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Acta Crystallogr Sect E Struct Rep Online. 2010 April 1; 66(Pt 4): o821.
Published online 2010 March 13. doi:  10.1107/S1600536810007750
PMCID: PMC2983785

Alaptide from synchrotron powder diffraction data

Abstract

The title compound [systematic name: (8S)-8-methyl-6,9-diaza­spiro­[4.5]decane-7,10-dione], C9H14N2O2, consists of two connected rings, viz. a piperazine-2,5-dione (DKP) ring and a five-membered ring. The DKP ring adopts a slight boat conformation and the bonded methyl group is in an equatorial position. The five-membered ring is in an envelope conformation. In the crystal structure, inter­molecular N—H(...)O hydrogen bonds link mol­ecules into chains running parallel to the c axis.

Related literature

For background to alaptide and its biological activity, see: Kasafírek et al. (1992 [triangle]); Hliňák et al. (1996 [triangle]). For a related structure, see: Symerský et al. (1987 [triangle]). For the original powder diffraction data, see: Maixner et al. (2009 [triangle]). For the synthetic procedure, see: Sturc & Kacafirek (1992 [triangle]). For a description of the Cambridge Structural Database, see: Allen (2002 [triangle]). For the March–Dollase orientation correction, see: (Dollase, 1986 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-66-0o821-scheme1.jpg

Experimental

Crystal data

  • C9H14N2O2
  • M r = 182.22
  • Orthorhombic, An external file that holds a picture, illustration, etc.
Object name is e-66-0o821-efi1.jpg
  • a = 21.14118 (7) Å
  • b = 7.22207 (2) Å
  • c = 6.14610 (3) Å
  • V = 938.41 (1) Å3
  • Z = 4
  • Synchrotron radiation, λ = 0.79984 Å
  • T = 293 K
  • Cylinder, 40 × 1 mm

Data collection

  • ID31 ESRF Grenoble diffractometer
  • Specimen mounting: capilary
  • Data collection mode: transmission
  • Scan method: step
  • min = 1.00°, 2θmax = 48.01°, 2θstep = 0.003°

Refinement

  • R p = 0.058
  • R wp = 0.089
  • R exp = 0.023
  • R Bragg = 0.102
  • χ2 = 15.210
  • 15671 data points
  • 53 parameters
  • 37 restraints
  • H-atom parameters not refined

Data collection: ESRF SPEC (Certified Scientific Software, 2003 [triangle]); cell refinement: EXPO2004 (Altomare et al., 1999 [triangle]); data reduction: CRYSFIRE2004 (Shirley, 2000 [triangle]); program(s) used to solve structure: EXPO2004; program(s) used to refine structure: GSAS (Larson & Von Dreele, 1994 [triangle]); molecular graphics: Mercury (Macrae et al., 2006 [triangle]) and PLATON (Spek, 2009 [triangle]); software used to prepare material for publication: enCIFer (Allen et al., 2004 [triangle]).

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536810007750/lh2977sup1.cif

Rietveld powder data: contains datablocks I. DOI: 10.1107/S1600536810007750/lh2977Isup2.rtv

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810007750/lh2977Isup3.hkl

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

Acknowledgments

This study was supported by the research programs MSM6046137302 and NPV II 2B08021 of the Ministry of Education, Youth and Sports of the Czech Republic.

supplementary crystallographic information

Comment

Alaptide is a small molecule belonging to the group of spirocyclic dipeptides (Kasafírek et al., 1992). The systematic research during the last twenty years has shown a positive effect of alaptide and its derivatives on the memory of animals and on healing of burns (Hliňák et al., 1996).

The molecular structure of the title compound is shown in Fig. 1. The crystal structure contains two types of intermolecular N—H···O hydrogen bonds between DKP rings. The DKP ring adopts a slight boat conformation and is connected via the spiro junction to a five-membered carbon ring which is in an envelope conformation. The methyl group bonded to the dipeptide ring is in an equatorial position. A search in the Cambridge Structural Database (Allen, 2002) found the crystal structure of a similar type of molecule, namely: (8S)-8-Hydroxymethyl-6,9-diazaspiro[4.5]decane-7,10-dione (CSD refcode FEPFOV; Symerský et al., 1987). This structure has the same spacegroup and comparable unit-cell parameters as the reported structure of the title copmound. Two similar hydrogen bonds N—H···O connecting DKP rings of neighboring molecules occur in both crystal structures. In both structures, the hydrogen bonding connects molecules to form one-dimensional chains. The third hydrogen bond O—H···O is missing in the structure of alaptide, which causes a different formation of extended chains in these structures, see Fig. 2.

Experimental

The title compound was synthesized according to the procedure of Sturc & Kacafirek (1992). Alaptide was crystallized from various solvents in order to check polymorphism, but only one solid form was found (Maixner et al., 2009). The sample for measurement was recrystallized from methanol by slow evaporation technique.

Refinement

X-Ray diffraction data were collected on the high resolution diffractometer ID31 of the European Synchrotron Radiation Facility. The monochromatic wavelength was fixed at 0.79984 (4) Å. Si (111) crystal multi-analyzer combined with Si (111) monochromator was used (beam offset angle α = 2°). A rotating 1-mm-diameter borosilicate glass capillary with alaptide powder was used for the experiment. Data were measured from 1.002° 2θ to 48.012° 2θ at the room temperature, steps scans were set to 0.003° 2θ.

Indexation was done in CRYSFIRE 2004 (Shirley, 2000) package. It confirmed previously presented unit-cell parameters and space group (Maixner et al., 2009): a = 21.136 (4), b = 7.212 (4), c = 6.126 (3) Å, P212121, V = 933.8 (8) Å3, and Z = 4. The structure was solved by using direct space methods implemented in EXPO2004 package (Altomare et al.,1999). All non-hydrogen atoms were found in the structure solution process. Hydrogen atoms were placed in their theoretical positions and structure was refined by Rietveld method as implemented in GSAS (Larson & Von Dreele, 1994). Bonds, angles and planar group restraints were used during refinement. At final stages atomic coordinates and Uiso parameters of non-hydrogen atoms were refined to the final agreement factors Rp = 0.059 and Rwp= 0.089. The diffraction profiles and differences between the measured and calculated profiles are shown in Fig. 3.

The isotropic displacement parameters of atoms C10, C11 and C12 are large compared to those of the other atoms. A disorder model was attempted but this did not improve the refinement and therefore was not used.

Figures

Fig. 1.
The molecular structure of alaptide showing the atomic numbering. Displacement spheres are drawn at 30% probability level.
Fig. 2.
Comparison of molecular packing (left - arrows show directions of dipeptide rings) and hydrogen bonding system (right) of two structures. Top: Structure of alaptide, bottom: Structure of (8S)-8-Hydroxymethyl-6,9-diazaspiro[4.5]decane-7,10-dione.
Fig. 3.
The final Rietveld plot showing the measured data (black thin-plus), calculated data (red line) and difference curve (blue line). Calculated positions of the reflection are shown by vertical bars.

Crystal data

C9H14N2O2F(000) = 392
Mr = 182.22Dx = 1.290 Mg m3
Orthorhombic, P212121Synchrotron radiation, λ = 0.79984 Å
Hall symbol: P 2ac 2abT = 293 K
a = 21.14118 (7) ÅParticle morphology: no specific habit
b = 7.22207 (2) Åwhite
c = 6.14610 (3) Åcylinder, 40 × 1 mm
V = 938.41 (1) Å3Specimen preparation: Prepared at 293 K and 101 kPa
Z = 4

Data collection

ID31 ESRF Grenoble diffractometerData collection mode: transmission
Radiation source: synchrotronScan method: step
Si(111)min = 1.00°, 2θmax = 48.01°, 2θstep = 0.003°
Specimen mounting: capilary

Refinement

Least-squares matrix: full53 parameters
Rp = 0.05837 restraints
Rwp = 0.0890 constraints
Rexp = 0.023H-atom parameters not refined
RBragg = 0.102Weighting scheme based on measured s.u.'s w = 1/σ(Yobs)2
χ2 = 15.210(Δ/σ)max = 0.06
15671 data pointsBackground function: Shifted Chebyschev
Excluded region(s): noPreferred orientation correction: March–Dollase (Dollase, 1986); direction of preferred orientation is 101; MD = 0.93

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2)

xyzUiso*/Ueq
C1−0.08373 (10)0.2121 (8)−0.0450 (5)0.027 (3)*
C2−0.01869 (8)0.3035 (3)−0.0158 (4)0.035 (3)*
C30.01033 (9)0.27000 (17)0.2032 (3)0.052 (3)*
N40.07052 (9)0.2345 (4)0.2137 (3)0.026 (2)*
C50.11718 (7)0.2470 (3)0.0365 (3)0.027 (3)*
C60.08529 (8)0.23092 (17)−0.1846 (3)0.025 (3)*
N70.02321 (9)0.2505 (4)−0.1936 (3)0.027 (2)*
O80.11977 (11)0.2014 (4)−0.3425 (4)0.047 (2)*
C90.16843 (14)0.0925 (6)0.0590 (5)0.043 (4)*
C100.15361 (16)0.4304 (5)0.0487 (5)0.133 (6)*
C110.20873 (16)0.3907 (9)0.1995 (5)0.165 (5)*
C120.22476 (14)0.1870 (9)0.1704 (8)0.114 (4)*
O13−0.02052 (12)0.2734 (4)0.3727 (4)0.0319 (18)*
H11−0.09920.2386−0.18750.0346*
H12−0.11210.25950.05980.0346*
H13−0.07950.0821−0.02820.0346*
H21−0.0250.4337−0.02860.0516*
H910.1810.0494−0.07960.063*
H920.1531−0.00610.14450.063*
H1010.16860.4665−0.09160.18*
H1020.12760.52690.10530.18*
H1110.24410.46640.16150.2445*
H1120.1970.41810.34640.2445*
H1210.26170.17460.0890.168*
H1220.23090.13350.3130.168*
H710.0060.2305−0.31810.0296*
H410.08480.20130.33840.0271*

Geometric parameters (Å, °)

O8—C61.232 (3)N4—H410.86
O13—C31.229 (3)N7—H710.86
N4—C31.300 (3)C1—H110.95
N4—C51.472 (3)C1—H120.94
N7—C21.458 (3)C1—H130.95
N7—C61.321 (3)C2—H210.95
C1—C21.536 (4)C9—H910.95
C2—C31.499 (3)C9—H920.94
C5—C61.521 (3)C10—H1010.95
C5—C91.561 (4)C10—H1020.95
C5—C101.534 (4)C11—H1110.96
C9—C121.534 (5)C11—H1120.96
C10—C111.516 (5)C12—H1210.93
C11—C121.520 (9)C12—H1220.97
C3—N4—C5127.39 (18)C2—C1—H13109
C2—N7—C6126.85 (18)H11—C1—H12110
N7—C2—C1110.1 (2)H11—C1—H13109
N7—C2—C3112.48 (16)H12—C1—H13110
C1—C2—C3113.7 (2)N7—C2—H21106
O13—C3—N4118.8 (2)C1—C2—H21107
O13—C3—C2122.7 (2)C3—C2—H21107
N4—C3—C2118.50 (17)C5—C9—H91111
N4—C5—C6111.05 (14)C5—C9—H92111
N4—C5—C9110.8 (2)C12—C9—H91109
N4—C5—C10110.7 (2)C12—C9—H92111
C6—C5—C9109.39 (18)H91—C9—H92111
C6—C5—C10109.39 (18)C5—C10—H101111
C9—C5—C10105.3 (2)C5—C10—H102111
O8—C6—N7124.94 (19)C11—C10—H101110
O8—C6—C5117.03 (17)C11—C10—H102111
N7—C6—C5118.02 (16)H101—C10—H102109
C5—C9—C12105.1 (3)C10—C11—H111110
C5—C10—C11104.6 (3)C10—C11—H112110
C10—C11—C12106.4 (4)C12—C11—H111111
C9—C12—C11108.1 (3)C12—C11—H112112
C3—N4—H41116H111—C11—H112108
C5—N4—H41116C9—C12—H121112
C2—N7—H71117C9—C12—H122109
C6—N7—H71116C11—C12—H121110
C2—C1—H11109C11—C12—H122108
C2—C1—H12109H121—C12—H122110

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
N4—H41···O8i0.862.102.929 (3)164
N7—H71···O13ii0.862.012.826 (3)159

Symmetry codes: (i) x, y, z+1; (ii) x, y, z−1.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: LH2977).

References

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