Issue contents
Download PDF of article
Download CIF
3D view
Navigation
Highlighting
Dictionary of Crystallography reference
IUPAC Gold Book reference
more ...
Download citation
FormatBIBTeX
EndNote
RefMan
Refer
Medline
CIF
SGML
Plain Text
share
Previous article
Next article
Previous article
Issue contents
Download PDF of article
Download CIF
3D view
Navigation
Highlighting
Dictionary of Crystallography reference
IUPAC Gold Book reference
more ...
Download citation
FormatBIBTeX
EndNote
RefMan
Refer
Medline
CIF
SGML
Plain Text
share
Next article

organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 71| Part 8| August 2015| Pages o608-o609
https://doi.org/10.1107/S205698901501378X

Crystal structure of 4,6-di­amino-2,2-di­methyl-3-[3-(2,4,5-tri­chloro­phen­­oxy)prop­­oxy]-2,3-di­hydro-1,3,5-triazin-1-ium chloride methanol monosolvate

Pattarapol Khongsuk,a Samran Prabpaia and Palangpon Kongsaereea*

aDepartment of Chemistry and Center of Excellence for Innovation in Chemistry, and Center for Excellence in Protein Structure and Function, Faculty of Science, Mahidol University, Bangkok 10400, Thailand
*Correspondence e-mail: palangpon.kon@mahidol.ac.th

Edited by H. Ishida, Okayama University, Japan (Received 9 July 2015; accepted 21 July 2015; online 29 July 2015)

In the title methanol-solvated salt, C14H19Cl3N5O2+·Cl−·CH3OH, the triazine mol­ecule is protonated at one of the triazine N atoms. In the crystal, the triazine cations are linked through a pair of N—H⋯N hydrogen bonds, with graph-set R22(8), forming an inversion dimer. The protonated N atom and the 2- and 4-amino groups of the triazine cation inter­act with the chloride anion through N—H⋯Cl hydrogen bonds, leading to the formation of a tape structure running along the b-axis direction. A short Cl⋯Cl contact [3.2937 (9) Å] is observed in the tape. The methanol mol­ecule is linked to the chloride anion and the triazine cation, respectively, by an O—H⋯Cl hydrogen bond and a C—H⋯O inter­action.

CCDC reference: 1414045

Similar articles

1. Related literature

For anti­folate anti­malarial drugs, see: Toyoda et al. (1997[Toyoda, T., Brobey, R. K. B., Sano, G.-I., Horii, T., Tomioka, N. & Itai, A. (1997). Biochem. Biophys. Res. Commun. 235, 515-519.]); Yuthavong (2002[Yuthavong, Y. (2002). Microbes Infect. 4, 175-182.]). For anti­folate drug resistance, see: Nzila (2006[Nzila, A. (2006). J. Antimicrob. Chemother. 57, 1043-1054.]); Rieckmann et al. (1996[Rieckmann, K. H., Yeo, A. E. & Edstein, M. D. (1996). Trans. R. Soc. Trop. Med. Hyg. 90, 568-571.]). For our previous work on the protein crystallographic analysis of di­hydro­folate reductase, see: Yuvaniyama et al. (2003[Yuvaniyama, J., Chitnumsub, P., Kamchonwongpaisan, S., Vanichtanankul, J., Sirawaraporn, W., Taylor, P., Walkinshaw, M. D. & Yuthavong, Y. (2003). Nat. Struct. Biol. 10, 357-365.]); Kongsaeree et al. (2005[Kongsaeree, P., Khongsuk, P., Leartsakulpanich, U., Chitnumsub, P., Tarnchompoo, B., Walkinshaw, M. D. & Yuthavong, Y. (2005). Proc. Natl Acad. Sci. USA, 102, 13046-13051.]).

[Scheme 1]

2. Experimental

2.1. Crystal data

  • C14H19Cl3N5O2+·Cl−·CH4O

  • Mr = 463.18

  • Triclinic, [P \overline 1]

  • a = 8.5930 (4) Å

  • b = 9.3510 (3) Å

  • c = 14.6970 (7) Å

  • α = 75.422 (3)°

  • β = 78.2260 (19)°

  • γ = 70.194 (3)°

  • V = 1066.13 (8) Å3

  • Z = 2

  • Mo Kα radiation

  • μ = 0.58 mm−1

  • T = 298 K

  • 0.32 × 0.20 × 0.18 mm

2.2. Data collection

  • Nonius KappaCCD diffractometer

  • 5032 measured reflections

  • 2935 independent reflections

  • 2681 reflections with I > 2σ(I)

  • Rint = 0.017

  • θmax = 23.3°

2.3. Refinement

  • R[F2 > 2σ(F2)] = 0.034

  • wR(F2) = 0.087

  • S = 1.06

  • 2935 reflections

  • 268 parameters

  • 6 restraints

  • H atoms treated by a mixture of independent and constrained refinement

  • Δρmax = 0.26 e Å−3

  • Δρmin = −0.26 e Å−3

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A D⋯A D—H⋯A
N1—H1⋯Cl4i 0.87 (1) 2.27 (1) 3.1236 (17) 167 (2)
N2—H2A⋯Cl4ii 0.87 (1) 2.64 (2) 3.3285 (17) 137 (2)
N2—H2B⋯N3iii 0.87 (1) 2.26 (1) 3.122 (2) 170 (2)
N4—H4A⋯Cl4iv 0.88 (1) 2.31 (1) 3.1419 (19) 158 (2)
O3—H3⋯Cl4 0.82 2.35 3.166 (2) 176
C14—H14⋯O3v 0.93 2.53 3.423 (3) 161
Symmetry codes: (i) -x+1, -y+1, -z+1; (ii) x+1, y, z; (iii) -x+2, -y, -z+1; (iv) -x+1, -y, -z+1; (v) -x, -y+1, -z+1.

Data collection: KappaCCD Software (Nonius, 1999[Nonius (1999). KappaCCD software. Nonius BV, Delft, The Netherlands.]); cell refinement: SCALEPACK (Otwinowski & Minor, 1997[Otwinowski, Z. & Minor, W. (1997). Methods in Enzymology, Vol. 276, Macromolecular Crystallography, Part A, edited by C. W. Carter Jr & R. M. Sweet, pp. 307-326. New York: Academic Press.]); data reduction: DENZO (Otwinowski & Minor, 1997[Otwinowski, Z. & Minor, W. (1997). Methods in Enzymology, Vol. 276, Macromolecular Crystallography, Part A, edited by C. W. Carter Jr & R. M. Sweet, pp. 307-326. New York: Academic Press.]); program(s) used to solve structure: SIR97 (Altomare et al., 1999[Altomare, A., Burla, M. C., Camalli, M., Cascarano, G. L., Giacovazzo, C., Guagliardi, A., Moliterni, A. G. G., Polidori, G. & Spagna, R. (1999). J. Appl. Cryst. 32, 115-119.]); program(s) used to refine structure: SHELXL2013 (Sheldrick, 2015[Sheldrick, G. M. (2015). Acta Cryst. C71, 3-8.]); molecular graphics: PLATON (Spek, 2009[Spek, A. L. (2009). Acta Cryst. D65, 148-155.]); software used to prepare material for publication: publCIF (Westrip, 2010[Westrip, S. P. (2010). J. Appl. Cryst. 43, 920-925.]).

Supporting information

CCDC reference: 1414045

Crystal structure: contains datablocks I, New_Global_Publ_Block. DOI: https://doi.org/10.1107/S205698901501378X/is5407sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S205698901501378X/is5407Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S205698901501378X/is5407Isup3.cml

checkCIF report


Comment top

The structure of the methanol-solvated salt compound, C14H19Cl3N5O2+.Cl-.CH3OH, was determined as part of a structural study of our dihydrofolate reductase (DHFR) in complex with its antifolate inhibitors. WR99210 {systematic name: 6,6-dimethyl-1-[3-(2,4,5-trichlorophenoxy)propoxy]-1,6-dihydro-1,3,5-triazine-2,4-diamine} is a potent inhibitor of dihydrofolate reductase enzyme (DHFR). With a structural resemblance with cycloguanil (Cyc), a metabolite of the antimalarial drug proguanil (Toyoda et al., 1997), WR99210 has a flexible propoxy linker and a phenyl group with three chlorine atoms (Yuthavong, 2002; Nzila, 2006). Studies in animal models demonstrated a low bioavailability of WR99210, preventing its further development as an antimalarial agent (Rieckmann et al., 1996). The crystal structures of the bifunctional Plasmodium falciparum DHFR-TS and the monofunctional P. vivax DHFR have been reported in complex with WR99210, and with pyrimethamines, respectively (Yuvaniyama et al., 2003; Kongsaeree et al., 2005). The protein structures complexed with WR99210 have provided valuable insight into interdomain interactions and also opened a new dimension in the design of new drugs to fight against malaria. Herein, we report a single crystal X-ray structure of 4,6-diamino-2,2-dimethyl-3-[3-(2,4,5-trichlorophenoxy)propoxy]-2,3-dihydro-1,3,5-triazin-1-ium chloride methanol solvate, (I).

In the title compound, the WR99210 molecule is protonated at one of the nitrogen atoms of the triazine moiety. This is evident from the increase in the internal angle at protonated N1 [C1—N1—C3 = 122.30 (16) Å] compared with that of the unprotanated atoms N3 [C2—N3—C1 = 116.03 (16) Å] and N5 [C2—N5—C3 = 117.77 (15) Å]. The triazine ring adopts the conformation described as an intermediate between a flatten screw-boat and a half-chair with C3 atom. The angle between the geminal flagpole and bowsprit methyl groups is 112.31 (18)°. In addition, the propoxy linker between the triazine and the trichlorophenyl group allowed free rotations of sp3-hybridized C6, C7 and C8 atoms (Fig. 1).

In the crystal, the triazine moiety is centrosymmetrically paired through N—H···N hydrogen bonds involving the 2-amino group and the N3 atom of the triazine, leading to a hydrogen-bonding pattern with a graph-set R22(8) (Fig. 2). The pairs further interact with the chloride anion through N—H···Cl hydrogen bonds. The chloride anion connects 2-amino and 4-amino groups on either side of the paired triazine, forming an eight-membered hydrogen bonded ring motif with a graph-set R32(8). The protonated N1 and 2-amino groups of the cationic triazine also interacted with two chloride anions to form a ring motif with a graph-set R42(12). In addition, we found a graph-set R32(15) ring motif through an O—H···Cl hydrogen bond between the methanol molecule and the chloride anion as well as a C—H···O hydrogen bond between the benzene ring (C14) and the methanol molecule (Table 1).

Related literature top

For antifolate antimalarial drugs, see: Toyoda et al. (1997); Yuthavong (2002). For antifolate drug resistance, see: Nzila (2006); Rieckmann et al. (1996). For our previous work on the protein crystallographic analysis of dihydrofolate reductase, see: Yuvaniyama et al. (2003); Kongsaeree et al. (2005).

Experimental top

WR99210 was a kind gift from Dr. Bongkoch Tarnchompoo, BIOTEC, National Science and Technology Development Agency, Thailand. Single crystals of the title compound were prepared from a methanolic solution by slow evaporation at 298 K. The colorless crystals suitable for X-ray diffraction were obtained after a few days.

Refinement top

The N-bound H atoms were located in a difference Fourier map and were refined with restraint of N—H = 0.88 (1) Å. All other H atoms were placed in idealized positions and refined as riding atoms, with C—H = 0.93–0.97 Å and O—H = 0.82 Å, and with Uiso(H) = 1.5Ueq(O, Cmethyl) and 1.2Ueq(C) for other H atoms.

Structure description top

The structure of the methanol-solvated salt compound, C14H19Cl3N5O2+.Cl-.CH3OH, was determined as part of a structural study of our dihydrofolate reductase (DHFR) in complex with its antifolate inhibitors. WR99210 {systematic name: 6,6-dimethyl-1-[3-(2,4,5-trichlorophenoxy)propoxy]-1,6-dihydro-1,3,5-triazine-2,4-diamine} is a potent inhibitor of dihydrofolate reductase enzyme (DHFR). With a structural resemblance with cycloguanil (Cyc), a metabolite of the antimalarial drug proguanil (Toyoda et al., 1997), WR99210 has a flexible propoxy linker and a phenyl group with three chlorine atoms (Yuthavong, 2002; Nzila, 2006). Studies in animal models demonstrated a low bioavailability of WR99210, preventing its further development as an antimalarial agent (Rieckmann et al., 1996). The crystal structures of the bifunctional Plasmodium falciparum DHFR-TS and the monofunctional P. vivax DHFR have been reported in complex with WR99210, and with pyrimethamines, respectively (Yuvaniyama et al., 2003; Kongsaeree et al., 2005). The protein structures complexed with WR99210 have provided valuable insight into interdomain interactions and also opened a new dimension in the design of new drugs to fight against malaria. Herein, we report a single crystal X-ray structure of 4,6-diamino-2,2-dimethyl-3-[3-(2,4,5-trichlorophenoxy)propoxy]-2,3-dihydro-1,3,5-triazin-1-ium chloride methanol solvate, (I).

In the title compound, the WR99210 molecule is protonated at one of the nitrogen atoms of the triazine moiety. This is evident from the increase in the internal angle at protonated N1 [C1—N1—C3 = 122.30 (16) Å] compared with that of the unprotanated atoms N3 [C2—N3—C1 = 116.03 (16) Å] and N5 [C2—N5—C3 = 117.77 (15) Å]. The triazine ring adopts the conformation described as an intermediate between a flatten screw-boat and a half-chair with C3 atom. The angle between the geminal flagpole and bowsprit methyl groups is 112.31 (18)°. In addition, the propoxy linker between the triazine and the trichlorophenyl group allowed free rotations of sp3-hybridized C6, C7 and C8 atoms (Fig. 1).

In the crystal, the triazine moiety is centrosymmetrically paired through N—H···N hydrogen bonds involving the 2-amino group and the N3 atom of the triazine, leading to a hydrogen-bonding pattern with a graph-set R22(8) (Fig. 2). The pairs further interact with the chloride anion through N—H···Cl hydrogen bonds. The chloride anion connects 2-amino and 4-amino groups on either side of the paired triazine, forming an eight-membered hydrogen bonded ring motif with a graph-set R32(8). The protonated N1 and 2-amino groups of the cationic triazine also interacted with two chloride anions to form a ring motif with a graph-set R42(12). In addition, we found a graph-set R32(15) ring motif through an O—H···Cl hydrogen bond between the methanol molecule and the chloride anion as well as a C—H···O hydrogen bond between the benzene ring (C14) and the methanol molecule (Table 1).

For antifolate antimalarial drugs, see: Toyoda et al. (1997); Yuthavong (2002). For antifolate drug resistance, see: Nzila (2006); Rieckmann et al. (1996). For our previous work on the protein crystallographic analysis of dihydrofolate reductase, see: Yuvaniyama et al. (2003); Kongsaeree et al. (2005).

Computing details top

Data collection: KappaCCD Software (Nonius, 1999); cell refinement: SCALEPACK (Otwinowski & Minor, 1997); data reduction: DENZO (Otwinowski & Minor, 1997); program(s) used to solve structure: SIR97 (Altomare et al., 1999); program(s) used to refine structure: SHELXL2013 (Sheldrick, 2015); molecular graphics: PLATON (Spek, 2009); software used to prepare material for publication: publCIF (Westrip, 2010).

Figures top
[Figure 1] Fig. 1. View of the molecular structure of the title compound, with displacement ellipsoids drawn at the 50% probability level.
[Figure 2] Fig. 2. Hydrogen bonding interactions, showing molecules linked through N—H···N, N—H···Cl and O—H···Cl (dashed lines), and C—H···O (dotted line) hydrogen bonds.
4,6-Diamino-2,2-dimethyl-3-[3-(2,4,5-trichlorophenoxy)propoxy]-2,3-dihydro-1,3,5-triazin-1-ium chloride methanol monosolvate top
Crystal data top
C14H19Cl3N5O2+·Cl−·CH4OZ = 2
Mr = 463.18F(000) = 480
Triclinic, P1Dx = 1.443 Mg m−3
a = 8.5930 (4) ÅMo Kα radiation, λ = 0.71073 Å
b = 9.3510 (3) ÅCell parameters from 2724 reflections
c = 14.6970 (7) Åθ = 2.9–23.3°
α = 75.422 (3)°µ = 0.58 mm−1
β = 78.2260 (19)°T = 298 K
γ = 70.194 (3)°Rod, colourless
V = 1066.13 (8) Å30.32 × 0.20 × 0.18 mm
Data collection top
Nonius KappaCCD
diffractometer		2681 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.017
Detector resolution: 9 pixels mm-1θmax = 23.3°, θmin = 3.1°
CCD scansh = −9→9
5032 measured reflectionsk = −10→9
2935 independent reflectionsl = −16→16
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.034Hydrogen site location: mixed
wR(F2) = 0.087H atoms treated by a mixture of independent and constrained refinement
S = 1.06 w = 1/[σ2(Fo2) + (0.0351P)2 + 0.5001P]
where P = (Fo2 + 2Fc2)/3
2935 reflections(Δ/σ)max = 0.001
268 parametersΔρmax = 0.26 e Å−3
6 restraintsΔρmin = −0.26 e Å−3
Crystal data top
C14H19Cl3N5O2+·Cl−·CH4Oγ = 70.194 (3)°
Mr = 463.18V = 1066.13 (8) Å3
Triclinic, P1Z = 2
a = 8.5930 (4) ÅMo Kα radiation
b = 9.3510 (3) ŵ = 0.58 mm−1
c = 14.6970 (7) ÅT = 298 K
α = 75.422 (3)°0.32 × 0.20 × 0.18 mm
β = 78.2260 (19)°
Data collection top
Nonius KappaCCD
diffractometer		2681 reflections with I > 2σ(I)
5032 measured reflectionsRint = 0.017
2935 independent reflectionsθmax = 23.3°
Refinement top
R[F2 > 2σ(F2)] = 0.0346 restraints
wR(F2) = 0.087H atoms treated by a mixture of independent and constrained refinement
S = 1.06Δρmax = 0.26 e Å−3
2935 reflectionsΔρmin = −0.26 e Å−3
268 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
xyzUiso*/Ueq
Cl1−0.26674 (7)−0.09037 (6)0.98859 (4)0.05048 (18)
Cl2−0.50317 (9)0.36361 (7)1.18779 (4)0.0669 (2)
Cl3−0.27290 (9)0.54749 (7)1.04479 (5)0.0658 (2)
Cl40.17598 (7)0.43814 (6)0.40327 (4)0.05568 (19)
O10.36692 (15)0.10928 (15)0.69350 (9)0.0364 (3)
O2−0.07327 (17)0.09663 (16)0.86849 (10)0.0423 (3)
O30.0138 (3)0.4448 (3)0.22657 (17)0.0928 (7)
H30.06010.44170.27090.139*
N10.6726 (2)0.30658 (19)0.58733 (12)0.0404 (4)
N20.9243 (2)0.2208 (2)0.49858 (14)0.0459 (4)
N30.77155 (19)0.05192 (18)0.56004 (11)0.0369 (4)
N40.5995 (2)−0.1015 (2)0.61841 (14)0.0491 (5)
N50.49520 (18)0.15639 (17)0.62848 (11)0.0327 (4)
C10.7877 (2)0.1939 (2)0.54981 (13)0.0338 (4)
C20.6256 (2)0.0339 (2)0.60370 (13)0.0334 (4)
C30.5346 (2)0.2785 (2)0.65866 (14)0.0356 (4)
C40.5862 (3)0.2234 (3)0.75760 (15)0.0501 (5)
H4C0.49380.20430.80260.060*
H4D0.61950.30150.77320.060*
H4E0.67790.12940.75960.060*
C50.3872 (3)0.4247 (2)0.65107 (18)0.0509 (6)
H5A0.29820.40960.70010.061*
H5B0.34980.44780.59030.061*
H5C0.42000.50940.65800.061*
C60.2207 (2)0.1419 (3)0.64724 (14)0.0422 (5)
H6A0.24900.09020.59390.051*
H6B0.17400.25250.62480.051*
C70.0993 (2)0.0797 (3)0.72291 (15)0.0421 (5)
H7A0.01030.07490.69350.051*
H7B0.1564−0.02490.75320.051*
C80.0247 (3)0.1781 (2)0.79714 (14)0.0418 (5)
H8A0.11190.19120.82410.050*
H8B−0.04480.27960.76980.050*
C9−0.1674 (2)0.1672 (2)0.94055 (13)0.0348 (4)
C10−0.2683 (2)0.0871 (2)1.00452 (13)0.0349 (4)
C11−0.3698 (3)0.1481 (2)1.07983 (14)0.0405 (5)
H11−0.43680.09391.12170.049*
C12−0.3719 (3)0.2895 (2)1.09306 (14)0.0419 (5)
C13−0.2726 (3)0.3696 (2)1.02998 (14)0.0418 (5)
C14−0.1711 (3)0.3094 (2)0.95396 (14)0.0407 (5)
H14−0.10530.36470.91180.049*
C150.0334 (5)0.2948 (4)0.2183 (3)0.1067 (12)
H15A−0.01070.29810.16250.160*
H15B−0.02540.24560.27320.160*
H15C0.14980.23690.21330.160*
H10.700 (3)0.3881 (18)0.5866 (17)0.053 (7)*
H2A0.944 (3)0.3083 (16)0.4926 (16)0.045 (6)*
H2B1.002 (2)0.144 (2)0.4770 (16)0.052 (7)*
H4A0.680 (2)−0.181 (2)0.6007 (17)0.057 (7)*
H4B0.507 (2)−0.108 (3)0.6546 (16)0.067 (8)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
Cl10.0612 (4)0.0386 (3)0.0568 (3)−0.0254 (3)0.0059 (3)−0.0153 (2)
Cl20.0924 (5)0.0554 (4)0.0519 (4)−0.0290 (3)0.0215 (3)−0.0243 (3)
Cl30.0963 (5)0.0422 (3)0.0678 (4)−0.0344 (3)0.0018 (3)−0.0180 (3)
Cl40.0613 (4)0.0410 (3)0.0719 (4)−0.0260 (3)0.0097 (3)−0.0241 (3)
O10.0292 (7)0.0467 (8)0.0340 (7)−0.0173 (6)0.0032 (5)−0.0070 (6)
O20.0422 (8)0.0407 (8)0.0426 (8)−0.0178 (6)0.0095 (6)−0.0107 (6)
O30.1093 (18)0.0790 (15)0.0964 (17)−0.0336 (13)−0.0224 (13)−0.0144 (12)
N10.0407 (9)0.0317 (9)0.0515 (10)−0.0178 (8)0.0047 (8)−0.0123 (8)
N20.0406 (10)0.0400 (11)0.0577 (11)−0.0220 (9)0.0091 (8)−0.0093 (9)
N30.0341 (9)0.0332 (9)0.0432 (9)−0.0151 (7)0.0078 (7)−0.0109 (7)
N40.0443 (11)0.0340 (10)0.0682 (13)−0.0196 (9)0.0168 (9)−0.0172 (9)
N50.0283 (8)0.0344 (9)0.0365 (8)−0.0138 (7)0.0058 (6)−0.0111 (7)
C10.0334 (10)0.0335 (11)0.0346 (10)−0.0140 (9)0.0008 (8)−0.0060 (8)
C20.0354 (10)0.0323 (10)0.0335 (10)−0.0135 (8)0.0018 (8)−0.0086 (8)
C30.0337 (10)0.0342 (10)0.0408 (11)−0.0117 (8)0.0014 (8)−0.0138 (8)
C40.0487 (13)0.0593 (14)0.0474 (13)−0.0177 (11)−0.0071 (10)−0.0173 (11)
C50.0450 (12)0.0382 (12)0.0661 (15)−0.0051 (10)−0.0028 (11)−0.0183 (10)
C60.0342 (11)0.0594 (13)0.0372 (11)−0.0190 (10)−0.0018 (8)−0.0124 (9)
C70.0345 (11)0.0544 (13)0.0433 (11)−0.0211 (9)−0.0007 (9)−0.0130 (10)
C80.0373 (11)0.0454 (12)0.0425 (11)−0.0194 (9)0.0047 (9)−0.0068 (9)
C90.0326 (10)0.0356 (11)0.0358 (10)−0.0116 (8)−0.0022 (8)−0.0065 (8)
C100.0379 (11)0.0301 (10)0.0379 (11)−0.0124 (8)−0.0048 (8)−0.0061 (8)
C110.0458 (12)0.0398 (12)0.0368 (11)−0.0210 (9)0.0022 (9)−0.0039 (9)
C120.0503 (12)0.0394 (12)0.0356 (11)−0.0151 (10)−0.0002 (9)−0.0091 (9)
C130.0526 (12)0.0325 (11)0.0431 (12)−0.0162 (9)−0.0068 (10)−0.0073 (9)
C140.0428 (11)0.0379 (11)0.0425 (11)−0.0202 (9)−0.0007 (9)−0.0030 (9)
C150.152 (4)0.064 (2)0.120 (3)−0.035 (2)−0.050 (3)−0.0171 (19)
Geometric parameters (Å, º) top
Cl1—C101.7290 (19)C4—H4D0.9600
Cl2—C121.734 (2)C4—H4E0.9600
Cl3—C131.730 (2)C5—H5A0.9600
O1—N51.4177 (19)C5—H5B0.9600
O1—C61.455 (2)C5—H5C0.9600
O2—C91.361 (2)C6—C71.509 (3)
O2—C81.436 (2)C6—H6A0.9700
O3—C151.389 (4)C6—H6B0.9700
O3—H30.8200C7—C81.506 (3)
N1—C11.325 (3)C7—H7A0.9700
N1—C31.462 (2)C7—H7B0.9700
N1—H10.866 (10)C8—H8A0.9700
N2—C11.324 (2)C8—H8B0.9700
N2—H2A0.868 (10)C9—C141.382 (3)
N2—H2B0.874 (10)C9—C101.396 (3)
N3—C21.332 (2)C10—C111.377 (3)
N3—C11.349 (2)C11—C121.378 (3)
N4—C21.317 (3)C11—H110.9300
N4—H4A0.883 (10)C12—C131.381 (3)
N4—H4B0.873 (10)C13—C141.383 (3)
N5—C21.369 (2)C14—H140.9300
N5—C31.481 (2)C15—H15A0.9600
C3—C51.514 (3)C15—H15B0.9600
C3—C41.519 (3)C15—H15C0.9600
C4—H4C0.9600
N5—O1—C6110.75 (13)O1—C6—H6A110.8
C9—O2—C8118.27 (15)C7—C6—H6A110.8
C15—O3—H3109.5O1—C6—H6B110.8
C1—N1—C3122.30 (16)C7—C6—H6B110.8
C1—N1—H1117.3 (16)H6A—C6—H6B108.9
C3—N1—H1116.2 (16)C8—C7—C6112.46 (17)
C1—N2—H2A121.4 (15)C8—C7—H7A109.1
C1—N2—H2B118.5 (16)C6—C7—H7A109.1
H2A—N2—H2B120 (2)C8—C7—H7B109.1
C2—N3—C1116.03 (16)C6—C7—H7B109.1
C2—N4—H4A119.9 (16)H7A—C7—H7B107.8
C2—N4—H4B114.9 (18)O2—C8—C7105.97 (16)
H4A—N4—H4B124 (2)O2—C8—H8A110.5
C2—N5—O1112.83 (14)C7—C8—H8A110.5
C2—N5—C3117.77 (15)O2—C8—H8B110.5
O1—N5—C3110.56 (13)C7—C8—H8B110.5
N2—C1—N1119.24 (17)H8A—C8—H8B108.7
N2—C1—N3117.74 (17)O2—C9—C14125.37 (17)
N1—C1—N3123.01 (16)O2—C9—C10115.84 (17)
N4—C2—N3120.33 (17)C14—C9—C10118.79 (18)
N4—C2—N5118.00 (17)C11—C10—C9120.85 (18)
N3—C2—N5121.51 (16)C11—C10—Cl1119.59 (14)
N1—C3—N5103.00 (14)C9—C10—Cl1119.56 (15)
N1—C3—C5108.81 (16)C10—C11—C12120.00 (18)
N5—C3—C5109.49 (16)C10—C11—H11120.0
N1—C3—C4111.45 (16)C12—C11—H11120.0
N5—C3—C4111.35 (16)C11—C12—C13119.49 (18)
C5—C3—C4112.31 (18)C11—C12—Cl2118.64 (15)
C3—C4—H4C109.5C13—C12—Cl2121.85 (16)
C3—C4—H4D109.5C12—C13—C14120.82 (18)
H4C—C4—H4D109.5C12—C13—Cl3120.49 (16)
C3—C4—H4E109.5C14—C13—Cl3118.68 (15)
H4C—C4—H4E109.5C9—C14—C13120.05 (18)
H4D—C4—H4E109.5C9—C14—H14120.0
C3—C5—H5A109.5C13—C14—H14120.0
C3—C5—H5B109.5O3—C15—H15A109.5
H5A—C5—H5B109.5O3—C15—H15B109.5
C3—C5—H5C109.5H15A—C15—H15B109.5
H5A—C5—H5C109.5O3—C15—H15C109.5
H5B—C5—H5C109.5H15A—C15—H15C109.5
O1—C6—C7104.82 (15)H15B—C15—H15C109.5
C6—O1—N5—C2−107.86 (18)O1—C6—C7—C872.4 (2)
C6—O1—N5—C3117.90 (17)C9—O2—C8—C7−174.20 (16)
C3—N1—C1—N2−168.24 (18)C6—C7—C8—O2−174.17 (16)
C3—N1—C1—N312.8 (3)C8—O2—C9—C14−3.3 (3)
C2—N3—C1—N2−173.42 (18)C8—O2—C9—C10176.05 (17)
C2—N3—C1—N15.6 (3)O2—C9—C10—C11−179.53 (18)
C1—N3—C2—N4−178.78 (19)C14—C9—C10—C11−0.1 (3)
C1—N3—C2—N55.9 (3)O2—C9—C10—Cl10.1 (2)
O1—N5—C2—N419.0 (2)C14—C9—C10—Cl1179.54 (15)
C3—N5—C2—N4149.69 (18)C9—C10—C11—C12−0.3 (3)
O1—N5—C2—N3−165.59 (16)Cl1—C10—C11—C12−179.98 (16)
C3—N5—C2—N3−34.9 (3)C10—C11—C12—C130.5 (3)
C1—N1—C3—N5−35.7 (2)C10—C11—C12—Cl2179.18 (16)
C1—N1—C3—C5−151.85 (19)C11—C12—C13—C14−0.1 (3)
C1—N1—C3—C483.8 (2)Cl2—C12—C13—C14−178.82 (17)
C2—N5—C3—N145.5 (2)C11—C12—C13—Cl3179.94 (17)
O1—N5—C3—N1177.24 (14)Cl2—C12—C13—Cl31.3 (3)
C2—N5—C3—C5161.15 (17)O2—C9—C14—C13179.80 (18)
O1—N5—C3—C5−67.12 (19)C10—C9—C14—C130.4 (3)
C2—N5—C3—C4−74.1 (2)C12—C13—C14—C9−0.3 (3)
O1—N5—C3—C457.68 (19)Cl3—C13—C14—C9179.62 (16)
N5—O1—C6—C7177.50 (15)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H1···Cl4i0.87 (1)2.27 (1)3.1236 (17)167 (2)
N2—H2A···Cl4ii0.87 (1)2.64 (2)3.3285 (17)137 (2)
N2—H2B···N3iii0.87 (1)2.26 (1)3.122 (2)170 (2)
N4—H4A···Cl4iv0.88 (1)2.31 (1)3.1419 (19)158 (2)
O3—H3···Cl40.822.353.166 (2)176
C14—H14···O3v0.932.533.423 (3)161
Symmetry codes: (i) −x+1, −y+1, −z+1; (ii) x+1, y, z; (iii) −x+2, −y, −z+1; (iv) −x+1, −y, −z+1; (v) −x, −y+1, −z+1.
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H1···Cl4i0.866 (10)2.274 (11)3.1236 (17)167 (2)
N2—H2A···Cl4ii0.868 (10)2.638 (17)3.3285 (17)137.3 (18)
N2—H2B···N3iii0.874 (10)2.258 (11)3.122 (2)170 (2)
N4—H4A···Cl4iv0.883 (10)2.307 (13)3.1419 (19)158 (2)
O3—H3···Cl40.822.353.166 (2)176
C14—H14···O3v0.932.533.423 (3)161
Symmetry codes: (i) −x+1, −y+1, −z+1; (ii) x+1, y, z; (iii) −x+2, −y, −z+1; (iv) −x+1, −y, −z+1; (v) −x, −y+1, −z+1.
 

Acknowledgements

The authors are grateful for financial support from the Thailand Research Fund (TRF), the Thailand–Tropical Diseases Research Program (T-2), and the Wellcome Trust. A scholarship from the Thailand Graduate Institute of Science and Technology (TGIST) to PK is acknowledged. This study was conducted in a facility supported by the Center of Excellence for Innovation in Chemistry (PERCH–CIC).

References

First citationAltomare, A., Burla, M. C., Camalli, M., Cascarano, G. L., Giacovazzo, C., Guagliardi, A., Moliterni, A. G. G., Polidori, G. & Spagna, R. (1999). J. Appl. Cryst. 32, 115–119.  Web of Science CrossRef CAS IUCr Journals Google Scholar
 First citationKongsaeree, P., Khongsuk, P., Leartsakulpanich, U., Chitnumsub, P., Tarnchompoo, B., Walkinshaw, M. D. & Yuthavong, Y. (2005). Proc. Natl Acad. Sci. USA, 102, 13046–13051.  Web of Science CrossRef PubMed CAS Google Scholar
 First citationNonius (1999). KappaCCD software. Nonius BV, Delft, The Netherlands.  Google Scholar
 First citationNzila, A. (2006). J. Antimicrob. Chemother. 57, 1043–1054.  CrossRef PubMed CAS Google Scholar
 First citationOtwinowski, Z. & Minor, W. (1997). Methods in Enzymology, Vol. 276, Macromolecular Crystallography, Part A, edited by C. W. Carter Jr & R. M. Sweet, pp. 307–326. New York: Academic Press.  Google Scholar
 First citationRieckmann, K. H., Yeo, A. E. & Edstein, M. D. (1996). Trans. R. Soc. Trop. Med. Hyg. 90, 568–571.  CrossRef CAS PubMed Google Scholar
 First citationSheldrick, G. M. (2015). Acta Cryst. C71, 3–8.  Web of Science CrossRef IUCr Journals Google Scholar
 First citationSpek, A. L. (2009). Acta Cryst. D65, 148–155.  Web of Science CrossRef CAS IUCr Journals Google Scholar
 First citationToyoda, T., Brobey, R. K. B., Sano, G.-I., Horii, T., Tomioka, N. & Itai, A. (1997). Biochem. Biophys. Res. Commun. 235, 515–519.  CrossRef CAS PubMed Web of Science Google Scholar
 First citationWestrip, S. P. (2010). J. Appl. Cryst. 43, 920–925.  Web of Science CrossRef CAS IUCr Journals Google Scholar
 First citationYuthavong, Y. (2002). Microbes Infect. 4, 175–182.  CrossRef PubMed CAS Google Scholar
 First citationYuvaniyama, J., Chitnumsub, P., Kamchonwongpaisan, S., Vanichtanankul, J., Sirawaraporn, W., Taylor, P., Walkinshaw, M. D. & Yuthavong, Y. (2003). Nat. Struct. Biol. 10, 357–365.  CrossRef PubMed CAS Google Scholar

This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 71| Part 8| August 2015| Pages o608-o609
https://doi.org/10.1107/S205698901501378X
Follow Acta Cryst. E
Sign up for e-alerts
E-alerts
Follow Acta Cryst. on Twitter
Twitter
Follow us on facebook
Facebook
Sign up for RSS feeds
RSS