Buy article online - an online subscription or single-article purchase is required to access this article.
Download citation
Download citation
link to html
A new polymorph of pergolide mesyl­ate or 8[beta]-[(methyl­sul­fan­yl)­methyl]-6-propyl­ergoline methane­sulfonate, C19H27N2S+·CH3SO3-, is reported. Pergolide mesyl­ate form II crystallizes in the trigonal system, which is unique for ergot derivatives. Although the hydrogen-bond system in form II differs completely from that in form I, the conformation of the pergolide moiety in various related structures is very similar.

Supporting information

cif

Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270103017499/sk1650sup1.cif
Contains datablocks global, I

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S0108270103017499/sk1650Isup2.hkl
Contains datablock I

CCDC reference: 224664

Comment top

Pergolide mesylate, (I), is a semisynthetic ergot derivative used as an important drug mainly in the treatment of Parkinson's disease (Wachtel, 1991). The crystal structure of pergolide mesylate [triclinic P1; a = 6.841 (2), b = 9.314 (2), c = 9.678 (2) Å, α = 64.42 (2), β = 69.67 (2), γ =76.74 (2)°] and the pergolide base have been described previously by Ma et al. (1987). The former structure refers to form I as described by Sprankle & Jensen (1992). Pergolide mesylate form II was described only in a mixture with form I based on only one new diffraction line that appeared in the powder diffraction data and by some differences in the fingerprint region of the IR spectrum (775, 607 and 544 cm−1). However, no more evidence of form II was ever reported. As well as the structures of pergolide and pergolide mesylate, the structure of pergolide sulfoxide, a pergolide metabolite exhibiting roughly equal pharmacological activity as pergolide, has been reported (Čejka et al., 1998).

Pergolide mesylate form II crystallizes in the trigonal space group P3221. Conformational analysis has shown that there are only subtle differences between the independent molecules in individual structures. The ergoline skeleton is virtually identical in all pergolide derivatives. Only one of the two independent molecules of pergolide sulfoxide differs in the orientation of the sulfoxy group (see Fig. 1). Although there are a number of coincidences of diffraction lines in powder diffractograms, pergolide mesylate forms I and II can be easily distinguished by the presence of the sole diffraction lines (014) 6.329 Å and (003) 14.96 Å in form II, and (001) 8.372 Å in form I, which can potentially serve also for the quantitative analysis of the mixtures.

The DTA thermogram for pergolide mesylate form II shows a sharp endotherm at 534.5 K (decomposition), which is identical, within experimental error, to pergolide mesylate form I. In addition to a number of subtle changes in the fingerprint region of the IR spectrum in the range 450–800 cm−1, there are also noticeable changes in the range 1400–1500 cm−1 (aliphatic C—H deformation), which can serve to discriminate between the two forms. More interestingly, changes in N—H deformation (~780 cm−1 for indole N—H), N+—H stretch (2556 cm−1 in form I and ~2600–2700 cm−1 in form II), and N—H stretch (3180 cm−1 in form I and 3200 cm−1 in form II for indole N—H) bands indicate the substantially different hydrogen-bond network in the individual forms. Although the same atoms and similar hydrogen bonds are utilized in the hydrogen-bond networks (see Table 2), the final arrangement is very different. In form I, the molecules form bridges to each other through the mesylate anions, forming simple narrow chains. In contrast, pergolide molecules and mesylate anions create zigzag screwed chains in several directions in form II. It should be noted that the orientations of the mesylate methyl groups are also different in both structures.

Experimental top

Pergolide mesylate (1.64 kg) was dissolved in a stainless steel drum in aqueous ethanol (22 l of ethanol, 4 l of water and 3.3 g of ascorbic acid) under nitrogen at 333 K. Crystals of pergolide mesylate form II (1.13 kg, 68.9%) were obtained upon cooling the solution to 295 K and these crystals were isolated by filtration and dried in air.

Refinement top

H atoms were placed in calculated positions and refined riding on their attached C atoms in distances of 1.0 Å. Atoms H511 and H521 were located in difference Fourier maps and refined fixed. The absolute configuration could not be determined reliably via anomalous dispersion and was choosen to be consistent with that of the natural product.

Computing details top

Data collection: COLLECT (Nonius, 1997); cell refinement: DENZO/SCALEPACK (Otwinowski & Minor, 1997); data reduction: DENZO/SCALEPACK; program(s) used to solve structure: SIR92 (Altomare et al., 1994); program(s) used to refine structure: CRYSTALS (Watkin et al., 2001); molecular graphics: ORTEP-3 (Farrugia, 1997); software used to prepare material for publication: CRYSTALS.

Figures top
[Figure 1] Fig. 1. ORTEP-3 (Farrugia, 1997) drawing of pergolide form II, with the atom-numbering scheme for non-H atoms and 50% probability displacement ellipsoids. H atoms are shown as small circles of arbitrary radii.
[Figure 2] Fig. 2. A packing diagram of pergolide form II (ORTEP-3; Farrugia, 1997), viewed normal to (010).
[Figure 3] Fig. 3. Fitted pergolide derivatives (fit based on fused rings to reveal differences in sidechains), form I black, form II dark grey, pergolide grey and the two independent molecules of pergolide sulfoxide light grey.
8β-[(methylsulfanyl)methyl]-6-propylergolinium methanesulfonate top
Crystal data top
C19H27N2S+·CH3O3SDx = 1.343 Mg m3
Mr = 410.60Melting point: not measured K
Trigonal, P3221Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 32 2"Cell parameters from 4009 reflections
a = 8.8510 (2) Åθ = 1.0–26.0°
c = 44.8860 (8) ŵ = 0.29 mm1
V = 3045.27 (11) Å3T = 293 K
Z = 6Block, white
F(000) = 13200.35 × 0.26 × 0.23 mm
Data collection top
Nonius KappaCCD
diffractometer
Rint = 0.02
Graphite monochromatorθmax = 26.0°, θmin = 1.4°
ϕ and ω scansh = 1010
7908 measured reflectionsk = 88
2389 independent reflectionsl = 5555
1937 reflections with I > 1.96σ(I)
Refinement top
Refinement on FPrimary atom site location: structure-invariant direct methods
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.030H-atom parameters constrained
wR(F2) = 0.034 Prince modified Chebychev polynomial (Watkin, 1994); W = [weight][1-(δF/6σF)2]2, with 0.551, 0.377 and 0.369
S = 1.15(Δ/σ)max = 0.000375
1937 reflectionsΔρmax = 0.22 e Å3
244 parametersΔρmin = 0.23 e Å3
Crystal data top
C19H27N2S+·CH3O3SZ = 6
Mr = 410.60Mo Kα radiation
Trigonal, P3221µ = 0.29 mm1
a = 8.8510 (2) ÅT = 293 K
c = 44.8860 (8) Å0.35 × 0.26 × 0.23 mm
V = 3045.27 (11) Å3
Data collection top
Nonius KappaCCD
diffractometer
1937 reflections with I > 1.96σ(I)
7908 measured reflectionsRint = 0.02
2389 independent reflections
Refinement top
R[F2 > 2σ(F2)] = 0.030244 parameters
wR(F2) = 0.034H-atom parameters constrained
S = 1.15Δρmax = 0.22 e Å3
1937 reflectionsΔρmin = 0.23 e Å3
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
S10.0225 (1)0.2082 (1)0.287236 (17)0.0408
S20.75195 (9)0.63950 (8)0.269633 (13)0.0265
O10.8441 (3)0.7483 (3)0.24427 (4)0.0423
O20.7400 (3)0.4696 (3)0.26815 (4)0.0406
O30.5855 (3)0.6273 (3)0.27508 (4)0.0449
N10.8724 (3)0.2581 (3)0.13712 (4)0.0315
N20.4787 (3)0.1462 (3)0.25224 (4)0.0232
C10.8867 (3)0.2171 (3)0.16622 (6)0.0295
C20.7598 (3)0.2207 (3)0.18304 (5)0.0260
C30.7082 (3)0.1864 (4)0.21541 (5)0.0259
C40.5177 (3)0.1455 (3)0.21902 (5)0.0227
C50.2942 (3)0.1055 (3)0.25720 (5)0.0270
C60.2597 (3)0.2388 (3)0.24219 (5)0.0249
C70.2921 (3)0.2389 (3)0.20885 (5)0.0274
C80.4777 (3)0.2767 (3)0.20301 (5)0.0235
C90.5242 (4)0.2896 (3)0.17023 (5)0.0269
C100.4484 (4)0.3299 (3)0.14667 (5)0.0295
C110.5184 (4)0.3524 (4)0.11764 (6)0.0326
C120.6629 (4)0.3351 (3)0.11112 (6)0.0310
C130.7362 (3)0.2894 (3)0.13471 (6)0.0289
C140.6645 (3)0.2666 (3)0.16348 (5)0.0256
C150.5150 (4)0.0259 (4)0.27087 (5)0.0280
C160.5175 (5)0.0577 (4)0.30384 (6)0.0404
C170.5497 (4)0.0671 (4)0.32167 (6)0.0362
C180.0732 (3)0.1986 (4)0.24846 (6)0.0327
C190.1359 (4)0.4391 (4)0.29398 (7)0.0440
C300.8833 (4)0.7397 (4)0.30097 (6)0.0372
H110.97620.18940.173890.0351*
H310.78710.29180.227470.0319*
H320.71820.08460.222490.0319*
H410.44270.02890.209560.0290*
H510.27340.10600.279090.0317*
H520.21260.01270.248870.0317*
H610.34040.35760.250410.0301*
H710.27500.33060.199010.0324*
H720.20750.12200.200390.0324*
H810.55400.39500.211780.0277*
H1010.34420.34320.150300.0339*
H1110.46170.38200.101130.0373*
H1210.71210.35430.090510.0324*
H1510.63130.04240.264980.0377*
H1520.42230.09700.266620.0377*
H1610.61140.17980.308240.0552*
H1620.40190.04260.309810.0552*
H1710.54990.04100.343350.0458*
H1720.66560.05260.316030.0458*
H1730.45610.18990.317600.0458*
H1810.05380.28500.237210.0386*
H1820.00870.07840.240950.0386*
H1910.11770.46180.315130.0551*
H1920.26340.48790.290230.0551*
H1930.09010.49620.280320.0551*
H3010.89810.85860.303600.0429*
H3020.82640.66780.319100.0429*
H3031.00010.75000.298050.0429*
H5110.93290.25930.125080.0500*
H5210.55250.25640.259080.0500*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
S10.0362 (4)0.0416 (4)0.0490 (4)0.0227 (4)0.0182 (3)0.0163 (3)
S20.0266 (3)0.0243 (3)0.0249 (3)0.0099 (3)0.0043 (3)0.0025 (2)
O10.0394 (12)0.0453 (12)0.0314 (9)0.013 (1)0.0026 (8)0.0111 (9)
O20.0453 (13)0.025 (1)0.0503 (12)0.017 (1)0.015 (1)0.0102 (9)
O30.0348 (12)0.0583 (15)0.0446 (11)0.0256 (11)0.0040 (9)0.008 (1)
N10.0317 (12)0.0298 (12)0.029 (1)0.012 (1)0.0081 (9)0.001 (1)
N20.0235 (11)0.022 (1)0.0244 (9)0.0113 (9)0.0006 (8)0.0001 (8)
C10.0280 (14)0.0279 (14)0.0321 (12)0.0137 (12)0.0012 (11)0.0003 (11)
C20.0262 (13)0.0222 (13)0.0273 (12)0.0104 (11)0.000 (1)0.002 (1)
C30.0257 (13)0.0285 (14)0.0265 (12)0.0158 (12)0.001 (1)0.001 (1)
C40.0263 (13)0.0238 (12)0.020 (1)0.014 (1)0.0011 (9)0.0006 (9)
C50.0236 (12)0.0246 (13)0.0315 (11)0.0111 (11)0.003 (1)0.003 (1)
C60.0206 (12)0.0242 (13)0.0309 (12)0.012 (1)0.001 (1)0.0018 (11)
C70.0263 (14)0.0229 (13)0.0318 (12)0.0115 (12)0.0021 (11)0.001 (1)
C80.0283 (14)0.0180 (12)0.0243 (12)0.0118 (11)0.002 (1)0.0013 (9)
C90.0310 (14)0.0184 (12)0.0279 (12)0.0098 (11)0.0003 (11)0.001 (1)
C100.0311 (15)0.0225 (13)0.0311 (12)0.0105 (12)0.0041 (11)0.0021 (11)
C110.0411 (17)0.0248 (14)0.0270 (13)0.0126 (13)0.0054 (12)0.001 (1)
C120.0344 (15)0.0208 (13)0.0252 (12)0.0044 (12)0.0013 (11)0.001 (1)
C130.0289 (13)0.0194 (13)0.0307 (13)0.0063 (12)0.001 (1)0.002 (1)
C140.0264 (13)0.0188 (13)0.0261 (11)0.0073 (11)0.000 (1)0.001 (1)
C150.0375 (15)0.0302 (15)0.0250 (12)0.0234 (13)0.0019 (11)0.002 (1)
C160.062 (2)0.0477 (18)0.0262 (12)0.0384 (17)0.0047 (13)0.0046 (12)
C170.0485 (18)0.0378 (16)0.0287 (12)0.0264 (14)0.0029 (12)0.0042 (12)
C180.0245 (13)0.0308 (15)0.0437 (15)0.0145 (11)0.0030 (11)0.0037 (12)
C190.0491 (19)0.0526 (19)0.0371 (14)0.0306 (16)0.0119 (14)0.0056 (13)
C300.0406 (17)0.0352 (16)0.0305 (12)0.0151 (13)0.0099 (12)0.0086 (12)
Geometric parameters (Å, º) top
S1—C181.810 (3)C7—H721.000
S1—C191.796 (3)C8—C91.517 (3)
S2—O11.450 (2)C8—H811.000
S2—O21.455 (2)C9—C101.391 (4)
S2—O31.443 (2)C9—C141.389 (4)
S2—C301.757 (3)C10—C111.413 (4)
N1—C11.378 (3)C10—H1011.000
N1—C131.369 (4)C11—C121.393 (4)
N1—H5110.757C11—H1111.000
N2—C41.531 (3)C12—C131.403 (4)
N2—C51.502 (3)C12—H1211.000
N2—C151.510 (3)C13—C141.408 (3)
N2—H5210.914C15—C161.505 (3)
C1—C21.367 (4)C15—H1511.000
C1—H111.000C15—H1521.000
C2—C31.508 (3)C16—C171.502 (4)
C2—C141.411 (3)C16—H1611.000
C3—C41.546 (3)C16—H1621.000
C3—H311.000C17—H1711.000
C3—H321.000C17—H1721.000
C4—C81.550 (3)C17—H1731.000
C4—H411.000C18—H1811.000
C5—C61.517 (3)C18—H1821.000
C5—H511.000C19—H1911.000
C5—H521.000C19—H1921.000
C6—C71.524 (3)C19—H1931.000
C6—C181.531 (4)C30—H3011.000
C6—H611.000C30—H3021.000
C7—C81.527 (4)C30—H3031.000
C7—H711.000
C18—S1—C19101.80 (13)C7—C8—H81104.55
O1—S2—O2112.12 (14)C9—C8—H81106.70
O1—S2—O3113.36 (13)C8—C9—C10127.5 (2)
O2—S2—O3112.75 (14)C8—C9—C14115.4 (2)
O1—S2—C30106.42 (13)C10—C9—C14116.9 (2)
O2—S2—C30104.25 (14)C9—C10—C11120.2 (3)
O3—S2—C30107.17 (14)C9—C10—H101119.87
C1—N1—C13109.5 (2)C11—C10—H101119.90
C1—N1—H511121.50C10—C11—C12122.7 (3)
C13—N1—H511128.95C10—C11—H111118.60
C4—N2—C5111.32 (18)C12—C11—H111118.74
C4—N2—C15114.11 (18)C11—C12—C13117.1 (2)
C5—N2—C15109.74 (19)C11—C12—H121121.41
C4—N2—H521106.84C13—C12—H121121.49
C5—N2—H521108.49N1—C13—C12134.3 (2)
C15—N2—H521106.01N1—C13—C14106.1 (2)
N1—C1—C2109.4 (2)C12—C13—C14119.6 (3)
N1—C1—H11125.41C2—C14—C9127.9 (2)
C2—C1—H11125.16C2—C14—C13108.7 (2)
C1—C2—C3134.2 (2)C9—C14—C13123.4 (2)
C1—C2—C14106.2 (2)N2—C15—C16113.7 (2)
C3—C2—C14119.6 (2)N2—C15—H151108.48
C2—C3—C4109.5 (2)C16—C15—H151108.35
C2—C3—H31109.47N2—C15—H152108.26
C4—C3—H31109.46C16—C15—H152108.56
C2—C3—H32109.48H151—C15—H152109.466
C4—C3—H32109.45C15—C16—C17112.1 (2)
H31—C3—H32109.467C15—C16—H161108.85
N2—C4—C3108.83 (19)C17—C16—H161109.23
N2—C4—C8108.18 (18)C15—C16—H162108.65
C3—C4—C8114.0 (2)C17—C16—H162108.47
N2—C4—H41112.52H161—C16—H162109.467
C3—C4—H41106.30C16—C17—H171109.10
C8—C4—H41107.08C16—C17—H172109.27
N2—C5—C6111.4 (2)H171—C17—H172109.476
N2—C5—H51108.98C16—C17—H173110.03
C6—C5—H51108.90H171—C17—H173109.476
N2—C5—H52108.98H172—C17—H173109.476
C6—C5—H52109.05S1—C18—C6115.43 (19)
H51—C5—H52109.467S1—C18—H181107.97
C5—C6—C7109.0 (2)C6—C18—H181107.88
C5—C6—C18110.6 (2)S1—C18—H182108.0
C7—C6—C18111.2 (2)C6—C18—H182108.02
C5—C6—H61109.73H181—C18—H182109.467
C7—C6—H61109.05S1—C19—H191109.51
C18—C6—H61107.31S1—C19—H192109.3
C6—C7—C8110.5 (2)H191—C19—H192109.476
C6—C7—H71109.22S1—C19—H193109.54
C8—C7—H71109.21H191—C19—H193109.476
C6—C7—H72109.24H192—C19—H193109.476
C8—C7—H72109.16S2—C30—H301109.4
H71—C7—H72109.467S2—C30—H302109.5
C4—C8—C7112.3 (2)H301—C30—H302109.476
C4—C8—C9110.6 (2)S2—C30—H303109.5
C7—C8—C9113.9 (2)H301—C30—H303109.476
C4—C8—H81108.32H302—C30—H303109.476

Experimental details

Crystal data
Chemical formulaC19H27N2S+·CH3O3S
Mr410.60
Crystal system, space groupTrigonal, P3221
Temperature (K)293
a, c (Å)8.8510 (2), 44.8860 (8)
V3)3045.27 (11)
Z6
Radiation typeMo Kα
µ (mm1)0.29
Crystal size (mm)0.35 × 0.26 × 0.23
Data collection
DiffractometerNonius KappaCCD
diffractometer
Absorption correction
No. of measured, independent and
observed [I > 1.96σ(I)] reflections
7908, 2389, 1937
Rint0.02
(sin θ/λ)max1)0.617
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.030, 0.034, 1.15
No. of reflections1937
No. of parameters244
No. of restraints?
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)0.22, 0.23

Computer programs: COLLECT (Nonius, 1997), DENZO/SCALEPACK (Otwinowski & Minor, 1997), DENZO/SCALEPACK, SIR92 (Altomare et al., 1994), CRYSTALS (Watkin et al., 2001), ORTEP-3 (Farrugia, 1997), CRYSTALS.

Hydrogen bonds (Å, °) in pergolide mesylate polymorphs top
Pergolide form Ia
N1—H···O2x, y − 1, z + 12.853
N2—H521···O2x + 1, y, z2.723
Pergolide form IIbSymmetry codeD ··· AD—H···A
N1—H511···O1x-y + 1, −y + 1, −z + 1/32.946 (3)176
N2—H521···O22.726 (2)166
Notes: (a) Ma et al. (1987); (b) this work.
 

Subscribe to Acta Crystallographica Section C: Structural Chemistry

The full text of this article is available to subscribers to the journal.

If you have already registered and are using a computer listed in your registration details, please email support@iucr.org for assistance.

Buy online

You may purchase this article in PDF and/or HTML formats. For purchasers in the European Community who do not have a VAT number, VAT will be added at the local rate. Payments to the IUCr are handled by WorldPay, who will accept payment by credit card in several currencies. To purchase the article, please complete the form below (fields marked * are required), and then click on `Continue'.
E-mail address* 
Repeat e-mail address* 
(for error checking) 

Format*   PDF (US $40)
   HTML (US $40)
   PDF+HTML (US $50)
In order for VAT to be shown for your country javascript needs to be enabled.

VAT number 
(non-UK EC countries only) 
Country* 
 

Terms and conditions of use
Contact us

Follow Acta Cryst. C
Sign up for e-alerts
Follow Acta Cryst. on Twitter
Follow us on facebook
Sign up for RSS feeds