Metal ion complexation by a new, highly sterically hindered, bowl-shaped carboxylate ligand

Abstract

A carboxylate encapsulated by arene groups arranged in a bowl-like shape coordinates to Fe(II), Co(II) and Cu(II) to form mononuclear complexes with atypical structures enforced by the extreme steric demands of the ligand.

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Carboxylate groups (from Asp or Glu side chains or C termini) play key roles as supporting ligands in a diverse array of metalloprotein active sites.¹ Such carboxylates are notable for the facility with which they adopt different binding modes,² in particular during the catalytic cycles of dioxygen-activating mono- and di-iron enzymes.³ In efforts to synthesize models of these metalloprotein active sites, we⁴ and others^5,6 have begun using sterically bulky carboxylate ligands in order to control coordination geometry, mimic the hydrophobic active site environment, and access coordinatively unsaturated species akin to those implicated during enzymatic catalysis. For example, novel biologically relevant structures and reactivity have been discovered for iron complexes of carboxylates 1⁴ and 2,⁵ which contain arene substituents on the benzoate unit that provide a high degree of hydrophobic ‘shielding’. In expectation of even greater encapsulation of metal sites in model complexes, we targeted 3, a carboxylate derivative of the known irregular ‘bowl-shaped’ 4-tert-butyl-2,6-bis[(2,2″,6,6″-tetramethyl-m -terphenyl-2′-yl)methyl]phenyl (Bmt) fragment that was used to isolate various species BmtX (X = Br, SH, SO, SI, SO₂H, AlH₃).⁷ Herein we report the successful synthesis and X-ray crystallographic characterization of BmtCO₂H (3-H) and Fe(II), Co(II) and Cu(II) complexes of 3, which adopt atypical structures owing to the extreme steric bulk of the new carboxylate ligand.

The synthesis of BmtCO₂H was achieved by lithiation of BmtBr,‡ addition of CO₂(g), acidification, and then column chromatography. The product was identified using spectroscopic (ESI†) and X-ray diffraction§ data. Treatment of BmtCO₂H with BuⁿLi in thf afforded the lithium carboxylate (BmtCO₂Li·2thf) that was isolated as an analytically pure solid for use as the starting material for the preparation of metal complexes.

Reaction of BmtCO₂Li·2thf (2 equiv.) with MCl₂ in MeOH afforded [M(BmtCO₂)₂(MeOH)_n]·m MeOH [M = Fe(II), Co(II), n = m = 4; M = Cu(II), n = 2, m = 0]. Use of >2 equiv. of the carboxylate yielded the same products, indicating that only two of these bulky ligands may be accommodated. The X-ray crystal structures§ of the Fe and Cu complexes are shown in Figs. 1 and 2, respectively. The Co structure is isomorphous with that of Fe, so only data for the Fe case is presented. Common to all of the complexes is a trans disposition of two BmtCO₂^– ligands that coordinate in a syn monodentate fashion. The noncoordinating carboxylate oxygen atoms participate in hydrogen bonding with the bound MeOH ligands (Fig. 3). Additional hydrogen bonding occurs in the Fe and Co complexes involving included solvent MeOH molecules. Similar intramolecular hydrogen bonding patterns have been seen in other Fe(II)⁸ and Cu(II)⁹ carboxylate complexes and have been suggested to play a role in stabilizing their structures.

Fig. 1 Representation of the X-ray crystal structure of [Fe(BmtCO₂)₂- (MeOH)₄]·4MeOH as 50% thermal ellipsoids, with H atoms and the solvent molecules omitted for clarity. Selected bond distances (Å) and angles (°): Fe(1)–O(2) 2.125(18), Fe(1)–O(3) 2.162(2), Fe(1)–O(4) 2.091(2), Fe(1)⋯O(1) 3.225(2); O(4)–Fe(1)–O(2) 89.69(8), O(4)–Fe(1)–O(3) 90.86(10), O(2)–Fe(1)–O(3) 89.30(8).

Fig. 2 Representation of the X-ray crystal structure of [Cu(BmtCO₂)₂- (MeOH)₂]as 50% thermal ellipsoids, with H atoms omitted for clarity. Selected bond distances (Å) and angles (°): Cu(1)–O(2) 1.893(2), Cu(1)–O(3) 1.950(2), Cu(1)⋯O(1) 3.245; O(2)–Cu(1)–O(3) 91.70(9), O(2)–Cu(1)–O(3a) 88.30(9).

Fig. 3 Coordination spheres of (a) [Fe(BmtCO₂)₂(MeOH)₄]·4MeOH (showing two of the MeOH solvent molecules; the other two are highly disordered) and (b) [Cu(BmtCO₂)₂(MeOH)₂], with hydrogen bonding interactions indicated by dashed lines. Relevant interatomic distances (Å): (a) O(1)⋯O(4a) 2.582(3), O(1)⋯O(3) 3.199(3), O(3)⋯O(6b) 2.718(7), (b) O(1)⋯O(3) 2.511(3) Å.

Mononuclear bis(carboxylato) iron(II) complexes possessing trans carboxylates are rare, ^4a,c,10 and [Fe(BmtCO₂)₂(MeOH)₄] is a unique example with an all-oxygen donor set. The O_carb–Fe–O_carb angle of 180° presumably results from the tendency of the BmtCO₂^– ligands to position themselves as far apart as possible. This angle in the other two known bis(carboxylato) iron(II) complexes with trans monodentate carboxylate groups deviates significantly from linearity [168.5(2) and 154.74(8)°].^4a,c,10 The small space remaining in the equatorial plane of the octahedral BmtCO₂^– complex is ideal for accommodation of small donors such as MeOH.

A Cu(II) complex possessing the same donor set as [Cu(BmtCO₂)₂(MeOH)₂] has been reported,^9a but in this complex of a functionalized benzoate (‘furosemide’) there are additional weak axial interactions between the Cu(II) center and the carboxylate oxygen atoms from adjacent molecules [Cu–O 2.720(4) Å]. In the BmtCO₂^– compound, no other potential donor ligand is within bonding distance to the square-planar Cu(II) center due to blocking of the apical site by the carboxylate xylyl groups. The mononuclear structure of the complex contrasts with the familiar dinuclear paddlewheel¹¹ or other common topologies in which carboxylates bridge between multiple Cu(II) centers.¹² The discrete structure of [Cu(BmtCO₂)₂(MeOH)₂] is also unusual insofar as many Cu(II) carboxylate complexes which exist as monomers in solution form intermolecular hydrogen bonded extended structures in the solid state.¹³

In conclusion, we have developed a synthesis of the carboxylate 3 in which the ligating unit is encapsulated in an irregular ‘molecular bowl’. The extreme steric demands of the ligand have been illustrated through characterization of the monomeric Fe(II), Co(II) and Cu(II) complexes comprising two molecules of 3 coordinated trans in a syn monodentate mode. Further studies will explore the potential for the use of 3 and the complexes described herein for accessing unusual structures pertinent to nonheme, carboxylate rich metalloprotein active sites.

Acknowledgements

We thank Dr Katherine Aubrecht and Dr Victor G. Young, Jr., for the structural determination of BmtCO₂H (3-H), Jamie Schneider for her efforts in improving the synthesis of BmtBr, and the NIH (GM38767 to L. Q.) for financial support.

Notes and references

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3. A. L. Feig and S. J. Lippard, Chem. Rev., 1994, 94, 759; L. Que, Jr., in Bionorganic Catalysis, ed. J. Reedijk and E. Bouman, Marcel Dekker, Inc., 1999; B. J. Wallar and J. D. Lipscomb, Chem. Rev., 1996, 96, 2625.
4. (a) J. R. Hagadorn, L. Que, Jr. and W. B. Tolman, J. Am. Chem. Soc., 1998, 120, 13531; (b) J. R. Hagadorn, L. Que, Jr., W. B. Tolman, I. Prisecaru and E. Münck, J. Am. Chem. Soc., 1999, 121, 9760; (c) J. R. Hagadorn, L. Que, Jr. and W. B. Tolman, Inorg. Chem., 2001, 40, in press..
5. (a) D. Lee and S. J. Lippard, J. Am. Chem. Soc., 1998, 120, 12153; (b) D. Lee, J. D. Bois, D. Petasis, M. P. Hendrich, C. Kres, B. H. Huynh and S. J. Lippard, J. Am. Chem. Soc., 1999, 121, 9893; (c) D. Lee, C. Krebs, B. H. Huynh, M. P. Hendrich and S. J. Lippard, J. Am. Chem. Soc., 2000, 122, 5000.
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8. S. Herold and S. J. Lippard, J. Am. Chem. Soc., 1997, 119, 145; M. M. Morelock, M. L. Good, L. M. Trefonas, R. Majeste and D. G. Karraker, Inorg. Chem., 1982, 21, 3044.
9. (a) For examples, see: P. Bontchev, H. Kadum, G. Gochev, B. Evtimova, J. Macicek and C. Nachev, Polyhedron, 1992, 11, 1973; (b) H. Muhonen, Acta Crystallogr., Sect. C, 1983, 39, 536.
10. B. Singh, J. R. Long, G. C. Papaefthymiou and P. Stavropoulos, J. Am. Chem. Soc., 1996, 118, 5824; B. Singh, J. R. Long, F. F. deBiani, D. Gatteschi and P. Stavropoulos, J. Am. Chem. Soc., 1997, 119, 7030.
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13. For example, see: H. Muhonen, Acta Crystallogr., Sect. C, 1983, 39, 536; C. K. Prout, R. A. Armstrong, J. R. Carruthers, J. G. Forrest, P. Murray-Rust and J. C. Rossotti, J. Chem. Soc. A, 1968, 2791; C. K. Prout, M. J. Barrow and F. J. C. Rossotti, J. Chem. Soc. A, 1971, 3326.

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Footnotes

† Electronic supplementary information (ESI) available: detailed procedures for the syntheses of BmtBr, BmtCO₂H and BmtCO₂Li as well as characterization data for all new compounds. See http://www.rsc.org/suppdata/cc/b0/b006647h/

‡ The precursor BmtBr was synthesized via the method described in ref. 7(e), but improvements were made that allowed the product to be isolated in higher yield (70% vs. 32%). For detailed procedures for the syntheses of BmtBr, BmtCO₂H and BmtCO₂Li, see ESI.†

§ Crystal data for BmtCO₂H (3-H): C₁₇₁H₁₇₄O₆, M = 2325.10, triclinic, space group P1̄, a = 13.2288(7), b = 21.7697(11), c = 26.0770(13) Å, α = 76.040 (1), β = 82.286(1), γ = 84.717(1)°, V = 7208(1) ų, T = 173(2) K, Z = 2, μ(Mo-Kα) = 0.062 mm^–1, 63469 reflections measured, 32161 unique (R_int = 0.027) which were used in all calculations. The final wR(F²) was 0.1298 (all data), R1 = 0.0541. For [Fe(BmtCO₂)₂(MeOH)₄]·4MeOH: C₁₂₂H₁₄₆O₁₂Fe, M = 1860.24, monoclinic, space group P2₁/n, a = 21.1152(13), b = 13.3988(9), c = 21.1719(13) Å, β = 115.0900(10)°, V = 5424.7(6) ų, T = 173(2) K, Z = 2, μ(Mo-Kα) = 0.198 mm^–1, 27850 reflections measured, 9562 unique (R_int = 0.0481) which were used in all calculations. The final wR(F²) was 0.1772 (all data), R1 = 0.0558. For [Cu(BmtCO₂)₂(MeOH)₂]: C₁₁₆H₁₂₂O₆Cu, M = 1675.68, monoclinic, space group P2₁/n, a = 15.2154(7), b = 11.1085(5), c = 27.7956(12) Å, β = 97.9700(10)°, V = 4652.6(4) ų, T = 173(2), Z = 2, μ(Mo-Kα) = 0.292 mm^–1, 23238 reflections measured, 8203 unique (R_int) = 0.0439) which were used in all calculations. The final wR(F²) was 0.1795 (all data), R1 = 0.0598. CCDC 182/1859. See http://www.rsc.org/suppdata/cc/b0/b006647h/ for crystallographic files in .cif format.

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