Sildenafil citrate monohydrate

(1)

organic papers

Acta Cryst.(2005). E61, o489±o491 doi:10.1107/S1600536805002564 H. S. Yathirajanet al. Sildenafil citrate monohydrate

o489

Acta Crystallographica Section E

Structure Reports Online

ISSN 1600-5368

Sildenafil citrate monohydrate

Hemmige S. Yathirajan,a

Basavegowda Nagaraj,a

Padmarajaiah Nagarajaa_and

Michael Bolteb_*

a_{Department of Studies in Chemistry, University}

of Mysore, Manasagangotri, Mysore 570 006, India, andb_{Institut fuÈr Anorganische Chemie,} J. W. Goethe-UniversitaÈt Frankfurt, Marie-Curie-Straûe 11, 60439 Frankfurt/Main, Germany

Correspondence e-mail: [email protected]

Key indicators Single-crystal X-ray study

T= 173 K

Mean(C±C) = 0.008 AÊ

Rfactor = 0.079

wRfactor = 0.154

Data-to-parameter ratio = 13.7

For details of how these key indicators were automatically derived from the article, see http://journals.iucr.org/e.

Sildena®l citrate is well known as Viagra for the treatment of erectile dysfuncion. In the title compound (systematic name:

1-{[3-(6,7-Dihydro-1-methyl-7-oxo-3-propyl-1H

-pyrazolo[4,3-d

]pyrimidin-5-yl)-4-ethoxyphenyl]sulfonyl}-4-methylpiperaz-inium citrate monohydrate), C22H31N6O4S+C6H7O7ÿH2O,

the pyrazolopyrimidone ring system and the benzene ring are almost coplanar, enabling an intramolecular hydrogen bond between the pyrazolopyrimidone NH group and the O atom of the ethoxy group. One of the N atoms of the piperazine ring is protonated and the citrate molecule exists as an anion. The crystal packing is stabilized by several hydrogen bonds.

Comment

Sildena®l citrate is used to treat male erectile dysfunction under the trade name Viagra. The parent base, sildena®l, is a potent selective inhibitor of the enzyme phosphodiesterase (PDE-5), which destroys cyclic guanosine monophosphate (cGMP), itself a dilator of blood vessels in the body (Terrettet

al., 1996). The discovery and development of sildena®l has

been a revolutionary event in medicine and society. A detailed review of sildena®l citrate has been published by McCullough (2002).

A perspective view of the title compound, (I), the mono-hydrate of sildena®l citrate, is shown in Fig. 1. Bond lengths

(2)

and angles can be regarded as normal (Cambridge Structural

Database, Version 1.6 plus three updates; MOGUL Version

1.0; Allen, 2002). The piperazine ring shows the expected chair conformation, with the methyl and sulfonyl groups attached equatorially. The propyl and ethoxy side chains are in atrans

conformation.

The crystal structure of isosildena®l, an isomeric compound of sildena®l, methylated at N2 of the pyrazolopyrimidone ring

system, has been reported by El-Abadelahet al. (1999). The

main difference between (I) and isosildena®l is that in the sildena®l cation of (I), the pyrazolopyrimidone ring system and the benzene ring are almost coplanar. The dihedral angle between the two cyclic groups is 11.6 (3)_{, whereas this angle is}

43.3 (1)_{in isosildena®l. As a result, in (I), there is a hydrogen}

bond between the pyrazolopyrimidone NH group and the O atom of the ethoxy group (Table 2). In isosildena®l, however, this interaction is signi®cantly weaker (NÐH = 0.95 AÊ, H O

= 2.35 AÊ, N O = 2.767 AÊ and NÐH O 106.1_).

Further-more, the conformation of the propyl chains differ. The

conformation is trans [ÿ173.4 (6)_{] in (I) and} _gauche _in

isosildena®l [ÿ60.6 (7)_{]. A least-squares ®t of (I) with}

isosildena®l is shown in Fig. 2. Apart from the intramolecular

hydrogen bond, there are several intermolecular hydrogen bonds. It is interesting to note that there is no direct hydrogen bond between the sildena®l molecules, but the citrate anions function as a link between them. The water molecule does not act as an acceptor but just as a donor to a citrate anion and to sulfonyl atom O1 of a sildena®l cation (Table 2). The depro-tonated carboxy group of the citrate molecule shows a signi®cantly different geometry than the two other carboxyl groups: the two CÐO bonds have the same length and the OÐCÐO angle is enlarged (Table 1).

The cell parameters of sildena®l citrate without any solvent, determined by powder diffraction (Melnikovet al., 2003), are totally different from those of the title compound:a= 26.98 AÊ,

b= 11.95 AÊ,c= 16.68 AÊ, and= 106.96_{V = 5143.9 AÊ}3_.

Experimental

Sildena®l citrate was obtained as a gift sample from CIPLA, Mumbai, India, and used without further puri®cation. Recrystallization from dimethylformamide yielded needles of (I) after slow evaporation of the solvent. The title compound melts at 460 K. IR (KBr,cmÿ1_): 3616 (m), 3478 (m), 3300 (s), 3029 (m), 2962 (m), 2870 (m), 2563 (w), 2362 (m), 1702 (vs), 1581 (s), 1491 (m), 1462 (m), 1394 (m), 1359 (m), 1280 (m), 1250 (m), 1172 (s), 1096 (w), 1027 (m), 995 (s), 940 (m), 808 (m), 736 (s), 690 (m), 657 (m), 617 (m), 588 (s), 557 (m);1_{H NMR} (DMSO-d6, p.p.m.): 0.86±0.90 (t, 3H, CH3±), 1.27±1.31 (t, 3H, CH3Ð), 1.64±1.73 (m, 2H, CH2Ð), 2.29 (s, 4H, CH2Ð), 2.55±2.75 (t, 2H, CH2Ð), 2.96 (bs, 1H, NHÐ), 3.94 (bm, 13H, NÐCHÐ), 4.11±4.2 (s, 3H, N+_ÐCH

3Ð), 7.34±7.36 (d, 1H, ArHÐ), 7.79±7.83 (d, 2H, ArHÐ ), 12.19 (bs, 1H, N+_HÐ);13_{C NMR (DMSO-}_d

6, p.p.m.): 14.24 (q, C42, CH3Ð), 14.67 (q, C29, CH3Ð), 22.13 (t, C41, CH2Ð), 27.53 (t, C2, CH2Ð), 38.3 (t, C40, CH2Ð), 39.1±40.35 (t, C12,C13,C15,C16, CH2Ð ), 43.64 (q, C37, CH3Ð), 44.71 (d, C35, C CÐ), 53.34 (d, C34, C CÐ), 65.39 (t, C28, CH2Ð), 72.59 (q, C17, CH3Ð), 124.03

organic papers

o490

H. S. Yathirajanet al. Sildenafil citrate monohydrate Acta Cryst.(2005). E61, o489±o491

Figure 1

Perspective view of the title compound, with the atom numbering; displacement ellipsoids are drawn at the 30% probability level.

Figure 2

(3)

(d, C26, ArCHÐ), 124.82 (d, C22, ArCHÐ), 126.52 (s, C23), 130.43 (d, C25, ArCHÐ), 132.02 (s, C24, ArCÐ), 138.18 (s, C21, ArC), 145.45 (s, C39, C NÐ), 148.55 (s, C6, COOÿ_{Ð), 154.24 (}_s_{, C5,}

HOOCÐ), 160.45 (s, C33, C O±), 171.87 (s, C31), 175.81 (s, C3, citrate CÐ). Analysis calculated for C28H40N6O12S: C 49.11, H 5.89, N 12.27%; found: C 49.31, H 5.81, N 12.4%.

Crystal data

C22H31N6O4S+C6H7O7ÿH2O Mr= 684.72

Orthorhombic,Pbca a= 24.002 (4) AÊ

b= 10.9833 (17) AÊ

c= 24.364 (3) AÊ

V= 6422.9 (17) AÊ3 Z= 8

Dx= 1.416 Mg mÿ3

MoKradiation Cell parameters from 8732

re¯ections = 2.0±23.1

= 0.17 mmÿ1 T= 173 (2) K Rod, colourless 0.260.120.11 mm

Data collection

Stoe IPDS-II two-circle diffractometer !scans

Absorption correction: multi-scan (MULABS; Spek, 2003; Blessing, 1995)

Tmin= 0.937,Tmax= 0.951

44385 measured re¯ections

5856 independent re¯ections 1970 re¯ections withI> 2(I)

Rint= 0.098

max= 25.4 h=ÿ28!28

k=ÿ13!13

l=ÿ29!27

Refinement

Re®nement onF2 R[F2_{> 2}₍_F2_{)] = 0.079} wR(F2_{) = 0.154} S= 0.78 5856 re¯ections 428 parameters

H-atom parameters constrained

w= 1/[2₍_F

o2) + (0.0407P)2]

whereP= (Fo2+ 2Fc2)/3

(/)max< 0.001 max= 0.38 e AÊÿ3 min=ÿ0.42 e AÊÿ3

Table 1

Selected geometric parameters (AÊ,_).

S1ÐO1 1.428 (4)

S1ÐO2 1.443 (4)

S1ÐN11 1.630 (5)

N11ÐC16 1.470 (7) N11ÐC12 1.485 (6) C13ÐN14 1.507 (7) N14ÐC17 1.486 (7) N14ÐC15 1.504 (7) C31ÐN36 1.295 (7) C31ÐN32 1.383 (7) N32ÐC33 1.367 (7) C33ÐC34 1.447 (8) C34ÐN37 1.359 (7)

C34ÐC35 1.385 (8) C35ÐN36 1.361 (7) C35ÐC39 1.417 (8) N37ÐN38 1.352 (6) N37ÐC37 1.450 (7)

C1ÐO11 1.204 (7)

C1ÐO12 1.293 (7)

C3ÐO3 1.423 (6)

C5ÐO51 1.224 (8)

C5ÐO52 1.318 (8)

C6ÐO61 1.258 (7)

C6ÐO62 1.259 (7)

O11ÐC1ÐO12 120.6 (7)

O51ÐC5ÐO52 119.9 (7) O61ÐC6ÐO62 126.3 (6)

Table 2

Hydrogen-bonding geometry (AÊ,_).

DÐH A DÐH H A D A DÐH A

N14ÐH14 O3 0.93 1.88 2.764 (6) 159 N14ÐH14 O62 0.93 2.30 2.911 (6) 123 N32ÐH32 O27 0.88 1.94 2.622 (6) 134 O12ÐH12 N38i _0.84 _1.98 _{2.771 (7)} ₁₅₇

O3ÐH3 O61ii _0.84 _1.77 _{2.605 (5)} ₁₇₃

O52ÐH52 O62ii _0.84 _1.73 _{2.490 (6)} ₁₄₉

O1WÐH1WA O1iii _0.84 _2.11 _{2.946 (13)} ₁₇₉

O1WÐH1WB O51 0.84 1.84 2.678 (16) 179

Symmetry codes: (i) 1ÿx;2ÿy;1ÿz; (ii)3

2ÿx;yÿ12;z; (iii)12x;y;12ÿz.

H atoms were located in a difference map, positioned geom-etrically and re®ned with ®xed individual displacement parameters [set to 1.2 timesUeqvalue of the parent atom (1.5 for methyl groups)] using a riding model, with NÐH = 0.88 AÊ, OÐH = 0.84 AÊ and CÐH distances ranging from 0.93 to 0.99 AÊ. In addition, the torsion angles about the hydroxyl groups and the methyl group at the pyrazolo-pyrimidone ring system were re®ned.

Data collection: X-AREA (Stoe & Cie, 2001); cell re®nement:

X-AREA; data reduction: X-AREA; program(s) used to solve structure:SHELXS97(Sheldrick, 1990); program(s) used to re®ne structure:SHELXL97(Sheldrick, 1997); molecular graphics:XPin

SHELXTL-Plus(Sheldrick, 1991); software used to prepare material for publication:SHELXL97.

One of the authors (PN) is grateful to CIPLA, Mumbai, for a gift sample of sildena®l citrate and HSY thanks C.Shiva-kumar (IISc) and K. M. L. Rai (UOM) for spectral studies.

References

Allen, F. H. (2002).Acta Cryst.B58, 380±388. Blessing, R. H. (1995).Acta Cryst.A51, 33±38.

El-Abadelah, M. M., Sabri, S. S., Khanfar, M. A., Voelter, W. & Maichle-MoÈssmer, C. (1999).Z. Naturforsch. Teil B,54, 1323±1326.

McCullough, A. R. (2002).Rev. Urol.4, 26±38.

Melnikov, P., Corbi, P. P., Cuin, A., Cavicchioli, M. & Guimares, W. R. (2003).J. Pharm. Sci.92, 2140±2143.

Sheldrick, G. M. (1990).Acta Cryst.A46, 467±473.

Sheldrick, G. M. (1991).SHELXTL-Plus.Release 4.1. Siemens Analytical X-ray Instruments Inc., Madison, Wisconsin, USA.

Sheldrick, G. M. (1997).SHELXL97. University of GoÈttingen, Germany. Stoe & Cie (2001).X-AREA. Stoe & Cie, Darmstadt, Germany. Spek, A. L. (2003).J. Appl. Cryst.36, 7±13.

Terrett, N. K., Bell, A. S., Brown, D. & Ellis, P. (1996).Bioorg. Med. Chem. Lett.6, 1819±1824.

organic papers

(4)

supporting information

sup-1 Acta Cryst. (2005). E61, o489–o491

supporting information

Acta Cryst. (2005). E61, o489–o491 [https://doi.org/10.1107/S1600536805002564]

Sildenafil citrate monohydrate

Hemmige S. Yathirajan, Basavegowda Nagaraj, Padmarajaiah Nagaraja and Michael Bolte

1-{[3-(6,7-Dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-

4-ethoxyphenyl]sulfonyl}-4-methylpiperazinium citrate monohydrate

Crystal data

C22H31N6O4S+·C6H7O7−·H2O

Mr = 684.72

Orthorhombic, Pbca Hall symbol: -P 2ac 2ab a = 24.002 (4) Å b = 10.9833 (17) Å c = 24.364 (3) Å V = 6422.9 (17) Å3

Z = 8

F(000) = 2896 Dx = 1.416 Mg m−3

Mo Kα radiation, λ = 0.71073 Å Cell parameters from 8732 reflections θ = 2.0–23.1°

µ = 0.17 mm−1

T = 173 K Needle, colourless 0.26 × 0.12 × 0.11 mm

Data collection

Stoe IPDS-II two-circle diffractometer

Radiation source: fine-focus sealed tube Graphite monochromator

ω scans

Absorption correction: multi-scan

(MULABS; Spek, 2003; Blessing, 1995) Tmin = 0.937, Tmax = 0.951

44385 measured reflections 5856 independent reflections 1970 reflections with I > 2σ(I) Rint = 0.098

θmax = 25.4°, θmin = 1.9°

h = −28→28 k = −13→13 l = −29→27

Refinement

Refinement on F2

Least-squares matrix: full R[F2_{> 2}_σ₍_F2_{)] = 0.079}

wR(F2_{) = 0.154}

S = 0.78 5856 reflections 428 parameters 0 restraints

Primary atom site location: structure-invariant direct methods

Secondary atom site location: difference Fourier map

Hydrogen site location: inferred from neighbouring sites

H-atom parameters constrained w = 1/[σ2₍_F

o2) + (0.0407P)2]

where P = (Fo2 + 2Fc2)/3

(Δ/σ)max < 0.001

Δρmax = 0.38 e Å−3

Δρmin = −0.42 e Å−3

Special details

(5)

supporting information

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₎

x y z Uiso*/Ueq

S1 0.51081 (6) 0.50964 (15) 0.29812 (6) 0.0445 (4) O1 0.46362 (14) 0.5885 (4) 0.29471 (17) 0.0515 (11) O2 0.50684 (18) 0.3861 (4) 0.27829 (17) 0.0606 (13) N11 0.56093 (17) 0.5749 (4) 0.26385 (18) 0.0330 (11) C12 0.6124 (2) 0.5013 (5) 0.2576 (2) 0.0376 (14)

H12A 0.6028 0.4164 0.2478 0.045*

H12B 0.6334 0.5002 0.2926 0.045*

C13 0.6476 (2) 0.5571 (5) 0.2131 (2) 0.0430 (15)

H13A 0.6276 0.5512 0.1776 0.052*

H13B 0.6828 0.5109 0.2097 0.052*

N14 0.66068 (18) 0.6888 (4) 0.22483 (19) 0.0372 (12)

H14 0.6816 0.6920 0.2569 0.045*

C15 0.6074 (2) 0.7577 (5) 0.2344 (2) 0.0391 (15)

H15A 0.6162 0.8430 0.2443 0.047*

H15B 0.5852 0.7586 0.2002 0.047*

C16 0.5742 (2) 0.7012 (5) 0.2790 (2) 0.0389 (15)

H16A 0.5957 0.7024 0.3137 0.047*

H16B 0.5393 0.7478 0.2847 0.047*

C17 0.6948 (3) 0.7416 (6) 0.1798 (3) 0.0536 (18)

H17A 0.7290 0.6938 0.1754 0.080*

H17B 0.7044 0.8259 0.1889 0.080*

H17C 0.6734 0.7398 0.1456 0.080*

C21 0.5329 (2) 0.5069 (5) 0.3659 (2) 0.0393 (14) C22 0.5178 (2) 0.5976 (5) 0.4018 (2) 0.0394 (15)

H22 0.4926 0.6585 0.3896 0.047*

C23 0.5382 (2) 0.6037 (5) 0.4554 (2) 0.0385 (15) C24 0.5757 (2) 0.5122 (6) 0.4726 (2) 0.0379 (14) C25 0.5904 (2) 0.4195 (6) 0.4369 (3) 0.0431 (15)

H25 0.6148 0.3570 0.4491 0.052*

C26 0.5705 (2) 0.4163 (6) 0.3842 (3) 0.0460 (16)

H26 0.5820 0.3533 0.3600 0.055*

O27 0.59346 (15) 0.5167 (4) 0.52518 (17) 0.0434 (11) C28 0.6344 (2) 0.4316 (6) 0.5457 (3) 0.0497 (17)

H28A 0.6694 0.4386 0.5244 0.060*

H28B 0.6204 0.3472 0.5423 0.060*

C29 0.6448 (3) 0.4610 (7) 0.6038 (3) 0.063 (2)

H29A 0.6724 0.4044 0.6188 0.094*

H29B 0.6099 0.4537 0.6245 0.094*

H29C 0.6588 0.5445 0.6067 0.094*

(6)

supporting information

N32 0.54446 (19) 0.7278 (5) 0.53903 (19) 0.0427 (13)

H32 0.5729 0.6802 0.5468 0.051*

C33 0.5318 (3) 0.8150 (6) 0.5771 (2) 0.0452 (16) O33 0.55788 (19) 0.8276 (4) 0.61949 (18) 0.0551 (12) C34 0.4839 (2) 0.8840 (5) 0.5588 (2) 0.0399 (14) C35 0.4605 (2) 0.8619 (5) 0.5079 (2) 0.0384 (15) N36 0.47678 (18) 0.7724 (4) 0.47275 (19) 0.0393 (12) N37 0.4565 (2) 0.9798 (5) 0.5815 (2) 0.0480 (13) C37 0.4657 (3) 1.0358 (6) 0.6346 (2) 0.062 (2)

H37A 0.4863 1.1121 0.6298 0.093*

H37B 0.4873 0.9804 0.6579 0.093*

H37C 0.4298 1.0529 0.6521 0.093*

N38 0.4156 (2) 1.0183 (5) 0.5475 (2) 0.0509 (14) C39 0.4177 (3) 0.9500 (6) 0.5026 (3) 0.0438 (16) C40 0.3769 (2) 0.9660 (6) 0.4569 (3) 0.0509 (18)

H40A 0.3926 0.9301 0.4230 0.061*

H40B 0.3714 1.0542 0.4503 0.061*

C41 0.3207 (3) 0.9077 (6) 0.4684 (3) 0.0580 (19)

H41A 0.3266 0.8219 0.4793 0.070*

H41B 0.3030 0.9503 0.4997 0.070*

C42 0.2820 (3) 0.9114 (9) 0.4202 (3) 0.098 (3)

H42A 0.2467 0.8725 0.4301 0.146*

H42B 0.2989 0.8678 0.3893 0.146*

H42C 0.2752 0.9963 0.4097 0.146*

C1 0.6952 (3) 0.7525 (6) 0.4388 (3) 0.0519 (18) O11 0.6764 (2) 0.7142 (6) 0.4812 (2) 0.100 (2) O12 0.6703 (2) 0.8386 (5) 0.41230 (19) 0.0703 (15)

H12 0.6446 0.8674 0.4318 0.084*

C2 0.7480 (3) 0.7061 (5) 0.4127 (2) 0.0430 (16)

H2A 0.7797 0.7518 0.4286 0.052*

H2B 0.7526 0.6197 0.4233 0.052*

C3 0.7523 (2) 0.7140 (4) 0.3512 (3) 0.0350 (14) O3 0.70777 (15) 0.6480 (3) 0.32673 (16) 0.0367 (10)

H3 0.7090 0.5751 0.3371 0.044*

C4 0.8086 (2) 0.6625 (5) 0.3308 (3) 0.0468 (17)

H4A 0.8395 0.7114 0.3463 0.056*

H4B 0.8129 0.5776 0.3439 0.056*

C5 0.8118 (2) 0.6649 (7) 0.2691 (3) 0.0549 (19) O51 0.82320 (19) 0.7579 (4) 0.2438 (2) 0.0765 (16) O52 0.79846 (19) 0.5650 (4) 0.24213 (19) 0.0582 (13)

H52 0.7845 0.5143 0.2640 0.070*

C6 0.7474 (3) 0.8472 (5) 0.3322 (3) 0.0417 (15) O61 0.78086 (16) 0.9203 (4) 0.35450 (18) 0.0492 (11) O62 0.71438 (16) 0.8711 (3) 0.29353 (16) 0.0420 (10) O1W 0.8948 (6) 0.7871 (11) 0.1605 (6) 0.311 (7)

H1WA 0.9145 0.7301 0.1728 0.374*

(7)

supporting information

Atomic displacement parameters (Å2₎

U11 _U22 _U33 _U12 _U13 _U23

(8)

supporting information

O62 0.047 (2) 0.029 (2) 0.050 (3) −0.0028 (18) −0.007 (2) 0.003 (2) O1W 0.42 (2) 0.199 (12) 0.311 (16) 0.052 (13) −0.035 (14) −0.013 (12)

Geometric parameters (Å, º)

S1—O1 1.428 (4) N32—H32 0.8800

S1—O2 1.443 (4) C33—O33 1.216 (7)

S1—N11 1.630 (5) C33—C34 1.447 (8)

S1—C21 1.734 (6) C34—N37 1.359 (7)

N11—C16 1.470 (7) C34—C35 1.385 (8)

N11—C12 1.485 (6) C35—N36 1.361 (7)

C12—C13 1.506 (7) C35—C39 1.417 (8)

C12—H12A 0.9900 N37—N38 1.352 (6)

C12—H12B 0.9900 N37—C37 1.450 (7)

C13—N14 1.507 (7) C37—H37A 0.9800

C13—H13A 0.9900 C37—H37B 0.9800

C13—H13B 0.9900 C37—H37C 0.9800

N14—C17 1.486 (7) N38—C39 1.328 (8)

N14—C15 1.504 (7) C39—C40 1.493 (8)

N14—H14 0.9300 C40—C41 1.519 (8)

C15—C16 1.484 (8) C40—H40A 0.9900

C15—H15A 0.9900 C40—H40B 0.9900

C15—H15B 0.9900 C41—C42 1.497 (9)

C16—H16A 0.9900 C41—H41A 0.9900

C16—H16B 0.9900 C41—H41B 0.9900

C17—H17A 0.9800 C42—H42A 0.9800

C17—H17B 0.9800 C42—H42B 0.9800

C17—H17C 0.9800 C42—H42C 0.9800

C21—C22 1.373 (7) C1—O11 1.204 (7)

C21—C26 1.417 (8) C1—O12 1.293 (7)

C22—C23 1.398 (8) C1—C2 1.506 (9)

C22—H22 0.9500 O12—H12 0.8400

C23—C24 1.413 (8) C2—C3 1.505 (8)

C23—C31 1.481 (8) C2—H2A 0.9900

C24—O27 1.350 (6) C2—H2B 0.9900

C24—C25 1.385 (8) C3—O3 1.423 (6)

C25—C26 1.370 (8) C3—C6 1.540 (8)

C25—H25 0.9500 C3—C4 1.546 (7)

C26—H26 0.9500 O3—H3 0.8400

O27—C28 1.446 (6) C4—C5 1.506 (9)

C28—C29 1.472 (8) C4—H4A 0.9900

C28—H28A 0.9900 C4—H4B 0.9900

C28—H28B 0.9900 C5—O51 1.224 (8)

C29—H29A 0.9800 C5—O52 1.318 (8)

C29—H29B 0.9800 O52—H52 0.8400

C29—H29C 0.9800 C6—O61 1.258 (7)

C31—N36 1.295 (7) C6—O62 1.259 (7)

(9)

supporting information

N32—C33 1.367 (7) O1W—H1WB 0.8401

(10)

supporting information

C22—C21—S1 120.9 (5) O11—C1—O12 120.6 (7) C26—C21—S1 120.5 (5) O11—C1—C2 124.1 (6) C21—C22—C23 122.6 (6) O12—C1—C2 115.3 (6)

C21—C22—H22 118.7 C1—O12—H12 109.5

C23—C22—H22 118.7 C3—C2—C1 117.3 (5)

C22—C23—C24 117.8 (5) C3—C2—H2A 108.0 C22—C23—C31 116.6 (5) C1—C2—H2A 108.0 C24—C23—C31 125.6 (5) C3—C2—H2B 108.0 O27—C24—C25 122.9 (6) C1—C2—H2B 108.0 O27—C24—C23 117.2 (5) H2A—C2—H2B 107.2 C25—C24—C23 119.9 (5) O3—C3—C2 109.6 (5) C26—C25—C24 121.3 (6) O3—C3—C6 107.5 (4)

C26—C25—H25 119.4 C2—C3—C6 110.4 (5)

C24—C25—H25 119.4 O3—C3—C4 109.6 (4)

C25—C26—C21 119.9 (6) C2—C3—C4 111.1 (5)

C25—C26—H26 120.0 C6—C3—C4 108.5 (5)

C21—C26—H26 120.0 C3—O3—H3 109.5

C24—O27—C28 121.3 (5) C5—C4—C3 111.0 (5) O27—C28—C29 107.8 (5) C5—C4—H4A 109.4

O27—C28—H28A 110.1 C3—C4—H4A 109.4

C29—C28—H28A 110.1 C5—C4—H4B 109.4

O27—C28—H28B 110.1 C3—C4—H4B 109.4

C29—C28—H28B 110.1 H4A—C4—H4B 108.0

H28A—C28—H28B 108.5 O51—C5—O52 119.9 (7) C28—C29—H29A 109.5 O51—C5—C4 122.0 (7) C28—C29—H29B 109.5 O52—C5—C4 118.0 (6)

H29A—C29—H29B 109.5 C5—O52—H52 109.5

C28—C29—H29C 109.5 O61—C6—O62 126.3 (6) H29A—C29—H29C 109.5 O61—C6—C3 115.3 (5) H29B—C29—H29C 109.5 O62—C6—C3 118.1 (5) N36—C31—N32 122.0 (5) H1WA—O1W—H1WB 90.4

(11)

supporting information

O1—S1—C21—C22 −19.7 (5) C33—C34—N37—C37 −5.1 (11) O2—S1—C21—C22 −151.2 (4) C34—N37—N38—C39 −1.6 (7) N11—S1—C21—C22 94.3 (5) C37—N37—N38—C39 179.9 (5) O1—S1—C21—C26 165.6 (4) N37—N38—C39—C35 1.4 (7) O2—S1—C21—C26 34.0 (5) N37—N38—C39—C40 178.2 (5) N11—S1—C21—C26 −80.4 (5) N36—C35—C39—N38 178.7 (6) C26—C21—C22—C23 −0.1 (8) C34—C35—C39—N38 −0.6 (7) S1—C21—C22—C23 −174.9 (4) N36—C35—C39—C40 2.2 (11) C21—C22—C23—C24 0.1 (8) C34—C35—C39—C40 −177.1 (6) C21—C22—C23—C31 −179.2 (5) N38—C39—C40—C41 −78.7 (8) C22—C23—C24—O27 −177.6 (5) C35—C39—C40—C41 97.5 (7) C31—C23—C24—O27 1.6 (8) C39—C40—C41—C42 −173.4 (6) C22—C23—C24—C25 −1.0 (8) O11—C1—C2—C3 151.0 (7) C31—C23—C24—C25 178.2 (5) O12—C1—C2—C3 −28.9 (8) O27—C24—C25—C26 178.3 (5) C1—C2—C3—O3 −58.5 (6) C23—C24—C25—C26 1.9 (9) C1—C2—C3—C6 59.8 (7) C24—C25—C26—C21 −1.9 (9) C1—C2—C3—C4 −179.8 (5) C22—C21—C26—C25 1.0 (8) O3—C3—C4—C5 56.0 (7) S1—C21—C26—C25 175.8 (5) C2—C3—C4—C5 177.3 (5) C25—C24—O27—C28 7.3 (8) C6—C3—C4—C5 −61.1 (7) C23—C24—O27—C28 −176.2 (5) C3—C4—C5—O51 80.0 (7) C24—O27—C28—C29 179.8 (5) C3—C4—C5—O52 −95.9 (6) C22—C23—C31—N36 10.5 (8) O3—C3—C6—O61 173.5 (5) C24—C23—C31—N36 −168.7 (5) C2—C3—C6—O61 53.9 (7) C22—C23—C31—N32 −168.3 (5) C4—C3—C6—O61 −68.0 (7) C24—C23—C31—N32 12.5 (8) O3—C3—C6—O62 −12.1 (7) N36—C31—N32—C33 2.6 (9) C2—C3—C6—O62 −131.6 (6) C23—C31—N32—C33 −178.6 (5) C4—C3—C6—O62 106.4 (6) C31—N32—C33—O33 −179.9 (6)

Hydrogen-bond geometry (Å, º)

D—H···A D—H H···A D···A D—H···A

N14—H14···O3 0.93 1.88 2.764 (6) 159

N14—H14···O62 0.93 2.30 2.911 (6) 123

N32—H32···O27 0.88 1.94 2.622 (6) 134

O12—H12···N38i _0.84 _1.98 _{2.771 (7)} ₁₅₇

O3—H3···O61ii _0.84 _1.77 _{2.605 (5)} ₁₇₃

O52—H52···O62ii _0.84 _1.73 _{2.490 (6)} ₁₄₉

O1W—H1WA···O1iii _0.84 _2.11 _{2.946 (13)} ₁₇₉

O1W—H1WB···O51 0.84 1.84 2.678 (16) 179