4,5-Bis(1H-imidazol-1-ylmeth­yl)acridine monohydrate

S Thenmozhi; S Ranjith; S Raja; P Rajakumar; A SubbiahPandi

doi:10.1107/S160053680903267X

. 2009 Aug 22;65(Pt 9):o2211. doi: 10.1107/S160053680903267X

4,5-Bis(1H-imidazol-1-ylmethyl)acridine monohydrate

S Thenmozhi ^a, S Ranjith ^a, S Raja ^b, P Rajakumar ^b, A SubbiahPandi ^a,^*

PMCID: PMC2969870 PMID: 21577612

Abstract

In the title compound, C₂₁H₁₇N₅·H₂O, the dihedral angles between the acridine ring system and the imidazole rings are 78.8 (1) and 71.2 (1)°. The crystal packing is stabilized by O—H⋯N, C—H⋯O, C—H⋯π and π–π interactions [centroid–centroid separations = 3.732 (1) and 3.569 (1) Å].

Related literature

For the biological activity of acridines, see: Talacki et al. (1974 ▶); Achenson (1956 ▶); Prasad Krishna et al. (1984 ▶); Asthana et al. (1991 ▶). For their antiprotozoal activity, see: Karolak-Wojciechowska et al. (1996 ▶). For the ability of acridine to intercalate between the base-pairs of DNA, see: Neidle (1979 ▶); Fan et al. (1997 ▶). For acridine compounds in the treatment of Alzheimer’s disease, see: Bandoli et al. (1994 ▶). For their toxicity, see: Di Giorgio et al. (2005 ▶).

Experimental

Crystal data

C₂₁H₁₇N₅·H₂O
M _r = 357.41
Monoclinic,
a = 14.3359 (6) Å
b = 6.9132 (3) Å
c = 17.7458 (8) Å
β = 92.895 (3)°
V = 1756.49 (13) Å³
Z = 4
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 293 K
0.25 × 0.22 × 0.19 mm

Data collection

Bruker Kappa APEXII CCD diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 1996 ▶) T _min = 0.978, T _max = 0.984
19520 measured reflections
4286 independent reflections
2652 reflections with I > 2σ(I)
R _int = 0.036

Refinement

R[F ² > 2σ(F ²)] = 0.046
wR(F ²) = 0.145
S = 1.06
4286 reflections
252 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.19 e Å⁻³
Δρ_min = −0.20 e Å⁻³

Data collection: APEX2 (Bruker, 2004 ▶); cell refinement: SAINT (Bruker, 2004 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 (Farrugia, 1997 ▶); software used to prepare material for publication: SHELXL97 and PLATON (Spek, 2009 ▶).

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S160053680903267X/bt5021sup1.cif

e-65-o2211-sup1.cif^{(21KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S160053680903267X/bt5021Isup2.hkl

e-65-o2211-Isup2.hkl^{(205.8KB, hkl)}

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C18—H18B⋯O1ⁱ	0.97	2.55	3.482 (3)	162
O1—H1A⋯N3	0.90 (3)	2.07 (3)	2.945 (3)	166 (3)
O1—H1B⋯N5ⁱⁱ	0.85 (3)	2.21 (3)	3.030 (3)	162 (3)
C7—H7⋯Cg1ⁱⁱⁱ	0.93	2.69	3.577 (2)	159
C20—H20⋯Cg1^iv	0.93	2.90	3.648 (2)	139

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) ; (iv) . Cg1 is the centroid of the N4/N5/C19–C21 ring.

Acknowledgments

ST and ASP thank Dr Babu Varghese, SAIF, IIT, Chennai, India, for the X-ray data collection.

supplementary crystallographic information

Comment

Acridines are found to have a wide range of biological activities, such as mutagenic, antitumour (Talacki et al., 1974), antibacterial (Achenson, 1956), antiamoebic (Prasad Krishna et al., 1984), hypersensitive, antiinflammatory and antiimplantation (Asthana et al., 1991) activities. A drug containing the acridine moiety has been found to possess antiprotozoal activity (Karolak-Wojciechowska et al., 1996). The ability of acridine to intercalate between the base-pairs of DNA is also well known (Neidle, 1979; Fan et al., 1997). Acridine compounds are considered to be efficient drugs for the treatment of Alzheimer's disease (Bandoli et al., 1994). Acridine derivatives have been shown to exert toxicity towards Plasmodium, Trypanosoma, and Leishmania parasites (Di Giorgio et al., 2005). The imidazole group have found a wide range of applications in coordination chemistry as ligands, in medicinal chemistry and materials science. Against this background, and in order to obtain detailed information on molecular conformations in the solid state, an X-ray study of the title compound has been carried out.

The two imidazole groups are almost parallel to each other, the dihedral angle between the mean planes being 39.5 (1)°; these planes are inclined at 78.9 (1)° and 71.2 (9)° with respect to the mean plane of the acridine system. The pseudo-torsion angle N2–C14···.C18–N4 [-145.8 (2)°], resulting in both imidazole group being approximately bisected by the plane of the acridine system. The acridine ring system and imidazole rings are essentially planar, with maximum deviations of 0.062 (3), 0.006 (2) and 0.001 (2) Å, for atoms C4, N3 and C19, respectively.

The crystal packing is stabilized by C–H···O, C–H···N, C–H···π (Table. 1) and π–π interactions with a Cg2···Cg2ⁱⁱ and a Cg4···Cg3^iv separation of 3.732 (1)Å and 3.569 (1) Å, respectively (Fig.2; Cg2, Cg3 and Cg4 are the centroids of the N2/N3/C15–C17 imidazole ring, N1/C1/C6/C7/C8/C13 pyridine ring and C8–C13 benzene ring, respectively, symmetry code as in Fig. 2).

Experimental

To a solution of imidazole, in the presence of acetonitrile (50 ml) and NaOH solution (7.5 ml) was added and stirred for 10 minutes, then 4,5-bis(bromomethyl) acridine in the presence of acetonitrile(20 ml) was added at once and stirred at room temperature for 48hrs. After completion of reaction, the solvent was evaporated in vaccum and the residue was extracted with CHCl₃(300 ml). Single crystals suitable for the X-ray diffraction were obtained by slow evaporation of a solution of the title compound in methanol at room temperature.