9-O-Ethyl­berberrubinium iodide monohydrate

Peter Grundt; Jennifer Pernat; Bogdana Krivogorsky; Melanie A Halverson; Steven M Berry

doi:10.1107/S1600536810036664

. 2010 Sep 18;66(Pt 10):o2585–o2586. doi: 10.1107/S1600536810036664

9-O-Ethylberberrubinium iodide monohydrate

Peter Grundt ^a,^*, Jennifer Pernat ^a, Bogdana Krivogorsky ^a, Melanie A Halverson ^a, Steven M Berry ^a,^*

PMCID: PMC2983369 PMID: 21587567

Abstract

In the title compound (systematic name: 9-ethoxy-10-methoxy-5,6-dihydro-1,3-dioxolo[4,5-g]isoquinolino[3,2-a]isoquinolin-7-ium iodide monohydrate), 2C₂₁H₂₀NO₄ ⁺·2I⁻·H₂O, two independent molecules pack in the unit cell, where interactions between the molecules are stabilized by weak intermolecular π–π stacking interactions [centroid–centroid distances in the range 3.571 (4) to 3.815 (4)Å]. Intermolecular C—H⋯O interactions are also observed. The iodide anions are disordered with occupancy ratios of 0.94 (1):0.06 (1) and 0.91 (1):0.09 (1). The cationic molecule is planar in structure with a small torsion resulting from the dihydropyridine ring.

Related literature

For the synthesis of the title compound, see: Iwasa et al. (1997 ▶). The title compound is a derivative of the natural product berberine. For the anti-parasitic activity of berberine and its derivatives, see: Nkwengoua et al. (2009 ▶); Acero et al. (1995 ▶); Ghosh et al. (1985 ▶); Wright et al. (2000 ▶); Iwasa et al. (1998 ▶); Sheng et al. 1997 ▶); McCall et al. (1994 ▶). For a related structure, see: Chen et al. (2009 ▶). For the Chebychev weighting scheme, see: Prince (1982 ▶); Watkin (1994 ▶).

Experimental

Crystal data

2C₂₁H₂₀NO₄ ⁺·2I⁻·H₂O
M _r = 972.61
Triclinic,
a = 11.036 (3) Å
b = 13.449 (4) Å
c = 14.086 (4) Å
α = 80.442 (6)°
β = 71.121 (5)°
γ = 76.875 (5)°
V = 1916.8 (9) Å³
Z = 2
Mo Kα radiation
μ = 1.70 mm⁻¹
T = 93 K
1.00 × 0.10 × 0.10 mm

Data collection

Rigaku R-AXIS RAPID II image plate diffractometer
Absorption correction: multi-scan (ABSCOR; Higashi, 1995 ▶) T _min = 0.469, T _max = 0.712
50086 measured reflections
8751 independent reflections
4563 reflections with I > 2.0σ(I)
R _int = 0.101

Refinement

R[F ² > 2σ(F ²)] = 0.059
wR(F ²) = 0.195
S = 0.96
8751 reflections
502 parameters
12 restraints
All H-atom parameters refined
Δρ_max = 1.75 e Å⁻³
Δρ_min = −2.26 e Å⁻³

Data collection: CrystalClear (Rigaku, 2009 ▶); cell refinement: HKL-2000 (Otwinowski & Minor, 1997 ▶); data reduction: CrystalClear; program(s) used to solve structure: CrystalStructure (Rigaku, 2009 ▶) and SIR2004 (Burla et al., 2005 ▶); program(s) used to refine structure: CRYSTALS (Betteridge et al., 2003 ▶); molecular graphics: CAMERON (Watkin et al., 1996 ▶); software used to prepare material for publication: CRYSTALS.

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536810036664/jj2056sup1.cif

e-66-o2585-sup1.cif^{(28.5KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810036664/jj2056Isup2.hkl

e-66-o2585-Isup2.hkl^{(437.5KB, 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
C9A—H10A⋯O5	0.93	2.47	3.358 (11)	159
C21B—H20B⋯O1Bⁱ	0.96	2.51	3.466 (11)	177

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Symmetry code: (i) Inline graphic .

Acknowledgments

This study was supported by the University of Minnesota Undergraduate Research Opportunities Program (UROP) and the NSF (grant CHE-0922366 for the X-ray diffractometer).

supplementary crystallographic information

Comment

The title compound, a derivative of the natural product berberine, is of interest with respect to its anti-parasite activity and biological properties Chen et al. (2009). Of particular interest is the discovery that berberine and its analogs inhibit the growth of strains of the parasites Leishmania (Nkwengoua et al., 2009, Acero et al., 1995, Ghosh et al., 1985), Trypanosoma (Nkwengoua et al., 2009), and Plasmodium (Wright et al., 2000, Iwasa et al., 1998, Sheng et al., 1997, McCall et al., 1994). Based on these findings and in our continued effort to characterize compounds that may inhibit the life cycle of the parasite Toxoplasma gondii we have synthesized the 9-ethyl analog of berberine.

The title compound, 2(C₂₁H₂₀NO₄⁺), 2(I^-), H₂O, crystallizes in the P-1 space group with two independent molecules in the unit cell. A solvent water molecule occupies the lattice at H-bonding distance from the disordered iodide (1.94 & 0.06) anions [O5—I1A 3.509 (6) and O5—I1B 3.600 (6) Å]. The compound crystallizes with a slightly twisted planar structure due to the dihydropyridine moiety, which results in torsion angles of 17.7 (5)° (C15A/C16A/C11A/C2A) and 6.1 (5)° (C15B/C16B/C11B/C2B) between the planes of the isoquiniline and benzodioxole moieties for molecules A and B respectively. The molecules are layered in the crystal lattice with normal π—π stacking distances between centroids of the rings of molecules A and B of 3.571 (4)Å (rings C6A/C7A/C8A/C9A/C15A/C16A to C2B/C11B/C12B/C13B/C14B/C18B), 3.839 (4)Å (rings N1A/C5A/C10A/C15A/C16A/C17A to N1B/C5B/C10B/C15B/C16B/C17B), and 3.686 (4)Å (rings C2A/C11A/C12A/C13A/C14A/C18A to C6B/C7B/C8B/C9B/C15B/C16B). Identical molecules neighboring each other are located at further stacking distances with the closest controid distance of 3.815 (4)Å between molecules A to A and 3.949 (4)Å between molecules B to B.

Experimental

The title compound was prepared by vacuum pyrolysis of berberine hydrochloride followed by alkylation with ethyl iodide (Iwasa et al., 1997). The crystals suitable for single-crystal X-ray diffraction were grown in DMSO-d6. The crystal was diffracted in the cold stream of an X-Stream 2000 Liquid nitrogen generator with an open-flow nitrogen cryostat with a nominal stability of 0.1 K.