Inorg. Chem. 1996, 35, 2415-2420
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Articles Bis(pyrazolylethyl) Ether Ligation to Zinc and Cobalt: Meridional vs Facial Coordination and the Suitability of Such Ligands in Providing a NNO Donor Set for Modeling Bioinorganic Aspects of Zinc Chemistry Conor Dowling, Vincent J. Murphy, and Gerard Parkin* Department of Chemistry, Columbia University, New York, New York 10027 ReceiVed October 2, 1995X
The structures of bis(pyrazolylethyl) ether derivatives of zinc and cobalt, namely [η3-O(CH2CH2pzPri2)2]Zn(NO3)2 and [η3-O(CH2CH2pzMe2)2]Co(NO3)2, have been determined with a view to addressing the applicability of such ligands in modeling bioinorganic aspects of zinc chemistry. Specific consideration is given to the possibility that bis(pyrazolylethyl) ether ligands may provide an NNO donor system which may model aspects of the binding of zinc to protein backbones in enzymes such as thermolysin. The structural studies demonstrate that the bis(pyrazolylethyl) ether ligands do indeed coordinate Via each of their NNO functionalities but that the relationship to the enzyme is limited by the adoption of meridional rather than facial coordination geometries. [η3-O(CH2CH2pzPri2)2]Zn(NO3)2 is monoclinic, P21/c (No. 14), with a ) 11.619(2) Å, b ) 14.380(3) Å, c ) 16.757(2) Å, β ) 90.44(2)°, and Z ) 4. [η3-O(CH2CH2pzMe2)2]Co(NO3)2 is monoclinic, C2/c (No. 15), with a ) 17.136(3) Å, b ) 10.505(2) Å, c ) 11.121(2) Å, β ) 104.62(3)°, and Z ) 4.
Introduction The discovery of zinc in the active site of a variety of enzymes, such as carbonic anhydrase, carboxypeptidase, thermolysin, and alcohol dehydrogenase,1 has stimulated much effort into the syntheses of simple model complexes that are designed to mimic the coordination environment of the active site. In particular, since the polypeptide backbone of zinc enzymes typically binds the metal Via a combination of N, O, and S donors, a variety of ligands comprising NxOySz functionalities have been synthesized with a view to modeling such enzyme sites. For example, NNN donor ligands have been used to model the active site of carbonic anhydrase,2-7 while NNO donor ligands have been studied in attempts to provide a model for the coordination environment of enzymes that also incorporate oxygen donors, e.g. carboxypeptidase and thermolysin.8-14 X Abstract published in AdVance ACS Abstracts, April 1, 1996. (1) (a) Bertini, I.; Luchinat, C. In Bioinorganic Chemistry; Bertini, I., Gray, H. B., Lippard, S. J., Valentine, J., Eds.; University Science Books: Mill Valley, CA, 1994. (b) Zinc Enzymes; Spiro, T. G., Ed.; Wiley: New York, 1983. (c) Zinc Enzymes; Bertini, I., Luchinat, C., Maret, W., Zeppezauer M., Eds.; Progress in Inorganic Biochemistry and Biophysics 1; Birkha¨user: Boston, MA, 1986. (d) Vallee, B. L.; Galdes, A. AdV. Enzymol. Relat. Areas Mol. Biol. 1984, 56, 283430. (e) Vallee, B. L.; Auld, D. S. In Matrix Metalloprotinases and Inhibitors; Birkedal-Hansen, H., Werb, Z., Welgus, H. G., van Wart, H. E., Eds.; Gustav Fischer Verlag: New York, 1992; pp 5-19. (2) Kimblin, C.; Allen, W. E.; Parkin, G. J. Chem. Soc., Chem. Commun. 1995, 1813-1815. (3) (a) Alsfasser, R.; Trofimenko, S.; Looney, A.; Parkin, G.; Vahrenkamp, H. Inorg. Chem. 1991, 30, 4098-4100. (b) Looney, A.; Parkin, G.; Alsfasser, R.; Ruf, M.; Vahrenkamp, H. Angew. Chem., Int. Ed. Engl. 1992, 31, 92-93. (c) Looney, A.; Han, R.; McNeill, K.; Parkin, G. J. Am. Chem. Soc. 1993, 115, 4690-4697. (d) Ruf, M.; Weis, K.; Vahrenkamp, H. J. Chem. Soc., Chem. Commun. 1994, 135-136. (e) Alsfasser, R.; Ruf, M.; Trofimenko, S.; Vahrenkamp, H. Chem. Ber. 1993, 126, 703-710. (f) Kitajima, N.; Hikichi, S.; Tananka, M.; Morooka, Y. J. Am. Chem. Soc. 1993, 115, 5496-5508.
0020-1669/96/1335-2415$12.00/0
In this paper, we discuss the suitability of bis(pyrazolylethyl) ether ligands in providing an NNO donor system that may model aspects of the binding of zinc to the protein backbone in enzymes such as thermolysin.15-17 (4) (a) Breslow, R.; Hunt, J. T.; Smiley, R.; Tarnowski, T. J. Am. Chem. Soc. 1983, 105, 5337-5342. (b) Tang, C. C.; Davalian, D.; Huang, P.; Breslow, R. J. Am. Chem. Soc. 1978, 100, 3918-3922. (c) Brown, R. S.; Huguet, J. Can. J. Chem. 1980, 58, 889-901. (d) Brown, R. S.; Zamkanei, M.; Cocho, J. L. J. Am. Chem. Soc. 1984, 106, 52225228. (e) Slebocka-Tilk, H.; Cocho, J. L.; Frakman, Z.; Brown, R. S. J. Am. Chem. Soc. 1984, 106, 2421-2431. (f) Brown, R. S.; Curtis, N. J.; Huguet, J. J. Am. Chem. Soc. 1981, 103, 6953-6959. (g) Brown, R. S.; Salmon, D.; Curtis, N. J.; Kusuma, S. J. Am. Chem. Soc. 1982, 104, 3188-3194. (h) Huguet, J.; Brown, R. S. J. Am. Chem. Soc. 1980, 102, 7571-7572. (5) (a) Kimura, E.; Shiota, T.; Koike, T.; Shiro, M.; Kodama, M. J. Am. Chem. Soc. 1990, 112, 5805-5811. (b) Kimura, E.; Kurogi, Y.; Shionoya, M.; Dhiro, M. Inorg. Chem. 1991, 30, 4524-4530. (c) Koike, T.; Kimura, E.; Nakamura, I.; Hashimoto, Y.; Shiro, M. J. Am. Chem. Soc. 1992, 114, 7338-7345. (d) Zhang, X.; van Eldik, R.; Koike, T.; Kimura, E. Inorg. Chem. 1993, 32, 5749-5755. (e) Kimura, E. Prog. Inorg. Chem. 1994, 41, 443-491. (6) Tabushi, I.; Kuroda, Y. J. Am. Chem. Soc. 1984, 106, 4580-4584. (7) Wirbser, J.; Vahrenkamp, H. Z. Naturforsch. 1992, 47B, 962-968. (8) Feinberg, H.; Greenblatt, H. M.; Behar, V.; Gilon, C.; Cohen, S.; Bino, A.; Shoham, G. Acta Crystallogr. 1995, D51, 428-449. (9) Brown, R. S.; Huguet, J.; Curtis, N. J. In Role of Metal Ions in Biological Systems; Sigel, H., Ed.; Marcel Dekker: New York, 1983; Vol. 5, pp 55-99. (10) Tandon, S. S.; Chander, S.; Thompson, L. K.; Bridson, J. N.; McKee, V. Inorg. Chim. Acta 1994, 219, 55-65. (11) Groves, J. T.; Olson, J. R. Inorg. Chem. 1985, 24, 2717-2720. (12) Schepartz, A.; Breslow, R. J. Am. Chem. Soc. 1987, 109, 1814-1826. (13) (a) Abufarag, A.; Vahrenkamp, H. Inorg. Chem. 1995, 34, 32793284. (b) Abufarag, A.; Vahrenkamp, H. Inorg. Chem. 1995, 34, 2207-2216. (14) For some related NNS and NS donor ligands, see: (a) Alsfasser, R.; Vahrenkamp, H. Inorg. Chim. Acta 1993, 209, 19-22. (b) Brand, U.; Vahrenkamp, H. Inorg. Chem. 1995, 34, 3285-3293. (c) Brand, U.; Vahrenkamp, H. Chem. Ber. 1995, 128, 787-791. (15) Holmes, M. A.; Matthews, B. W. J. Mol. Biol. 1982, 160, 623-639.
© 1996 American Chemical Society
2416 Inorganic Chemistry, Vol. 35, No. 9, 1996
Dowling et al.
Scheme 1
Figure 1. Molecular structure of [η3-O(CH2CH2pzPri2)2]Zn(NO3)2.
Results and Discussion (i) Meridional Ws Facial Coordination of Bis(pyrazolylethyl) Ether Ligands. As an extension of our previous studies concerned with modeling the NNN donor environment of carbonic anhydrase,3c we are presently interested in evaluating ligands with related NNO functionalities as models for the active site of zinc enzymes such as thermolysin, an enzyme that hydrolyzes the amide bond of polypeptide substrates.15,16 In particular, since the nitrogen donors in zinc enzymes are typically histidine residues, we are especially interested in NNO ligands that are derived from either imidazole or pyrazole functionalities. Our selection of bis(pyrazolylethyl) ether ligands for the present study is, in part, a consequence of the fact that related NNS and NNN donors are also known for this system18 and that structural comparisons within the series should prove informative. The bis[(3,5-diisopropylpyrazolyl)ethyl]ether ligand O(CH2CH2pzPri2)2 is readily obtained by the reaction of O(CH2CH2Cl)2 with 2 equiv of the sodium salt of 3,5-diisopropylpyrazole (eq 1), a procedure analogous to that described by Sorrell for
the preparation of O(CH2CH2pzMe2)2.18 The ability of O(CH2CH2pzPri2)2 to act as a ligand for zinc is clearly indicated by the facile reaction with zinc nitrate to give [η3-O(CH2CH2pzPri2)2](16) Matthews, B. W. Acc. Chem. Res. 1988, 21, 333-340. (17) Feinberg, H.; Greenblatt, H. M.; Behar, V.; Gilon, C.; Cohen, S.; Bino, A.; Shoham, G. Acta Crystallogr. 1995, D51, 428-449. (18) Sorrell has described the preparation of a series of bis[(3,5-dimethylpyrazolyl)ethyl] ether and sulfide, and bis[(3,5-dimethylpyrazolyl)ethyl]amine ligands, i.e. O(CH2CH2pzMe2)2, S(CH2CH2pzMe2)2, and HN(CH2CH2pzMe2)2. See: Sorrell, T. N.; Malachowski, M. R. Inorg. Chem. 1983, 22, 1883-1887.
Figure 2. Molecular structure of [η3-O(CH2CH2pzMe2)2]Co(NO3)2. Table 1. Selected Bond Lengths (Å) and Angles (deg) for [η3-O(CH2CH2pzPri2)2]Zn(NO3)2 Zn-O12 Zn-O13 Zn-N11 Zn-O3
2.183(3) 2.397(4) 2.127(3) 2.217(2)
Zn-O22 Zn‚‚‚O23 Zn-N21
2.116(3) 2.647(5) 2.127(3)
O12-Zn-O13 O13-Zn-O22 O13-Zn-O3 O12-Zn-N11 O22-Zn-N21 O22-Zn-N21 N11-Zn-N21 Zn-O13-N1 Zn-O23-N2
54.7(1) 120.1(1) 142.8(1) 92.2(1) 89.1(1) 90.6(1) 169.7(1) 89.7(3) 82.2(5)
O12-Zn-O22 O12-Zn-O3 O22-Zn-O3 O13-Zn-N11 O3-Zn-N11 O13-Zn-N21 O3-Zn-N21 Zn-O12-N1 Zn-O22-N2
174.7(1) 91.0(1) 94.2(1) 108.0(1) 84.9(1) 81.0(1) 84.8(1) 99.7(3) 106.1(3)
Zn(NO3)2 (Scheme 1), which has been structurally characterized by X-ray diffraction (Figure 1). Since cobalt-substituted thermolysin is also an active enzyme (and, in fact, more active than the native enzyme by a factor of 2),1a we have also synthesized and structurally characterized the analogous cobalt complex [η3O(CH2CH2pzMe2)2]Co(NO3)2 (Figure 2). Selected bond lengths and angles for [η3-O(CH2CH2pzPri2)2]Zn(NO3)2 and [η3-O(CH2CH2pzMe2)2]Co(NO3)2 are listed in Tables 1 and 2, respectively. Of most interest to the present study are the coordination modes adopted by the bis(pyrazolylethyl) ether ligands in [η3O(CH2CH2pzPri2)2]Zn(NO3)2 and [η3-O(CH2CH2pzMe2)2]Co(NO3)2. Specifically, since protein backbones typically bind zinc in a facial manner (i.e. the zinc has a pseudotetrahedral
Bis(pyrazolylethyl) Ether Ligation to Zn and Co
Inorganic Chemistry, Vol. 35, No. 9, 1996 2417
Table 2. Selected Bond Distances (Å) and Angles (deg) for [η3-O(CH2CH2pzMe2)2]Co(NO3)2 Co1-O1 Co1-O3
2.125(1) 2.186(3)
Co1-O2 Co1-N1
2.308(3) 2.133(2)
O1-Co1-O2 O2-Co1-O3 O2-Co1-N1 O2-Co1-O2′ Co1-O3-N3
141.3(1) 56.8(1) 82.5(1) 77.5(1) 96.3(2)
O1-Co1-O3 O1-Co1-N1 O3-Co1-N1 Co1-O2-N3
86.4(1) 87.5(1) 92.0(1) 90.9(2) Figure 4. Criteria for assigning nitrate coordination modes. Table 3. Criteria for Assigning Nitrate Coordination Modes (See Ref 27) d2 - d1 (Å) θ1 - θ2 (deg)
unidentate
anisobidentate
bidentate
>0.6 >28
0.3-0.6 14-28
