) | 0.0300 (7) | |
C8D | −0.0052 (2) | 0.8418 (2) | 0.3911 (2) | 0.0310 (9) | |
C9D | −0.0130 (2) | 0.7747 (2) | 0.45613 (19) | 0.0290 (9) | |
C10D | 0.0686 (2) | 0.7187 (2) | 0.44284 (19) | 0.0296 (9) | |
C11D | −0.1844 (2) | 0.8154 (2) | 0.5425 (2) | 0.0377 (10) | |
H11J | −0.2326 | 0.7908 | 0.5875 | 0.0478 (16)* | |
H11K | −0.1787 | 0.8682 | 0.5563 | 0.0478 (16)* | |
H11L | −0.1983 | 0.8234 | 0.4940 | 0.0478 (16)* | |
N12D | 0.2214 (2) | 0.7939 (2) | 0.24910 (18) | 0.0350 (9) | |
N13D | −0.0715 (2) | 0.9046 (2) | 0.3927 (2) | 0.0438 (10) | |
C14D | −0.1817 (2) | 0.6574 (2) | 0.6469 (2) | 0.0339 (10) | |
H14G | −0.2287 | 0.6638 | 0.6247 | 0.0264 (15)* | |
H14H | −0.2027 | 0.6935 | 0.6913 | 0.0264 (15)* | |
N15D | −0.1710 (2) | 0.5721 (2) | 0.68058 (17) | 0.0343 (8) | |
C16D | −0.1497 (2) | 0.5498 (3) | 0.7501 (2) | 0.0329 (10) | |
C17D | −0.1619 (2) | 0.4695 (2) | 0.78974 (19) | 0.0295 (9) | |
H17D | −0.1829 | 0.4318 | 0.7693 | 0.0264 (15)* | |
C18D | −0.1422 (2) | 0.4472 (2) | 0.8598 (2) | 0.0295 (9) | |
C19D | −0.1113 (2) | 0.5041 (2) | 0.89089 (19) | 0.0297 (9) | |
C20D | −0.0984 (2) | 0.5828 (2) | 0.8513 (2) | 0.0305 (9) | |
C21D | −0.1179 (2) | 0.6064 (2) | 0.78055 (19) | 0.0323 (9) | |
H21D | −0.1095 | 0.6594 | 0.7540 | 0.0264 (15)* | |
O22D | −0.15137 (16) | 0.37041 (16) | 0.90407 (13) | 0.0346 (6) | |
C23D | −0.1749 (3) | 0.3081 (3) | 0.8709 (2) | 0.0421 (11) | |
H23J | −0.1279 | 0.2966 | 0.8180 | 0.0478 (16)* | |
H23K | −0.1811 | 0.2583 | 0.9075 | 0.0478 (16)* | |
H23L | −0.2317 | 0.3274 | 0.8646 | 0.0478 (16)* | |
O24D | −0.09359 (16) | 0.47976 (16) | 0.96293 (12) | 0.0336 (6) | |
C25D | −0.0053 (3) | 0.4303 (3) | 0.9456 (2) | 0.0389 (10) | |
H25J | 0.0421 | 0.4642 | 0.9134 | 0.0478 (16)* | |
H25K | 0.0013 | 0.4094 | 0.9965 | 0.0478 (16)* | |
H25L | −0.0007 | 0.3845 | 0.9154 | 0.0478 (16)* | |
O26D | −0.06626 (17) | 0.63389 (16) | 0.88488 (14) | 0.0394 (7) | |
C27D | −0.0396 (3) | 0.7114 (3) | 0.8389 (2) | 0.0489 (11) | |
H27J | −0.0913 | 0.7446 | 0.8312 | 0.0478 (16)* | |
H27K | −0.0175 | 0.7408 | 0.8686 | 0.0478 (16)* | |
H27L | 0.0079 | 0.7006 | 0.7860 | 0.0478 (16)* | |
S1 | 0.52004 (8) | 0.60969 (8) | 0.42897 (6) | 0.0550 (3) | |
O10 | 0.4202 (2) | 0.6042 (2) | 0.47965 (18) | 0.0783 (11) | |
C10 | 0.5622 (3) | 0.5290 (3) | 0.3629 (2) | 0.0539 (12) | |
H10A | 0.5245 | 0.5311 | 0.3322 | 0.090 (5)* | |
H10B | 0.6237 | 0.5355 | 0.3254 | 0.090 (5)* | |
H10C | 0.5614 | 0.4764 | 0.3949 | 0.090 (5)* | |
C11 | 0.5236 (4) | 0.6931 (3) | 0.3520 (3) | 0.0740 (15) | |
H11M | 0.4963 | 0.7440 | 0.3778 | 0.090 (5)* | |
H11N | 0.5859 | 0.6978 | 0.3159 | 0.090 (5)* | |
H11O | 0.4905 | 0.6825 | 0.3208 | 0.090 (5)* | |
S2 | 0.81210 (8) | 0.11711 (8) | 0.52811 (6) | 0.0506 (3) | |
O20 | 0.80403 (18) | 0.04328 (17) | 0.49061 (14) | 0.0480 (8) | |
C20 | 0.7034 (3) | 0.1397 (3) | 0.6094 (2) | 0.0562 (13) | |
H20A | 0.6564 | 0.1471 | 0.588 | 0.090 (5)* | |
H20B | 0.7021 | 0.1897 | 0.6323 | 0.090 (5)* | |
H20C | 0.6932 | 0.0944 | 0.6516 | 0.090 (5)* | |
C21 | 0.8023 (3) | 0.2082 (3) | 0.4606 (3) | 0.0655 (14) | |
H21E | 0.8555 | 0.2066 | 0.4101 | 0.090 (5)* | |
H21F | 0.7970 | 0.2571 | 0.4869 | 0.090 (5)* | |
H21G | 0.7490 | 0.2094 | 0.4487 | 0.090 (5)* | |
O1 | 0.27720 (19) | 0.92696 (19) | 0.10636 (15) | 0.0400 (8) | |
O2 | 0.77114 (19) | 0.4361 (2) | 0.11907 (16) | 0.0414 (8) | |
O3 | 0.2827 (2) | 0.5073 (2) | 0.50438 (16) | 0.0490 (8) | |
H12G | 0.269 (2) | 0.749 (2) | 0.2418 (18) | 0.0264 (15)* | |
H15D | −0.195 (2) | 0.537 (2) | 0.6678 (19) | 0.0264 (15)* | |
H12A | 0.755 (2) | 0.255 (2) | 0.2439 (19) | 0.0264 (15)* | |
H12E | 0.752 (2) | 0.122 (2) | 0.3346 (19) | 0.0264 (15)* | |
H15A | 0.293 (2) | 0.006 (2) | 0.6728 (19) | 0.0264 (15)* | |
H12B | 0.716 (2) | 0.332 (2) | 0.2244 (19) | 0.0264 (15)* | |
H13C | 0.613 (2) | 0.450 (2) | 0.146 (2) | 0.0264 (15)* | |
H12C | 0.293 (2) | 0.548 (2) | 0.3731 (19) | 0.0264 (15)* | |
H13A | 0.418 (2) | 0.420 (2) | 0.3487 (19) | 0.0264 (15)* | |
H13E | 1.076 (2) | −0.069 (2) | 0.21 (2) | 0.0264 (15)* | |
H12H | 0.227 (2) | 0.824 (2) | 0.214 (2) | 0.0264 (15)* | |
H13B | 0.357 (2) | 0.382 (2) | 0.4318 (19) | 0.0264 (15)* | |
H13G | −0.115 (2) | 0.916 (2) | 0.4384 (19) | 0.0264 (15)* | |
H12F | 0.811 (2) | 0.055 (2) | 0.363 (2) | 0.0264 (15)* | |
H13F | 1.124 (2) | −0.040 (2) | 0.1296 (19) | 0.0264 (15)* | |
H13D | 0.565 (2) | 0.421 (2) | 0.228 (2) | 0.0264 (15)* | |
H12D | 0.251 (2) | 0.624 (2) | 0.3504 (19) | 0.0264 (15)* | |
H15B | 0.585 (2) | 0.663 (2) | −0.21 (2) | 0.0264 (15)* | |
H13H | −0.064 (2) | 0.943 (2) | 0.351 (19) | 0.0264 (15)* | |
H15C | 1.063 (2) | 0.167 (2) | −0.216 (2) | 0.0264 (15)* | |
H11 | 0.280 (3) | 0.966 (3) | 0.131 (2) | 0.060 (6)* | |
H12 | 0.313 (3) | 0.935 (3) | 0.063 (2) | 0.060 (6)* | |
H21 | 0.806 (3) | 0.443 (3) | 0.076 (2) | 0.060 (6)* | |
H22 | 0.769 (3) | 0.482 (3) | 0.143 (2) | 0.060 (6)* | |
H31 | 0.327 (3) | 0.540 (3) | 0.506 (2) | 0.060 (6)* | |
H32 | 0.249 (3) | 0.507 (3) | 0.553 (2) | 0.060 (6)* | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
C1A | 0.031 (2) | 0.030 (2) | 0.0268 (19) | 0.0006 (19) | −0.0094 (17) | 0.0024 (17) |
C2A | 0.030 (2) | 0.033 (3) | 0.0232 (18) | −0.001 (2) | −0.0060 (16) | 0.0059 (17) |
C3A | 0.038 (2) | 0.028 (2) | 0.0270 (19) | 0.002 (2) | −0.0085 (18) | 0.0077 (17) |
C4A | 0.030 (2) | 0.032 (3) | 0.028 (2) | 0.0041 (19) | −0.0055 (17) | 0.0058 (18) |
N5A | 0.0237 (17) | 0.028 (2) | 0.0240 (15) | 0.0008 (15) | −0.0029 (13) | 0.0069 (14) |
C6A | 0.028 (2) | 0.029 (2) | 0.0225 (19) | −0.004 (2) | −0.0036 (17) | 0.0017 (18) |
N7A | 0.0303 (19) | 0.026 (2) | 0.0259 (16) | 0.0041 (16) | −0.0065 (14) | 0.0022 (14) |
C8A | 0.024 (2) | 0.029 (2) | 0.0235 (19) | 0.0039 (19) | −0.0036 (16) | −0.0014 (17) |
C9A | 0.026 (2) | 0.029 (2) | 0.0216 (18) | 0.0006 (18) | −0.0056 (16) | 0.0022 (16) |
C10A | 0.030 (2) | 0.030 (2) | 0.0231 (18) | 0.0030 (19) | −0.0096 (17) | 0.0005 (17) |
C11A | 0.031 (2) | 0.035 (3) | 0.030 (2) | 0.002 (2) | 0.0006 (17) | 0.0128 (18) |
N12A | 0.033 (2) | 0.027 (2) | 0.0322 (19) | 0.0052 (17) | −0.0041 (17) | 0.0108 (15) |
N13A | 0.027 (2) | 0.040 (2) | 0.0324 (19) | 0.0020 (19) | 0.0023 (15) | 0.0159 (17) |
C14A | 0.028 (2) | 0.038 (3) | 0.0284 (19) | −0.0028 (19) | −0.0067 (17) | 0.0030 (18) |
N15A | 0.037 (2) | 0.030 (2) | 0.0267 (16) | −0.0049 (16) | −0.0089 (15) | 0.0069 (15) |
C16A | 0.023 (2) | 0.040 (3) | 0.0196 (18) | −0.0041 (19) | −0.0006 (16) | −0.0008 (18) |
C17A | 0.033 (2) | 0.034 (3) | 0.026 (2) | −0.008 (2) | 0.0001 (17) | 0.0047 (18) |
C18A | 0.028 (2) | 0.038 (3) | 0.026 (2) | −0.004 (2) | 0.0011 (17) | −0.0070 (19) |
C19A | 0.024 (2) | 0.040 (3) | 0.0237 (19) | 0.0019 (19) | −0.0065 (16) | −0.0047 (19) |
C20A | 0.019 (2) | 0.035 (3) | 0.0246 (19) | 0.0001 (18) | −0.0018 (16) | 0.0034 (18) |
C21A | 0.022 (2) | 0.030 (2) | 0.0252 (19) | −0.0046 (18) | −0.0049 (16) | 0.0020 (17) |
O22A | 0.0468 (18) | 0.061 (2) | 0.0374 (15) | −0.0242 (16) | −0.0030 (13) | −0.0076 (15) |
C23A | 0.086 (4) | 0.082 (4) | 0.060 (3) | −0.038 (3) | −0.025 (3) | −0.004 (3) |
O24A | 0.0293 (15) | 0.0478 (19) | 0.0274 (13) | 0.0013 (14) | −0.0071 (11) | −0.0043 (12) |
C25A | 0.040 (3) | 0.045 (3) | 0.033 (2) | 0.004 (2) | −0.0155 (18) | −0.0056 (19) |
O26A | 0.0387 (16) | 0.0379 (18) | 0.0318 (13) | −0.0110 (14) | −0.0152 (12) | 0.0089 (13) |
C27A | 0.042 (3) | 0.042 (3) | 0.045 (2) | −0.010 (2) | −0.022 (2) | 0.014 (2) |
C1B | 0.0183 (19) | 0.029 (2) | 0.0275 (19) | −0.0031 (18) | −0.0040 (15) | 0.0005 (17) |
C2B | 0.023 (2) | 0.033 (3) | 0.0265 (19) | −0.0027 (19) | −0.0057 (16) | 0.0020 (18) |
C3B | 0.034 (2) | 0.026 (2) | 0.031 (2) | −0.003 (2) | −0.0123 (18) | 0.0110 (17) |
C4B | 0.023 (2) | 0.026 (2) | 0.030 (2) | −0.0006 (17) | −0.0066 (16) | 0.0040 (17) |
N5B | 0.0212 (16) | 0.035 (2) | 0.0232 (15) | 0.0021 (15) | −0.0055 (13) | 0.0039 (14) |
C6B | 0.026 (2) | 0.033 (3) | 0.0241 (19) | −0.003 (2) | −0.0083 (17) | 0.0062 (18) |
N7B | 0.0248 (18) | 0.034 (2) | 0.0272 (16) | 0.0022 (16) | −0.0061 (14) | 0.0073 (14) |
C8B | 0.025 (2) | 0.025 (2) | 0.029 (2) | 0.0004 (19) | −0.0109 (17) | 0.0033 (17) |
C9B | 0.022 (2) | 0.026 (2) | 0.031 (2) | 0.0000 (18) | −0.0094 (16) | 0.0041 (17) |
C10B | 0.024 (2) | 0.029 (2) | 0.0236 (18) | −0.0024 (18) | −0.0050 (16) | −0.0001 (17) |
C11B | 0.030 (2) | 0.037 (3) | 0.0282 (19) | 0.001 (2) | −0.0063 (17) | 0.0043 (18) |
N12B | 0.034 (2) | 0.034 (2) | 0.0229 (18) | 0.0083 (17) | −0.0039 (16) | 0.0058 (16) |
N13B | 0.030 (2) | 0.043 (2) | 0.0245 (18) | 0.005 (2) | 0.0004 (15) | 0.0110 (17) |
C14B | 0.031 (2) | 0.035 (3) | 0.0277 (19) | −0.0077 (19) | −0.0055 (17) | 0.0039 (18) |
N15B | 0.043 (2) | 0.044 (3) | 0.0233 (18) | −0.0103 (18) | −0.0115 (15) | 0.0021 (16) |
C16B | 0.024 (2) | 0.036 (3) | 0.029 (2) | −0.005 (2) | −0.0005 (17) | −0.0054 (19) |
C17B | 0.026 (2) | 0.034 (3) | 0.0271 (19) | −0.0018 (19) | −0.0040 (17) | 0.0032 (17) |
C18B | 0.030 (2) | 0.034 (3) | 0.0248 (19) | −0.001 (2) | −0.0034 (17) | −0.0030 (18) |
C19B | 0.037 (2) | 0.028 (3) | 0.029 (2) | −0.007 (2) | −0.0054 (18) | 0.0035 (18) |
C20B | 0.032 (2) | 0.036 (3) | 0.0230 (19) | 0.005 (2) | −0.0042 (17) | 0.0055 (18) |
C21B | 0.030 (2) | 0.041 (3) | 0.0209 (18) | −0.006 (2) | −0.0074 (16) | 0.0050 (18) |
O22B | 0.0439 (16) | 0.0418 (19) | 0.0342 (14) | −0.0126 (14) | −0.0146 (13) | 0.0091 (13) |
C23B | 0.060 (3) | 0.058 (3) | 0.030 (2) | −0.019 (3) | −0.019 (2) | 0.011 (2) |
O24B | 0.0460 (18) | 0.0376 (19) | 0.0357 (14) | −0.0083 (15) | −0.0111 (13) | 0.0060 (13) |
C25B | 0.053 (3) | 0.053 (3) | 0.040 (2) | −0.023 (2) | −0.012 (2) | 0.010 (2) |
O26B | 0.0429 (17) | 0.0454 (19) | 0.0310 (14) | −0.0022 (14) | −0.0145 (13) | 0.0100 (13) |
C27B | 0.039 (2) | 0.049 (3) | 0.037 (2) | 0.000 (2) | −0.013 (2) | 0.014 (2) |
C1C | 0.020 (2) | 0.028 (2) | 0.0270 (19) | −0.0041 (18) | −0.0066 (16) | 0.0029 (17) |
C2C | 0.026 (2) | 0.029 (2) | 0.0237 (18) | −0.0040 (19) | −0.0044 (16) | 0.0024 (17) |
C3C | 0.032 (2) | 0.026 (2) | 0.0272 (19) | −0.0055 (19) | −0.0116 (17) | 0.0070 (17) |
C4C | 0.023 (2) | 0.026 (2) | 0.033 (2) | 0.0004 (18) | −0.0066 (17) | 0.0022 (17) |
N5C | 0.0256 (17) | 0.031 (2) | 0.0208 (15) | 0.0001 (15) | −0.0031 (13) | 0.0029 (14) |
C6C | 0.026 (2) | 0.030 (2) | 0.0225 (19) | −0.0027 (19) | −0.0053 (17) | −0.0014 (17) |
N7C | 0.0230 (17) | 0.030 (2) | 0.0224 (15) | 0.0015 (15) | −0.0060 (13) | 0.0039 (13) |
C8C | 0.019 (2) | 0.028 (2) | 0.0277 (19) | −0.0034 (18) | −0.0079 (16) | 0.0037 (17) |
C9C | 0.028 (2) | 0.023 (2) | 0.0262 (19) | −0.0069 (18) | −0.0084 (16) | 0.0040 (16) |
C10C | 0.024 (2) | 0.030 (2) | 0.029 (2) | −0.0039 (18) | −0.0105 (17) | 0.0044 (17) |
C11C | 0.032 (2) | 0.042 (3) | 0.0243 (19) | −0.002 (2) | −0.0075 (16) | −0.0012 (18) |
N12C | 0.0244 (19) | 0.034 (2) | 0.0248 (17) | 0.0066 (16) | −0.0042 (15) | 0.0066 (15) |
N13C | 0.027 (2) | 0.040 (2) | 0.0224 (18) | 0.0013 (19) | −0.0011 (14) | 0.0078 (16) |
C14C | 0.038 (2) | 0.030 (2) | 0.0275 (19) | −0.007 (2) | −0.0087 (17) | 0.0046 (18) |
N15C | 0.040 (2) | 0.039 (2) | 0.0255 (17) | −0.0110 (18) | −0.0112 (15) | 0.0037 (16) |
C16C | 0.028 (2) | 0.034 (3) | 0.0230 (19) | −0.005 (2) | 0.0023 (17) | 0.0002 (18) |
C17C | 0.033 (2) | 0.036 (3) | 0.0254 (19) | −0.003 (2) | −0.0067 (17) | 0.0032 (18) |
C18C | 0.034 (2) | 0.042 (3) | 0.027 (2) | −0.010 (2) | −0.0061 (18) | −0.0027 (19) |
C19C | 0.033 (2) | 0.031 (3) | 0.029 (2) | −0.006 (2) | −0.0050 (18) | 0.0067 (18) |
C20C | 0.030 (2) | 0.037 (3) | 0.0249 (19) | 0.001 (2) | −0.0024 (17) | 0.0024 (19) |
C21C | 0.034 (2) | 0.041 (3) | 0.0249 (19) | −0.004 (2) | −0.0079 (17) | −0.0012 (19) |
O22C | 0.0495 (17) | 0.0422 (19) | 0.0423 (15) | −0.0098 (15) | −0.0237 (14) | 0.0096 (14) |
C23C | 0.073 (3) | 0.044 (3) | 0.074 (3) | −0.014 (3) | −0.052 (3) | 0.010 (2) |
O24C | 0.0407 (17) | 0.0322 (18) | 0.0429 (15) | −0.0041 (15) | −0.0130 (13) | 0.0092 (13) |
C25C | 0.048 (3) | 0.039 (3) | 0.049 (2) | −0.002 (2) | −0.021 (2) | 0.004 (2) |
O26C | 0.0460 (17) | 0.0311 (17) | 0.0347 (14) | 0.0002 (14) | −0.0167 (13) | 0.0057 (13) |
C27C | 0.061 (3) | 0.037 (3) | 0.037 (2) | 0.001 (2) | −0.024 (2) | −0.002 (2) |
C1D | 0.024 (2) | 0.032 (2) | 0.0268 (19) | −0.0009 (18) | −0.0068 (16) | −0.0002 (17) |
C2D | 0.032 (2) | 0.030 (2) | 0.0230 (18) | −0.004 (2) | −0.0050 (16) | 0.0046 (17) |
C3D | 0.038 (2) | 0.031 (2) | 0.027 (2) | −0.001 (2) | −0.0128 (18) | 0.0098 (17) |
C4D | 0.023 (2) | 0.036 (3) | 0.0280 (19) | 0.0046 (18) | −0.0055 (17) | 0.0035 (18) |
N5D | 0.0267 (18) | 0.035 (2) | 0.0204 (15) | −0.0013 (15) | −0.0010 (13) | 0.0039 (14) |
C6D | 0.027 (2) | 0.028 (2) | 0.025 (2) | −0.0024 (19) | −0.0035 (17) | −0.0002 (18) |
N7D | 0.0273 (18) | 0.026 (2) | 0.0276 (16) | 0.0015 (16) | −0.0058 (14) | 0.0045 (14) |
C8D | 0.029 (2) | 0.031 (3) | 0.026 (2) | 0.001 (2) | −0.0071 (17) | 0.0045 (17) |
C9D | 0.030 (2) | 0.026 (2) | 0.0269 (19) | −0.0008 (19) | −0.0096 (17) | 0.0034 (17) |
C10D | 0.033 (2) | 0.026 (2) | 0.0248 (19) | 0.0002 (19) | −0.0094 (17) | 0.0037 (17) |
C11D | 0.031 (2) | 0.039 (3) | 0.030 (2) | −0.001 (2) | −0.0034 (17) | 0.0091 (18) |
N12D | 0.033 (2) | 0.027 (2) | 0.0269 (18) | 0.0055 (17) | −0.0003 (17) | 0.0103 (15) |
N13D | 0.033 (2) | 0.045 (3) | 0.0256 (18) | 0.0112 (19) | 0.0040 (15) | 0.0144 (17) |
C14D | 0.027 (2) | 0.039 (3) | 0.030 (2) | −0.0007 (19) | −0.0091 (17) | 0.0061 (18) |
N15D | 0.037 (2) | 0.037 (2) | 0.0261 (17) | −0.0061 (17) | −0.0118 (14) | 0.0094 (16) |
C16D | 0.021 (2) | 0.042 (3) | 0.0247 (19) | 0.0021 (19) | −0.0032 (16) | 0.0050 (19) |
C17D | 0.025 (2) | 0.034 (3) | 0.0251 (19) | −0.0026 (18) | −0.0073 (16) | 0.0022 (17) |
C18D | 0.022 (2) | 0.032 (3) | 0.0242 (19) | −0.0035 (18) | −0.0013 (16) | 0.0063 (18) |
C19D | 0.022 (2) | 0.038 (3) | 0.0232 (19) | 0.0019 (19) | −0.0082 (16) | 0.0047 (18) |
C20D | 0.027 (2) | 0.032 (3) | 0.029 (2) | −0.0040 (19) | −0.0088 (17) | 0.0047 (18) |
C21D | 0.028 (2) | 0.034 (3) | 0.027 (2) | −0.0026 (19) | −0.0062 (17) | 0.0078 (18) |
O22D | 0.0391 (16) | 0.0317 (17) | 0.0328 (14) | −0.0068 (13) | −0.0158 (12) | 0.0066 (13) |
C23D | 0.039 (2) | 0.040 (3) | 0.044 (2) | −0.006 (2) | −0.0167 (19) | 0.012 (2) |
O24D | 0.0318 (15) | 0.0383 (17) | 0.0263 (13) | 0.0024 (13) | −0.0111 (11) | 0.0026 (12) |
C25D | 0.042 (3) | 0.038 (3) | 0.035 (2) | 0.005 (2) | −0.0182 (19) | 0.0002 (19) |
O26D | 0.0492 (17) | 0.0326 (18) | 0.0400 (15) | −0.0098 (14) | −0.0222 (13) | 0.0063 (13) |
C27D | 0.056 (3) | 0.040 (3) | 0.058 (3) | −0.013 (2) | −0.030 (2) | 0.003 (2) |
S1 | 0.0592 (8) | 0.0563 (9) | 0.0477 (6) | −0.0058 (7) | −0.0212 (6) | 0.0004 (6) |
O10 | 0.046 (2) | 0.098 (3) | 0.069 (2) | −0.013 (2) | 0.0031 (17) | −0.011 (2) |
C10 | 0.057 (3) | 0.049 (3) | 0.054 (3) | −0.010 (2) | −0.021 (2) | 0.002 (2) |
C11 | 0.092 (4) | 0.061 (4) | 0.066 (3) | −0.008 (3) | −0.033 (3) | 0.010 (3) |
S2 | 0.0513 (7) | 0.0598 (9) | 0.0377 (6) | −0.0044 (6) | −0.0177 (5) | 0.0040 (6) |
O20 | 0.0603 (19) | 0.0409 (19) | 0.0337 (14) | 0.0074 (15) | −0.0158 (13) | 0.0010 (13) |
C20 | 0.051 (3) | 0.063 (4) | 0.052 (3) | −0.002 (3) | −0.018 (2) | −0.008 (2) |
C21 | 0.087 (4) | 0.058 (4) | 0.060 (3) | −0.022 (3) | −0.038 (3) | 0.012 (3) |
O1 | 0.0336 (17) | 0.046 (2) | 0.0297 (15) | −0.0043 (15) | −0.0044 (12) | 0.0056 (14) |
O2 | 0.0370 (17) | 0.046 (2) | 0.0326 (16) | −0.0083 (16) | −0.0072 (13) | 0.0075 (14) |
O3 | 0.047 (2) | 0.052 (2) | 0.0333 (15) | 0.0020 (16) | −0.0062 (14) | 0.0064 (15) |
Geometric parameters (Å, º) top
C1A—C2A | 1.389 (5) | C6C—N12C | 1.371 (4) |
C1A—C9A | 1.452 (4) | N7C—C8C | 1.334 (4) |
C1A—C11A | 1.508 (5) | C8C—N13C | 1.336 (5) |
C2A—C3A | 1.408 (5) | C8C—C9C | 1.451 (5) |
C2A—C14A | 1.540 (4) | C9C—C10C | 1.437 (5) |
C3A—C4A | 1.367 (5) | C11C—H11G | 0.9600 |
C3A—H3A | 0.9300 | C11C—H11H | 0.9600 |
C4A—C10A | 1.407 (5) | C11C—H11I | 0.9600 |
C4A—H4A | 0.9300 | N12C—H12E | 0.88 (4) |
N5A—C6A | 1.319 (4) | N12C—H12F | 0.80 (3) |
N5A—C10A | 1.382 (4) | N13C—H13E | 0.85 (3) |
C6A—N12A | 1.359 (4) | N13C—H13F | 0.78 (3) |
C6A—N7A | 1.364 (4) | C14C—N15C | 1.442 (5) |
N7A—C8A | 1.340 (4) | C14C—H14E | 0.9700 |
C8A—N13A | 1.346 (5) | C14C—H14F | 0.9700 |
C8A—C9A | 1.451 (5) | N15C—C16C | 1.370 (5) |
C9A—C10A | 1.423 (5) | N15C—H15C | 0.75 (3) |
C11A—H11A | 0.9600 | C16C—C17C | 1.399 (5) |
C11A—H11B | 0.9600 | C16C—C21C | 1.409 (5) |
C11A—H11C | 0.9600 | C17C—C18C | 1.384 (5) |
N12A—H12A | 0.83 (3) | C17C—H17C | 0.9300 |
N12A—H12B | 0.80 (3) | C18C—O22C | 1.387 (4) |
N13A—H13A | 0.92 (3) | C18C—C19C | 1.403 (5) |
N13A—H13B | 0.84 (3) | C19C—O24C | 1.385 (4) |
C14A—N15A | 1.449 (5) | C19C—C20C | 1.396 (5) |
C14A—H14A | 0.9700 | C20C—O26C | 1.379 (4) |
C14A—H14B | 0.9700 | C20C—C21C | 1.383 (5) |
N15A—C16A | 1.387 (4) | C21C—H21C | 0.9300 |
N15A—H15A | 0.90 (3) | O22C—C23C | 1.432 (4) |
C16A—C17A | 1.393 (5) | C23C—H23G | 0.9600 |
C16A—C21A | 1.404 (5) | C23C—H23H | 0.9600 |
C17A—C18A | 1.403 (5) | C23C—H23I | 0.9600 |
C17A—H17A | 0.9300 | O24C—C25C | 1.447 (4) |
C18A—O22A | 1.378 (4) | C25C—H25G | 0.9600 |
C18A—C19A | 1.386 (5) | C25C—H25H | 0.9600 |
C19A—O24A | 1.399 (4) | C25C—H25I | 0.9600 |
C19A—C20A | 1.401 (5) | O26C—C27C | 1.432 (4) |
C20A—O26A | 1.382 (4) | C27C—H27G | 0.9600 |
C20A—C21A | 1.386 (4) | C27C—H27H | 0.9600 |
C21A—H21A | 0.9300 | C27C—H27I | 0.9600 |
O22A—C23A | 1.362 (5) | C1D—C2D | 1.399 (5) |
C23A—H23A | 0.9600 | C1D—C9D | 1.441 (4) |
C23A—H23B | 0.9600 | C1D—C11D | 1.517 (5) |
C23A—H23C | 0.9600 | C2D—C3D | 1.409 (5) |
O24A—C25A | 1.442 (4) | C2D—C14D | 1.540 (5) |
C25A—H25A | 0.9600 | C3D—C4D | 1.373 (4) |
C25A—H25B | 0.9600 | C3D—H3D | 0.9300 |
C25A—H25C | 0.9600 | C4D—C10D | 1.406 (5) |
O26A—C27A | 1.421 (4) | C4D—H4D | 0.9300 |
C27A—H27A | 0.9600 | N5D—C6D | 1.325 (4) |
C27A—H27B | 0.9600 | N5D—C10D | 1.375 (4) |
C27A—H27C | 0.9600 | C6D—N12D | 1.345 (4) |
C1B—C2B | 1.392 (5) | C6D—N7D | 1.371 (4) |
C1B—C9B | 1.442 (4) | N7D—C8D | 1.348 (4) |
C1B—C11B | 1.514 (5) | C8D—N13D | 1.343 (5) |
C2B—C3B | 1.399 (5) | C8D—C9D | 1.456 (5) |
C2B—C14B | 1.539 (4) | C9D—C10D | 1.423 (5) |
C3B—C4B | 1.364 (4) | C11D—H11J | 0.9600 |
C3B—H3B | 0.9300 | C11D—H11K | 0.9600 |
C4B—C10B | 1.405 (5) | C11D—H11L | 0.9600 |
C4B—H4B | 0.9300 | N12D—H12G | 0.95 (3) |
N5B—C6B | 1.330 (4) | N12D—H12H | 0.72 (3) |
N5B—C10B | 1.387 (4) | N13D—H13G | 0.85 (3) |
C6B—N7B | 1.355 (4) | N13D—H13H | 0.89 (3) |
C6B—N12B | 1.361 (4) | C14D—N15D | 1.447 (5) |
N7B—C8B | 1.349 (4) | C14D—H14G | 0.9700 |
C8B—N13B | 1.325 (5) | C14D—H14H | 0.9700 |
C8B—C9B | 1.453 (5) | N15D—C16D | 1.395 (4) |
C9B—C10B | 1.413 (5) | N15D—H15D | 0.85 (3) |
C11B—H11D | 0.9600 | C16D—C21D | 1.395 (5) |
C11B—H11E | 0.9600 | C16D—C17D | 1.404 (5) |
C11B—H11F | 0.9600 | C17D—C18D | 1.389 (5) |
N12B—H12C | 0.78 (3) | C17D—H17D | 0.9300 |
N12B—H12D | 0.89 (3) | C18D—O22D | 1.380 (4) |
N13B—H13C | 0.74 (3) | C18D—C19D | 1.397 (5) |
N13B—H13D | 0.89 (3) | C19D—C20D | 1.382 (5) |
C14B—N15B | 1.441 (5) | C19D—O24D | 1.409 (4) |
C14B—H14C | 0.9700 | C20D—O26D | 1.366 (4) |
C14B—H14D | 0.9700 | C20D—C21D | 1.401 (5) |
N15B—C16B | 1.371 (5) | C21D—H21D | 0.9300 |
N15B—H15B | 0.78 (3) | O22D—C23D | 1.422 (4) |
C16B—C17B | 1.393 (5) | C23D—H23J | 0.9600 |
C16B—C21B | 1.413 (5) | C23D—H23K | 0.9600 |
C17B—C18B | 1.388 (5) | C23D—H23L | 0.9600 |
C17B—H17B | 0.9300 | O24D—C25D | 1.449 (4) |
C18B—O22B | 1.372 (4) | C25D—H25J | 0.9600 |
C18B—C19B | 1.416 (5) | C25D—H25K | 0.9600 |
C19B—O24B | 1.367 (4) | C25D—H25L | 0.9600 |
C19B—C20B | 1.394 (5) | O26D—C27D | 1.439 (4) |
C20B—O26B | 1.377 (4) | C27D—H27J | 0.9600 |
C20B—C21B | 1.378 (5) | C27D—H27K | 0.9600 |
C21B—H21B | 0.9300 | C27D—H27L | 0.9600 |
O22B—C23B | 1.430 (4) | S1—O10 | 1.507 (3) |
C23B—H23D | 0.9600 | S1—C10 | 1.756 (4) |
C23B—H23E | 0.9600 | S1—C11 | 1.778 (4) |
C23B—H23F | 0.9600 | C10—H10A | 0.9600 |
O24B—C25B | 1.440 (4) | C10—H10B | 0.9600 |
C25B—H25D | 0.9600 | C10—H10C | 0.9600 |
C25B—H25E | 0.9600 | C11—H11M | 0.9600 |
C25B—H25F | 0.9600 | C11—H11N | 0.9600 |
O26B—C27B | 1.425 (4) | C11—H11O | 0.9600 |
C27B—H27D | 0.9600 | S2—O20 | 1.510 (3) |
C27B—H27E | 0.9600 | S2—C20 | 1.786 (4) |
C27B—H27F | 0.9600 | S2—C21 | 1.800 (4) |
C1C—C2C | 1.397 (5) | C20—H20A | 0.9600 |
C1C—C9C | 1.445 (4) | C20—H20B | 0.9600 |
C1C—C11C | 1.506 (5) | C20—H20C | 0.9600 |
C2C—C3C | 1.402 (5) | C21—H21E | 0.9600 |
C2C—C14C | 1.541 (4) | C21—H21F | 0.9600 |
C3C—C4C | 1.376 (4) | C21—H21G | 0.9600 |
C3C—H3C | 0.9300 | O1—H11 | 0.85 (4) |
C4C—C10C | 1.405 (5) | O1—H12 | 0.76 (4) |
C4C—H4C | 0.9300 | O2—H21 | 0.75 (4) |
N5C—C6C | 1.320 (4) | O2—H22 | 0.90 (4) |
N5C—C10C | 1.380 (4) | O3—H31 | 0.98 (4) |
C6C—N7C | 1.362 (4) | O3—H32 | 0.82 (4) |
| | | |
C2A—C1A—C9A | 118.8 (3) | N7C—C8C—N13C | 114.3 (3) |
C2A—C1A—C11A | 119.0 (3) | N7C—C8C—C9C | 121.7 (3) |
C9A—C1A—C11A | 122.2 (3) | N13C—C8C—C9C | 123.9 (3) |
C1A—C2A—C3A | 120.1 (3) | C10C—C9C—C1C | 119.2 (3) |
C1A—C2A—C14A | 121.5 (3) | C10C—C9C—C8C | 113.8 (3) |
C3A—C2A—C14A | 118.5 (3) | C1C—C9C—C8C | 127.0 (3) |
C4A—C3A—C2A | 121.7 (3) | N5C—C10C—C4C | 117.7 (3) |
C4A—C3A—H3A | 119.1 | N5C—C10C—C9C | 123.1 (3) |
C2A—C3A—H3A | 119.1 | C4C—C10C—C9C | 119.2 (3) |
C3A—C4A—C10A | 120.7 (4) | C1C—C11C—H11G | 109.5 |
C3A—C4A—H4A | 119.7 | C1C—C11C—H11H | 109.5 |
C10A—C4A—H4A | 119.7 | H11G—C11C—H11H | 109.5 |
C6A—N5A—C10A | 116.0 (3) | C1C—C11C—H11I | 109.5 |
N5A—C6A—N12A | 117.4 (3) | H11G—C11C—H11I | 109.5 |
N5A—C6A—N7A | 126.2 (3) | H11H—C11C—H11I | 109.5 |
N12A—C6A—N7A | 116.3 (3) | C6C—N12C—H12E | 116 (2) |
C8A—N7A—C6A | 118.3 (3) | C6C—N12C—H12F | 114 (2) |
N7A—C8A—N13A | 114.4 (3) | H12E—N12C—H12F | 125 (3) |
N7A—C8A—C9A | 121.6 (3) | C8C—N13C—H13E | 118 (2) |
N13A—C8A—C9A | 123.8 (3) | C8C—N13C—H13F | 121 (3) |
C10A—C9A—C1A | 119.7 (3) | H13E—N13C—H13F | 116 (4) |
C10A—C9A—C8A | 113.9 (3) | N15C—C14C—C2C | 114.6 (3) |
C1A—C9A—C8A | 126.4 (3) | N15C—C14C—H14E | 108.6 |
N5A—C10A—C4A | 117.4 (3) | C2C—C14C—H14E | 108.6 |
N5A—C10A—C9A | 123.6 (3) | N15C—C14C—H14F | 108.6 |
C4A—C10A—C9A | 119.0 (3) | C2C—C14C—H14F | 108.6 |
C1A—C11A—H11A | 109.5 | H14E—C14C—H14F | 107.6 |
C1A—C11A—H11B | 109.5 | C16C—N15C—C14C | 125.3 (3) |
H11A—C11A—H11B | 109.5 | C16C—N15C—H15C | 120 (3) |
C1A—C11A—H11C | 109.5 | C14C—N15C—H15C | 115 (3) |
H11A—C11A—H11C | 109.5 | N15C—C16C—C17C | 121.5 (3) |
H11B—C11A—H11C | 109.5 | N15C—C16C—C21C | 119.7 (4) |
C6A—N12A—H12A | 119 (2) | C17C—C16C—C21C | 118.7 (4) |
C6A—N12A—H12B | 125 (3) | C18C—C17C—C16C | 120.3 (4) |
H12A—N12A—H12B | 115 (3) | C18C—C17C—H17C | 119.8 |
C8A—N13A—H13A | 117 (2) | C16C—C17C—H17C | 119.8 |
C8A—N13A—H13B | 122 (2) | C17C—C18C—O22C | 123.9 (3) |
H13A—N13A—H13B | 119 (3) | C17C—C18C—C19C | 121.2 (4) |
N15A—C14A—C2A | 114.4 (3) | O22C—C18C—C19C | 114.8 (3) |
N15A—C14A—H14A | 108.7 | O24C—C19C—C20C | 121.2 (3) |
C2A—C14A—H14A | 108.7 | O24C—C19C—C18C | 120.6 (3) |
N15A—C14A—H14B | 108.7 | C20C—C19C—C18C | 118.1 (4) |
C2A—C14A—H14B | 108.7 | O26C—C20C—C21C | 124.6 (4) |
H14A—C14A—H14B | 107.6 | O26C—C20C—C19C | 114.0 (3) |
C16A—N15A—C14A | 123.6 (3) | C21C—C20C—C19C | 121.3 (4) |
C16A—N15A—H15A | 116 (2) | C20C—C21C—C16C | 120.3 (4) |
C14A—N15A—H15A | 118 (2) | C20C—C21C—H21C | 119.9 |
N15A—C16A—C17A | 122.1 (3) | C16C—C21C—H21C | 119.9 |
N15A—C16A—C21A | 118.6 (3) | C18C—O22C—C23C | 116.7 (3) |
C17A—C16A—C21A | 119.3 (3) | O22C—C23C—H23G | 109.5 |
C16A—C17A—C18A | 120.1 (4) | O22C—C23C—H23H | 109.5 |
C16A—C17A—H17A | 120.0 | H23G—C23C—H23H | 109.5 |
C18A—C17A—H17A | 120.0 | O22C—C23C—H23I | 109.5 |
O22A—C18A—C19A | 119.0 (3) | H23G—C23C—H23I | 109.5 |
O22A—C18A—C17A | 120.4 (4) | H23H—C23C—H23I | 109.5 |
C19A—C18A—C17A | 120.6 (4) | C19C—O24C—C25C | 114.6 (3) |
C18A—C19A—O24A | 121.3 (3) | O24C—C25C—H25G | 109.5 |
C18A—C19A—C20A | 119.1 (3) | O24C—C25C—H25H | 109.5 |
O24A—C19A—C20A | 119.5 (3) | H25G—C25C—H25H | 109.5 |
O26A—C20A—C21A | 124.8 (3) | O24C—C25C—H25I | 109.5 |
O26A—C20A—C19A | 114.4 (3) | H25G—C25C—H25I | 109.5 |
C21A—C20A—C19A | 120.7 (3) | H25H—C25C—H25I | 109.5 |
C20A—C21A—C16A | 120.1 (3) | C20C—O26C—C27C | 117.2 (3) |
C20A—C21A—H21A | 119.9 | O26C—C27C—H27G | 109.5 |
C16A—C21A—H21A | 119.9 | O26C—C27C—H27H | 109.5 |
C23A—O22A—C18A | 115.9 (3) | H27G—C27C—H27H | 109.5 |
O22A—C23A—H23A | 109.5 | O26C—C27C—H27I | 109.5 |
O22A—C23A—H23B | 109.5 | H27G—C27C—H27I | 109.5 |
H23A—C23A—H23B | 109.5 | H27H—C27C—H27I | 109.5 |
O22A—C23A—H23C | 109.5 | C2D—C1D—C9D | 119.3 (3) |
H23A—C23A—H23C | 109.5 | C2D—C1D—C11D | 118.8 (3) |
H23B—C23A—H23C | 109.5 | C9D—C1D—C11D | 121.8 (3) |
C19A—O24A—C25A | 112.5 (2) | C1D—C2D—C3D | 118.9 (3) |
O24A—C25A—H25A | 109.5 | C1D—C2D—C14D | 122.5 (3) |
O24A—C25A—H25B | 109.5 | C3D—C2D—C14D | 118.5 (3) |
H25A—C25A—H25B | 109.5 | C4D—C3D—C2D | 122.5 (3) |
O24A—C25A—H25C | 109.5 | C4D—C3D—H3D | 118.8 |
H25A—C25A—H25C | 109.5 | C2D—C3D—H3D | 118.8 |
H25B—C25A—H25C | 109.5 | C3D—C4D—C10D | 119.9 (3) |
C20A—O26A—C27A | 116.6 (3) | C3D—C4D—H4D | 120.1 |
O26A—C27A—H27A | 109.5 | C10D—C4D—H4D | 120.1 |
O26A—C27A—H27B | 109.5 | C6D—N5D—C10D | 116.7 (3) |
H27A—C27A—H27B | 109.5 | N5D—C6D—N12D | 117.4 (3) |
O26A—C27A—H27C | 109.5 | N5D—C6D—N7D | 125.9 (3) |
H27A—C27A—H27C | 109.5 | N12D—C6D—N7D | 116.6 (3) |
H27B—C27A—H27C | 109.5 | C8D—N7D—C6D | 117.9 (3) |
C2B—C1B—C9B | 117.8 (3) | N13D—C8D—N7D | 113.7 (3) |
C2B—C1B—C11B | 119.1 (3) | N13D—C8D—C9D | 124.7 (3) |
C9B—C1B—C11B | 123.0 (3) | N7D—C8D—C9D | 121.6 (3) |
C1B—C2B—C3B | 120.4 (3) | C10D—C9D—C1D | 119.7 (3) |
C1B—C2B—C14B | 119.7 (3) | C10D—C9D—C8D | 114.1 (3) |
C3B—C2B—C14B | 119.8 (3) | C1D—C9D—C8D | 126.0 (3) |
C4B—C3B—C2B | 122.1 (3) | N5D—C10D—C4D | 117.3 (3) |
C4B—C3B—H3B | 118.9 | N5D—C10D—C9D | 123.4 (3) |
C2B—C3B—H3B | 118.9 | C4D—C10D—C9D | 119.3 (3) |
C3B—C4B—C10B | 119.8 (3) | C1D—C11D—H11J | 109.5 |
C3B—C4B—H4B | 120.1 | C1D—C11D—H11K | 109.5 |
C10B—C4B—H4B | 120.1 | H11J—C11D—H11K | 109.5 |
C6B—N5B—C10B | 115.8 (3) | C1D—C11D—H11L | 109.5 |
N5B—C6B—N7B | 126.4 (3) | H11J—C11D—H11L | 109.5 |
N5B—C6B—N12B | 117.5 (3) | H11K—C11D—H11L | 109.5 |
N7B—C6B—N12B | 116.1 (3) | C6D—N12D—H12G | 116.5 (19) |
C8B—N7B—C6B | 118.1 (3) | C6D—N12D—H12H | 127 (3) |
N13B—C8B—N7B | 114.6 (3) | H12G—N12D—H12H | 116 (4) |
N13B—C8B—C9B | 124.5 (3) | C8D—N13D—H13G | 120 (2) |
N7B—C8B—C9B | 120.9 (3) | C8D—N13D—H13H | 121 (2) |
C10B—C9B—C1B | 120.3 (3) | H13G—N13D—H13H | 117 (3) |
C10B—C9B—C8B | 114.5 (3) | N15D—C14D—C2D | 114.5 (3) |
C1B—C9B—C8B | 125.1 (3) | N15D—C14D—H14G | 108.6 |
N5B—C10B—C4B | 117.7 (3) | C2D—C14D—H14G | 108.6 |
N5B—C10B—C9B | 123.1 (3) | N15D—C14D—H14H | 108.6 |
C4B—C10B—C9B | 119.2 (3) | C2D—C14D—H14H | 108.6 |
C1B—C11B—H11D | 109.5 | H14G—C14D—H14H | 107.6 |
C1B—C11B—H11E | 109.5 | C16D—N15D—C14D | 123.0 (3) |
H11D—C11B—H11E | 109.5 | C16D—N15D—H15D | 116 (2) |
C1B—C11B—H11F | 109.5 | C14D—N15D—H15D | 118 (2) |
H11D—C11B—H11F | 109.5 | N15D—C16D—C21D | 120.8 (3) |
H11E—C11B—H11F | 109.5 | N15D—C16D—C17D | 118.8 (3) |
C6B—N12B—H12C | 117 (3) | C21D—C16D—C17D | 120.4 (3) |
C6B—N12B—H12D | 117 (2) | C18D—C17D—C16D | 119.2 (3) |
H12C—N12B—H12D | 113 (3) | C18D—C17D—H17D | 120.4 |
C8B—N13B—H13C | 120 (3) | C16D—C17D—H17D | 120.4 |
C8B—N13B—H13D | 119 (2) | O22D—C18D—C17D | 124.7 (3) |
H13C—N13B—H13D | 119 (4) | O22D—C18D—C19D | 114.9 (3) |
N15B—C14B—C2B | 114.1 (3) | C17D—C18D—C19D | 120.4 (3) |
N15B—C14B—H14C | 108.7 | C20D—C19D—C18D | 120.3 (3) |
C2B—C14B—H14C | 108.7 | C20D—C19D—O24D | 120.9 (3) |
N15B—C14B—H14D | 108.7 | C18D—C19D—O24D | 118.9 (3) |
C2B—C14B—H14D | 108.7 | O26D—C20D—C19D | 116.4 (3) |
H14C—C14B—H14D | 107.6 | O26D—C20D—C21D | 123.5 (3) |
C16B—N15B—C14B | 122.4 (3) | C19D—C20D—C21D | 120.1 (3) |
C16B—N15B—H15B | 125 (3) | C16D—C21D—C20D | 119.6 (4) |
C14B—N15B—H15B | 109 (3) | C16D—C21D—H21D | 120.2 |
N15B—C16B—C17B | 121.4 (4) | C20D—C21D—H21D | 120.2 |
N15B—C16B—C21B | 119.4 (3) | C18D—O22D—C23D | 116.9 (3) |
C17B—C16B—C21B | 119.2 (4) | O22D—C23D—H23J | 109.5 |
C18B—C17B—C16B | 120.5 (4) | O22D—C23D—H23K | 109.5 |
C18B—C17B—H17B | 119.7 | H23J—C23D—H23K | 109.5 |
C16B—C17B—H17B | 119.7 | O22D—C23D—H23L | 109.5 |
O22B—C18B—C17B | 124.9 (3) | H23J—C23D—H23L | 109.5 |
O22B—C18B—C19B | 114.5 (3) | H23K—C23D—H23L | 109.5 |
C17B—C18B—C19B | 120.5 (4) | C19D—O24D—C25D | 111.9 (2) |
O24B—C19B—C20B | 121.5 (3) | O24D—C25D—H25J | 109.5 |
O24B—C19B—C18B | 120.4 (3) | O24D—C25D—H25K | 109.5 |
C20B—C19B—C18B | 118.0 (4) | H25J—C25D—H25K | 109.5 |
O26B—C20B—C21B | 124.0 (3) | O24D—C25D—H25L | 109.5 |
O26B—C20B—C19B | 114.1 (3) | H25J—C25D—H25L | 109.5 |
C21B—C20B—C19B | 121.9 (3) | H25K—C25D—H25L | 109.5 |
C20B—C21B—C16B | 119.7 (3) | C20D—O26D—C27D | 117.8 (3) |
C20B—C21B—H21B | 120.2 | O26D—C27D—H27J | 109.5 |
C16B—C21B—H21B | 120.2 | O26D—C27D—H27K | 109.5 |
C18B—O22B—C23B | 117.3 (3) | H27J—C27D—H27K | 109.5 |
O22B—C23B—H23D | 109.5 | O26D—C27D—H27L | 109.5 |
O22B—C23B—H23E | 109.5 | H27J—C27D—H27L | 109.5 |
H23D—C23B—H23E | 109.5 | H27K—C27D—H27L | 109.5 |
O22B—C23B—H23F | 109.5 | O10—S1—C10 | 108.2 (2) |
H23D—C23B—H23F | 109.5 | O10—S1—C11 | 105.7 (2) |
H23E—C23B—H23F | 109.5 | C10—S1—C11 | 97.0 (2) |
C19B—O24B—C25B | 112.4 (3) | S1—C10—H10A | 109.5 |
O24B—C25B—H25D | 109.5 | S1—C10—H10B | 109.5 |
O24B—C25B—H25E | 109.5 | H10A—C10—H10B | 109.5 |
H25D—C25B—H25E | 109.5 | S1—C10—H10C | 109.5 |
O24B—C25B—H25F | 109.5 | H10A—C10—H10C | 109.5 |
H25D—C25B—H25F | 109.5 | H10B—C10—H10C | 109.5 |
H25E—C25B—H25F | 109.5 | S1—C11—H11M | 109.5 |
C20B—O26B—C27B | 117.3 (3) | S1—C11—H11N | 109.5 |
O26B—C27B—H27D | 109.5 | H11M—C11—H11N | 109.5 |
O26B—C27B—H27E | 109.5 | S1—C11—H11O | 109.5 |
H27D—C27B—H27E | 109.5 | H11M—C11—H11O | 109.5 |
O26B—C27B—H27F | 109.5 | H11N—C11—H11O | 109.5 |
H27D—C27B—H27F | 109.5 | O20—S2—C20 | 105.42 (18) |
H27E—C27B—H27F | 109.5 | O20—S2—C21 | 107.35 (18) |
C2C—C1C—C9C | 119.0 (3) | C20—S2—C21 | 96.5 (2) |
C2C—C1C—C11C | 119.4 (3) | S2—C20—H20A | 109.5 |
C9C—C1C—C11C | 121.6 (3) | S2—C20—H20B | 109.5 |
C1C—C2C—C3C | 120.3 (3) | H20A—C20—H20B | 109.5 |
C1C—C2C—C14C | 120.4 (3) | S2—C20—H20C | 109.5 |
C3C—C2C—C14C | 119.2 (3) | H20A—C20—H20C | 109.5 |
C4C—C3C—C2C | 121.7 (3) | H20B—C20—H20C | 109.5 |
C4C—C3C—H3C | 119.2 | S2—C21—H21E | 109.5 |
C2C—C3C—H3C | 119.2 | S2—C21—H21F | 109.5 |
C3C—C4C—C10C | 120.4 (4) | H21E—C21—H21F | 109.5 |
C3C—C4C—H4C | 119.8 | S2—C21—H21G | 109.5 |
C10C—C4C—H4C | 119.8 | H21E—C21—H21G | 109.5 |
C6C—N5C—C10C | 115.9 (3) | H21F—C21—H21G | 109.5 |
N5C—C6C—N7C | 126.7 (3) | H11—O1—H12 | 103 (4) |
N5C—C6C—N12C | 118.0 (3) | H21—O2—H22 | 103 (4) |
N7C—C6C—N12C | 115.3 (3) | H31—O3—H32 | 98 (4) |
C8C—N7C—C6C | 118.2 (3) | | |
| | | |
C9A—C1A—C2A—C3A | 0.8 (5) | C9C—C1C—C2C—C3C | 1.4 (5) |
C11A—C1A—C2A—C3A | −177.6 (3) | C11C—C1C—C2C—C3C | 179.1 (3) |
C9A—C1A—C2A—C14A | −178.7 (3) | C9C—C1C—C2C—C14C | −175.9 (3) |
C11A—C1A—C2A—C14A | 3.0 (5) | C11C—C1C—C2C—C14C | 1.8 (5) |
C1A—C2A—C3A—C4A | 1.2 (5) | C1C—C2C—C3C—C4C | −3.1 (5) |
C14A—C2A—C3A—C4A | −179.4 (3) | C14C—C2C—C3C—C4C | 174.2 (3) |
C2A—C3A—C4A—C10A | −1.4 (5) | C2C—C3C—C4C—C10C | 0.1 (5) |
C10A—N5A—C6A—N12A | 177.1 (3) | C10C—N5C—C6C—N7C | 6.3 (5) |
C10A—N5A—C6A—N7A | −2.6 (5) | C10C—N5C—C6C—N12C | −170.7 (3) |
N5A—C6A—N7A—C8A | 4.6 (5) | N5C—C6C—N7C—C8C | −5.5 (5) |
N12A—C6A—N7A—C8A | −175.1 (3) | N12C—C6C—N7C—C8C | 171.6 (3) |
C6A—N7A—C8A—N13A | −177.4 (3) | C6C—N7C—C8C—N13C | 179.8 (3) |
C6A—N7A—C8A—C9A | −1.7 (5) | C6C—N7C—C8C—C9C | −2.0 (5) |
C2A—C1A—C9A—C10A | −2.5 (5) | C2C—C1C—C9C—C10C | 3.1 (5) |
C11A—C1A—C9A—C10A | 175.7 (3) | C11C—C1C—C9C—C10C | −174.5 (3) |
C2A—C1A—C9A—C8A | 174.9 (3) | C2C—C1C—C9C—C8C | −177.6 (3) |
C11A—C1A—C9A—C8A | −6.8 (5) | C11C—C1C—C9C—C8C | 4.8 (5) |
N7A—C8A—C9A—C10A | −2.4 (5) | N7C—C8C—C9C—C10C | 7.3 (5) |
N13A—C8A—C9A—C10A | 172.8 (3) | N13C—C8C—C9C—C10C | −174.8 (3) |
N7A—C8A—C9A—C1A | −179.9 (3) | N7C—C8C—C9C—C1C | −172.0 (3) |
N13A—C8A—C9A—C1A | −4.7 (6) | N13C—C8C—C9C—C1C | 5.9 (6) |
C6A—N5A—C10A—C4A | 177.6 (3) | C6C—N5C—C10C—C4C | 179.2 (3) |
C6A—N5A—C10A—C9A | −2.2 (5) | C6C—N5C—C10C—C9C | 0.2 (5) |
C3A—C4A—C10A—N5A | 179.7 (3) | C3C—C4C—C10C—N5C | −174.6 (3) |
C3A—C4A—C10A—C9A | −0.5 (5) | C3C—C4C—C10C—C9C | 4.5 (5) |
C1A—C9A—C10A—N5A | −177.8 (3) | C1C—C9C—C10C—N5C | 173.0 (3) |
C8A—C9A—C10A—N5A | 4.5 (5) | C8C—C9C—C10C—N5C | −6.4 (5) |
C1A—C9A—C10A—C4A | 2.4 (5) | C1C—C9C—C10C—C4C | −6.1 (5) |
C8A—C9A—C10A—C4A | −175.3 (3) | C8C—C9C—C10C—C4C | 174.6 (3) |
C1A—C2A—C14A—N15A | 176.9 (3) | C1C—C2C—C14C—N15C | 174.2 (3) |
C3A—C2A—C14A—N15A | −2.5 (5) | C3C—C2C—C14C—N15C | −3.1 (5) |
C2A—C14A—N15A—C16A | 92.0 (4) | C2C—C14C—N15C—C16C | 85.5 (4) |
C14A—N15A—C16A—C17A | −12.1 (5) | C14C—N15C—C16C—C17C | −2.9 (5) |
C14A—N15A—C16A—C21A | 167.5 (3) | C14C—N15C—C16C—C21C | 176.3 (3) |
N15A—C16A—C17A—C18A | 177.5 (3) | N15C—C16C—C17C—C18C | 177.6 (3) |
C21A—C16A—C17A—C18A | −2.1 (5) | C21C—C16C—C17C—C18C | −1.6 (5) |
C16A—C17A—C18A—O22A | −177.7 (3) | C16C—C17C—C18C—O22C | 179.7 (3) |
C16A—C17A—C18A—C19A | 0.4 (5) | C16C—C17C—C18C—C19C | −0.4 (5) |
O22A—C18A—C19A—O24A | 2.4 (5) | C17C—C18C—C19C—O24C | −174.3 (3) |
C17A—C18A—C19A—O24A | −175.7 (3) | O22C—C18C—C19C—O24C | 5.6 (5) |
O22A—C18A—C19A—C20A | 179.3 (3) | C17C—C18C—C19C—C20C | 1.5 (5) |
C17A—C18A—C19A—C20A | 1.2 (5) | O22C—C18C—C19C—C20C | −178.6 (3) |
C18A—C19A—C20A—O26A | −179.8 (3) | O24C—C19C—C20C—O26C | −2.0 (5) |
O24A—C19A—C20A—O26A | −2.9 (4) | C18C—C19C—C20C—O26C | −177.8 (3) |
C18A—C19A—C20A—C21A | −0.9 (5) | O24C—C19C—C20C—C21C | 175.2 (3) |
O24A—C19A—C20A—C21A | 176.0 (3) | C18C—C19C—C20C—C21C | −0.6 (5) |
O26A—C20A—C21A—C16A | 177.9 (3) | O26C—C20C—C21C—C16C | 175.5 (3) |
C19A—C20A—C21A—C16A | −0.9 (5) | C19C—C20C—C21C—C16C | −1.4 (5) |
N15A—C16A—C21A—C20A | −177.2 (3) | N15C—C16C—C21C—C20C | −176.7 (3) |
C17A—C16A—C21A—C20A | 2.4 (5) | C17C—C16C—C21C—C20C | 2.5 (5) |
C19A—C18A—O22A—C23A | 110.2 (4) | C17C—C18C—O22C—C23C | −3.0 (5) |
C17A—C18A—O22A—C23A | −71.7 (5) | C19C—C18C—O22C—C23C | 177.1 (3) |
C18A—C19A—O24A—C25A | −102.0 (4) | C20C—C19C—O24C—C25C | 75.4 (4) |
C20A—C19A—O24A—C25A | 81.1 (4) | C18C—C19C—O24C—C25C | −108.9 (4) |
C21A—C20A—O26A—C27A | 7.4 (5) | C21C—C20C—O26C—C27C | −2.3 (5) |
C19A—C20A—O26A—C27A | −173.8 (3) | C19C—C20C—O26C—C27C | 174.9 (3) |
C9B—C1B—C2B—C3B | 1.4 (5) | C9D—C1D—C2D—C3D | 6.4 (5) |
C11B—C1B—C2B—C3B | 178.1 (3) | C11D—C1D—C2D—C3D | −176.2 (3) |
C9B—C1B—C2B—C14B | −177.0 (3) | C9D—C1D—C2D—C14D | −170.8 (3) |
C11B—C1B—C2B—C14B | −0.3 (5) | C11D—C1D—C2D—C14D | 6.6 (5) |
C1B—C2B—C3B—C4B | −3.6 (5) | C1D—C2D—C3D—C4D | −5.6 (5) |
C14B—C2B—C3B—C4B | 174.8 (3) | C14D—C2D—C3D—C4D | 171.7 (3) |
C2B—C3B—C4B—C10B | −0.1 (5) | C2D—C3D—C4D—C10D | 0.0 (6) |
C10B—N5B—C6B—N7B | 9.1 (5) | C10D—N5D—C6D—N12D | −179.6 (3) |
C10B—N5B—C6B—N12B | −169.2 (3) | C10D—N5D—C6D—N7D | 2.7 (5) |
N5B—C6B—N7B—C8B | −3.9 (5) | N5D—C6D—N7D—C8D | 2.0 (5) |
N12B—C6B—N7B—C8B | 174.5 (3) | N12D—C6D—N7D—C8D | −175.8 (3) |
C6B—N7B—C8B—N13B | 173.3 (3) | C6D—N7D—C8D—N13D | 175.3 (3) |
C6B—N7B—C8B—C9B | −7.0 (5) | C6D—N7D—C8D—C9D | −6.4 (5) |
C2B—C1B—C9B—C10B | 4.2 (5) | C2D—C1D—C9D—C10D | −1.9 (5) |
C11B—C1B—C9B—C10B | −172.3 (3) | C11D—C1D—C9D—C10D | −179.2 (3) |
C2B—C1B—C9B—C8B | −178.8 (3) | C2D—C1D—C9D—C8D | 173.0 (3) |
C11B—C1B—C9B—C8B | 4.6 (5) | C11D—C1D—C9D—C8D | −4.2 (6) |
N13B—C8B—C9B—C10B | −169.0 (4) | N13D—C8D—C9D—C10D | −175.9 (4) |
N7B—C8B—C9B—C10B | 11.4 (5) | N7D—C8D—C9D—C10D | 6.0 (5) |
N13B—C8B—C9B—C1B | 13.9 (6) | N13D—C8D—C9D—C1D | 8.9 (6) |
N7B—C8B—C9B—C1B | −165.8 (3) | N7D—C8D—C9D—C1D | −169.2 (3) |
C6B—N5B—C10B—C4B | 175.6 (3) | C6D—N5D—C10D—C4D | 175.1 (3) |
C6B—N5B—C10B—C9B | −3.5 (5) | C6D—N5D—C10D—C9D | −2.9 (5) |
C3B—C4B—C10B—N5B | −173.4 (3) | C3D—C4D—C10D—N5D | −173.5 (3) |
C3B—C4B—C10B—C9B | 5.7 (5) | C3D—C4D—C10D—C9D | 4.6 (5) |
C1B—C9B—C10B—N5B | 171.3 (3) | C1D—C9D—C10D—N5D | 174.3 (3) |
C8B—C9B—C10B—N5B | −6.0 (5) | C8D—C9D—C10D—N5D | −1.2 (5) |
C1B—C9B—C10B—C4B | −7.8 (5) | C1D—C9D—C10D—C4D | −3.6 (5) |
C8B—C9B—C10B—C4B | 174.9 (3) | C8D—C9D—C10D—C4D | −179.2 (3) |
C1B—C2B—C14B—N15B | 178.8 (3) | C1D—C2D—C14D—N15D | 164.9 (3) |
C3B—C2B—C14B—N15B | 0.4 (5) | C3D—C2D—C14D—N15D | −12.3 (5) |
C2B—C14B—N15B—C16B | 80.9 (4) | C2D—C14D—N15D—C16D | 92.8 (4) |
C14B—N15B—C16B—C17B | −6.6 (5) | C14D—N15D—C16D—C21D | −14.2 (5) |
C14B—N15B—C16B—C21B | 173.2 (3) | C14D—N15D—C16D—C17D | 165.1 (3) |
N15B—C16B—C17B—C18B | 177.3 (3) | N15D—C16D—C17D—C18D | −179.0 (3) |
C21B—C16B—C17B—C18B | −2.5 (5) | C21D—C16D—C17D—C18D | 0.3 (5) |
C16B—C17B—C18B—O22B | 179.3 (3) | C16D—C17D—C18D—O22D | 180.0 (3) |
C16B—C17B—C18B—C19B | −1.0 (5) | C16D—C17D—C18D—C19D | 0.4 (5) |
O22B—C18B—C19B—O24B | −0.1 (5) | O22D—C18D—C19D—C20D | 179.3 (3) |
C17B—C18B—C19B—O24B | −179.8 (3) | C17D—C18D—C19D—C20D | −1.1 (5) |
O22B—C18B—C19B—C20B | −176.8 (3) | O22D—C18D—C19D—O24D | −0.7 (4) |
C17B—C18B—C19B—C20B | 3.5 (5) | C17D—C18D—C19D—O24D | 178.9 (3) |
O24B—C19B—C20B—O26B | 2.0 (5) | C18D—C19D—C20D—O26D | −178.7 (3) |
C18B—C19B—C20B—O26B | 178.6 (3) | O24D—C19D—C20D—O26D | 1.3 (5) |
O24B—C19B—C20B—C21B | −179.1 (3) | C18D—C19D—C20D—C21D | 1.1 (5) |
C18B—C19B—C20B—C21B | −2.4 (5) | O24D—C19D—C20D—C21D | −178.9 (3) |
O26B—C20B—C21B—C16B | 177.8 (3) | N15D—C16D—C21D—C20D | 178.9 (3) |
C19B—C20B—C21B—C16B | −1.1 (5) | C17D—C16D—C21D—C20D | −0.4 (5) |
N15B—C16B—C21B—C20B | −176.2 (3) | O26D—C20D—C21D—C16D | 179.4 (3) |
C17B—C16B—C21B—C20B | 3.6 (5) | C19D—C20D—C21D—C16D | −0.3 (5) |
C17B—C18B—O22B—C23B | −17.9 (5) | C17D—C18D—O22D—C23D | 5.8 (5) |
C19B—C18B—O22B—C23B | 162.4 (3) | C19D—C18D—O22D—C23D | −174.7 (3) |
C20B—C19B—O24B—C25B | −93.5 (4) | C20D—C19D—O24D—C25D | −99.5 (4) |
C18B—C19B—O24B—C25B | 90.0 (4) | C18D—C19D—O24D—C25D | 80.5 (4) |
C21B—C20B—O26B—C27B | 5.2 (5) | C19D—C20D—O26D—C27D | 171.1 (3) |
C19B—C20B—O26B—C27B | −175.9 (3) | C21D—C20D—O26D—C27D | −8.6 (5) |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
N12A—H12A···N5C | 0.83 (3) | 2.26 (3) | 3.081 (4) | 168 (3) |
N12A—H12B···O2 | 0.79 (3) | 2.34 (3) | 3.111 (4) | 165 (3) |
N12B—H12C···O3 | 0.77 (3) | 2.28 (3) | 3.016 (4) | 160 (3) |
N12B—H12D···N5D | 0.90 (3) | 2.10 (3) | 2.979 (5) | 167 (3) |
N12C—H12E···N5A | 0.88 (3) | 2.08 (3) | 2.950 (5) | 172 (3) |
N12C—H12F···O20 | 0.80 (3) | 2.21 (3) | 2.919 (4) | 149 (3) |
N12D—H12G···N5B | 0.95 (3) | 2.07 (3) | 3.000 (5) | 167 (3) |
N12D—H12H···O1 | 0.72 (3) | 2.33 (3) | 3.038 (4) | 165 (4) |
N13A—H13A···N7B | 0.92 (3) | 2.07 (3) | 2.983 (4) | 173 (3) |
N13A—H13B···O3 | 0.85 (3) | 2.45 (3) | 3.030 (4) | 127 (3) |
N13B—H13C···O2 | 0.74 (3) | 2.37 (4) | 2.976 (5) | 140 (3) |
N13B—H13D···N7A | 0.89 (3) | 2.07 (3) | 2.955 (4) | 169 (3) |
N13C—H13E···N7Di | 0.85 (3) | 2.24 (3) | 3.091 (4) | 173 (3) |
N13C—H13F···O1i | 0.77 (3) | 2.31 (4) | 2.945 (5) | 140 (3) |
N13D—H13G···O20ii | 0.85 (3) | 2.36 (3) | 2.995 (4) | 132 (3) |
N13D—H13H···N7Cii | 0.88 (3) | 2.15 (3) | 3.028 (4) | 171 (3) |
N15A—H15A···N12Ciii | 0.91 (3) | 2.22 (3) | 3.115 (5) | 168 (3) |
N15D—H15D···N12Biv | 0.85 (3) | 2.58 (3) | 3.411 (5) | 167 (3) |
O1—H11···O24Bv | 0.84 (5) | 2.16 (4) | 2.929 (4) | 152 (4) |
O1—H12···O24Avi | 0.76 (4) | 2.11 (4) | 2.864 (4) | 167 (5) |
O2—H21···O24Dvii | 0.75 (4) | 2.10 (4) | 2.839 (4) | 170 (5) |
O2—H22···O22Cviii | 0.90 (5) | 2.08 (5) | 2.968 (4) | 167 (4) |
O3—H31···O10 | 0.98 (5) | 1.85 (5) | 2.803 (5) | 165 (3) |
O3—H32···O24Cix | 0.81 (3) | 2.38 (3) | 3.146 (3) | 156 (5) |
O3—H32···O26Cix | 0.81 (3) | 2.52 (5) | 3.130 (4) | 132 (4) |
C10—H10A···N7B | 0.96 | 2.50 | 3.454 (6) | 172 |
C25B—H25E···N7Dv | 0.96 | 2.54 | 3.495 (6) | 172 |
Symmetry codes: (i) x+1, y−1, z; (ii) x−1, y+1, z; (iii) −x+1, −y, −z+1; (iv) −x, −y+1, −z+1; (v) −x+1, −y+2, −z; (vi) x, y+1, z−1; (vii) x+1, y, z−1; (viii) −x+2, −y+1, −z; (ix) x−1, y, z+1. |
Experimental details
Crystal data |
Chemical formula | 4C19H23N5O3·2C2H6OS·3H2O |
Mr | 1688.02 |
Crystal system, space group | Triclinic, P1 |
Temperature (K) | 100 |
a, b, c (Å) | 16.124 (2), 16.371 (2), 17.766 (1) |
α, β, γ (°) | 81.676 (3), 66.289 (2), 80.050 (3) |
V (Å3) | 4214.4 (8) |
Z | 2 |
Radiation type | Mo Kα |
µ (mm−1) | 0.14 |
Crystal size (mm) | 0.50 × 0.40 × 0.37 |
|
Data collection |
Diffractometer | Nonius KappaCCD diffractometer |
Absorption correction | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 16962, 16962, 6946 |
Rint | 0.000 |
(sin θ/λ)max (Å−1) | 0.626 |
|
Refinement |
R[F2 > 2σ(F2)], wR(F2), S | 0.065, 0.168, 0.88 |
No. of reflections | 16962 |
No. of parameters | 1174 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.36, −0.47 |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
N12A—H12A···N5C | 0.83 (3) | 2.26 (3) | 3.081 (4) | 168 (3) |
N12A—H12B···O2 | 0.79 (3) | 2.34 (3) | 3.111 (4) | 165 (3) |
N12B—H12C···O3 | 0.77 (3) | 2.28 (3) | 3.016 (4) | 160 (3) |
N12B—H12D···N5D | 0.90 (3) | 2.10 (3) | 2.979 (5) | 167 (3) |
N12C—H12E···N5A | 0.88 (3) | 2.08 (3) | 2.950 (5) | 172 (3) |
N12C—H12F···O20 | 0.80 (3) | 2.21 (3) | 2.919 (4) | 149 (3) |
N12D—H12G···N5B | 0.95 (3) | 2.07 (3) | 3.000 (5) | 167 (3) |
N12D—H12H···O1 | 0.72 (3) | 2.33 (3) | 3.038 (4) | 165 (4) |
N13A—H13A···N7B | 0.92 (3) | 2.07 (3) | 2.983 (4) | 173 (3) |
N13A—H13B···O3 | 0.85 (3) | 2.45 (3) | 3.030 (4) | 127 (3) |
N13B—H13C···O2 | 0.74 (3) | 2.37 (4) | 2.976 (5) | 140 (3) |
N13B—H13D···N7A | 0.89 (3) | 2.07 (3) | 2.955 (4) | 169 (3) |
N13C—H13E···N7Di | 0.85 (3) | 2.24 (3) | 3.091 (4) | 173 (3) |
N13C—H13F···O1i | 0.77 (3) | 2.31 (4) | 2.945 (5) | 140 (3) |
N13D—H13G···O20ii | 0.85 (3) | 2.36 (3) | 2.995 (4) | 132 (3) |
N13D—H13H···N7Cii | 0.88 (3) | 2.15 (3) | 3.028 (4) | 171 (3) |
N15A—H15A···N12Ciii | 0.91 (3) | 2.22 (3) | 3.115 (5) | 168 (3) |
N15D—H15D···N12Biv | 0.85 (3) | 2.58 (3) | 3.411 (5) | 167 (3) |
O1—H11···O24Bv | 0.84 (5) | 2.16 (4) | 2.929 (4) | 152 (4) |
O1—H12···O24Avi | 0.76 (4) | 2.11 (4) | 2.864 (4) | 167 (5) |
O2—H21···O24Dvii | 0.75 (4) | 2.10 (4) | 2.839 (4) | 170 (5) |
O2—H22···O22Cviii | 0.90 (5) | 2.08 (5) | 2.968 (4) | 167 (4) |
O3—H31···O10 | 0.98 (5) | 1.85 (5) | 2.803 (5) | 165 (3) |
O3—H32···O24Cix | 0.81 (3) | 2.38 (3) | 3.146 (3) | 156 (5) |
O3—H32···O26Cix | 0.81 (3) | 2.52 (5) | 3.130 (4) | 132 (4) |
Symmetry codes: (i) x+1, y−1, z; (ii) x−1, y+1, z; (iii) −x+1, −y, −z+1; (iv) −x, −y+1, −z+1; (v) −x+1, −y+2, −z; (vi) x, y+1, z−1; (vii) x+1, y, z−1; (viii) −x+2, −y+1, −z; (ix) x−1, y, z+1. |
Trimetrexate (TMQ), a lipophilic antifolate, is a well known dihydrofolate reductase (DHFR) inhibitor and is widely used in cancer therapy and for the treatment of a variety of non-malignant disorders. We elucidated the present particular crystal structure of TMQ as a continuation of our studies into the effects of increased lipophilicity on the conformational properties and stereochemical parameters in antifolates, which may indicate a direction in development of new agents with better pharmacological profiles.
The asymmetric unit of the present crystal structure, (I), consists of four independent TMQ molecules, all adopting trans,gauche conformations [molecule A: τ1 = 176.9 (3)° and τ2 = 92.0 (4)°; molecule B: 178.8 (3)° and 80.9 (4)°; molecule C: 174.2 (3)° and 85.5 (4)°; molecule D: 164.9 (3)° and 92.8 (4)°; the τ1 and τ2 torsion angles are defined by C1—C2—C14—N15 and C2—C14–N15—-C16, respectively], two dimethyl sulfoxide molecules and three water molecules. All four TMQ molecules show partially folded conformations, with the planes of the trimethoxyanilino rings twisted from those of the quinazoline rings by 84.3 (1), 86.7 (1), 89.8 (1) and 85.8 (1)° for molecules A, B, C and D, respectively. In previously reported crystal forms of trimetrexate (Sutton & Cody, 1987; Hempel et al., 1988), the molecules exhibited gauche,trans conformations. There is substantial evidence, however, that the trans,gauche conformations observed for the first time in the present crystal structure is the one responsible for enzyme inhibition. The crystal structure of DHFR with methotrexate (MTX) (Bolin et al., 1982) showed MTX to have a similar trans,gauche conformation when bound to the enzyme. Simulated annealing calculations performed for the solution structure of the complex of Lactobacillus casei DHFR with MTX (Gargaro et al., 1998) showed that the stereochemistry of the binary complex in solution is very similar to that reported for the crystal structure. Similar calculations based on an analysis of the multidimensional NMR spectra of the complex of Lactobacillus casei DHFR with TMQ in solution have produced a family of 22 conformations of TMQ, all exclusively in the trans,gauche form, implying that this conformation of TMQ (molecules A or B in this report) is also that which is present in the active site of dihydrofolate reductase (Polshakov et al., 1999).
A conformational analysis of TMQ using empirical force-field and AM1 quantum mechanical methods, concluded that TMQ prefers a gauche,trans rather than a trans,gauche conformation, in contrast with MTX which prefers an approximate trans,gauche conformatio (Hoffman & Welsh, 1995). While this conclusion is in agreement with the conformations observed in the crystal structures of trimetrexate reported previously, it is not true for the crystal structure presented in this study, where TMQ molecules adopt the opposite trans,gauche form. A comparison of the stereochemistry of molecule A of TMQ with that of MTX bound to DHFR in the crystal structure complex is shown in Fig. 2. The two structures are conformationally very closely related, indicating possible replacement of MTX by TMQ with little change in the stereochemistry of the enzyme–inhibitor binding.
The four independent TMQ molecules are hydrogen bonded among themselves through N···N base-pairing interactions involving the N7···N13 and N5···N12 systems (Table 1 and Fig. 3). In other antifolate structures, only partial base-pairing interactions have been reported, i.e. N7···N13 for TMQ monoacetate monohydrate and free base (Hempel et al., 1988), N7···N12 for quinespar (Mastropaolo et al., 1986) and no base-pairing in TMQ dimethyl sulfoxide hydrate (Sutton & Cody, 1987). Interestingly, no direct N···O hydrogen bonds exist between TMQ molecules in the crystal packing. The N···O bond occurs exclusively between TMQ and solvent (water and dimethyl sulfoxide) molecules. The water molecules connect TMQ molecules through hydrogen bonds to methoxy O atoms and the N12 and N13 atoms of the quinazoline. Curiously, the two potential hydrogen-bond donors (N15B—H15B and N15C—H15C), being surrounded by N13 and N7 atom pairs from different molecules, do not participate in classical hydrogen bonding due to longer than usual D···A distances.