rac-3- exo-Ammonio-7- anti-carb­oxy­tricyclo­[2.2.1.0. 2,6]heptane-3- endo-carboxyl­ate monohydrate

Smith, Graham a * Wermuth, Urs D. b Jenkins, Ian D. c [a ] Science and Engineering Faculty, Queensland University of Technology, GPO Box 2434, Brisbane, Queensland 4001, Australia [b ] School of Biomolecular and Physical Sciences, Griffith University, Nathan, Queensland, 4111, Australia [c ] Eskitis Institute, Griffith University, Nathan, Queensland, 4111, Australia

Abstract

The racemic title compound, C 9H 11NO 4·H 2O, a tricyclic rearranged amino­norbornane dicarb­oxy­lic acid, is a conformationally rigid analogue of glutamic acid and exists as an ammonium-carboxyl­ate zwitterion, with the bridghead carb­oxy­lic acid group anti-related. In the crystal, N—H⋯O and O—H⋯O hydrogen bonds involving the ammonium, carb­oxy­lic acid and water donor groups with both water and carboxyl O-atom acceptors give a three-dimensional framework structure.

Related literature  

For background to G-protein receptors, see: Liu & Doller (2011 ). For the Strecher and Bucherer–Bergs reactions, see: Strecher (1850 ); Bucherer & Steiner (1934 ). For the synthesis of amino­norbornane carb­oxy­lic acids, see: Apgar & Ludwig (1972 ); Tager & Christensen (1972 ); Wermuth (1995 ). For the chemistry of hydantoins, see: Avendaño López & González Trigo (1985 ). For the structure of a similar monocarb­oxy­lic acid tricyclic cage compound, see: Fortier et al. (1979 ). For graph-set analysis, see: Etter et al. (1990 ). e-68-o1468-scheme1.jpg

Experimental  

Crystal data  

  • C 9H 11NO 4·H 2O

  • M r = 215.20

  • Monoclinic, e-68-o1468-efi1.jpg

  • a = 7.7565 (2) Å

  • b = 11.4103 (2) Å

  • c = 10.3339 (3) Å

  • β = 94.888 (2)°

  • V = 911.27 (4) Å 3

  • Z = 4

  • Mo Kα radiation

  • μ = 0.13 mm −1

  • T = 223 K

  • 0.30 × 0.30 × 0.15 mm

Data collection  

  • Oxford Diffraction Gemini-S Ultra CCD-detector diffractometer

  • Absorption correction: multi-scan ( CrysAlis PRO; Oxford Diffraction, 2010 ) T min = 0.990, T max = 1.000

  • 7572 measured reflections

  • 2128 independent reflections

  • 1589 reflections with I > 2σ( I)

  • R int = 0.026

Refinement  

  • R[ F 2 > 2σ( F 2)] = 0.038

  • wR( F 2) = 0.091

  • S = 0.97

  • 2128 reflections

  • 160 parameters

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

  • Δρ max = 0.31 e Å −3

  • Δρ min = −0.25 e Å −3

Data collection: CrysAlis PRO (Oxford Diffraction, 2010 ); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SIR92 (Altomare et al., 1994 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ) within WinGX (Farrugia, 1999 ); molecular graphics: PLATON (Spek, 2009 ); software used to prepare material for publication: PLATON.

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536812016236/lh5454sup1.cif

e-68-o1468-sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812016236/lh5454Isup2.hkl

e-68-o1468-Isup2.hkl

Supplementary material file. DOI: 10.1107/S1600536812016236/lh5454Isup3.cml

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

Notes

[1] Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: LH5454).

Acknowledgements

The authors acknowledge financial support from the Australian Research Council, the Science and Engineering Faculty and the University Library, Queensland University of Technology and Griffith University.

Appendices

supplementary crystallographic information

Comment

G-protein-coupled receptors (GPCRs) constitute a superfamily of proteins whose main function is to convert extracellular stimuli into intracellular signals (Liu & Doller, 2011). Metabotropic glutamate (mGu) receptors belong to the class C GPCR group and are activated by L-glutamate. The title compound, C 9H 11NO 4. H 2O (I), is a hydrated tricyclic rearranged aminonorbornane dicarboxylic acid cage compound which is a conformationally rigid analogue of glutamic acid, and was synthesized as a potential ligand for metabotropic glutamate receptors in order to explore the requirements for activity at these receptors (Wermuth, 1995). For the synthesis of amino-substituted norbornane carboxylic acids, see also Tager & Christensen (1972) and Apgar & Ludwig (1972).

The title compound exists as an ammonium carboxylate zwitterion with the C3 carboxylate group endo-oriented (Fig. 1). Note that the stereochemical assignment of exo and endo on such nortricyclic systems is somewhat arbitrary and depends on how the system is drawn. The carboxylic acid group at C7 in (I) is exo and has the acid H-atom (H72) anti-located, forming a hydrogen bond with the water molecule of solvation (Table 1). This water molecule gives intermolecular hydrogen-bonding associations with carboxyl O-atom acceptors, while the ammonium group also forms four hydrogen bonds with carboxyl O-atom acceptors. These include a symmetric cyclic N—H···O, O' head-to-tail association [graph set R 2 1(4) (Etter et al., 1990)] which links the molecules along (100). Overall, a three-dimensional framework structure is formed (Fig. 2).

The structures of similar tricyclic norbornane compounds are rare in the crystallographic literature. The nortricyclic keto acid which served as the precursor to (IV) in the synthesis of (I) (Fig. 3) is known (Fortier et al. , 1979).

Experimental

The title compound (I) was synthesized (Wermuth, 1995) by the hydrolysis with Ba(OH) 2 of the diasteroisomeric hydantoin mixture (II), which was obtained by a Read synthesis (Avendaño López & González Trigo, 1985) performed on the nortricyclic keto-ester (IV) (Fig. 3). Briefly, a Strecker aminonitrile (Streker, 1850) is formed in the usual manner (50% yield) and this was converted to a hydrochloride (III) and reacted with KOCN in an acetic acid–water mixture at 273K for 1 h followed by the addition of conc. HCl and heating for a further 15 min at 273K. The product was a diastereomeric mixture of hydantoins in 49% yield after recrystallization from 50% aqueous ethanol. The stereochemistry of the amino acid moiety is the inverse (carboxylic acid group exo) of that normally formed in the Bucherer-Bergs reaction (Bucherer & Steiner, 1934). The colourless product obtained gave an elemental analysis consistent with a 0.25 hydrate but recrystallization from various solvents gave no crystals suitable for X-ray analysis. However, colourless plates of a monohydrate (I) were obtained from the attempted reaction of this partial hydrate with picrylsulfonic acid in 80% propan-2-ol-water and a specimen suitable for the X-ray analysis was cleaved from a larger crystal.

Refinement

Ammonium and water H atoms were located in a difference Fourier map and both positional and isotropic displacenment parameters were refined. Other H atoms were included in the refinement at calculated positions [C—H = 0.97–0.98 Å] with U iso(H) = 1.2 U eq(C), using a riding-model approximation. The relative configuration of the molecule described for (I) is C1( R), C2( S), C3( R), C4( R), C6( S), C7( R).

Figures

Fig. 1.

Molecular configuration and atom naming scheme of the zwitterionic title compound (I). The inter-species hydrogen bond is shown as a dashed line and displacement ellipsoids are drawn at the 40% probability level.

Molecular configuration and atom naming scheme of the zwitterionic title compound (I). The inter-species hydrogen bond is shown as a dashed line and displacement ellipsoids are drawn at the 40% probability level.
Fig. 2.

Hydrogen-bonding (shown as dashed lines) in the three-dimensionlal structure of the title compound, viewed approximately along the c axis. The symmetry codes are as in Table 1.

Hydrogen-bonding (shown as dashed lines) in the three-dimensionlal structure of the title compound, viewed approximately along the c axis. The symmetry codes are as in Table 1.
Fig. 3.

The reaction scheme for the synthesis of the title compound.

The reaction scheme for the synthesis of the title compound.

Crystal data

C 9H 11NO 4·H 2O F(000) = 456
M r = 215.20 D x = 1.569 Mg m 3
Monoclinic, P2 1/ c Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc Cell parameters from 3396 reflections
a = 7.7565 (2) Å θ = 3.2–28.6°
b = 11.4103 (2) Å µ = 0.13 mm 1
c = 10.3339 (3) Å T = 223 K
β = 94.888 (2)° Plate, colourless
V = 911.27 (4) Å 3 0.30 × 0.30 × 0.15 mm
Z = 4

Data collection

Oxford Diffraction Gemini-S Ultra CCD-detector diffractometer 2128 independent reflections
Radiation source: Enhance (Mo) X-ray source 1589 reflections with I > 2σ( I)
Graphite monochromator R int = 0.026
Detector resolution: 16.077 pixels mm -1 θ max = 28.6°, θ min = 3.2°
ω scans h = −9→10
Absorption correction: multi-scan ( CrysAlis PRO; Oxford Diffraction, 2010) k = −15→15
T min = 0.990, T max = 1.000 l = −13→13
7572 measured reflections

Refinement

Refinement on F 2 Primary atom site location: structure-invariant direct methods
Least-squares matrix: full Secondary atom site location: difference Fourier map
R[ F 2 > 2σ( F 2)] = 0.038 Hydrogen site location: inferred from neighbouring sites
wR( F 2) = 0.091 H atoms treated by a mixture of independent and constrained refinement
S = 0.97 w = 1/[σ 2( F o 2) + (0.0525 P) 2 + 0.0562 P] where P = ( F o 2 + 2 F c 2)/3
2128 reflections (Δ/σ) max = 0.001
160 parameters Δρ max = 0.31 e Å 3
0 restraints Δρ min = −0.25 e Å 3

Special details

Geometry. Bond distances, angles etc. have been calculated using the rounded fractional coordinates. All su's are estimated from the variances of the (full) variance-covariance matrix. The cell e.s.d.'s are taken into account in the estimation of distances, angles and torsion angles
Refinement. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2, conventional R-factors R are based on F, with F set to zero for negative F 2. The threshold expression of F 2 > σ( F 2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 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 (Å 2)

x y z U iso*/ U eq
O31 0.60834 (14) 0.12616 (8) 0.03042 (10) 0.0217 (3)
O32 0.57555 (15) 0.27409 (8) 0.16495 (11) 0.0291 (4)
O71 −0.10727 (14) 0.05736 (9) 0.32326 (12) 0.0311 (4)
O72 −0.08102 (14) −0.06274 (9) 0.16170 (11) 0.0273 (3)
N31 0.53370 (17) −0.03193 (10) 0.20183 (13) 0.0166 (3)
C1 0.26343 (19) 0.07189 (12) 0.39029 (14) 0.0190 (4)
C2 0.43453 (18) 0.12186 (11) 0.35275 (13) 0.0165 (4)
C3 0.45247 (17) 0.08675 (11) 0.21340 (13) 0.0142 (4)
C4 0.25626 (18) 0.08423 (11) 0.16738 (13) 0.0152 (4)
C5 0.19989 (19) 0.20682 (11) 0.20992 (13) 0.0176 (4)
C6 0.27559 (19) 0.19863 (12) 0.35020 (14) 0.0184 (4)
C7 0.18333 (18) 0.00565 (12) 0.27376 (13) 0.0171 (4)
C31 0.55486 (18) 0.17107 (11) 0.13073 (14) 0.0163 (4)
C71 −0.01187 (19) 0.00291 (12) 0.25744 (15) 0.0210 (4)
O1W 0.10015 (16) −0.21234 (11) 0.05407 (12) 0.0312 (4)
H1 0.24590 0.04870 0.47950 0.0230*
H2 0.53470 0.13290 0.41600 0.0200*
H4 0.22510 0.06230 0.07670 0.0180*
H5A 0.25210 0.26910 0.16270 0.0210*
H5B 0.07510 0.21590 0.20280 0.0210*
H6 0.26610 0.26310 0.41190 0.0220*
H7 0.23080 −0.07380 0.27130 0.0210*
H31A 0.509 (3) −0.0598 (15) 0.117 (2) 0.033 (5)*
H31B 0.650 (3) −0.0273 (14) 0.2222 (17) 0.028 (5)*
H31C 0.501 (2) −0.0843 (15) 0.2564 (18) 0.024 (4)*
H72 −0.007 (4) −0.115 (2) 0.124 (2) 0.063 (7)*
H11W 0.108 (3) −0.283 (2) 0.092 (2) 0.063 (7)*
H12W 0.207 (3) −0.1929 (19) 0.026 (2) 0.054 (6)*

Atomic displacement parameters (Å 2)

U 11 U 22 U 33 U 12 U 13 U 23
O31 0.0263 (6) 0.0193 (5) 0.0209 (5) −0.0048 (4) 0.0095 (4) −0.0035 (4)
O32 0.0346 (7) 0.0157 (5) 0.0393 (7) −0.0075 (5) 0.0158 (5) −0.0080 (5)
O71 0.0185 (6) 0.0331 (6) 0.0433 (7) 0.0021 (5) 0.0119 (5) −0.0028 (5)
O72 0.0153 (5) 0.0251 (5) 0.0410 (7) −0.0032 (5) 0.0002 (5) −0.0035 (5)
N31 0.0143 (6) 0.0135 (5) 0.0223 (7) 0.0010 (5) 0.0038 (5) 0.0020 (5)
C1 0.0167 (7) 0.0230 (7) 0.0175 (7) 0.0017 (6) 0.0032 (6) 0.0026 (5)
C2 0.0156 (7) 0.0182 (6) 0.0157 (7) −0.0008 (6) 0.0008 (5) −0.0003 (5)
C3 0.0126 (7) 0.0126 (6) 0.0176 (7) 0.0006 (5) 0.0020 (5) −0.0021 (5)
C4 0.0135 (7) 0.0164 (6) 0.0156 (7) −0.0001 (5) 0.0008 (5) −0.0002 (5)
C5 0.0167 (7) 0.0160 (6) 0.0203 (7) 0.0025 (6) 0.0030 (6) 0.0009 (5)
C6 0.0187 (7) 0.0182 (6) 0.0187 (7) 0.0015 (6) 0.0034 (6) −0.0031 (6)
C7 0.0140 (7) 0.0158 (6) 0.0220 (7) 0.0021 (6) 0.0038 (6) 0.0026 (5)
C31 0.0127 (7) 0.0167 (6) 0.0193 (7) −0.0005 (5) 0.0008 (5) 0.0002 (5)
C71 0.0172 (7) 0.0168 (6) 0.0294 (8) −0.0010 (6) 0.0047 (6) 0.0055 (6)
O1W 0.0263 (7) 0.0294 (6) 0.0394 (7) −0.0032 (5) 0.0118 (5) 0.0012 (5)

Geometric parameters (Å, º)

O31—C31 1.2580 (17) C2—C6 1.511 (2)
O32—C31 1.2341 (16) C3—C4 1.5556 (19)
O71—C71 1.2174 (19) C3—C31 1.5498 (19)
O72—C71 1.3180 (18) C4—C7 1.5615 (19)
O72—H72 0.94 (3) C4—C5 1.5407 (18)
O1W—H11W 0.90 (2) C5—C6 1.520 (2)
O1W—H12W 0.93 (2) C7—C71 1.509 (2)
N31—C3 1.5026 (17) C1—H1 0.9800
N31—H31A 0.94 (2) C2—H2 0.9800
N31—H31B 0.91 (2) C4—H4 0.9800
N31—H31C 0.874 (18) C5—H5A 0.9700
C1—C7 1.510 (2) C5—H5B 0.9700
C1—C6 1.5095 (19) C6—H6 0.9800
C1—C2 1.525 (2) C7—H7 0.9800
C2—C3 1.5125 (19)
C71—O72—H72 116.7 (16) C1—C7—C4 97.18 (11)
H11W—O1W—H12W 109 (2) C4—C7—C71 110.69 (11)
H31A—N31—H31B 110.8 (18) O31—C31—O32 125.46 (13)
C3—N31—H31C 114.7 (11) O31—C31—C3 114.95 (11)
C3—N31—H31A 109.1 (12) O32—C31—C3 119.58 (12)
C3—N31—H31B 110.1 (10) O71—C71—C7 125.36 (13)
H31B—N31—H31C 103.1 (15) O72—C71—C7 115.84 (12)
H31A—N31—H31C 108.9 (16) O71—C71—O72 118.79 (14)
C6—C1—C7 106.96 (12) C2—C1—H1 122.00
C2—C1—C7 106.99 (11) C6—C1—H1 122.00
C2—C1—C6 59.72 (9) C7—C1—H1 122.00
C3—C2—C6 106.15 (11) C1—C2—H2 122.00
C1—C2—C6 59.64 (9) C3—C2—H2 122.00
C1—C2—C3 107.21 (11) C6—C2—H2 122.00
N31—C3—C4 111.41 (10) C5—C4—H4 117.00
N31—C3—C31 106.12 (11) C7—C4—H4 117.00
N31—C3—C2 112.81 (11) C3—C4—H4 117.00
C2—C3—C31 116.96 (11) C4—C5—H5A 112.00
C4—C3—C31 112.14 (11) C6—C5—H5A 112.00
C2—C3—C4 97.41 (10) C6—C5—H5B 112.00
C3—C4—C5 100.95 (10) C4—C5—H5B 112.00
C5—C4—C7 101.06 (11) H5A—C5—H5B 110.00
C3—C4—C7 101.48 (10) C2—C6—H6 122.00
C4—C5—C6 96.91 (10) C5—C6—H6 122.00
C2—C6—C5 107.50 (11) C1—C6—H6 122.00
C1—C6—C5 107.01 (11) C4—C7—H7 111.00
C1—C6—C2 60.64 (9) C71—C7—H7 111.00
C1—C7—C71 116.11 (12) C1—C7—H7 111.00
C6—C1—C2—C3 −98.97 (12) C2—C3—C4—C7 −50.96 (11)
C7—C1—C2—C3 1.10 (14) C31—C3—C4—C5 −70.29 (13)
C7—C1—C2—C6 100.07 (12) C31—C3—C4—C7 −174.09 (10)
C2—C1—C6—C5 100.87 (12) N31—C3—C31—O31 34.29 (16)
C7—C1—C6—C2 −100.12 (12) N31—C3—C31—O32 −146.79 (13)
C7—C1—C6—C5 0.76 (15) C2—C3—C31—O31 161.14 (12)
C2—C1—C7—C4 −31.88 (13) C2—C3—C31—O32 −19.94 (19)
C2—C1—C7—C71 −149.16 (12) C4—C3—C31—O31 −87.56 (14)
C6—C1—C7—C4 30.86 (13) C4—C3—C31—O32 91.36 (15)
C6—C1—C7—C71 −86.42 (14) C3—C4—C5—C6 −51.88 (12)
C1—C2—C3—N31 −86.65 (13) C7—C4—C5—C6 52.27 (12)
C1—C2—C3—C4 30.35 (12) C3—C4—C7—C1 51.65 (12)
C1—C2—C3—C31 149.86 (11) C3—C4—C7—C71 173.10 (11)
C6—C2—C3—N31 −149.18 (11) C5—C4—C7—C1 −52.08 (12)
C6—C2—C3—C4 −32.19 (12) C5—C4—C7—C71 69.37 (13)
C6—C2—C3—C31 87.33 (14) C4—C5—C6—C1 −32.48 (14)
C1—C2—C6—C5 −100.06 (12) C4—C5—C6—C2 31.34 (13)
C3—C2—C6—C1 100.80 (12) C1—C7—C71—O71 6.7 (2)
C3—C2—C6—C5 0.74 (14) C1—C7—C71—O72 −174.76 (12)
N31—C3—C4—C5 170.94 (11) C4—C7—C71—O71 −102.86 (16)
N31—C3—C4—C7 67.13 (13) C4—C7—C71—O72 75.74 (15)
C2—C3—C4—C5 52.85 (11)

Hydrogen-bond geometry (Å, º)

D—H··· A D—H H··· A D··· A D—H··· A
O1 W—H11 W···O71 i 0.90 (2) 2.02 (2) 2.9161 (16) 176 (2)
O1 W—H12 W···O31 ii 0.93 (2) 1.77 (2) 2.6792 (16) 168 (2)
N31—H31 A···O31 ii 0.94 (2) 1.87 (2) 2.7712 (17) 161 (2)
N31—H31 B···O71 iii 0.91 (2) 2.29 (2) 3.1261 (17) 153.0 (15)
N31—H31 B···O72 iii 0.91 (2) 2.27 (2) 3.0720 (17) 147.6 (15)
N31—H31 C···O32 iv 0.874 (18) 1.925 (17) 2.7769 (16) 164.4 (17)
O72—H72···O1 W 0.94 (3) 1.60 (3) 2.5282 (16) 174 (3)
C5—H5 A···O32 0.97 2.51 3.0865 (19) 118
C6—H6···O72 v 0.98 2.53 3.1105 (17) 118
C7—H7···N31 0.98 2.56 2.9097 (19) 101
C7—H7···O32 iv 0.98 2.35 3.2678 (17) 155

Symmetry codes: (i) − x, y−1/2, − z+1/2; (ii) − x+1, − y, − z; (iii) x+1, y, z; (iv) − x+1, y−1/2, − z+1/2; (v) − x, y+1/2, − z+1/2.

References

1  

Altomare, A., Cascarano, G., Giacovazzo, C., Guagliardi, A., Burla, M. C., Polidori, G. & Camalli, M. (1994). J. Appl. Cryst. 27, 435.

2  

Apgar, P. A. & Ludwig, M. L. (1972). J. Am. Chem. Soc. 94, 964–967.

3  

Avendaño López, C. & González Trigo, G. (1985). Advances in Heterocyclic Chemistry, Vol. 38, edited by A. R. Katritsky, pp. 177–228. Amsterdam: Elsevier.

4  

Bucherer, H. T. & Steiner, W. J. (1934). J. Prakt. Chem. 140, 291–316.

5  

Etter, M. C., MacDonald, J. C. & Bernstein, J. (1990). Acta Cryst. B 46, 256–262.

6  

Farrugia, L. J. (1999). J. Appl. Cryst. 32, 837–838.

7  

Fortier, S., DeTitta, G., Fronckowiak, M., Smith, G. D. & Hauptman, H. A. (1979). Acta Cryst. B 35, 2062–2066.

8  

Liu, K. G. & Doller, D. (2011). Annual Reports in Medicinal Chemistry, pp. 3–17. Amsterdam: Elsevier.

9  

Oxford Diffraction (2010). CrysAlis PRO Oxford Diffraction Ltd, Yarnton, England.

10  

Sheldrick, G. M. (2008). Acta Cryst. A 64, 112–122.

11  

Spek, A. L. (2009). Acta Cryst. D 65, 148–155.

12  

Strecher, A. (1850). Ann. Chem. Pharm. 75, 27–45.

13  

Tager, H. S. & Christensen, H. N. (1972). J. Am. Chem. Soc. 94, 968–972.

14  

Wermuth, U. D. (1995). PhD thesis, Griffith University, Nathan, Australia.

Figures and Tables

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯ A D—H H⋯ A DA D—H⋯ A
O1 W—H11 W⋯O71 i 0.90 (2) 2.02 (2) 2.9161 (16) 176 (2)
O1 W—H12 W⋯O31 ii 0.93 (2) 1.77 (2) 2.6792 (16) 168 (2)
N31—H31 A⋯O31 ii 0.94 (2) 1.87 (2) 2.7712 (17) 161 (2)
N31—H31 B⋯O71 iii 0.91 (2) 2.29 (2) 3.1261 (17) 153.0 (15)
N31—H31 B⋯O72 iii 0.91 (2) 2.27 (2) 3.0720 (17) 147.6 (15)
N31—H31 C⋯O32 iv 0.874 (18) 1.925 (17) 2.7769 (16) 164.4 (17)
O72—H72⋯O1 W 0.94 (3) 1.60 (3) 2.5282 (16) 174 (3)

Symmetry codes: (i) e-68-o1468-efi2.jpg ; (ii) e-68-o1468-efi3.jpg ; (iii) e-68-o1468-efi4.jpg ; (iv) e-68-o1468-efi5.jpg .