Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270102008089/sk1549sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S0108270102008089/sk1549IIsup2.hkl |
CCDC reference: 188629
A stirred solution of 9-chloro-1-methyl-1H-imidazo[5,4-f]quinoline (0.35 g, 1.5 mmol), prepared previously (Milata, 2001), and solid NaOH (0.15 g) was hydrogenated at 120 kPa on Raney nickel until the theoretical amount of hydrogen (60 ml) was consumed. The catalyst was filtered off, and the filtrate was neutralized with 10% HCl and purified by column chromatography (silica gel, chloroform-methanol 10:1). Crystallization from ethanol-water (2:1) afforded the title compound, (II) (yield 40%, m.p. 601–603 K).
Although all the H atoms were seen in a difference Fourier map, they were refined with fixed geometry (C—H = 0.93–0.96 Å and N—H = 0.86 Å) riding on their carrier atoms, with Uiso(H) set to 1.2 (1.5 for the methyl H atoms) times Ueq of the parent atom, except for the water H atoms, the coordinates of which were kept fixed at their experimentally found values, with Uiso equal to 1.2Ueq of the O(W) atom.
Data collection: Syntex software (Syntex, 1973); cell refinement: Syntex software; data reduction: XP21 (Pavelčík, 1987); program(s) used to solve structure: SHELXS97 (Sheldrick, 1990); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEPII (Johnson, 1976); software used to prepare material for publication: SHELXL97.
Fig. 1. A view of the cation of (II) showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 35% probability level and H atoms are shown as small circles of arbitrary radii. |
C11H10N3+·Cl−·H2O | Z = 2 |
Mr = 237.69 | F(000) = 248 |
Triclinic, P1 | Dx = 1.448 Mg m−3 Dm = 1.45 (1) Mg m−3 Dm measured by flotation in bromoform/c-hexane |
Hall symbol: -P 1 | Melting point: 602 K |
a = 7.544 (5) Å | Mo Kα radiation, λ = 0.71073 Å |
b = 9.084 (6) Å | Cell parameters from 15 reflections |
c = 9.152 (8) Å | θ = 8–22° |
α = 72.65 (6)° | µ = 0.33 mm−1 |
β = 66.61 (5)° | T = 293 K |
γ = 76.96 (7)° | Prism, colourless |
V = 545.3 (7) Å3 | 0.35 × 0.30 × 0.20 mm |
Syntex P21 diffractometer | Rint = 0.000 |
Radiation source: fine-focus sealed tube | θmax = 27.6°, θmin = 2.4° |
Graphite monochromator | h = 0→9 |
θ/2θ scans | k = −11→11 |
2511 measured reflections | l = −10→11 |
2511 independent reflections | 2 standard reflections every 98 reflections |
1197 reflections with I > 2σ(I) | intensity decay: 2% |
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)] = 0.070 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.201 | H atoms treated by a mixture of independent and constrained refinement |
S = 0.92 | w = 1/[σ2(Fo2) + (0.1128P)2] where P = (Fo2 + 2Fc2)/3 |
2511 reflections | (Δ/σ)max = 0.002 |
146 parameters | Δρmax = 0.34 e Å−3 |
0 restraints | Δρmin = −0.44 e Å−3 |
C11H10N3+·Cl−·H2O | γ = 76.96 (7)° |
Mr = 237.69 | V = 545.3 (7) Å3 |
Triclinic, P1 | Z = 2 |
a = 7.544 (5) Å | Mo Kα radiation |
b = 9.084 (6) Å | µ = 0.33 mm−1 |
c = 9.152 (8) Å | T = 293 K |
α = 72.65 (6)° | 0.35 × 0.30 × 0.20 mm |
β = 66.61 (5)° |
Syntex P21 diffractometer | Rint = 0.000 |
2511 measured reflections | 2 standard reflections every 98 reflections |
2511 independent reflections | intensity decay: 2% |
1197 reflections with I > 2σ(I) |
R[F2 > 2σ(F2)] = 0.070 | 0 restraints |
wR(F2) = 0.201 | H atoms treated by a mixture of independent and constrained refinement |
S = 0.92 | Δρmax = 0.34 e Å−3 |
2511 reflections | Δρmin = −0.44 e Å−3 |
146 parameters |
x | y | z | Uiso*/Ueq | ||
N1 | 0.0186 (5) | −0.3262 (4) | 1.2599 (4) | 0.0416 (8) | |
C1 | 0.0797 (7) | −0.4649 (5) | 1.1981 (5) | 0.0516 (11) | |
H1A | 0.0101 | −0.5475 | 1.2785 | 0.077* | |
H1B | 0.2168 | −0.4942 | 1.1753 | 0.077* | |
H1C | 0.0529 | −0.4456 | 1.0994 | 0.077* | |
C2 | −0.1204 (6) | −0.3133 (6) | 1.4065 (5) | 0.0509 (11) | |
H2 | −0.1892 | −0.3948 | 1.4789 | 0.061* | |
N3 | −0.1499 (5) | −0.1772 (5) | 1.4376 (4) | 0.0522 (10) | |
C4 | 0.0093 (6) | 0.0611 (5) | 1.2689 (5) | 0.0476 (11) | |
H4 | −0.0600 | 0.1205 | 1.3457 | 0.057* | |
C5 | 0.1396 (6) | 0.1237 (5) | 1.1234 (5) | 0.0420 (10) | |
H5 | 0.1604 | 0.2266 | 1.0999 | 0.050* | |
N6 | 0.3736 (5) | 0.0998 (4) | 0.8600 (4) | 0.0409 (8) | |
H6 | 0.3878 | 0.1958 | 0.8414 | 0.049* | |
C7 | 0.4771 (6) | 0.0241 (5) | 0.7462 (5) | 0.0462 (10) | |
H7 | 0.5616 | 0.0754 | 0.6476 | 0.055* | |
C8 | 0.4630 (6) | −0.1304 (5) | 0.7697 (5) | 0.0479 (11) | |
H8 | 0.5374 | −0.1836 | 0.6883 | 0.057* | |
C9 | 0.3384 (6) | −0.2035 (5) | 0.9142 (5) | 0.0402 (9) | |
H9 | 0.3292 | −0.3083 | 0.9325 | 0.048* | |
C10 | −0.0204 (5) | −0.0939 (5) | 1.3028 (5) | 0.0381 (9) | |
C11 | 0.2439 (5) | 0.0340 (4) | 1.0074 (5) | 0.0383 (9) | |
C12 | 0.2238 (5) | −0.1231 (4) | 1.0360 (4) | 0.0342 (9) | |
C13 | 0.0850 (5) | −0.1829 (4) | 1.1890 (5) | 0.0351 (9) | |
Cl | 0.43405 (18) | 0.43774 (13) | 0.80011 (14) | 0.0563 (4) | |
W | 0.3008 (5) | 0.6826 (4) | 0.5189 (4) | 0.0737 (11) | |
H1W | 0.3750 | 0.6300 | 0.4340 | 0.110* | |
H2W | 0.3350 | 0.6050 | 0.6030 | 0.110* |
U11 | U22 | U33 | U12 | U13 | U23 | |
N1 | 0.0397 (18) | 0.049 (2) | 0.0349 (18) | −0.0092 (15) | −0.0120 (15) | −0.0062 (15) |
C1 | 0.058 (3) | 0.043 (2) | 0.050 (3) | −0.014 (2) | −0.018 (2) | −0.001 (2) |
C2 | 0.038 (2) | 0.066 (3) | 0.042 (2) | −0.008 (2) | −0.0124 (19) | −0.004 (2) |
N3 | 0.046 (2) | 0.069 (3) | 0.0365 (19) | −0.0080 (19) | −0.0100 (17) | −0.0122 (18) |
C4 | 0.049 (3) | 0.055 (3) | 0.045 (2) | 0.006 (2) | −0.019 (2) | −0.026 (2) |
C5 | 0.044 (2) | 0.040 (2) | 0.049 (2) | −0.0063 (18) | −0.022 (2) | −0.0129 (19) |
N6 | 0.0433 (19) | 0.0377 (18) | 0.0437 (19) | −0.0109 (15) | −0.0199 (16) | −0.0019 (15) |
C7 | 0.040 (2) | 0.054 (3) | 0.040 (2) | −0.012 (2) | −0.0113 (19) | −0.003 (2) |
C8 | 0.040 (2) | 0.060 (3) | 0.043 (2) | −0.003 (2) | −0.012 (2) | −0.018 (2) |
C9 | 0.041 (2) | 0.040 (2) | 0.043 (2) | −0.0054 (18) | −0.0155 (19) | −0.0124 (17) |
C10 | 0.037 (2) | 0.049 (2) | 0.034 (2) | −0.0016 (18) | −0.0192 (17) | −0.0112 (18) |
C11 | 0.035 (2) | 0.045 (2) | 0.040 (2) | −0.0058 (17) | −0.0192 (18) | −0.0084 (18) |
C12 | 0.034 (2) | 0.041 (2) | 0.034 (2) | −0.0046 (16) | −0.0195 (17) | −0.0078 (17) |
C13 | 0.033 (2) | 0.040 (2) | 0.038 (2) | −0.0061 (16) | −0.0179 (17) | −0.0087 (16) |
Cl | 0.0733 (8) | 0.0456 (6) | 0.0580 (7) | −0.0087 (5) | −0.0298 (6) | −0.0135 (5) |
W | 0.076 (2) | 0.059 (2) | 0.065 (2) | 0.0032 (18) | −0.0143 (19) | −0.0075 (17) |
N1—C2 | 1.355 (5) | N6—C7 | 1.307 (5) |
N1—C13 | 1.378 (5) | N6—C11 | 1.367 (5) |
N1—C1 | 1.441 (5) | N6—H6 | 0.8600 |
C1—H1A | 0.9600 | C7—C8 | 1.377 (6) |
C1—H1B | 0.9600 | C7—H7 | 0.9300 |
C1—H1C | 0.9600 | C8—C9 | 1.358 (6) |
C2—N3 | 1.302 (6) | C8—H8 | 0.9300 |
C2—H2 | 0.9300 | C9—C12 | 1.400 (5) |
N3—C10 | 1.367 (5) | C9—H9 | 0.9300 |
C4—C5 | 1.351 (6) | C10—C13 | 1.387 (5) |
C4—C10 | 1.399 (6) | C11—C12 | 1.404 (5) |
C4—H4 | 0.9300 | C12—C13 | 1.411 (5) |
C5—C11 | 1.405 (5) | W—H1W | 0.9488 |
C5—H5 | 0.9300 | W—H2W | 0.9530 |
C2—N1—C13 | 105.6 (4) | N6—C7—C8 | 121.1 (4) |
C2—N1—C1 | 125.1 (4) | N6—C7—H7 | 119.4 |
C13—N1—C1 | 129.3 (3) | C8—C7—H7 | 119.4 |
N1—C1—H1A | 109.5 | C9—C8—C7 | 118.7 (4) |
N1—C1—H1B | 109.5 | C9—C8—H8 | 120.7 |
H1A—C1—H1B | 109.5 | C7—C8—H8 | 120.7 |
N1—C1—H1C | 109.5 | C8—C9—C12 | 120.8 (4) |
H1A—C1—H1C | 109.5 | C8—C9—H9 | 119.6 |
H1B—C1—H1C | 109.5 | C12—C9—H9 | 119.6 |
N3—C2—N1 | 114.4 (4) | N3—C10—C13 | 110.9 (4) |
N3—C2—H2 | 122.8 | N3—C10—C4 | 128.8 (4) |
N1—C2—H2 | 122.8 | C13—C10—C4 | 120.3 (4) |
C2—N3—C10 | 104.0 (3) | N6—C11—C12 | 117.5 (4) |
C5—C4—C10 | 119.3 (4) | N6—C11—C5 | 119.5 (4) |
C5—C4—H4 | 120.4 | C12—C11—C5 | 123.0 (4) |
C10—C4—H4 | 120.4 | C9—C12—C11 | 118.6 (4) |
C4—C5—C11 | 120.3 (4) | C9—C12—C13 | 126.8 (4) |
C4—C5—H5 | 119.8 | C11—C12—C13 | 114.6 (3) |
C11—C5—H5 | 119.8 | N1—C13—C10 | 105.0 (3) |
C7—N6—C11 | 123.2 (4) | N1—C13—C12 | 132.5 (4) |
C7—N6—H6 | 118.4 | C10—C13—C12 | 122.5 (4) |
C11—N6—H6 | 118.4 | H1W—W—H2W | 95.6 |
C13—N1—C2—N3 | −0.3 (5) | N6—C11—C12—C9 | 0.8 (5) |
C1—N1—C2—N3 | 179.2 (4) | C5—C11—C12—C9 | −178.2 (4) |
N1—C2—N3—C10 | −0.5 (5) | N6—C11—C12—C13 | −178.8 (3) |
C10—C4—C5—C11 | 0.1 (6) | C5—C11—C12—C13 | 2.2 (5) |
C11—N6—C7—C8 | −1.0 (6) | C2—N1—C13—C10 | 0.9 (4) |
N6—C7—C8—C9 | 0.2 (6) | C1—N1—C13—C10 | −178.5 (4) |
C7—C8—C9—C12 | 1.1 (6) | C2—N1—C13—C12 | −177.9 (4) |
C2—N3—C10—C13 | 1.1 (5) | C1—N1—C13—C12 | 2.8 (7) |
C2—N3—C10—C4 | 178.8 (4) | N3—C10—C13—N1 | −1.2 (4) |
C5—C4—C10—N3 | −176.7 (4) | C4—C10—C13—N1 | −179.2 (4) |
C5—C4—C10—C13 | 0.9 (6) | N3—C10—C13—C12 | 177.7 (3) |
C7—N6—C11—C12 | 0.5 (6) | C4—C10—C13—C12 | −0.3 (6) |
C7—N6—C11—C5 | 179.5 (4) | C9—C12—C13—N1 | −2.2 (7) |
C4—C5—C11—N6 | 179.3 (4) | C11—C12—C13—N1 | 177.4 (4) |
C4—C5—C11—C12 | −1.7 (6) | C9—C12—C13—C10 | 179.3 (4) |
C8—C9—C12—C11 | −1.6 (6) | C11—C12—C13—C10 | −1.1 (5) |
C8—C9—C12—C13 | 178.0 (4) |
Experimental details
Crystal data | |
Chemical formula | C11H10N3+·Cl−·H2O |
Mr | 237.69 |
Crystal system, space group | Triclinic, P1 |
Temperature (K) | 293 |
a, b, c (Å) | 7.544 (5), 9.084 (6), 9.152 (8) |
α, β, γ (°) | 72.65 (6), 66.61 (5), 76.96 (7) |
V (Å3) | 545.3 (7) |
Z | 2 |
Radiation type | Mo Kα |
µ (mm−1) | 0.33 |
Crystal size (mm) | 0.35 × 0.30 × 0.20 |
Data collection | |
Diffractometer | Syntex P21 diffractometer |
Absorption correction | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 2511, 2511, 1197 |
Rint | 0.000 |
(sin θ/λ)max (Å−1) | 0.651 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.070, 0.201, 0.92 |
No. of reflections | 2511 |
No. of parameters | 146 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.34, −0.44 |
Computer programs: Syntex software (Syntex, 1973), Syntex software, XP21 (Pavelčík, 1987), SHELXS97 (Sheldrick, 1990), SHELXL97 (Sheldrick, 1997), ORTEPII (Johnson, 1976), SHELXL97.
N1—C2 | 1.355 (5) | N6—C7 | 1.307 (5) |
N1—C13 | 1.378 (5) | N6—C11 | 1.367 (5) |
N1—C1 | 1.441 (5) | C7—C8 | 1.377 (6) |
C2—N3 | 1.302 (6) | C8—C9 | 1.358 (6) |
N3—C10 | 1.367 (5) | C9—C12 | 1.400 (5) |
C4—C5 | 1.351 (6) | C10—C13 | 1.387 (5) |
C4—C10 | 1.399 (6) | C11—C12 | 1.404 (5) |
C5—C11 | 1.405 (5) | C12—C13 | 1.411 (5) |
C2—N1—C13 | 105.6 (4) | N3—C10—C4 | 128.8 (4) |
C2—N1—C1 | 125.1 (4) | C13—C10—C4 | 120.3 (4) |
C13—N1—C1 | 129.3 (3) | N6—C11—C12 | 117.5 (4) |
N3—C2—N1 | 114.4 (4) | N6—C11—C5 | 119.5 (4) |
C2—N3—C10 | 104.0 (3) | C12—C11—C5 | 123.0 (4) |
C5—C4—C10 | 119.3 (4) | C9—C12—C11 | 118.6 (4) |
C4—C5—C11 | 120.3 (4) | C9—C12—C13 | 126.8 (4) |
C7—N6—C11 | 123.2 (4) | C11—C12—C13 | 114.6 (3) |
N6—C7—C8 | 121.1 (4) | N1—C13—C10 | 105.0 (3) |
C9—C8—C7 | 118.7 (4) | N1—C13—C12 | 132.5 (4) |
C8—C9—C12 | 120.8 (4) | C10—C13—C12 | 122.5 (4) |
N3—C10—C13 | 110.9 (4) |
Imidazoquinolines, produced in cooked meats, have long been known as strong mutagens and carcinogens (Nagao et al., 1977; Weissberger & Taylor, 1981). On the other hand, in the last few years some derivatives incorporating the imidazoquinoline nucleus have been reported to possess antimutagenic/antitumour activity (Lankaputhra & Shah, 1998; Bishop et al., 2001). It is obvious that the mutagenicity/antimutagenicity depends sensitively on the substitution pattern of the imidazoquinoline nucleus; for example, 2-amino-3-methylimidazo[4,5-f]quinolines are typical mutagens, while removal of the 2-amino group and substitution on the pyridine-fused ring promotes antimutagenic activity. It is, however, unclear whether the influence of the substituents reflects their effect on the charge distribution of the heterocyclic ring (and hence determines the orientation of the molecule in the DNA intercalation site) or results from interaction of the substituents with minor groove functionalities of DNA. Thus, detailed information on the three-dimensional and electronic structures of these heterocycles is indispensable for an analysis of structure-function relationships.
Though highly important, there have been only a few reports on these subjects. Of the electronic characteristics, only protonation, tautomerization and valence tautomerism of selected imidazo[4,5-f]quinolines have been studied using theoretical methods in the past few years (Ögretir & Kaniskan, 1993; Milata, 2001).
Similarly, as revealed by a search of the Cambridge Structural Database (CSD, Version?; Allen & Kennard, 1993), only one crystal structure of the imidazo[4,5-f]quinoline family, namely 2-amino-3-methylimidazo[4,5-f]quinoline, (I) (Yokoyama et al., 1980), has so far been reported. Consequently, the present crystal structure determination was undertaken in order to establish the precise molecular dimensions (bond lengths) of another derivative, the title compound, (II), which is a deamino isomerically methylated analogue of (I), as the chloride monohydrate. \sch
The asymmetric part of the unit cell of (II) consists of a protonated molecule of 1-methyl-1H-imidazo[5,4-f]quinoline, one Cl- anion and one water molecule. A perspective view of the cation, along with the atom-numbering scheme, is shown in Fig. 1. The molecule as a whole (i.e. including the exocyclic methyl group) is planar within the limits of experimental error [r.m.s. deviation 0.025 (4) Å].
As can be seen in Fig.1, the first protonation has taken place at the pyridine atom N6 rather than at the imidazole N atom; this is in line with the theoretical calculations, which predicted the energy difference between the two protonated forms to be 8.7 kcal mol-1 (1 kcal mol-1 = 4.184 kJ mol-1; Ögretir & Kaniskan, 1993).
As mentioned above, the main purpose of this work was to compare the molecular dimensions of the present derivative, (II), with its 2-amino analogue, (I), in order to shed more light on the relationship between the structure and (anti)mutagenic properties of compounds incorporating the imidazoquinoline heterocycle. This comparison has shown that the corresponding bond lengths in the two molecules are equal to within experimental error, except for the C2—N3 bond distance, which is 0.035 (5) Å shorter in (II) than in (I), obviously due to conjugation of the lone pair electrons on the amine N atom with the adjacent double bond in (I). Thus, as judged from the distribution of bond lengths in molecules (I) and (II), the conjugation in (I) does not extend beyond the C═N double bond of the heterocyclic system. This means that the large difference in pharmacological properties between (I) and (II) lies in the interaction of the additional amino group with DNA functionalities, and not in the effect of the amino group on the π-electron distribution of the heterocyclic π system. These results will form the basis for subsequent quantum chemical calculations of the electronic structure and molecular modelling (docking) studies of DNA-ligand interactions.
The positive charge of the protonated molecule in (II) is neutralized by the Cl- anion, which is involved in a hydrogen bond with N6+—H [for N6—H···Cl, N6—H 0.86 Å, H···Cl 2.20 Å, N···Cl 3.060 (4) Å and N—H···Cl 177°]. The molecule of water of crystallization forms two rather weak hydrogen bonds to symmetrically related Cl- ions. Apart from these hydrogen-bond interactions, there are no other contacts substantially shorter than the sum of the van der Waals radii of the atoms concerned.