Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270108020313/dn3093sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S0108270108020313/dn3093Isup2.hkl |
CCDC reference: 700023
The title compound was synthesized by heating together 1 mmol quantities of quinacrium dichloride dihydrate (atabrine or mepacrine) (O'Neil, 2001) and 3-carboxy-4-hydroxybenzenesulfonic acid (5-sulfosalicylic acid = 5-SSA) in 50% ethanol–water (50 ml) under reflux for 10 min. After concentration to ca 30 ml, partial room-temperature evaporation of the hot-filtered solution gave yellow blocks of (I) (m.p. 523 K).
H atoms potentially involved in hydrogen-bonding interactions (aminium, carboxylic, phenolic and water) were located by difference methods and their positional and isotropic displacement parameters were refined. Other H atoms were included in the refinement at calculated positions as riding atoms, with C—H = 0.93 (aromatic) or C—H = 0.96 or 0.97 Å (aliphatic), and with Uiso(I) = 1.2Ueq(C).
Data collection: CrysAlis CCD (Oxford Diffraction, 2008); cell refinement: CrysAlis RED (Oxford Diffraction, 2008); data reduction: CrysAlis RED (Oxford Diffraction, 2008); program(s) used to solve structure: SIR92 (Altomare et al., 1994); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: PLATON (Spek, 2003); software used to prepare material for publication: PLATON (Spek, 2003).
C23H32ClN3O2+·C7H4O6S2−·2H2O | F(000) = 1384 |
Mr = 654.17 | Dx = 1.356 Mg m−3 |
Monoclinic, P21/n | Melting point: 523 K |
Hall symbol: -P 2yn | Mo Kα radiation, λ = 0.71073 Å |
a = 10.1753 (3) Å | Cell parameters from 9373 reflections |
b = 30.8461 (7) Å | θ = 2.9–28.9° |
c = 10.3671 (2) Å | µ = 0.24 mm−1 |
β = 99.966 (3)° | T = 297 K |
V = 3204.81 (14) Å3 | Block, yellow |
Z = 4 | 0.20 × 0.20 × 0.15 mm |
Oxford Diffraction Gemini-S Ultra CCD detector diffractometer | 5455 independent reflections |
Radiation source: Enhance (Mo) X-ray tube | 3568 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.049 |
ω scans | θmax = 25.0°, θmin = 2.9° |
Absorption correction: multi-scan (SADABS; Sheldrick, 1996) | h = −11→11 |
Tmin = 0.906, Tmax = 0.960 | k = −36→36 |
29865 measured reflections | l = −12→12 |
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)] = 0.040 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.100 | H atoms treated by a mixture of independent and constrained refinement |
S = 0.99 | w = 1/[σ2(Fo2) + (0.0552P)2] where P = (Fo2 + 2Fc2)/3 |
5455 reflections | (Δ/σ)max = 0.002 |
433 parameters | Δρmax = 0.26 e Å−3 |
0 restraints | Δρmin = −0.26 e Å−3 |
C23H32ClN3O2+·C7H4O6S2−·2H2O | V = 3204.81 (14) Å3 |
Mr = 654.17 | Z = 4 |
Monoclinic, P21/n | Mo Kα radiation |
a = 10.1753 (3) Å | µ = 0.24 mm−1 |
b = 30.8461 (7) Å | T = 297 K |
c = 10.3671 (2) Å | 0.20 × 0.20 × 0.15 mm |
β = 99.966 (3)° |
Oxford Diffraction Gemini-S Ultra CCD detector diffractometer | 5455 independent reflections |
Absorption correction: multi-scan (SADABS; Sheldrick, 1996) | 3568 reflections with I > 2σ(I) |
Tmin = 0.906, Tmax = 0.960 | Rint = 0.049 |
29865 measured reflections |
R[F2 > 2σ(F2)] = 0.040 | 0 restraints |
wR(F2) = 0.100 | H atoms treated by a mixture of independent and constrained refinement |
S = 0.99 | Δρmax = 0.26 e Å−3 |
5455 reflections | Δρmin = −0.26 e Å−3 |
433 parameters |
Geometry. Bond distances, angles etc. have been calculated using the rounded fractional coordinates. All su's are estimated from the variances of the (full) variance-covariance matrix. The cell e.s.d.'s are taken into account in the estimation of distances, angles and torsion angles |
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. |
x | y | z | Uiso*/Ueq | ||
Cl6 | 0.73514 (8) | 1.07667 (2) | 1.02838 (7) | 0.0788 (3) | |
O2 | 1.37199 (16) | 0.93866 (5) | 0.46659 (16) | 0.0572 (6) | |
N10 | 1.1183 (2) | 1.02589 (6) | 0.81378 (18) | 0.0449 (7) | |
N91 | 0.91323 (18) | 0.92482 (5) | 0.61055 (17) | 0.0361 (6) | |
N141 | 1.10064 (19) | 0.78100 (6) | 0.88969 (17) | 0.0405 (6) | |
C1 | 1.1711 (2) | 0.94843 (6) | 0.5586 (2) | 0.0406 (8) | |
C2 | 1.3003 (2) | 0.95817 (7) | 0.5492 (2) | 0.0442 (8) | |
C3 | 1.3695 (2) | 0.99067 (7) | 0.6276 (2) | 0.0507 (8) | |
C4 | 1.3091 (2) | 1.01273 (7) | 0.7137 (2) | 0.0488 (9) | |
C5 | 0.9350 (3) | 1.04771 (6) | 0.9128 (2) | 0.0465 (9) | |
C6 | 0.8050 (3) | 1.04374 (7) | 0.9227 (2) | 0.0487 (9) | |
C7 | 0.7218 (3) | 1.01360 (7) | 0.8475 (2) | 0.0516 (9) | |
C8 | 0.7741 (2) | 0.98673 (6) | 0.7649 (2) | 0.0445 (8) | |
C9 | 0.9721 (2) | 0.95988 (6) | 0.66931 (18) | 0.0328 (7) | |
C11 | 1.1046 (2) | 0.97092 (6) | 0.64782 (18) | 0.0345 (7) | |
C12 | 1.1765 (2) | 1.00352 (6) | 0.7248 (2) | 0.0393 (8) | |
C13 | 0.9900 (2) | 1.02031 (6) | 0.82663 (19) | 0.0400 (8) | |
C14 | 0.9107 (2) | 0.98788 (6) | 0.75396 (19) | 0.0356 (7) | |
C21 | 1.3163 (3) | 0.90073 (8) | 0.3983 (3) | 0.0663 (10) | |
C101 | 0.8054 (2) | 0.89728 (6) | 0.64293 (19) | 0.0368 (7) | |
C102 | 0.6813 (2) | 0.90126 (7) | 0.5384 (2) | 0.0498 (8) | |
C111 | 0.8531 (2) | 0.85013 (6) | 0.65477 (19) | 0.0372 (7) | |
C121 | 0.9708 (2) | 0.84169 (6) | 0.7633 (2) | 0.0415 (8) | |
C131 | 1.0014 (2) | 0.79360 (6) | 0.77116 (19) | 0.0395 (7) | |
C151 | 1.0970 (3) | 0.73304 (7) | 0.9145 (2) | 0.0619 (10) | |
C161 | 1.1456 (4) | 0.70609 (8) | 0.8109 (3) | 0.0925 (13) | |
C171 | 1.2371 (2) | 0.79845 (8) | 0.8845 (2) | 0.0501 (8) | |
C181 | 1.3376 (3) | 0.78939 (10) | 1.0066 (2) | 0.0729 (10) | |
S5A | 0.68492 (6) | 0.71943 (2) | 0.92440 (5) | 0.0413 (2) | |
O2A | 0.53028 (18) | 0.90192 (5) | 0.81392 (17) | 0.0557 (6) | |
O51A | 0.73433 (17) | 0.70207 (5) | 0.81288 (15) | 0.0579 (6) | |
O52A | 0.55973 (19) | 0.69969 (5) | 0.94051 (19) | 0.0735 (7) | |
O53A | 0.7816 (2) | 0.71921 (5) | 1.04214 (15) | 0.0764 (7) | |
O71A | 0.82953 (17) | 0.87392 (5) | 1.12651 (16) | 0.0625 (6) | |
O72A | 0.69527 (18) | 0.92267 (5) | 1.01919 (16) | 0.0664 (7) | |
C1A | 0.6696 (2) | 0.85020 (6) | 0.94699 (18) | 0.0336 (7) | |
C2A | 0.5708 (2) | 0.86055 (6) | 0.83976 (19) | 0.0386 (7) | |
C3A | 0.5132 (2) | 0.82784 (7) | 0.75500 (19) | 0.0411 (8) | |
C4A | 0.5496 (2) | 0.78537 (6) | 0.77900 (18) | 0.0362 (7) | |
C5A | 0.6446 (2) | 0.77423 (6) | 0.88733 (17) | 0.0318 (7) | |
C6A | 0.7042 (2) | 0.80682 (6) | 0.96911 (18) | 0.0342 (7) | |
C7A | 0.7363 (2) | 0.88417 (7) | 1.0383 (2) | 0.0446 (8) | |
O1W | 1.0461 (3) | 0.82390 (8) | 1.10118 (19) | 0.0795 (9) | |
O2W | 0.9675 (2) | 0.88264 (6) | 0.37879 (17) | 0.0581 (7) | |
H1 | 1.12630 | 0.92680 | 0.50590 | 0.0490* | |
H3 | 1.45720 | 0.99710 | 0.62040 | 0.0610* | |
H4 | 1.35570 | 1.03410 | 0.76600 | 0.0590* | |
H5 | 0.98800 | 1.06830 | 0.96240 | 0.0560* | |
H7 | 0.63180 | 1.01190 | 0.85380 | 0.0620* | |
H8 | 0.71830 | 0.96700 | 0.71430 | 0.0530* | |
H10 | 1.170 (3) | 1.0455 (8) | 0.863 (3) | 0.072 (8)* | |
H91 | 0.947 (2) | 0.9120 (6) | 0.546 (2) | 0.047 (6)* | |
H101 | 0.78380 | 0.90660 | 0.72720 | 0.0440* | |
H102 | 0.61160 | 0.88340 | 0.56160 | 0.0750* | |
H103 | 0.70140 | 0.89190 | 0.45570 | 0.0750* | |
H104 | 0.65240 | 0.93090 | 0.53200 | 0.0750* | |
H111 | 0.77930 | 0.83200 | 0.66940 | 0.0450* | |
H112 | 0.87750 | 0.84140 | 0.57210 | 0.0450* | |
H121 | 1.04820 | 0.85760 | 0.74590 | 0.0500* | |
H122 | 0.95000 | 0.85170 | 0.84620 | 0.0500* | |
H131 | 0.91920 | 0.77780 | 0.77190 | 0.0470* | |
H132 | 1.03570 | 0.78500 | 0.69330 | 0.0470* | |
H141 | 1.076 (2) | 0.7959 (7) | 0.957 (2) | 0.064 (8)* | |
H151 | 1.00610 | 0.72470 | 0.91930 | 0.0740* | |
H152 | 1.15170 | 0.72680 | 0.99870 | 0.0740* | |
H161 | 1.13280 | 0.67590 | 0.82780 | 0.1110* | |
H162 | 1.23880 | 0.71160 | 0.81270 | 0.1110* | |
H163 | 1.09630 | 0.71360 | 0.72640 | 0.1110* | |
H171 | 1.23090 | 0.82960 | 0.87090 | 0.0600* | |
H172 | 1.26880 | 0.78580 | 0.80990 | 0.0600* | |
H181 | 1.29800 | 0.79510 | 1.08240 | 0.0880* | |
H182 | 1.36480 | 0.75960 | 1.00690 | 0.0880* | |
H183 | 1.41400 | 0.80770 | 1.00800 | 0.0880* | |
H211 | 1.29930 | 0.87930 | 0.46040 | 0.0800* | |
H212 | 1.37800 | 0.88930 | 0.34660 | 0.0800* | |
H213 | 1.23420 | 0.90820 | 0.34200 | 0.0800* | |
H2A | 0.574 (3) | 0.9157 (8) | 0.888 (3) | 0.086 (10)* | |
H3A | 0.44990 | 0.83490 | 0.68210 | 0.0490* | |
H4A | 0.51040 | 0.76380 | 0.72230 | 0.0430* | |
H6A | 0.76900 | 0.79950 | 1.04060 | 0.0410* | |
H11W | 0.985 (3) | 0.8378 (9) | 1.107 (3) | 0.081 (12)* | |
H12W | 1.101 (3) | 0.8184 (10) | 1.168 (3) | 0.104 (12)* | |
H21W | 0.916 (3) | 0.8823 (9) | 0.300 (3) | 0.105 (11)* | |
H22W | 0.999 (3) | 0.8564 (9) | 0.394 (3) | 0.076 (9)* |
U11 | U22 | U33 | U12 | U13 | U23 | |
Cl6 | 0.1021 (7) | 0.0648 (4) | 0.0759 (5) | 0.0126 (4) | 0.0335 (4) | −0.0225 (3) |
O2 | 0.0417 (11) | 0.0654 (10) | 0.0662 (11) | −0.0010 (8) | 0.0138 (8) | −0.0109 (8) |
N10 | 0.0482 (15) | 0.0376 (10) | 0.0476 (11) | −0.0108 (10) | 0.0048 (10) | −0.0111 (8) |
N91 | 0.0384 (12) | 0.0317 (9) | 0.0384 (10) | −0.0051 (8) | 0.0074 (8) | −0.0066 (8) |
N141 | 0.0402 (13) | 0.0499 (11) | 0.0320 (9) | 0.0121 (9) | 0.0078 (8) | 0.0050 (8) |
C1 | 0.0428 (16) | 0.0341 (11) | 0.0428 (12) | −0.0018 (10) | 0.0014 (10) | −0.0013 (9) |
C2 | 0.0411 (17) | 0.0456 (13) | 0.0459 (13) | 0.0015 (12) | 0.0079 (11) | 0.0030 (10) |
C3 | 0.0386 (15) | 0.0557 (14) | 0.0574 (15) | −0.0116 (12) | 0.0072 (12) | 0.0034 (12) |
C4 | 0.0428 (17) | 0.0448 (13) | 0.0573 (15) | −0.0146 (12) | 0.0041 (12) | −0.0044 (11) |
C5 | 0.0611 (19) | 0.0361 (12) | 0.0418 (13) | −0.0022 (11) | 0.0077 (12) | −0.0092 (9) |
C6 | 0.064 (2) | 0.0366 (12) | 0.0471 (13) | 0.0098 (12) | 0.0145 (12) | −0.0038 (10) |
C7 | 0.0555 (17) | 0.0416 (12) | 0.0586 (15) | 0.0078 (12) | 0.0124 (12) | −0.0017 (11) |
C8 | 0.0463 (17) | 0.0355 (11) | 0.0505 (13) | 0.0025 (11) | 0.0051 (11) | −0.0066 (10) |
C9 | 0.0413 (14) | 0.0250 (10) | 0.0295 (10) | 0.0023 (9) | −0.0008 (9) | 0.0028 (8) |
C11 | 0.0376 (14) | 0.0289 (10) | 0.0349 (11) | −0.0023 (9) | 0.0006 (9) | 0.0038 (8) |
C12 | 0.0452 (16) | 0.0304 (11) | 0.0402 (12) | −0.0023 (10) | 0.0018 (10) | 0.0013 (9) |
C13 | 0.0495 (17) | 0.0309 (11) | 0.0380 (12) | −0.0010 (11) | 0.0032 (10) | 0.0000 (9) |
C14 | 0.0410 (15) | 0.0269 (10) | 0.0367 (11) | 0.0016 (9) | 0.0003 (10) | 0.0023 (8) |
C21 | 0.0591 (19) | 0.0708 (17) | 0.0708 (18) | 0.0023 (14) | 0.0163 (14) | −0.0199 (14) |
C101 | 0.0342 (14) | 0.0359 (11) | 0.0394 (11) | −0.0016 (10) | 0.0042 (10) | −0.0030 (9) |
C102 | 0.0438 (16) | 0.0454 (13) | 0.0556 (14) | 0.0003 (11) | −0.0045 (12) | 0.0053 (10) |
C111 | 0.0393 (14) | 0.0333 (11) | 0.0368 (11) | −0.0010 (9) | 0.0005 (10) | −0.0001 (8) |
C121 | 0.0389 (15) | 0.0411 (12) | 0.0418 (12) | 0.0011 (10) | −0.0002 (10) | −0.0014 (9) |
C131 | 0.0392 (14) | 0.0430 (12) | 0.0347 (11) | 0.0054 (10) | 0.0022 (10) | 0.0032 (9) |
C151 | 0.070 (2) | 0.0565 (15) | 0.0585 (16) | 0.0093 (13) | 0.0094 (14) | 0.0250 (12) |
C161 | 0.141 (3) | 0.0528 (16) | 0.080 (2) | 0.0324 (18) | 0.009 (2) | 0.0029 (14) |
C171 | 0.0366 (16) | 0.0707 (15) | 0.0430 (13) | 0.0080 (12) | 0.0070 (11) | 0.0048 (11) |
C181 | 0.0465 (18) | 0.123 (2) | 0.0472 (15) | 0.0158 (16) | 0.0026 (13) | 0.0065 (15) |
S5A | 0.0520 (4) | 0.0364 (3) | 0.0345 (3) | −0.0019 (3) | 0.0051 (2) | −0.0023 (2) |
O2A | 0.0672 (13) | 0.0427 (9) | 0.0524 (10) | 0.0099 (8) | −0.0032 (9) | 0.0021 (8) |
O51A | 0.0681 (12) | 0.0578 (10) | 0.0506 (10) | 0.0141 (9) | 0.0180 (9) | −0.0086 (7) |
O52A | 0.0761 (14) | 0.0456 (9) | 0.1081 (15) | −0.0168 (9) | 0.0418 (12) | 0.0011 (9) |
O53A | 0.1123 (16) | 0.0506 (10) | 0.0505 (10) | 0.0125 (10) | −0.0304 (10) | 0.0000 (8) |
O71A | 0.0579 (12) | 0.0603 (10) | 0.0586 (10) | 0.0028 (9) | −0.0195 (9) | −0.0249 (8) |
O72A | 0.0837 (14) | 0.0377 (9) | 0.0697 (11) | −0.0015 (9) | −0.0094 (10) | −0.0127 (8) |
C1A | 0.0325 (13) | 0.0354 (11) | 0.0325 (11) | −0.0048 (9) | 0.0045 (9) | −0.0032 (8) |
C2A | 0.0390 (14) | 0.0379 (12) | 0.0393 (12) | −0.0004 (10) | 0.0081 (10) | 0.0026 (9) |
C3A | 0.0389 (15) | 0.0504 (13) | 0.0309 (11) | −0.0043 (11) | −0.0024 (10) | 0.0031 (9) |
C4A | 0.0361 (14) | 0.0420 (12) | 0.0294 (10) | −0.0093 (10) | 0.0024 (9) | −0.0060 (9) |
C5A | 0.0314 (13) | 0.0379 (11) | 0.0268 (10) | −0.0068 (9) | 0.0071 (9) | −0.0036 (8) |
C6A | 0.0302 (13) | 0.0427 (12) | 0.0282 (10) | −0.0031 (9) | 0.0012 (9) | −0.0039 (8) |
C7A | 0.0483 (17) | 0.0419 (13) | 0.0433 (13) | −0.0057 (11) | 0.0068 (12) | −0.0095 (10) |
O1W | 0.0739 (17) | 0.1240 (18) | 0.0380 (11) | 0.0435 (15) | 0.0028 (11) | −0.0088 (11) |
O2W | 0.0767 (14) | 0.0510 (11) | 0.0422 (10) | 0.0128 (10) | −0.0021 (9) | −0.0110 (8) |
Cl6—C6 | 1.734 (3) | C3—H3 | 0.9300 |
S5A—O53A | 1.4290 (18) | C4—H4 | 0.9300 |
S5A—C5A | 1.7661 (19) | C5—H5 | 0.9300 |
S5A—O52A | 1.447 (2) | C7—H7 | 0.9300 |
S5A—O51A | 1.4413 (17) | C8—H8 | 0.9300 |
O2—C2 | 1.358 (3) | C111—C121 | 1.517 (3) |
O2—C21 | 1.433 (3) | C121—C131 | 1.515 (3) |
O2A—C2A | 1.354 (2) | C21—H213 | 0.9600 |
O71A—C7A | 1.239 (3) | C21—H212 | 0.9600 |
O72A—C7A | 1.263 (3) | C21—H211 | 0.9600 |
O2A—H2A | 0.92 (3) | C151—C161 | 1.508 (4) |
O1W—H12W | 0.83 (3) | C171—C181 | 1.509 (3) |
O1W—H11W | 0.77 (3) | C101—H101 | 0.9800 |
O2W—H21W | 0.89 (3) | C1A—C2A | 1.401 (3) |
O2W—H22W | 0.88 (3) | C1A—C6A | 1.393 (3) |
N10—C12 | 1.366 (3) | C1A—C7A | 1.494 (3) |
N10—C13 | 1.346 (3) | C102—H102 | 0.9600 |
N91—C9 | 1.332 (2) | C102—H103 | 0.9600 |
N91—C101 | 1.472 (3) | C102—H104 | 0.9600 |
N10—H10 | 0.90 (3) | C2A—C3A | 1.398 (3) |
N141—C171 | 1.499 (3) | C3A—C4A | 1.372 (3) |
N141—C131 | 1.500 (3) | C4A—C5A | 1.392 (3) |
N141—C151 | 1.503 (3) | C5A—C6A | 1.385 (3) |
N91—H91 | 0.90 (2) | C111—H112 | 0.9700 |
N141—H141 | 0.91 (2) | C111—H111 | 0.9700 |
C1—C2 | 1.368 (3) | C121—H121 | 0.9700 |
C1—C11 | 1.418 (3) | C121—H122 | 0.9700 |
C2—C3 | 1.401 (3) | C131—H132 | 0.9700 |
C3—C4 | 1.352 (3) | C131—H131 | 0.9700 |
C4—C12 | 1.403 (3) | C151—H151 | 0.9700 |
C5—C13 | 1.414 (3) | C151—H152 | 0.9700 |
C5—C6 | 1.350 (4) | C161—H162 | 0.9600 |
C6—C7 | 1.400 (3) | C161—H163 | 0.9600 |
C7—C8 | 1.364 (3) | C161—H161 | 0.9600 |
C8—C14 | 1.414 (3) | C171—H171 | 0.9700 |
C9—C11 | 1.445 (3) | C171—H172 | 0.9700 |
C9—C14 | 1.448 (3) | C181—H181 | 0.9600 |
C11—C12 | 1.408 (3) | C181—H182 | 0.9600 |
C13—C14 | 1.417 (3) | C181—H183 | 0.9600 |
C101—C102 | 1.520 (3) | C3A—H3A | 0.9300 |
C1—H1 | 0.9300 | C4A—H4A | 0.9300 |
C101—C111 | 1.531 (3) | C6A—H6A | 0.9300 |
O52A—S5A—C5A | 104.58 (10) | H211—C21—H212 | 109.00 |
O53A—S5A—C5A | 106.86 (9) | N141—C131—C121 | 113.62 (16) |
O51A—S5A—C5A | 106.33 (9) | N141—C151—C161 | 113.58 (19) |
O51A—S5A—O52A | 111.87 (10) | N141—C171—C181 | 113.63 (19) |
O51A—S5A—O53A | 113.53 (11) | C102—C101—H101 | 109.00 |
O52A—S5A—O53A | 112.89 (11) | C111—C101—H101 | 109.00 |
C2—O2—C21 | 117.64 (19) | N91—C101—H101 | 109.00 |
C2A—O2A—H2A | 100.6 (16) | C2A—C1A—C6A | 118.43 (17) |
H11W—O1W—H12W | 119 (3) | C2A—C1A—C7A | 121.87 (17) |
H21W—O2W—H22W | 107 (3) | C6A—C1A—C7A | 119.70 (17) |
C12—N10—C13 | 122.91 (18) | H102—C102—H103 | 109.00 |
C9—N91—C101 | 131.19 (17) | C101—C102—H104 | 109.00 |
C12—N10—H10 | 116.3 (19) | C101—C102—H103 | 109.00 |
C13—N10—H10 | 120.8 (19) | C101—C102—H102 | 109.00 |
C131—N141—C171 | 111.96 (16) | H103—C102—H104 | 110.00 |
C131—N141—C151 | 111.23 (17) | H102—C102—H104 | 109.00 |
C151—N141—C171 | 114.21 (19) | O2A—C2A—C3A | 118.41 (18) |
C9—N91—H91 | 120.0 (13) | O2A—C2A—C1A | 121.62 (17) |
C101—N91—H91 | 108.3 (13) | C1A—C2A—C3A | 119.97 (17) |
C131—N141—H141 | 105.2 (13) | C2A—C3A—C4A | 120.28 (18) |
C171—N141—H141 | 103.1 (13) | C3A—C4A—C5A | 120.65 (18) |
C151—N141—H141 | 110.4 (13) | S5A—C5A—C4A | 120.97 (14) |
C2—C1—C11 | 120.78 (18) | C4A—C5A—C6A | 118.94 (17) |
O2—C2—C1 | 125.11 (19) | S5A—C5A—C6A | 120.05 (14) |
O2—C2—C3 | 114.33 (18) | C1A—C6A—C5A | 121.67 (18) |
C1—C2—C3 | 120.55 (19) | O72A—C7A—C1A | 117.29 (18) |
C2—C3—C4 | 120.19 (19) | O71A—C7A—C1A | 119.63 (19) |
C3—C4—C12 | 120.39 (19) | O71A—C7A—O72A | 123.1 (2) |
C6—C5—C13 | 119.6 (2) | C101—C111—H112 | 109.00 |
Cl6—C6—C5 | 120.61 (17) | C101—C111—H111 | 108.00 |
Cl6—C6—C7 | 117.8 (2) | H111—C111—H112 | 108.00 |
C5—C6—C7 | 121.6 (2) | C121—C111—H112 | 109.00 |
C6—C7—C8 | 119.3 (3) | C121—C111—H111 | 109.00 |
C7—C8—C14 | 122.0 (2) | C131—C121—H122 | 110.00 |
N91—C9—C14 | 123.69 (19) | C111—C121—H122 | 110.00 |
C11—C9—C14 | 117.71 (17) | C111—C121—H121 | 110.00 |
N91—C9—C11 | 118.61 (17) | H121—C121—H122 | 108.00 |
C9—C11—C12 | 119.23 (17) | C131—C121—H121 | 110.00 |
C1—C11—C12 | 117.35 (18) | C121—C131—H132 | 109.00 |
C1—C11—C9 | 123.27 (17) | C121—C131—H131 | 109.00 |
N10—C12—C11 | 120.01 (19) | N141—C131—H132 | 109.00 |
C4—C12—C11 | 120.73 (19) | H131—C131—H132 | 108.00 |
N10—C12—C4 | 119.24 (18) | N141—C131—H131 | 109.00 |
N10—C13—C5 | 118.87 (19) | H151—C151—H152 | 108.00 |
N10—C13—C14 | 120.69 (18) | C161—C151—H151 | 109.00 |
C5—C13—C14 | 120.4 (2) | N141—C151—H151 | 109.00 |
C8—C14—C9 | 124.53 (18) | N141—C151—H152 | 109.00 |
C8—C14—C13 | 116.87 (17) | C161—C151—H152 | 109.00 |
C9—C14—C13 | 118.52 (18) | H161—C161—H162 | 109.00 |
N91—C101—C111 | 109.15 (16) | C151—C161—H162 | 109.00 |
C102—C101—C111 | 110.28 (16) | C151—C161—H161 | 109.00 |
C11—C1—H1 | 120.00 | H162—C161—H163 | 109.00 |
N91—C101—C102 | 110.55 (16) | H161—C161—H163 | 110.00 |
C2—C1—H1 | 120.00 | C151—C161—H163 | 109.00 |
C2—C3—H3 | 120.00 | C181—C171—H172 | 109.00 |
C4—C3—H3 | 120.00 | N141—C171—H172 | 109.00 |
C12—C4—H4 | 120.00 | H171—C171—H172 | 108.00 |
C3—C4—H4 | 120.00 | C181—C171—H171 | 109.00 |
C6—C5—H5 | 120.00 | N141—C171—H171 | 109.00 |
C13—C5—H5 | 120.00 | C171—C181—H183 | 109.00 |
C6—C7—H7 | 120.00 | C171—C181—H181 | 109.00 |
C8—C7—H7 | 120.00 | C171—C181—H182 | 109.00 |
C7—C8—H8 | 119.00 | H182—C181—H183 | 109.00 |
C14—C8—H8 | 119.00 | H181—C181—H183 | 109.00 |
C101—C111—C121 | 114.90 (16) | H181—C181—H182 | 110.00 |
O2—C21—H212 | 110.00 | C4A—C3A—H3A | 120.00 |
H212—C21—H213 | 109.00 | C2A—C3A—H3A | 120.00 |
C111—C121—C131 | 109.66 (16) | C3A—C4A—H4A | 120.00 |
H211—C21—H213 | 110.00 | C5A—C4A—H4A | 120.00 |
O2—C21—H211 | 109.00 | C5A—C6A—H6A | 119.00 |
O2—C21—H213 | 109.00 | C1A—C6A—H6A | 119.00 |
O52A—S5A—C5A—C4A | −58.41 (19) | Cl6—C6—C7—C8 | −178.98 (16) |
O53A—S5A—C5A—C4A | −178.33 (17) | C6—C7—C8—C14 | 0.9 (3) |
O51A—S5A—C5A—C6A | −122.24 (17) | C7—C8—C14—C13 | −4.0 (3) |
O52A—S5A—C5A—C6A | 119.25 (18) | C7—C8—C14—C9 | 179.25 (19) |
O53A—S5A—C5A—C6A | −0.7 (2) | C14—C9—C11—C12 | 10.2 (3) |
O51A—S5A—C5A—C4A | 60.10 (19) | N91—C9—C11—C1 | 5.5 (3) |
C21—O2—C2—C3 | 170.4 (2) | N91—C9—C11—C12 | −169.92 (18) |
C21—O2—C2—C1 | −10.0 (3) | C14—C9—C11—C1 | −174.41 (18) |
C12—N10—C13—C14 | 5.0 (3) | N91—C9—C14—C8 | −12.8 (3) |
C13—N10—C12—C4 | 177.11 (19) | N91—C9—C14—C13 | 170.54 (18) |
C13—N10—C12—C11 | −4.4 (3) | C11—C9—C14—C8 | 167.09 (18) |
C12—N10—C13—C5 | −174.21 (19) | C11—C9—C14—C13 | −9.6 (3) |
C9—N91—C101—C111 | −125.0 (2) | C9—C11—C12—C4 | 174.99 (18) |
C101—N91—C9—C11 | 157.06 (19) | C1—C11—C12—C4 | −0.7 (3) |
C101—N91—C9—C14 | −23.1 (3) | C9—C11—C12—N10 | −3.4 (3) |
C9—N91—C101—C102 | 113.6 (2) | C1—C11—C12—N10 | −179.10 (18) |
C9—N91—C101—C111 | −125.0 (2) | N10—C13—C14—C8 | −174.69 (18) |
N91—C101—C111—C121 | 62.6 (2) | C5—C13—C14—C9 | −178.53 (18) |
C101—C111—C121—C131 | 175.79 (16) | N10—C13—C14—C9 | 2.2 (3) |
C111—C121—C131—N141 | −170.13 (16) | C5—C13—C14—C8 | 4.6 (3) |
C121—C131—N141—C151 | 163.03 (18) | C2A—C1A—C7A—O71A | −175.0 (2) |
C121—C131—N141—C171 | −67.9 (2) | C2A—C1A—C7A—O72A | 3.6 (3) |
C131—N141—C151—C161 | 67.4 (3) | C6A—C1A—C7A—O71A | 6.0 (3) |
C131—N141—C171—C181 | 175.61 (19) | C6A—C1A—C7A—O72A | −175.40 (19) |
C2—C1—C11—C9 | −175.11 (19) | C7A—C1A—C2A—O2A | −0.4 (3) |
C11—C1—C2—O2 | −179.66 (19) | C7A—C1A—C2A—C3A | 178.50 (19) |
C11—C1—C2—C3 | −0.1 (3) | C2A—C1A—C6A—C5A | 0.7 (3) |
C2—C1—C11—C12 | 0.4 (3) | C7A—C1A—C6A—C5A | 179.74 (19) |
C1—C2—C3—C4 | 0.1 (3) | C6A—C1A—C2A—O2A | 178.64 (19) |
O2—C2—C3—C4 | 179.73 (19) | C6A—C1A—C2A—C3A | −2.5 (3) |
C2—C3—C4—C12 | −0.4 (3) | O2A—C2A—C3A—C4A | −178.77 (19) |
C3—C4—C12—C11 | 0.7 (3) | C1A—C2A—C3A—C4A | 2.3 (3) |
C3—C4—C12—N10 | 179.16 (19) | C2A—C3A—C4A—C5A | −0.3 (3) |
C13—C5—C6—Cl6 | 179.58 (15) | C3A—C4A—C5A—C6A | −1.5 (3) |
C6—C5—C13—C14 | −2.0 (3) | C3A—C4A—C5A—S5A | 176.24 (16) |
C13—C5—C6—C7 | −1.3 (3) | S5A—C5A—C6A—C1A | −176.46 (16) |
C6—C5—C13—N10 | 177.24 (19) | C4A—C5A—C6A—C1A | 1.3 (3) |
C5—C6—C7—C8 | 1.9 (3) |
D—H···A | D—H | H···A | D···A | D—H···A |
O2A—H2A···O72A | 0.92 (3) | 1.69 (3) | 2.554 (2) | 156 (3) |
N10—H10···O71Ai | 0.90 (3) | 2.49 (2) | 3.178 (2) | 134 (2) |
N10—H10···O72Ai | 0.90 (3) | 1.94 (3) | 2.825 (3) | 168 (2) |
N91—H91···O2W | 0.90 (2) | 2.00 (2) | 2.869 (2) | 163.6 (19) |
N141—H141···O1W | 0.91 (2) | 1.80 (2) | 2.700 (3) | 173.3 (19) |
O1W—H11W···O71A | 0.77 (3) | 1.97 (3) | 2.740 (3) | 179 (3) |
O1W—H12W···O51Aii | 0.83 (3) | 1.95 (3) | 2.770 (3) | 172 (3) |
O2W—H21W···O71Aiii | 0.89 (3) | 1.88 (3) | 2.759 (2) | 170 (3) |
O2W—H22W···O52Aiv | 0.88 (3) | 1.87 (3) | 2.744 (2) | 175 (3) |
C1—H1···O2W | 0.93 | 2.34 | 3.248 (3) | 166 |
C6A—H6A···O53A | 0.93 | 2.48 | 2.879 (2) | 106 |
Symmetry codes: (i) −x+2, −y+2, −z+2; (ii) x+1/2, −y+3/2, z+1/2; (iii) x, y, z−1; (iv) x+1/2, −y+3/2, z−1/2. |
Experimental details
Crystal data | |
Chemical formula | C23H32ClN3O2+·C7H4O6S2−·2H2O |
Mr | 654.17 |
Crystal system, space group | Monoclinic, P21/n |
Temperature (K) | 297 |
a, b, c (Å) | 10.1753 (3), 30.8461 (7), 10.3671 (2) |
β (°) | 99.966 (3) |
V (Å3) | 3204.81 (14) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.24 |
Crystal size (mm) | 0.20 × 0.20 × 0.15 |
Data collection | |
Diffractometer | Oxford Diffraction Gemini-S Ultra CCD detector diffractometer |
Absorption correction | Multi-scan (SADABS; Sheldrick, 1996) |
Tmin, Tmax | 0.906, 0.960 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 29865, 5455, 3568 |
Rint | 0.049 |
(sin θ/λ)max (Å−1) | 0.595 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.040, 0.100, 0.99 |
No. of reflections | 5455 |
No. of parameters | 433 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.26, −0.26 |
Computer programs: CrysAlis CCD (Oxford Diffraction, 2008), CrysAlis RED (Oxford Diffraction, 2008), SIR92 (Altomare et al., 1994), SHELXL97 (Sheldrick, 2008), PLATON (Spek, 2003).
D—H···A | D—H | H···A | D···A | D—H···A |
O2A—H2A···O72A | 0.92 (3) | 1.69 (3) | 2.554 (2) | 156 (3) |
N10—H10···O71Ai | 0.90 (3) | 2.49 (2) | 3.178 (2) | 134 (2) |
N10—H10···O72Ai | 0.90 (3) | 1.94 (3) | 2.825 (3) | 168 (2) |
N91—H91···O2W | 0.90 (2) | 2.00 (2) | 2.869 (2) | 163.6 (19) |
N141—H141···O1W | 0.91 (2) | 1.80 (2) | 2.700 (3) | 173.3 (19) |
O1W—H11W···O71A | 0.77 (3) | 1.97 (3) | 2.740 (3) | 179 (3) |
O1W—H12W···O51Aii | 0.83 (3) | 1.95 (3) | 2.770 (3) | 172 (3) |
O2W—H21W···O71Aiii | 0.89 (3) | 1.88 (3) | 2.759 (2) | 170 (3) |
O2W—H22W···O52Aiv | 0.88 (3) | 1.87 (3) | 2.744 (2) | 175 (3) |
Symmetry codes: (i) −x+2, −y+2, −z+2; (ii) x+1/2, −y+3/2, z+1/2; (iii) x, y, z−1; (iv) x+1/2, −y+3/2, z−1/2. |
Torsion angle (°) | (I) | Quinacrinium dichloride dihydrate |
C11–C9–N91–C101 | 157.06 (19) | 174.4 (5) |
C9–N91–C101–C111 | -125.0 (2) | -142.9 (6) |
N91–C101–C111–C121 | 62.6 (2) | 64.4 (5) |
C101–C111–C121–C131 | 175.79 (16) | 172.8 (4) |
C111–C121–C131–N141 | -170.13 (16) | -165.3 (4) |
C121–C131–N141–C151 | 163.03 (18) | 64.7 (5) |
C121–C131–N141–C171 | -67.9 (2) | -66.1 (6) |
C131–N141–C151–C161 | 67.4 (2) | 55.7 (8) |
C131–N141–C171–C181 | 175.61 (19) | -147.1 (8) |
Quinacrine [N'-(6-chloro-2-methoxyacridin-9-yl)-N,N-diethylpentane-1,4-diamine] was synthesized in 1931 by Bayer [Is a reference or patent available?] and, as the dihydrochloride dehydrate (atabrine, mepacrine), introduced as a drug which was the first alternative to quinine for the treatment of malaria and other parasite-borne diseases (e.g. Chaga's disease, giardiasis). Its use in the treatment of malaria has largely been superceded by chloroquine, which has fewer of the undesirable adverse physiological side effects of quinacrine, e.g. aplastic anaemia and hyperpigmentation (Wilson et al., 1991). However, its more recent experimental and sometimes controversial uses include the possible treatment of Creutzfeldt–Jacob disease, where it has been found to inhibit the accumulation of pathogenic prion protein in cultured neuroblastoma cells (Doh-Ura et al., 2000), and for non-surgical female sterilization (Zipper et al., 1980). The crystal structure of the Trypanosoma cruzi trypanothione reducatase (TR) complex with quinacrine (Jacobi et al., 1996) showed that specific sites on the acridine ring system (the hetero N, C2 methoxy O and C6 chloro substituent groups), as well as the two amino groups of the C9 substituent side chain, are fixed at active sites of the TR enzyme.
The crystal structure of racemic atabrine (quinacrine dihydrochloride dihydrate; Courseille et al., 1973) showed the molecule to be protonated at the hetero N atom of the acridine ring and at the tertiary terminal N atom of the C9 side chain. In addition, the acridine ring systems showed interactive π–π stacking effects. Considering the difficulty in obtaining good crystals of atabrine, we have prepared the salts of this base with the strong aromatic organic acids 3,5-dinitrosalicylic acid (DNSA) and 3-carboxy-4-hydroxybenzenesulfonic acid (5-sulfosalicylic acid, 5-SSA) for the purpose of crystallographic examination. This approach has been used previously by us and other research groups with reasonable success since these acids, particularly when used in their anionic forms, are recognized as useful synthons for molecular assembly achieved through hydrogen-bonding interactions involving potentially all interactive substituent functional groups. The method allows the structures of difficult-to-crystallize Lewis base compounds, such as many pharmaceuticals, to be determined.
The crystal structures have been reported of the 1:1 salts of 5-SSA with theophylline (a monohydrate; Madarasz et al., 2002), trimethoprim (a dihydrate; Raj et al., 2003), and pyrimethamine (Hemamalini et al., 2005) and brucine (Smith, Wermuth, Healy & White, 2006) (both anhydrates). With DNSA, the structures of 1:1 anhydrous salts with both brucine (Smith, Wermuth, Healy & White, 2006) and strychnine (Smith et al., 2005) are also known. With the 5-SSA anions formed in the reaction of the acid with Lewis bases, all of the substituent groups provide hydrogen-bonding donor or acceptor atoms with potential for both primary and secondary structure extension. In some examples, particularly those salts with polycyclic heteroaromatic amines (Smith, Wermuth & White, 2004), the structures feature anion–anion or anion–cation π–π interactions. We obtained good crystals of the atabrine salt with 5-SSA from an aqueous ethanol solution but not with the DNSA salt prepared under similar conditions.
The crystal structure of the 5-SSA salt reported here is that of racemic quinacrinium 5-sulfosalicylate dihydrate, C23H32ClN3O2+.C7H4O6S2-.2H2O, (I). The quinacrine molecule is protonated at both the acridine N (N10) and the terminal tertiary diethylamino N atom (N141), while generating a 5-SSA dianion by deprotonation of both the sulfonic acid and carboxylic acid groups. Dianionic 5-SSA anions are not common among the known structures in the crystallographic literature but some are known, e.g. the salts with guanidine (Smith, Wermuth & Healy, 2004), benzylamine (Smith, Wermuth & Healy, 2006), 2-aminopyridine (Yang & Qu, 2006) and piperazine (Su & Li, 2007).
In the asymmetric unit of (I) (Fig. 1), the dication has primary hydrogen-bonding interactions involving the protonated tertiary amine N atom (N141) and one of the water molecules (O1W), as well as the secondary amine N atom (N91) and the second water molecule (O2W), while the H atom of the acridinium N atom is involved in secondary interactions with a carboxyl group of the 5-SSA dianion [cyclic three-centre asymmetric, graph set R21(4) (Etter et al., 1990)] (Table 1). Other secondary inter-species hydrogen bonds generate a three-dimensional framework structure (Fig. 2), which is also found in the structure of quinacrinium chloride dihydrate (Courseille et al., 1973). However, in that structure, the acridinium H atom has a primary interaction with one of the chloride anions, which is in turn associated with the solvent water molecules in structure extension. Conformationally the two structures are similar, with the C91 side chain adopting a comparable perpendicular attitude with respect to the acridine ring (Table 2), which is also the case in the structures of other C9 extended-chain-substituted 6-chloro-2-methoxyacridines, e.g. in the anti-tumour acridine analogues (Berman & Glusker, 1972; Carrell, 1972; Glusker et al., 1972). The only major difference between (I) and the dichloride is found, not unexpectedly, within the terminal diethylamino group. Also in (I) there are no cation–cation or cation–anion aromatic ring π–π interactions, which are present in the structure of the hydrochloride [minimum centroid separation of the inversion-related six-membered rings N10–C13 and C5–C15 = 4.1834 (13) Å].
With the 5-SSA anion species for (I), similar structural and conformational features to those previously observed (Smith, Wermuth & White, 2004) are found. The usual intramolecular Ophenolic—H···Ocarboxyl hydrogen bond is found [series range 2.598 (3)–2.625 (2) Å], giving essentially coplanarity of the carboxylic acid group and the benzene ring [torsion angle C2—C1—C7—O71 = -175.0 (2)°]. In addition, the common aromatic C6A—H6A···O52Asulfonate interaction [2.879 (2) Å] is present. It may be concluded that the chemically stable and structurally similar 5-sulfosalicylate salt of quinacrine, (I), could be considered a possible alternative to atabrine as a drug.