research communications\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

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ISSN: 2056-9890

Crystal structure of 16-ferrocenylmethyl-3β-hy­droxy­estra-1,3,5(10)-trien-17-one: a potential chemotherapeutic drug

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aUniversity of Puerto Rico, Department of Chemistry, PO Box 9019, Mayaguez, PR 00681, Puerto Rico, bUniversity of Puerto Rico, Department of Chemical Engineering, PO Box 9000, Mayaguez, PR 00681, Puerto Rico, and cUniversity of California–San Diego, Department of Chemistry and Biochemistry, Urey Hall 5128, 9500 Gilman Drive, La Jolla, CA 92093-0358, USA
*Correspondence e-mail: enrique.melendez@upr.edu

Edited by R. F. Baggio, Comisión Nacional de Energía Atómica, Argentina (Received 18 May 2016; accepted 24 May 2016; online 27 May 2016)

A new ferrocene complex, 16-ferrocenylmethyl-3β-hy­droxy­estra-1,3,5(10)-trien-17-one dimethyl sulfoxide monosolvate, [Fe(C5H5)(C24H27O2)]·C2H6OS, has been synthesized and structurally characterized by single-crystal X-ray diffraction techniques. The mol­ecule crystallizes in the space group P21 with one mol­ecule of dimethyl sulfoxide. A hydrogen bond links the phenol group and the dimethyl sulfoxide O atom, with an O⋯O distance of 2.655 (5) Å. The ferrocene group is positioned in the β face of the estrone moiety, with an O—C—C—C torsion angle of 44.1 (5)°, and the carbonyl bond length of the hormone moiety is 1.216 (5) Å, typical of a C=O double bond. The average Fe—C bond length of the substituted Cp ring [Fe—C(Cp*)] is similar to that of the unsubstituted one [Fe—C(Cp)], i.e. 2.048 (3) versus 2.040 (12) Å. The structure of the complex is compared with those of estrone and eth­oxy­methyl­estrone.

1. Chemical context

The discovery of cisplatin anti­neoplastic activity was a notable event in medicinal chemistry history, opening new alternatives and routes on the use of metal-based drugs and their structure–activity relationships in cancer chemotherapy. However, its remarkable success (Galanski et al., 2005[Galanski, M., Jakupec, M. A. & Keppler, B. K. (2005). Curr. Med. Chem. 12, 2075-2094.]; Sandler et al., 2011[Sandler, A., Graham, C., Baggstrom, M., Herbst, R., Zergebel, C., Saito, K. & Jones, D. (2011). J. Thorac. Oncol. 6, 1400-1406.]) came at the high cost of undesired detrimental side effects (neurotoxicity, nephrotoxicity, etc; Pabla & Dong, 2008[Pabla, N. & Dong, Z. (2008). Kidney Int. 73, 994-1007.]). In this context, our research group has been working on other transition metals (e.g., titanium, iron, vanadium and tungsten, among others) with promising results for chemotherapeutic applications (Domínguez-García et al., 2013[Domínguez-García, M., Ortega-Zúñiga, C. & Meléndez, E. (2013). J. Biol. Inorg. Chem. 18, 195-209.]; Ramos et al., 2014[Ramos, G., Loperena, Y., Ortiz, G., Reyes, F., Szeto, A., Vera, J., Velez, J., Morales, J., Morrero, D., Castillo, L., Dharmawardhane, S., Melendez, E. & Washington, A. V. (2014). Anticancer Res. 34, 1609-1615.]; Vera et al., 2014[Vera, J. L., Rullán, J., Santos, N., Jiménez, J., Rivera, J., Santana, A., Briggs, J., Rheingold, A. L., Matta, J. & Meléndez, E. (2014). J. Organomet. Chem. 749, 204-214.]). Recently, particular attention has been focused on the anti­neoplastic activity of ferrocene complexes (Richard et al., 2015[Richard, M.-A., Hamels, D., Pigeon, P., Top, S., Dansette, P. M., Lee, H. Z. S., Vessières, A., Mansuy, D. & Jaouen, G. (2015). ChemMedChem, 10, 981-990.]) due to their desired physical and chemical properties such as aqueous stability and high synthetic homology to benzene chemistry, with the advantage that they exhibit fewer toxic side effects than cisplatin. Our group has been working on the synthesis and application of ferrocene complexes coupled to hormones in order to develop new metal-based therapeutic drugs with high selective index for hormone-dependent-breast-cancer treatment (Vera et al., 2011[Vera, J., Gao, L. M., Santana, A., Matta, J. & Meléndez, E. (2011). Dalton Trans. 40, 9557-9565.], 2014[Vera, J. L., Rullán, J., Santos, N., Jiménez, J., Rivera, J., Santana, A., Briggs, J., Rheingold, A. L., Matta, J. & Meléndez, E. (2014). J. Organomet. Chem. 749, 204-214.]). In connection with the relationship between structure and the activity against hormone-dependent breast cancer, we intend to explore the function­alization of estrogens at C16 position with ferrocene using estrone (1) as starting material, due to the versatility which, for synthetic transformations, provides the carbonyl group over other estrogens not containing a carbonyl group. In this context, we present herein the synthesis and crystal structure of 16-ferrocenylmethyl-3β-hy­droxy­estra-1,3,5(10)-trien-17-one dimethyl sulfoxide monosolvate (2) and compare it with the structure of estrogen (1) and 16β-eth­oxy­methyl­estrone (3) (Allan et al., 2006[Allan, G. M., Lawrence, H. R., Cornet, J., Bubert, C., Fischer, D. S., Vicker, N., Smith, A., Tutill, H. J., Purohit, A., Day, J. M., Mahon, M. F., Reed, M. J. & Potter, B. V. L. (2006). J. Med. Chem. 49, 1325-1345.]).

[Scheme 1]

2. Structural commentary

The ferrocenylmethyl group of 2 is positioned at the beta face of the estrone moiety (Fig. 1[link]). As a result, a new stereogenic center was formed after substitution at position 16 (C16) of estrone with a ferrocenylmethyl group. This C16 atom has an R stereochemical configuration. Table 1[link] contains the most relevant bond lengths and angles. The carbonyl bond (C17=O2) of the hormone moiety of 2 is 1.216 (5) Å, which is very similar to in estrogen and 16β-eth­oxy­methyl­estrone [1.215 (2) and 1.219 (2) Å, respectively], corresponding to a carbon–oxygen double (C=O) bond. However, the substitution at C16 of the steroid in 2 and 3, ferrocenylmethyl and eth­oxy­methyl groups, respectively, makes torsion angles and bond angles at the 16-position slightly different. Both substituents are located on the beta face but, the torsion angle (between C19 and carbonyl group) defined as C19–C16—C17—O2 in 2 is smaller than in 3 (between the carbonyl and the meth­oxy groups), 44.1 (5) and 49.7 (2)°, respectively. The ferrocene moiety is positioned at 112.6 (3)° from C16 (∠C20—C19—C16) while the eth­oxy­methyl group is at 108.4 (1)° (∠C16—C1—O3). The average Fe—C bond length of the substituted Cp ring [Fe—C(Cp*] is similar to the unsubstituted one, 2.048 (3) vs 2.040 (12) Å (McAdam et al., 2015[McAdam, C. J., Moratti, S. C. & Simpson, J. (2015). Acta Cryst. C71, 1100-1105.]). We might expect that the substitution on the Cp ring with a electron-donating methyl group could enhance the Fe—C(Cp*) bonding, but such an effect is not observed. It is not clear if this is a steric rather than an electronic effect. It is worth mentioning the steroselectivity of this reaction showed the beta steroisomer but it is also the position of the eth­oxy­methyl group on eth­oxy­methyl­estrone. We might expect the beta face of the estrone moiety to be more hindered due to the methyl group on C13 which is located in this face but, according to the mechanism of hydrogen addition to a double bond, the addition is favored on the less hindered alpha face and, as a consequence, the ferrocenyl group is positioned on the beta face.

Table 1
Selected geometrical parameters (Å, °) for compounds 1, 2 and 3

  1 2 3
Bond lengths      
Fe—C(Cp)avg   2.040 (12)  
Fe—C(Cp*)subt   2.048 (3)  
C(Cp)subt—CH2   1.505 (5)  
C17—O2 1.219 (2) 1.216 (5) 1.215 (2)
C3—O1 1.374 (2) 1.368 (5) 1.371 (2)
       
Hydrogen-bond parameters      
D—H 0.86 0.84 0.84
H⋯A 1.97 (O2⋯H1) 1.82 [O3(DMSO)⋯H1] 1.93 (O2⋯H1)
DA 2.819 (2) (O1⋯O2) 2.655 (5) (O1⋯O3) 2.760 (2) (O1⋯O2)
D—H⋯A 174 174 170
       
Bond angles      
C20—C19—C16   112.6 (3)  
O3—C1—C16     108.4 (1)
       
Torsion angles      
O2—C17—C16—C19   44.1 (5) 49.7 (2) [O(2)—C(17)—C(16)—C(1)]
[Figure 1]
Figure 1
The asymmetric unit of 2. Displacement ellipsoids are drawn at the 50% probability level.

3. Supra­molecular features

In the crystal structure of 2 there is a hydrogen bond involving the hydroxyl group at C3 and the DMSO oxygen (Table 2[link], Fig. 2[link]). No head-to-tail hydrogen bonding is observed, as is the case in 1 and 3 (Shikii et al., 2004[Shikii, K., Sakamoto, S., Seki, H., Utsumi, H. & Yamaguchi, K. (2004). Tetrahedron, 60, 3487-3492.]; Allan et al., 2006[Allan, G. M., Lawrence, H. R., Cornet, J., Bubert, C., Fischer, D. S., Vicker, N., Smith, A., Tutill, H. J., Purohit, A., Day, J. M., Mahon, M. F., Reed, M. J. & Potter, B. V. L. (2006). J. Med. Chem. 49, 1325-1345.]). In the latter structures, the hydrogen bonds at the two ends are the driving force for packing. It seems that the ferrocenylmethyl substitution on C16 inhibits the hydrogen bonding at the carbonyl oxygen atom, thus eliminating the head-to-tail hydrogen-bonding network existing in 1 and 3.

Table 2
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA D—H⋯A
O1—H1⋯O3i 0.84 1.82 2.655 (5) 174
Symmetry code: (i) x+1, y, z.
[Figure 2]
Figure 2
Packing diagram for 2, projected along the b axis. The ferrocene moieties are shown in polyhedral representation for clarity. The O—H⋯O hydrogen bonds are highlighted (in cyan dashed lines).

4. Synthesis and crystallization

In a 500 mL Parr bottle, 16-ferrocenyl­idene-3β-hy­droxy­estra-1,3,5(10)-trien-17-one complex was dissolved in a mixture of tetra­hydro­furan (THF) and ethanol (1:1) and Pd/C (10wt%, catalytic). The system was purged three times with H2 at 40 psi. The reaction mixture was stirred overnight at room temperature under 40 psi of H2. The mixture was then filtered through Celite, and the filtrate was evaporated in vacuo, resulting in a yellow solid that was purified by column chromatography using CHCl3: ethyl acetate (9:1) as mobile phase, affording 67% of 2 as a yellow solid. Yellow rod-shaped crystals were obtained after dissolving the solid 16-ferro­cenyl­methyl-3β-hy­droxy­estra-1,3,5(10)-trien-17-one in a solution of CH2Cl2 with a few drops of dimethyl sulfoxide, to assure a concentrate solution, layered in hexane.

5. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 3[link]. H atoms were positioned in idealized locations: d(C—H) = 0.95 Å, Uiso(H) = 1.2Ueq(C); d(C—H2) = 0.99 Å,Uiso(H) = 1.2 Ueq (C); d(C—H3) = 0.98 Å, Uiso(H) = 1.5Ueq(C).

Table 3
Experimental details

Crystal data
Chemical formula [Fe(C5H5)(C24H27O2)]·C2H6OS
Mr 546.52
Crystal system, space group Monoclinic, P21
Temperature (K) 100
a, b, c (Å) 7.4178 (12), 11.2436 (15), 16.1160 (18)
β (°) 93.148 (4)
V3) 1342.1 (3)
Z 2
Radiation type Mo Kα
μ (mm−1) 0.67
Crystal size (mm) 0.30 × 0.25 × 0.03
 
Data collection
Diffractometer Bruker APEXII Ultra
Absorption correction Multi-scan (SADABS; Bruker, 2013[Bruker (2013). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.])
Tmin, Tmax 0.064, 0.093
No. of measured, independent and observed [I > 2σ(I)] reflections 9583, 5327, 4816
Rint 0.048
(sin θ/λ)max−1) 0.625
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.043, 0.097, 1.02
No. of reflections 5327
No. of parameters 329
No. of restraints 1
H-atom treatment H-atom parameters constrained
Δρmax, Δρmin (e Å−3) 0.32, −0.44
Absolute structure Flack x determined using 1990 quotients [(I+)−(I)]/[(I+)+(I)] (Parsons et al., 2013[Parsons, S., Flack, H. D. & Wagner, T. (2013). Acta Cryst. B69, 249-259.])
Absolute structure parameter 0.004 (14)
Computer programs: APEX2 and SAINT (Bruker, 2013[Bruker (2013). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]), SHELXT (Sheldrick, 2015a[Sheldrick, G. M. (2015a). Acta Cryst. A71, 3-8.]), SHELXL2014 (Sheldrick, 2015b[Sheldrick, G. M. (2015b). Acta Cryst. C71, 3-8.]) and OLEX2 (Dolomanov et al., 2009[Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339-341.]).

Supporting information


Computing details top

Data collection: APEX2 (Bruker, 2013); cell refinement: SAINT (Bruker, 2013); data reduction: SAINT (Bruker, 2013); program(s) used to solve structure: SHELXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015b); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009).

16-Ferrocenylmethyl-3β-hydroxyestra-1,3,5(10)-trien-17-one dimethyl sulfoxide monosolvate top
Crystal data top
[Fe(C5H5)(C24H27O2)]·C2H6OSF(000) = 580
Mr = 546.52Dx = 1.352 Mg m3
Monoclinic, P21Mo Kα radiation, λ = 0.71073 Å
a = 7.4178 (12) ÅCell parameters from 4213 reflections
b = 11.2436 (15) Åθ = 3.0–26.2°
c = 16.1160 (18) ŵ = 0.67 mm1
β = 93.148 (4)°T = 100 K
V = 1342.1 (3) Å3Block, yellow
Z = 20.3 × 0.25 × 0.03 mm
Data collection top
Bruker APEXII Ultra
diffractometer
5327 independent reflections
Radiation source: Micro Focus Rotating Anode, Bruker TXS4816 reflections with I > 2σ(I)
Double Bounce Multilayer Mirrors monochromatorRint = 0.048
Detector resolution: 7.9 pixels mm-1θmax = 26.4°, θmin = 2.2°
ω and φ scansh = 99
Absorption correction: multi-scan
(SADABS; Bruker, 2013)
k = 1314
Tmin = 0.064, Tmax = 0.093l = 2019
9583 measured reflections
Refinement top
Refinement on F2Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: fullH-atom parameters constrained
R[F2 > 2σ(F2)] = 0.043 w = 1/[σ2(Fo2) + (0.0266P)2]
where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.097(Δ/σ)max = 0.001
S = 1.02Δρmax = 0.32 e Å3
5327 reflectionsΔρmin = 0.44 e Å3
329 parametersAbsolute structure: Flack x determined using 1990 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013)
1 restraintAbsolute structure parameter: 0.004 (14)
Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
Fe10.29444 (8)0.50023 (5)1.06433 (3)0.01977 (16)
S10.26603 (16)0.46255 (9)0.35262 (6)0.0224 (3)
O30.1244 (5)0.4378 (3)0.41388 (17)0.0285 (8)
O20.2299 (4)0.2860 (3)0.79220 (17)0.0247 (7)
O10.9351 (4)0.6126 (3)0.47762 (17)0.0232 (7)
H10.98860.55480.45690.035*
C170.1502 (6)0.3780 (4)0.7790 (2)0.0176 (9)
C130.0422 (6)0.3895 (4)0.7523 (2)0.0181 (9)
C80.2258 (6)0.5542 (4)0.6908 (2)0.0163 (9)
H80.31080.54840.74100.020*
C150.0744 (6)0.5880 (4)0.7724 (2)0.0188 (9)
H15A0.11750.66290.74580.023*
H15B0.00550.60680.82510.023*
C140.0394 (5)0.5159 (4)0.7143 (2)0.0170 (8)
H140.03470.50950.66080.020*
C220.0406 (7)0.4352 (4)1.0540 (3)0.0219 (10)
H220.02030.38091.09100.026*
C50.5284 (6)0.6214 (4)0.5951 (2)0.0166 (9)
C100.4657 (5)0.5020 (4)0.58935 (19)0.0168 (8)
C210.1534 (6)0.4044 (4)0.9831 (3)0.0202 (10)
H210.18110.32590.96460.024*
C240.1427 (7)0.6073 (4)0.9925 (3)0.0212 (10)
H240.16190.68940.98110.025*
C120.1022 (6)0.3007 (4)0.6877 (2)0.0225 (10)
H12A0.01110.29780.64050.027*
H12B0.11120.22040.71270.027*
C20.7268 (6)0.4550 (4)0.5087 (2)0.0198 (9)
H20.79450.39800.48000.024*
C70.2328 (7)0.6806 (4)0.6564 (3)0.0195 (10)
H7A0.16000.68540.60310.023*
H7B0.18130.73680.69600.023*
C190.3372 (5)0.5193 (4)0.8660 (2)0.0208 (9)
H19A0.39820.59760.86410.025*
H19B0.43160.45710.86710.025*
C300.1457 (6)0.4879 (5)0.2554 (2)0.0270 (10)
H30A0.08240.41500.23750.041*
H30B0.23080.51060.21370.041*
H30C0.05780.55190.26150.041*
C10.5698 (6)0.4215 (4)0.5459 (2)0.0200 (9)
H1A0.53170.34100.54170.024*
C110.2860 (6)0.3367 (4)0.6560 (3)0.0218 (10)
H11A0.38010.32740.70150.026*
H11B0.31640.28270.61030.026*
C200.2179 (5)0.5112 (5)0.9444 (2)0.0184 (9)
C30.7837 (6)0.5728 (4)0.5137 (2)0.0192 (10)
C160.2314 (5)0.5037 (4)0.7870 (2)0.0200 (8)
H160.32050.51400.73860.024*
C60.4272 (6)0.7143 (4)0.6427 (2)0.0193 (9)
H6A0.42830.79040.61190.023*
H6B0.49160.72720.69740.023*
C40.6851 (6)0.6544 (4)0.5575 (2)0.0182 (9)
H40.72570.73440.56190.022*
C290.3916 (9)0.5424 (7)1.1756 (3)0.059 (2)
H290.32440.58031.22000.071*
C310.3441 (7)0.6100 (4)0.3730 (3)0.0266 (11)
H31A0.24070.66240.38040.040*
H31B0.41110.63830.32610.040*
H31C0.42350.61060.42360.040*
C180.1621 (6)0.3784 (4)0.8337 (2)0.0225 (10)
H18A0.12840.44010.87280.034*
H18B0.28910.38810.82140.034*
H18C0.14450.29980.85840.034*
C230.0348 (6)0.5606 (4)1.0600 (2)0.0224 (10)
H230.02990.60551.10180.027*
C280.4933 (9)0.5984 (6)1.1132 (4)0.0490 (17)
H280.50900.68191.10790.059*
C90.2869 (6)0.4657 (4)0.6246 (2)0.0177 (9)
H90.19410.46980.57730.021*
C260.5157 (9)0.4035 (6)1.0890 (4)0.0523 (18)
H260.54830.32941.06420.063*
C270.5681 (6)0.5152 (7)1.0601 (3)0.0412 (14)
H270.64320.53111.01170.049*
C250.4046 (9)0.4208 (7)1.1623 (4)0.059 (2)
H250.34930.36031.19600.071*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
Fe10.0179 (3)0.0243 (3)0.0174 (3)0.0018 (3)0.0034 (2)0.0014 (3)
S10.0250 (6)0.0214 (6)0.0210 (5)0.0067 (5)0.0035 (4)0.0027 (4)
O30.039 (2)0.0249 (18)0.0233 (15)0.0017 (15)0.0130 (14)0.0014 (13)
O20.0264 (19)0.0243 (17)0.0239 (16)0.0099 (15)0.0072 (14)0.0039 (13)
O10.0227 (18)0.0230 (17)0.0243 (16)0.0023 (14)0.0042 (13)0.0020 (13)
C170.019 (2)0.023 (2)0.0106 (18)0.0015 (19)0.0024 (16)0.0033 (17)
C130.020 (2)0.018 (2)0.016 (2)0.0036 (19)0.0002 (17)0.0001 (17)
C80.019 (2)0.016 (2)0.0147 (18)0.0000 (18)0.0002 (16)0.0002 (16)
C150.020 (2)0.018 (2)0.018 (2)0.0025 (19)0.0000 (17)0.0006 (17)
C140.019 (2)0.018 (2)0.0145 (17)0.0011 (19)0.0001 (14)0.0002 (17)
C220.021 (3)0.025 (3)0.020 (2)0.006 (2)0.0048 (19)0.0007 (19)
C50.019 (2)0.019 (2)0.0121 (19)0.0009 (18)0.0024 (16)0.0005 (16)
C100.020 (2)0.0190 (19)0.0116 (16)0.001 (2)0.0015 (14)0.002 (2)
C210.022 (3)0.023 (2)0.016 (2)0.003 (2)0.0014 (18)0.0052 (18)
C240.019 (2)0.020 (2)0.024 (2)0.003 (2)0.0042 (19)0.0035 (19)
C120.026 (3)0.018 (2)0.024 (2)0.007 (2)0.0057 (19)0.0033 (18)
C20.024 (2)0.019 (2)0.0165 (19)0.0005 (19)0.0031 (17)0.0040 (17)
C70.024 (3)0.017 (2)0.018 (2)0.0002 (19)0.0030 (18)0.0009 (17)
C190.014 (2)0.027 (3)0.0211 (18)0.001 (2)0.0012 (15)0.0017 (19)
C300.029 (2)0.029 (3)0.0219 (19)0.002 (2)0.0025 (17)0.000 (2)
C10.025 (2)0.019 (2)0.0168 (19)0.0036 (19)0.0014 (17)0.0016 (17)
C110.028 (3)0.016 (2)0.022 (2)0.005 (2)0.0076 (19)0.0018 (18)
C200.0141 (19)0.025 (2)0.0164 (17)0.001 (2)0.0029 (14)0.0025 (19)
C30.018 (2)0.025 (2)0.0145 (19)0.0017 (19)0.0002 (17)0.0051 (18)
C160.017 (2)0.025 (2)0.0171 (17)0.000 (2)0.0013 (15)0.000 (2)
C60.026 (2)0.014 (2)0.018 (2)0.0020 (18)0.0011 (17)0.0023 (17)
C40.022 (2)0.017 (2)0.0158 (19)0.0018 (18)0.0022 (17)0.0018 (16)
C290.030 (3)0.121 (7)0.029 (3)0.024 (4)0.018 (2)0.026 (3)
C310.027 (3)0.028 (3)0.024 (2)0.007 (2)0.0020 (19)0.001 (2)
C180.022 (2)0.024 (2)0.021 (2)0.006 (2)0.0005 (18)0.0057 (18)
C230.017 (3)0.033 (3)0.017 (2)0.003 (2)0.0016 (18)0.003 (2)
C280.033 (4)0.043 (4)0.074 (4)0.003 (3)0.033 (3)0.009 (3)
C90.024 (2)0.016 (2)0.0133 (17)0.0004 (18)0.0009 (16)0.0023 (16)
C260.040 (4)0.053 (4)0.067 (4)0.028 (3)0.030 (3)0.022 (3)
C270.018 (2)0.076 (5)0.030 (2)0.004 (3)0.0067 (19)0.006 (3)
C250.039 (4)0.092 (6)0.049 (4)0.016 (4)0.020 (3)0.048 (4)
Geometric parameters (Å, º) top
Fe1—C222.035 (5)C12—H12A0.9900
Fe1—C212.030 (4)C12—H12B0.9900
Fe1—C242.049 (5)C12—C111.536 (6)
Fe1—C202.047 (3)C2—H20.9500
Fe1—C292.026 (5)C2—C11.391 (6)
Fe1—C232.047 (5)C2—C31.392 (6)
Fe1—C282.035 (6)C7—H7A0.9900
Fe1—C262.026 (6)C7—H7B0.9900
Fe1—C272.035 (5)C7—C61.518 (6)
Fe1—C252.025 (6)C19—H19A0.9900
S1—O31.506 (3)C19—H19B0.9900
S1—C301.783 (4)C19—C201.505 (5)
S1—C311.781 (4)C19—C161.543 (5)
O2—C171.216 (5)C30—H30A0.9800
O1—H10.8400C30—H30B0.9800
O1—C31.368 (5)C30—H30C0.9800
C17—C131.518 (6)C1—H1A0.9500
C17—C161.545 (6)C11—H11A0.9900
C13—C141.548 (6)C11—H11B0.9900
C13—C121.527 (5)C11—C91.536 (6)
C13—C181.548 (5)C3—C41.389 (6)
C8—H81.0000C16—H161.0000
C8—C141.516 (5)C6—H6A0.9900
C8—C71.527 (6)C6—H6B0.9900
C8—C91.545 (5)C4—H40.9500
C15—H15A0.9900C29—H290.9500
C15—H15B0.9900C29—C281.376 (9)
C15—C141.527 (5)C29—C251.387 (10)
C15—C161.529 (6)C31—H31A0.9800
C14—H141.0000C31—H31B0.9800
C22—H220.9500C31—H31C0.9800
C22—C211.422 (6)C18—H18A0.9800
C22—C231.414 (6)C18—H18B0.9800
C5—C101.422 (6)C18—H18C0.9800
C5—C61.519 (6)C23—H230.9500
C5—C41.390 (6)C28—H280.9500
C10—C11.402 (6)C28—C271.365 (9)
C10—C91.527 (5)C9—H91.0000
C21—H210.9500C26—H260.9500
C21—C201.423 (7)C26—C271.387 (10)
C24—H240.9500C26—C251.416 (9)
C24—C201.425 (6)C27—H270.9500
C24—C231.415 (6)C25—H250.9500
C22—Fe1—C2468.00 (19)C1—C2—C3119.4 (4)
C22—Fe1—C2068.81 (16)C3—C2—H2120.3
C22—Fe1—C2340.53 (16)C8—C7—H7A109.7
C22—Fe1—C28156.9 (2)C8—C7—H7B109.7
C21—Fe1—C2240.95 (17)H7A—C7—H7B108.2
C21—Fe1—C2468.24 (16)C6—C7—C8109.7 (4)
C21—Fe1—C2040.86 (19)C6—C7—H7A109.7
C21—Fe1—C2368.60 (19)C6—C7—H7B109.7
C21—Fe1—C28161.4 (2)H19A—C19—H19B107.8
C21—Fe1—C27124.8 (2)C20—C19—H19A109.1
C20—Fe1—C2440.73 (18)C20—C19—H19B109.1
C29—Fe1—C22122.2 (2)C20—C19—C16112.6 (3)
C29—Fe1—C21156.4 (3)C16—C19—H19A109.1
C29—Fe1—C24126.6 (2)C16—C19—H19B109.1
C29—Fe1—C20162.2 (3)S1—C30—H30A109.5
C29—Fe1—C23109.5 (2)S1—C30—H30B109.5
C29—Fe1—C2839.6 (3)S1—C30—H30C109.5
C29—Fe1—C2667.7 (3)H30A—C30—H30B109.5
C29—Fe1—C2766.9 (2)H30A—C30—H30C109.5
C29—Fe1—C2540.0 (3)H30B—C30—H30C109.5
C23—Fe1—C2440.42 (18)C10—C1—H1A118.7
C23—Fe1—C2068.75 (16)C2—C1—C10122.5 (4)
C28—Fe1—C24109.4 (2)C2—C1—H1A118.7
C28—Fe1—C20125.3 (2)C12—C11—H11A109.2
C28—Fe1—C23122.5 (2)C12—C11—H11B109.2
C26—Fe1—C22125.9 (3)H11A—C11—H11B107.9
C26—Fe1—C21107.1 (2)C9—C11—C12112.2 (4)
C26—Fe1—C24154.4 (2)C9—C11—H11A109.2
C26—Fe1—C20119.2 (2)C9—C11—H11B109.2
C26—Fe1—C23163.4 (3)C21—C20—Fe168.9 (2)
C26—Fe1—C2866.6 (2)C21—C20—C24106.9 (3)
C26—Fe1—C2739.9 (3)C21—C20—C19125.9 (4)
C27—Fe1—C22162.4 (2)C24—C20—Fe169.7 (2)
C27—Fe1—C24120.7 (2)C24—C20—C19127.3 (5)
C27—Fe1—C20106.95 (17)C19—C20—Fe1128.0 (3)
C27—Fe1—C23155.6 (2)O1—C3—C2122.7 (4)
C27—Fe1—C2839.2 (3)O1—C3—C4117.9 (4)
C25—Fe1—C22108.7 (2)C4—C3—C2119.4 (4)
C25—Fe1—C21120.9 (3)C17—C16—H16106.6
C25—Fe1—C24163.2 (3)C15—C16—C17104.5 (3)
C25—Fe1—C20155.1 (3)C15—C16—C19118.9 (3)
C25—Fe1—C23126.4 (2)C15—C16—H16106.6
C25—Fe1—C2866.7 (3)C19—C16—C17113.0 (4)
C25—Fe1—C2640.9 (3)C19—C16—H16106.6
C25—Fe1—C2767.5 (2)C5—C6—C7113.7 (3)
O3—S1—C30105.8 (2)C5—C6—H6A108.8
O3—S1—C31106.4 (2)C5—C6—H6B108.8
C31—S1—C3098.9 (2)C7—C6—H6A108.8
C3—O1—H1109.5C7—C6—H6B108.8
O2—C17—C13126.6 (4)H6A—C6—H6B107.7
O2—C17—C16124.6 (4)C5—C4—H4119.3
C13—C17—C16108.8 (4)C3—C4—C5121.4 (4)
C17—C13—C14101.4 (3)C3—C4—H4119.3
C17—C13—C12116.8 (3)Fe1—C29—H29125.0
C17—C13—C18105.0 (3)C28—C29—Fe170.6 (3)
C14—C13—C18113.8 (3)C28—C29—H29126.1
C12—C13—C14109.2 (3)C28—C29—C25107.9 (6)
C12—C13—C18110.5 (4)C25—C29—Fe169.9 (4)
C14—C8—H8108.7C25—C29—H29126.1
C14—C8—C7113.9 (4)S1—C31—H31A109.5
C14—C8—C9107.3 (3)S1—C31—H31B109.5
C7—C8—H8108.7S1—C31—H31C109.5
C7—C8—C9109.4 (3)H31A—C31—H31B109.5
C9—C8—H8108.7H31A—C31—H31C109.5
H15A—C15—H15B109.2H31B—C31—H31C109.5
C14—C15—H15A111.3C13—C18—H18A109.5
C14—C15—H15B111.3C13—C18—H18B109.5
C14—C15—C16102.5 (3)C13—C18—H18C109.5
C16—C15—H15A111.3H18A—C18—H18B109.5
C16—C15—H15B111.3H18A—C18—H18C109.5
C13—C14—H14105.7H18B—C18—H18C109.5
C8—C14—C13111.5 (3)Fe1—C23—H23126.3
C8—C14—C15123.1 (4)C22—C23—Fe169.3 (3)
C8—C14—H14105.7C22—C23—C24107.6 (4)
C15—C14—C13103.9 (3)C22—C23—H23126.2
C15—C14—H14105.7C24—C23—Fe169.9 (3)
Fe1—C22—H22126.2C24—C23—H23126.2
C21—C22—Fe169.3 (3)Fe1—C28—H28126.1
C21—C22—H22125.9C29—C28—Fe169.8 (4)
C23—C22—Fe170.2 (3)C29—C28—H28125.3
C23—C22—H22125.9C27—C28—Fe170.4 (3)
C23—C22—C21108.2 (4)C27—C28—C29109.4 (6)
C10—C5—C6120.9 (4)C27—C28—H28125.3
C4—C5—C10120.1 (4)C8—C9—H9106.3
C4—C5—C6119.0 (4)C10—C9—C8112.2 (3)
C5—C10—C9121.1 (4)C10—C9—C11113.3 (4)
C1—C10—C5117.1 (4)C10—C9—H9106.3
C1—C10—C9121.7 (4)C11—C9—C8111.9 (3)
Fe1—C21—H21125.8C11—C9—H9106.3
C22—C21—Fe169.7 (3)Fe1—C26—H26125.4
C22—C21—H21125.8C27—C26—Fe170.3 (3)
C22—C21—C20108.3 (4)C27—C26—H26126.4
C20—C21—Fe170.2 (2)C27—C26—C25107.2 (6)
C20—C21—H21125.8C25—C26—Fe169.5 (4)
Fe1—C24—H24126.8C25—C26—H26126.4
C20—C24—Fe169.6 (2)Fe1—C27—H27125.6
C20—C24—H24125.5C28—C27—Fe170.4 (3)
C23—C24—Fe169.7 (3)C28—C27—C26108.2 (5)
C23—C24—H24125.5C28—C27—H27125.9
C23—C24—C20108.9 (4)C26—C27—Fe169.7 (3)
C13—C12—H12A109.5C26—C27—H27125.9
C13—C12—H12B109.5Fe1—C25—H25125.6
C13—C12—C11110.6 (3)C29—C25—Fe170.0 (4)
H12A—C12—H12B108.1C29—C25—C26107.3 (6)
C11—C12—H12A109.5C29—C25—H25126.4
C11—C12—H12B109.5C26—C25—Fe169.6 (3)
C1—C2—H2120.3C26—C25—H25126.4
Fe1—C22—C21—C2059.8 (3)C7—C8—C9—C1050.4 (4)
Fe1—C22—C23—C2459.6 (3)C7—C8—C9—C11179.0 (4)
Fe1—C21—C20—C2459.6 (3)C1—C10—C9—C8162.9 (3)
Fe1—C21—C20—C19122.3 (4)C1—C10—C9—C1135.0 (5)
Fe1—C24—C20—C2159.1 (3)C1—C2—C3—O1179.0 (4)
Fe1—C24—C20—C19122.9 (4)C1—C2—C3—C41.5 (6)
Fe1—C24—C23—C2259.2 (4)C20—C24—C23—Fe158.6 (3)
Fe1—C29—C28—C2759.4 (4)C20—C24—C23—C220.5 (6)
Fe1—C29—C25—C2659.9 (4)C20—C19—C16—C1765.7 (5)
Fe1—C28—C27—C2659.7 (4)C20—C19—C16—C1557.3 (6)
Fe1—C26—C27—C2860.1 (4)C3—C2—C1—C100.4 (6)
Fe1—C26—C25—C2960.2 (5)C16—C17—C13—C1420.6 (4)
O2—C17—C13—C14159.3 (4)C16—C17—C13—C12139.1 (3)
O2—C17—C13—C1240.7 (6)C16—C17—C13—C1898.1 (4)
O2—C17—C13—C1882.0 (5)C16—C15—C14—C1343.4 (4)
O2—C17—C16—C15174.7 (4)C16—C15—C14—C8171.2 (3)
O2—C17—C16—C1944.1 (5)C16—C19—C20—Fe1169.8 (4)
O1—C3—C4—C5179.2 (4)C16—C19—C20—C2179.7 (5)
C17—C13—C14—C8173.9 (3)C16—C19—C20—C2497.9 (5)
C17—C13—C14—C1539.3 (4)C6—C5—C10—C1178.5 (3)
C17—C13—C12—C11170.1 (4)C6—C5—C10—C95.1 (5)
C13—C17—C16—C155.4 (4)C6—C5—C4—C3179.5 (3)
C13—C17—C16—C19136.0 (3)C4—C5—C10—C11.0 (5)
C13—C12—C11—C953.2 (5)C4—C5—C10—C9175.5 (3)
C8—C7—C6—C549.2 (4)C4—C5—C6—C7161.2 (4)
C14—C13—C12—C1155.8 (5)C29—C28—C27—Fe159.1 (4)
C14—C8—C7—C6174.5 (3)C29—C28—C27—C260.6 (6)
C14—C8—C9—C10174.3 (3)C18—C13—C14—C861.8 (4)
C14—C8—C9—C1157.1 (4)C18—C13—C14—C1572.8 (4)
C14—C15—C16—C1729.6 (4)C18—C13—C12—C1170.0 (4)
C14—C15—C16—C19156.7 (3)C23—C22—C21—Fe159.6 (4)
C22—C21—C20—Fe159.5 (3)C23—C22—C21—C200.2 (6)
C22—C21—C20—C240.1 (4)C23—C24—C20—Fe158.7 (3)
C22—C21—C20—C19178.1 (4)C23—C24—C20—C210.4 (5)
C5—C10—C1—C20.8 (6)C23—C24—C20—C19178.4 (4)
C5—C10—C9—C820.9 (5)C28—C29—C25—Fe160.7 (4)
C5—C10—C9—C11148.8 (3)C28—C29—C25—C260.8 (8)
C10—C5—C6—C719.3 (5)C9—C8—C14—C1361.4 (4)
C10—C5—C4—C30.0 (6)C9—C8—C14—C15174.1 (3)
C21—C22—C23—Fe159.1 (3)C9—C8—C7—C665.6 (4)
C21—C22—C23—C240.4 (6)C9—C10—C1—C2175.6 (4)
C12—C13—C14—C862.1 (4)C27—C26—C25—Fe160.5 (4)
C12—C13—C14—C15163.2 (3)C27—C26—C25—C290.4 (7)
C12—C11—C9—C854.3 (5)C25—C29—C28—Fe160.3 (5)
C12—C11—C9—C10177.6 (3)C25—C29—C28—C270.9 (7)
C2—C3—C4—C51.3 (6)C25—C26—C27—Fe160.0 (4)
C7—C8—C14—C13177.5 (3)C25—C26—C27—C280.2 (6)
C7—C8—C14—C1553.0 (5)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O1—H1···O3i0.841.822.655 (5)174
Symmetry code: (i) x+1, y, z.
Selected geometrical parameters (Å, °) for compounds 1, 2 and 3 top
123
Bond lengths
Fe—C(Cp)avg2.029 (12)
Fe—C(Cp*)subt2.042 (10)
C(Cp)subt—CH21.505 (5)
C17—O21.219 (2)1.216 (5)1.215 (2)
C3—O11.374 (2)1.368 (5)1.371 (2)
Hydrogen-bond parameters
D—H0.860.840.84
H···A1.97 (O2···H1)1.82 [O3(DMSO)···H1]1.93 (O2···H1)
D···A2.819 (2) (O1···O2)2.655 (5) (O1···O3)2.760 (2) (O1···O2)
D—H···A174174170
Bond angles
C20—C19—C16112.6 (3)
O3—C1—C16108.4 (1)
Torsion angles
O2—C17—C16—C1944.1 (5)49.7 (2) O(2)—C(17)—C(16)—C(1)
 

Acknowledgements

We thank the NIH, the Alfred P. Sloan Program and its representative Dr Rodolfo Romañach for financial support. We also extend special thanks to Dr Robert Ríos for allowing JACN to perform the synthesis in his research laboratory. EM acknowledges the financial support of NSF–CREST II 000743–00002.

References

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