Magnetic, Spectroscopic, and Structural Studies of Dicobalt

Modeling Spin Interactions in a Triangular Cobalt(II) Complex with Triaminoguanidine Ligand Framework: Synthesis, Structure, and Magnetic Properties. ...
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Magnetic, Spectroscopic, and Structural Studies of Dicobalt Hydroxamates and Model Hydrolases| David A. Brown,*,† W. Errington,‡ W. K. Glass,† W. Haase,§ T. J. Kemp,‡ H. Nimir,† S. M. Ostrovsky,§ and R. Werner§ Department of Chemistry, University College Dublin, Belfield, Dublin 4, Ireland, Department of Chemistry, University of Warwick, Coventry CV4 7AL, U.K., and Institut fu¨r Physikalische Chemie, Technische Universita¨t, Darmstadt, Germany ReceiVed March 27, 2001

The cobalt(II) urease model complex [Co2(µ-OAc)3(urea)(tmen)2][OTf] (2) prepared from the cobalt model hydrolase [Co2(µ-H2O)(µ-OAc)2(OAc)2(tmen)2] (1) undergoes facile reaction with acetohydroxamic acid (AHA) to give the monobridged hydroxamate complex [Co2(µ-OAc)2(µ-AA)(urea)(tmen)2][OTf] (3) while 1 gives the dibridged hydroxamate complex [Co2(µ-OAc)(µ-AA)2(tmen)2][OTf] (4). The structures and Co-Co distances of the hydroxamate derivatives of 1 and 2 are very close to those of their nickel analogues and suggest that hydroxamic acids can also inhibit cobalt-based hydrolases as well as inhibiting urease. 1 also reacts with glutarodihydroxamic acid (gluH2A2) to eliminate hydroxylamine with formation of [Co2(µ-OAc)2{µ-O(N) (OC)2(CH2)3}(tmen)2][OTf] (5), the structure of which is very close to that of its nickel analogue. Both 1 and 3 show weak antiferromagnetic coupling. Oxidation of 1 with H2O2 gives three dicobalt(III) hydroxy complexes (7-9), the first of which [Co2(µ-OAc)2(OAc)2(µ-OH)(tmen)2][OTf] (7) contains a bridging hydroxyl and the second [Co2(µ-OAc)2(OAc)(µOH)(OH)(tmen)2][OTf] (8) containing both a bridging and terminal hydroxyl, while the third [Co2(µ-OAc) (OAc)2(µ-OH)2(tmen)2][OTf] (9) contains two bridging OH groups with mixed-valence Co(II)/(Co(III) intermediates.

Introduction Dinuclear metallohydrolases are an important group of metalloenzymes which catalyze the hydrolysis of a range of peptide and phosphate ester bonds and include the amidohydrolases, amidinohydrolases, and peptide hydrolases.1 A common structural feature of these metallohydrolases is a dinuclear metal active site featuring Zn(II), Ni(II), Co(II), and Mn(II) and carboxylate bridges which occur respectively in leucine aminopeptidase,2 urease,3 methionine aminopeptidase,4 and arginase.5 Although crystal structural data are now available for these metallohydrolases,2-5 the mechanism involved in their catalytic hydrolysis of various substrates is still a matter for discussion. The generally accepted mechanism is based on that first proposed by Zerner6 for the action of urease in which one nickel(II) center activates the urea substrate by coordination of the carbonyl oxygen while the other nickel center coordinates a water molecule which is deprotonated by a suitably oriented * Author for correspondence. † University College Dublin. ‡ University of Warwick. § Technische Universita ¨ t. | Abbreviations: OAc, CH COO-; tmen, N,N,N′,N′-tetramethylethyl3 enediamine; TMS-OTf, (trimethylsilyl)triflate; OTf (triflate), CF3SO3-; AHA, acetohydroxamic acid; AA, acetohydroxamate anion; gluH2A2, glutarodihydroxamic acid; gluA2, glutarodihydroxamate dianion. (1) Wilcox, D. E. Chem. ReV. 1996, 96, 2435-2458. (2) Stra¨ter, N.; Lipscomb, W. N. Biochemistry 1995, 34, 14792-14800. (3) Jabri, E.; Carr, M. B.; Hausinger, R. P.; Karplus, P. A. Science 1995, 268, 998-1004. (4) Roderick, S. L.; Matthews, B. W. Biochemistry 1993, 32, 3907-3912. (5) Kanyo, Z. F.; Scolnick, L. R.; Ash, D. E.; Christianson, D. W. Nature 1996, 383, 554-557. (6) Dixon, N. E.; Riddles, C.; Gazzola, C.; Blakely, R. L.; Zerner, B. Can. J. Biochem. 1980, 58, 1335-1345.

base of the protein to produce a hydroxide which then attacks the activated urea carbonyl carbon atom to give a tetrahedral intermediate which decomposes to give eventually ammonia and carbon dioxide. One problem in mechanistic discussions based on structural evidence is the uncertainty in the protonation state of the solvent water molecule; that is, is it a neutral molecule, a hydroxide, or even a bridging oxide? More recent discussions stress the importance of hydrogen bonding to various amino acid residues by the amino hydrogens of the urea substrate7 although controversy remains since it has recently been suggested that one of the amino groups of urea approaches the six- coordinated Ni(II) center and eventually bridges the two nickel centers, thereby polarizing the C-O and C-NH2 bonds and assisting nucleophilic attack.8 Some support for this mechanism is provided by the isolation of complexes such as [L2Ni2(µ-OAc)(urea)](ClO4)2 (L ) pyrazolate derivative), where H bonding by the NH2 groups to an oxygen atom of a bridging carboxylate is confirmed by structural data.9 Most recently, it has been suggested on the basis of model studies that hydrolysis of urea at a dinickel center may proceed through initial elimination of ammonia from the coordinated urea molecule followed by hydrolysis of the resulting bridged cyanate complex.10 In other cases, e.g. methionine aminopeptidase (MAP) and arginase, the mechanisms of hydrolysis are not clear but presumed to be based (7) Karplus, P. A.; Pearson, M. A.; Hausinger, R. P. Acc. Chem. Res. 1997, 30, 330-37. (8) Benini, S.; Rypniewski, W. R.; Wilson, K. S.; Miletti, S.; Ciurli, S.; Mangani, S. Structure 1999, 7, 205-216. (9) Konrad, M.; Meyer, F.; Jacobi, A.; Kircher, P.; Rutsch, P.; Zsolnai, L. Inorg. Chem. 1999, 38, 4559-4566. (10) Barrios, A. M.; Lippard, S. J. J. Am. Chem. Soc. 2000, 122, 91729177.

10.1021/ic0103345 CCC: $20.00 © 2001 American Chemical Society Published on Web 10/12/2001

Dicobalt Hydroxamates and Model Hydrolases on the Zerner scheme.5 The inhibition of metalloenzymes is also of current interest especially because of possible therapeutic applications. For example, the inhibition of matrix metalloproteinases by various hydroxamate-based inhibitors generally involves chelation of a mononuclear zinc center by the hydroxamate function.11 Hydroxamic acids are also potent inhibitors of urease,12 but in this case the structure of the acetohydroxamate-inhibited C319A variant of Klebsiella aerogenes urease shows the deprotonated hydroxyl oxygen of the hydroxamic acid bridging the two nickel centers with the carbonyl oxygen bonding one nickel center only13 in contrast to normal O,O chelation of a metal ion by a hydroxamic acid. A similar structure is found in the dizinc metalloenzyme Aeromonas proteolytica aminopeptidase Zn2 AAP inhibited by p-iodo-Dphenylalanine hydroxamic acid.14 These dinuclear metalloenzymes often exchange metal ions within the above sequence with varying effects on their activities with respect to various substrates. For example, exchange of Ni(II) by Zn(II) or Co(II) in urease results in a large decrease in activity with urea15 and similarly replacement of Ni(II) by Mn(II) in urease also results in a marked decrease in activity with urea.5 In contrast, substitution of 2 mol atoms of Zn in Zn2AAP by Co(II), Cu(II), and Ni(II) gives hyperactive substituted enzymes with rate enhancements of 6.5, 7.7, and 25, respectively, in reactivity compared to that of the parent zinc enzyme with certain substrates. Moreover, addition of 1 mol of these ions to apo-AAP followed by equilibration and then addition of 1 mol of the second metal ion gives a discrete heterodimetallic site that is also enzymatically active.16 In previous papers,17,18we have attempted to model the inhibition of urease by hydroxamic acids by the reactions of acetohydroxamic acid (AHA) with the model complex [Ni2(µ-OAc)3(urea)(tmen)2][OTf] (A), which reacts rapidly with acetohydroxamic acid (AHA) to give the monobridged hydroxamate complex [Ni2(µ-OAc)2(µ-AA)(urea)(tmen)2][OTf] with a structure very similar to that of the acetohydroxamate inhibited C319A variant of Klebsiella aerogenes urease.13 In view of the use of a number of dinuclear divalent metal centers, [Zn(II)]2, [Ni(II)]2, and [Mn(II)]2 by metallohydrolases and their ability to exchange metals ions within this sequence, we have extended our previous modeling of ureases17,18 to related dicobalt(II) systems and their reactions with hydroxamic acids as possible models for methionine aminopeptidase (MAP) which has been proved by a crystal structure determination to contain a dicobalt center and to be inhibited by various reagents including epoxides although the position with regard to inhibition by hydroxamic acids is not clear; however, the above dizinc metalloenzyme, Aeromonas proteolytica aminopeptidase, Zn2AAP, is clearly inhibited by p-iodo-D-phenylalanine hydroxamic (11) Beckett, R. P.; Davidson, A. H.; Drummond, A. H.; Huxley, P.; Whitetaker, M. Drug DiscoVery Today 1996, 1, 16-26 (12) Karger, S. In Chemistry and Biology of Hydroxamic Acids; Kehl, H., Ed.; Basel, 1982. (13) Pearson, M. A.; Michel, L, O.; Hausinger, R. P.; Karplus, P. A.; Biochemistry 1997, 36, 8164-8172. (14) Chevrier, B.; D’Orchymoant, H.; Schalk, C.; Tamus, C.; Moras D. Eur. J. Biochem. 1996, 237, 393-398. (15) King, G. J.; Zerner, B. Inorg. Chim. Acta 1997, 255, 381-388. (16) Prescot, J. M.; Wagner, F. W.; Holmquist, B.; Vallee, B. L. Biochem. Biophys. Res. Commun. 1983, 114, 646-652. (17) Arnold, M.; Brown, D. A.; Deeg, O.; Errington, W.; Haase, W.; Herlihy, K.; Kemp, T. J., Nimir, H.; Werner R. Inorg. Chem. 1998, 37, 2920-2928. (18) Brown, D. A.; Cuffe, L. P., Deeg, O.; Errington, W.; Fitzpatrick, N. J.; Glass, W. K.; Herlihy, K.; Kemp, T. J.; Nimir. H. J. Chem. Soc., Chem. Commun. 1998, 2433-2434.

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Figure 1. Molecular structure of the cation of dicobalt(II) complex 2, [Co2(µ-OAc)3(urea)(tmen)2]+ .

acid with a structure similar to that of the inhibited urease14 and the above model complex.17 As discussed above, it was decided to attempt the synthesis of model dicobalt(III) complexes with bridging hydroxo groups by oxidation of the model dicobalt(II) complexes and compare their behavior with those containing bridging water molecules. Results and Discussion The cobalt(II) analogue (2) of the urease model complex, [Ni2(OAc)3(urea)(tmen)2][OTf],19 was prepared similarly from the previously reported [Co2(µ-H2O)(µ-OAc)2(OAc)2(tmen)2] (1)20 by its reaction with urea in dichloromethane in the presence of triflate. The monobridged hydroxamate cobalt dimer [Co2(µOAc)2(µ-AA)(urea)(tmen)2][OTf] (3) was prepared by the reaction of acetohydroxamic acid (AHA) with 2 in a 1:1 ratio in dichloromethane. The dibridged acetohydroxamate complex [Co2(µ-OAc)(µ-AA)2(tmen)2][OTf] (4) was obtained as pink crystals by the reaction of 1 with acetohydroxamic acid in a 2:1 molar ratio in acetone in the presence of triflate. As in the analogous nickel(II) complexes,17 the above reactions are facile and occur very rapidly at room temperature and in other solvents such as methanol. Reaction of 1 with glutarodihydroxamic acid, (CH2)3(CONHOH)2, gluH2A2, at room temperature in methanol in the presence of triflate gave [Co2(µ-OAc)2{µ-O(N)(OC)2(CH2)3}(tmen)2][OTf] (5) which contains a deprotonated bridging N-hydroxyglutarimide (Figure 4) as in the analogous dinickel complex.18 Crystal Structures of 2-5. The crystal structures of the urea adduct [Co2(µ-OAc)3(urea)(tmen)2][OTf] (2), the monobridged acetohydroxamate complex [Co2(µ-OAc)2(µ-AA)(urea)(tmen)2][OTf] (3), the dibridged acetohydroxamate complex [Co2(µOAc)(µ-AA)2(tmen)2][OTf] (4), and the deprotonated N-hydroxyglutarimide-bridged complex [Co2(µ-OAc)2{µ-O(N)(OC)2(CH2)3}(tmen)2][OTf] (5) are shown in Figures 1-4, respectively, with crystallographic data in Table 1 and selected bond lengths and angles in Tables 2-5, respectively. In all four complexes, the structures shown in Figures 1-4 are very close to those of the corresponding nickel complexes,17,18 with the acetohydroxamate bridging groups in both the mono- and (19) Wages, H. E.; Taft, K. L.; Lippard, S. J. Inorg. Chem. 1993, 32, 49854987. (20) Turpeinein, U.; Ha¨ma¨la¨inen, R.; Reedijk, J. Polyhedron 1987, 6, 16031610.

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Figure 2. Molecular structure for the cation of dicobalt(II) monobridged acetohydroxamate complex 3, [Co2(µ-OAc)2(µ-AA)(urea)(tmen)2]+.

Figure 3. Molecular structure for the cation of dicobalt(II) dibridged acetohydroxamate complex 4, [Co2(µ-OAc)(µ-AA)2(tmen)2]+.

Figure 4. Molecular structure for the cation of dicobalt(II) complex 5, [Co2(µ-OAc)2{µ-O(N)(OC)2(CH2)3}(tmen)2]+.

dibridged complexes, 3 and 4 and I and II,17 exhibiting exactly the same coordination modes in both the dicobalt and dinickel series. In all cases, the deprotonated hydroxamate hydroxyl oxygen bridges the two metal centers while the carbonyl oxygen coordinates only one metal center.

Brown et al. The coordination about the cobalt atoms in 3 is distorted octahedral compared to the parent compound 2 (Figure 2); for example in complex 3, O(5)-Co(1)-O(1) is 94.10(6)˚ whereas the equivalent angle O(1)-Co(l)-O(6) in 2 is 90.89(6)˚. As a consequence of forming only a single acetohydroxamate bridge in 3 by simple replacement of the monodenate bridging acetate in 2, the Co---Co distance in 3 is 3.4316(17) Å (Table 3), which is greater than that in the native dicobalt MAP, 2.9 Å, but is close to that in the parent compound 2, 3.4813(3) Å, and slightly less than that in the hydroxamate inhibited dizinc Aeromonas proteolytica aminopeptidase Zn2AAP, 3.7 Å.14 The urea molecule remains coordinated via its oxygen atom O(7) to Co(1), and there is a slight increase in the Co(1)-O(7)(urea) distance in 3, 2.1406(16) Å, compared to 2.0978(14) Å in the parent complex 2. This may indicate a decrease in the metal Lewis acidity upon hydroxamate coordination compared to acetate coordination, which is consistent with the inhibition of metaldependent hydrolases by hydroxamic acids. Figure 3 shows the structure obtained for the cation of 4. In this molecule, hydroxamate coordination results in the loss of one of the bridging acetates, both terminal acetates, and the bridging water molecule in 1. The hydroxamate moieties are bound in a similar manner as in 3, by using the deprotonated oxygens, O(3) and O(5), as bridging atoms and carbonyl oxygens, O(4) and O(6), as monodentate atoms. Both cobalt atoms in 4 are in a distorted octahedral environment which is exemplified by the angles O(1)-Co(1)-O(3) of 97.96(10)˚ and O(2)-Co(2)-O(5) of 95.69(11)˚ (Table 4). The formation of two acetohydroxamate bridges in 4 results in a decrease in the Co---Co distance to 3.0971(6) Å compared to 3.4316(17) Å in 3, but it is close to that reported for the related dinickel dibridged salicylhydroxamate urease model of 3.016 Å.21 The ability of cobalt(II) to form a series of complexes analogous to those of nickel(II), including formation of hydroxamate-bridged complexes and elimination of hydroxylamine from glutarodihydroxamic acid, is in accord with studies of the exchange of metal(II) centers within metalloenyzmes as noted in the Introduction. The formation of the bridged hydroxamate complexes (3 and 4) suggests inhibition of dicobalt-based metalloenzymes similar to that observed in the acetohydroxamate complex with the C319A variant of urease involving a dinickel-bridged hydroxamate structure and the very similar dizinc-bridged structure in the p-iodo-d-phenylalanine hydroxamate complex with Aeromonas proteolytica aminopeptidase AAP.14 In the case of the closely related methionine aminopeptidase containing a dicobalt active site with approximately octahedral coordination of the Co(II) centers by both carboxylate and a histidine nitrogen,4 inhibition by the epoxide-containing compounds fumagillin and ovalicin occurs by modification of a histidine center although there is spectroscopic evidence for some interaction at the dicobalt center.22 The above expoxides also inhibit angiogenesis which may be therapeutically important, and the related compound TNP-470 is currently on trial as an anticancer reagent. However, to date, inhibition of MAP by hydroxamic acids has not been structurally characterized. The crystal structure of the N-hydroxyglutarimide dicobalt 5 (Figure 4) shows that the deprotonated N-OH oxygen of the N-hydroxyglutarimide residue O(11) bridges the two cobalt ions Co(1) and Co(2) and the two carbonyl oxygens O(16) and O(17) coordinate to their respective cobalt atoms Co(1) and Co(2). (21) Stemmler, A. J.; Kampt, J. W.; Kirk, M. L.; Pecoraro, V. L. J. Am. Chem. Soc. 1995, 117, 6368-6369. (22) Lowther, T. W.; McMillen, D. A.; Orville, A. M.; Matthews, B. W. Proc. Natl. Acad. Sci. U.S.A. 1998, 95, 12153-12157.

Dicobalt Hydroxamates and Model Hydrolases

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Table 1. Crystal Data and Structure Refinement for Compounds 2-5 and 7-9 param Formula Mr cryst system space group a/Å b/Å c/Å R/deg β/deg γ/deg V/Å3 T/K Z λ/Å F(calcd)/Mg m-3 cryst size/mm µ/mm-1 hkl ranges no. of reflcns collcd indepdt reflcns max and min transm R(F) [I > 2σ(I)]/% Rw(F2) (all data)/% goodness of fit on F2 largest peak and hole/e Å-3

2

3

4

5

7

8

9

C20H45Co2F3N6O10S 736.54 Triclinic P1h 9.7021(1) 11.5985(2) 15.2967(3) 101.921(1) 95.710(1) 96.481(1) 1660.04(5) 180(2) 2 0.710 73 1.474 0.30 × 0.30 × 0.30 1.133 -12, 12; -14, 10; -20, 19 9900 7200 (Rint ) 0.0197) 0.7618, 0.8437 3.40 7.90 0.905 0.412, -0.790

C20H46Co2F3N7O10S 751.56 monoclinic P21/c 11.0745(6) 13.6540(7) 22.6864(11) 90 94.47(3) 90 3420.0(3) 180(2) 4 0.710 73 1.460 0.40 × 0.38 × 0.12 1.103 -14, 11; -14, 17; -29, 30 20 291 8065 (Rint ) 0.023) 0.8791, 0.6668 3.94 9.66 1.065 0.623, -0.542

C19H45Co2F3N6O10S 724.53 triclinic P1h 10.4771(5) 11.4398(6) 14.9218(7) 77.148(1) 81.757(1) 71.299(1) 1646.57(14) 180(2) 2 0.710 73 1.461 0.40 × 0.30 × 0.14 1.141 -12, 8; -14, 13; -18, 18 8971 6276 (Rint ) 0.016) 0.8566, 0.6582 4.80 12.53 1.064 0.958, -0.548

C22H44Co2F3N5O10S 745.54 triclinic P1h 10.7949(8) 15.7459(10) 20.9128(18) 74.076(2) 84.566(3) 81.201(3) 3372.8(4) 180(2) 4 0.710 73 1.468 0.30 × 0.20 × 0.20 1.116 -14, 13; -21, 20; -27, 17 20 461 14 888 (Rint ) 0.003) 0.8076, 0.7307 8.28 20.79 1.071 1.296, -1.058

C21H45Co2F3N4O12S 752.53 monoclinic P21/c 8.3982(3) 13.2386(6) 29.0771(6) 90 95.698(3) 90 3216.8(2) 180(2) 4 0.710 73 1.554 0.30 × 0.24 × 0.10 1.174 -11, 10; -9, 17; -35, 38 19 711 7796 (Rint ) 0.045) 0.9165, 0.6364 4.21 9.30 1.004 0.390, -0.636

C19H43Co2F3N4O11S 710.29 monoclinic P21/n 8.5756(6) 22.1861(12) 16.4845(12) 90 100.936(3) 90 3079.4(4) 180(2) 4 0.710 73 1.533 0.40 × 0.10 × 0.04 1.219 -10, 10; -26, 23; -11, 19 15 801 5428 (Rint ) 0.047) 0.9528, 0.6412 4.63 11.40 1.031 0.529, -0.427

C19H43F3Co2N4O11S 710.29 monoclinic P21/c 8.0482(9) 29.076(3) 12.8882(14) 90 93.965(3) 90 3008.8(6) 180(2) 4 0.710 73 1.568 0.20 × 0.20 × 0.20 1.248 -9, 9;-34, 23; 15, -15 15 319 5285 (Rint ) 0.037) 0.8312, 0.6716 6.95 18.90 1.048 1.838, -0.739

Table 2. Selected Bond Lengths (Å) and Angles (deg) for Complex 2 Co(1)-Co(2) Co(1)-O(7) Co(1)-N(1) Co(2)-O(2) Co(2)-N(4) Co(2)-O(6) Co(2)-C(17) O(4)-Co(1)-O(1) O(1)-Co(1)-O(7) O(1)-Co(1)-O(6) O(4)-Co(1)-N(1) O(7)-Co(1)-N(1) O(4)-Co(1)-N(2) O(7)-Co(2)-N(2) O(2)-Co(2)-O(5) N(4)-Co(2)-O(5) O(3)-Co(2)-O(6) O(5)-Co(2)-O(6) O(3)-Co(2)-N(3)

3.4813(3) 2.0978(14) 2.209(2) 2.009(2) 2.144(2) 2.1875(14) 2.519(2) 94.76(6) 175.16(6) 90.89(6) 171.46(7) 85.40(6) 89.98(7) 91.19(7) 163.67(6) 95.25(7) 96.64(6) 60.42(6) 170.77(7)

Co(1)-O(4) Co(1)-O(1) Co(1)-O(6) Co(1)-N(2) Co(2)-O(3) Co(2)-O(5) Co(2)-N(3) O(4)-Co(1)-O(7) O(4)-Co(1)-O(6) O(7)-Co(1)-O(6) O(2)-Co(2)-O(3) O(3)-Co(2)-N(4) O(3)-Co(2)-O(5) O(2)-Co(2)-O(6) O(5)-Co(2)-N(3) O(2)-Co(2)-C(17) N(4)-Co(2)-C(17) O(6)-Co(2)-C(17)

2.076(2) 2.0815(14) 2.140(2) 2.215(2) 2.070(2) 2.155(2) 2.279(2) 89.84(6) 92.29(6) 90.41(6) 91.83(7) 88.51(8) 92.77(7) 103.47(6) 90.51(7) 134.03(7) 124.88(8) 30.64(6)

Formation of 5 involves the novel elimination of hydroxylamine. We suggest that the two cobalt(II) centers in 5 act as Lewis acids polarizing both carbonyl groups of glutarodihydroxamic acid; protonation of one of the hydroxamate nitrogens and subsequent attack by the nucleophilic nitrogen at the other end of the dihydroxamic acid leads to the loss of the NH2OH group, ring closure, and formation of a tetrahedral intermediate, which collapses on release of a proton and formation of 5 as proposed for the nickel analogue.18 This mechanism is related to that proposed for the cleavage of the C-N bond in peptide hydrolysis catalyzed by a dizinc center in aminopeptidases, in particular that proposed for the hydrolysis of an N-terminal amino acid at bILAP.2 Spectroscopic Studies. The electronic spectra of 2-5 measured in CH2Cl2 are very similar and typical of a distorted octahedral environment about a Co(II) center with bands in the visible region at ca. 525 nm assigned to the 4T1g(F) f 4TIg(P)

Table 3. Selected Bond Lengths (Å) and Angles (deg) for Complex 3 Co(1)-Co(2) Co(1)-O(1) Co(1)-N(1) Co(2)-O(2) Co(2)-O(5) Co(2)-N(3) Co(2)-N(4) O(3)-Co(1)-O(5) O(5)-Co(1)-O(1) O(5)-Co(1)-O(7) O(3)-Co(1)-N(1) O(1)-Co(1)-N(1) O(3)-Co(1)-N(2) O(1)-Co(2)-N(2) N(1)-Co(1)-N(2) O(2)-Co(2)-O(5) O(2)-Co(2)-O(6) O(5)-Co(2)-O(6) O(4)-Co(2)-N(3) O(6)-Co(2)-N(3) O(4)-Co(2)-N(4) O(6)-Co(2)-N(4)

3.4316(17) 2.0813(16) 2.219(2) 2.0523(18) 2.0840(16) 2.199(2) 2.245(2) 95.49(6) 94.10(6) 88.61(6) 91.57(7) 87.20(7) 172.63(7) 88.88(7) 81.67(8) 95.06(7) 174.28(8) 79.22(7) 87.87(8) 92.76(9) 169.83(8) 93.43(8)

Co(1)-O(3) Co(1)-O(5) Co(1)-O(7) Co(1)-N(2) Co(2)-O(4) Co(2)-O(6) O(3)-Co(1)-O(1) O(3)-Co(1)-O(7) O(1)-Co(1)-O(7) O(5)-Co(1)-N(1) O(1)-Co(1)-N(1) O(5)-Co(1)-N(2) O(7)-Co(1)-N(2) O(2)-Co(2)-O(4) O(4)-Co(2)-O(5) O(4)-Co(2)-O(6) O(2)-Co(2)-N(3) O(5)-Co(2)-N(3) O(2)-Co(2)-N(4) O(5)-Co(2)-N(4) N(3)-Co(2)-N(4)

2.0774(17) 2.0779(16) 2.1406(16) 2.260(2) 2.0802(17) 2.0986(18) 93.75(7) 89.83(6) 175.27(7) 172.71(8) 89.62(7) 91.18(7) 87.20(7) 92.42(7) 97.96(7) 88.53(8) 92.92(9) 169.89(8) 86.62(8) 92.21(8) 82.07(9)

transition and in the near-infrared region at ca. 1090 nm assigned to the 4T1g(F) f 4T2g transition (see Supporting Information, Table S1). The infrared spectra of 3 and 4 measured in KBr disks and in CH2Cl2, acetone, and methanol solutions (Table 9) are very similar to those of the analogous nickel complexes17 and provide further support for the occurrence of both a carboxylate shift and a hydroxamate shift in 3 and 4 as suggested previously for the analogous nickel complexes. Thus while both 3 and 4 show peaks at 1626-1624 and 1603-1610 cm-1 in CH2Cl2 assigned to a bridging acetate and coordinated hydroxamate, respectively, there are again additional peaks at 1552 and 1558 cm-1 in 3 and 4, respectively, which are absent in the KBr spectra and which are assigned to a carboxylate shift in which a bidentate acetate is in equilibrium with a monodentate bridging intermediate.23 Similarly, 3 shows a new peak at 1613 cm-1 which again

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Brown et al.

Table 4. Selected Bond Lengths (Å) and Angles (deg) for Complex 4 Co(1)-Co(2) Co(1)-O(1) Co(1)-O(5) Co(1)-N(3) Co(2)-O(2) Co(2)-O(5) Co(2)-N(5) O(1)-Co(1)-O(4) O(4)-Co(1)-O(5) O(4)-Co(1)-O(3) O(1)-Co(1)-N(3) O(5)-Co(1)-N(3) O(1)-Co(1)-N(4) O(5)-Co(1)-N(4) N(3)-Co(1)-N(4) O(2)-Co(2)-O(5) O(2)-Co(2)-O(3) O(5)-Co(2)-O(3) O(6)-Co(2)-N(5) O(3)-Co(2)-N(5) O(6)-Co(2)-N(6) O(3)-Co(2)-N(6)

Table 6. Selected Bond Lengths (Å) and Angles (deg) for Complex 8

3.0971(6) 2.045(3) 2.121(2) 2.175(3) 2.040(3) 2.088(2) 2.195(3)

Co(1)-O(4) Co(1)-O(3) Co(1)-N(4) Co(2)-O(6) Co(2)-O(3) Co(2)-N(6)

2.060(2) 2.170(2) 2.248(3) 2.070(2) 2.183(2) 2.226(3)

176.61(11) 93.60(10) 79.15(9) 90.08(12) 98.09(11) 88.12(13) 175.76(11) 82.56(12) 95.69(11) 90.07(10) 82.08(9) 95.15(12) 98.73(10) 89.89(11) 177.67(11)

O(1)-Co(1)-O(5) O(1)-Co(1)-O(3) O(5)-Co(1)-O(3) O(4)-Co(1)-N(3) O(3)-Co(1)-N(3) O(4)-Co(1)-N(4) O(3)-Co(1)-N(4) O(2)-Co(2)-O(6) O(6)-Co(2)-O(5) O(6)-Co(2)-O(3) O(2)-Co(2)-N(5) O(5)-Co(2)-N(5) O(2)-Co(2)-N(6) O(5)-Co(2)-N(6) N(5)-Co(2)-N(6)

87.69(10) 97.96(10) 81.62(9) 92.84(11) 171.93(10) 90.55(12) 98.33(10) 175.04(12) 80.08(10) 91.90(9) 89.05(12) 175.20(11) 88.03(12) 96.77(11) 82.58(12)

Table 5. Selected Bond Lengths (Å) and Angles (deg) for Complex 5 Co(1)-Co(2) Co(1)-O(12) Co(1)-O(11) Co(1)-O(16) Co(2)-O(13) Co(2)-O(11) Co(2)-O(17) Co(3)-O(24) Co(3)-O(22) Co(3)-O(27) Co(4)-O(25) Co(4)-O(21) Co(4)-O(26)

3.4128(11), 3.4219(11) 2.059(4) 2.083(4) 2.210(4) 2.031(4) 2.071(4) 2.184(4) 2.055(4) 2.083(4) 2.192(4) 2.036(4) 2.081(4) 2.199(4)

Co(1)-O(14) Co(1)-N(13) Co(1)-N(12) Co(2)-O(15) Co(2)-N(14) Co(2)-N(15) Co(3)-O(21) Co(3)-N(23) Co(3)-N(22) Co(4)-O(23) Co(4)-N(25) Co(4)-O(24)

2.060(4) 2.172(5) 2.212(6) 2.063(4) 2.168(6) 2.230(6) 2.070(4) 2.153(5) 2.240(5) 2.057(5) 2.166(6) 2.230(6)

O(12)-Co(1)-O(14) 96.79(18) O(12)-Co(1)-O(11) 101.14(16) O(14)-Co(1)-O(11) 89.57(16) O(12)-Co(1)-N(13) 90.79(18) O(14)-Co(1)-N(13) 89.83(19) O(11)-Co(1)-N(13) 168.04(18) O(12)-Co(1)-O(16) 175.51(17) O(14)-Co(1)-O(16) 85.42(17) O(11)-Co(1)-O(16) 74.91(16) N(13)-Co(1)-O(16) 93.13(18) O(12)-Co(1)-N(12) 89.1(2) O(14)-Co(1)-N(12) 170.7(2) O(11)-Co(1)-N(12) 96.3(2) N(13)-Co(1)-N(12) 83.0(2) O(16)-Co(1)-N(12) 89.19(19) O(13)-Co(2)-O(15) 97.45(19) O(13)-Co(2)-O(11) 99.14(17) O(15)-Co(2)-O(11) 91.14(16) O(13)-Co(2)-N(14) 90.0(2) O(15)-Co(2)-N(14) 89.73(19) O(11)-Co(2)-N(14) 170.65(19) O(13)-Co(2)-O(17) 174.82(19) O(15)-Co(2)-O(17) 84.72(18) O(11)-Co(2)-O(17) 76.06(16) N(14)-Co(2)-O(17) 94.75(19) O(13)-Co(2)-N(15) 90.8(2) O(15)-Co(2)-N(15) 169.11(19) O(11)-Co(2)-N(15) 94.5(2) N(14)-Co(2)-N(15) 83.2(2) O(17)-Co(2)-N(15) 87.6(2)

is assigned to a “hydroxamate shift”17 in which a monodentate bridging hydroxamate is in equilibrium with a form in which there is a weak interaction between the hydroxamate carbonyl oxygen and the metal center. The spectra in acetone and methanol show results similar to those in CH2Cl2 (Table 9). Magnetic Susceptibility Measurements. The theoretical treatment of dinuclear Co(II) complexes belongs to one of the more difficult chapters of magnetochemistry. The Co(II) d7 ion is strongly anisotropic, and the first-order orbital momentum is no longer negligible so the isotropic exchange interaction is insufficient to discuss these complexes and must be supplemented by considerations of orbitally dependent exchange interactions. This leads to invoking a large number of parameters (23) Rardin, L. R.; Tolman, W. B.; Lippard, S. J. New J. Chem. 1991, 15, 417-430.

Co(1)-Co(2) Co(1)-O(5) Co(1)-O(6) Co(1)-N(1) Co(2)-O(5) Co(2)-O(2) Co(2)-O(8) O(5)-Co(1)-O(1) O(1)-Co(1)-O(6) O(1)-Co(1)-O(3) O(5)-Co(1)-N(1) O(6)-Co(1)-N(1) O(5)-Co(1)-N(2) O(6)-Co(1)-N(2) N(1)-Co(1)-N(2) O(5)-Co(2)-O(2)

3.3466(7) 1.873(3) 1.899(3) 2.019(3) 1.997(3) 2.104(3) 2.199(4)

Co(1)-O(1) Co(1)-O(3) Co(1)-N(2) Co(2)-O(4) Co(2)-N(3) Co(2)-N(4)

1.889(3) 1.916(3) 2.071(3) 2.064(3) 2.191(3) 2.206(3)

90.61(13) 175.16(12) 90.88(12) 89.23(13) 91.23(13) 176.40(13) 85.88(13) 87.17(13) 88.70(11)

O(5)-Co(1)-O(6) O(5)-Co(1)-O(3) O(6)-Co(1)-O(3) O(1)-Co(1)-N(1) O(3)-Co(1)-N(1) O(1)-Co(1)-N(2) O(3)-Co(1)-N(2) O(5)-Co(2)-O(4) O(4)-Co(2)-O(2)

94.17(13) 99.45(12) 89.03(12) 88.13(13) 171.28(12) 89.30(13) 84.16(12) 94.68(11) 89.99(11)

Table 7. Selected Bond Lengths (Å) and Angles (deg) for Complex 7 Co(1)-Co(2) Co(1)-O(5) Co(1)-O(3) Co(1)-N(1) Co(2)-O(5) Co(2)-O(4) O(5)-Co(1)-O(6) O(6)-Co(1)-O(3) O(6)-Co(1)-O(1) O(5)-Co(1)-N(1) O(3)-Co(1)-N(1) O(5)-Co(1)-N(2) O(3)-Co(1)-N(2) N(1)-Co(1)-N(2) O(5)-Co(2)-O(4) O(5)-Co(2)-O(2) O(4)-Co(2)-O(2)

3.2635(5) 1.8819(19) 1.9029(17) 2.023(2) 1.8681(18) 1.9025(17) 89.53(8) 95.81(8) 177.02(8) 88.51(9) 172.77(9) 175.23(9) 85.61(8) 87.19(9) 95.05(8) 90.54(8) 91.82(8)

Co(1)-O(6) Co(1)-O(1) Co(1)-N(2) Co(2)-O(8) Co(2)-O(2) O(5)-Co(1)-O(3) O(5)-Co(1)-O(1) O(3)-Co(1)-O(1) O(6)-Co(1)-N(1) O(1)-Co(1)-N(1) O(6)-Co(1)-N(2) O(1)-Co(1)-N(2) O(5)-Co(2)-O(8) O(8)-Co(2)-O(4) O(8)-Co(2)-O(2)

1.8904(18) 1.9101(18) 2.029(2) 1.8950(18) 1.9125(18) 98.66(8) 88.97(8) 86.96(8) 85.12(8) 92.27(9) 92.16(9) 89.14(9) 94.53(8) 88.02(8) 174.92(8)

Table 8. Selected Bond Lengths (Å) and Angles (deg) for Complex 9 Co(1)-Co(2) Co(1)-O(1) Co(1)-O(2) Co(1)-N(2) Co(2)-O(2) Co(2)-O(1) Co(2)-N(3)

2.83 1.905(4) 1.906(4) 2.031(5) 1.897(4) 1.903(4) 2.026(5)

Co(1)-O(3) Co(1)-O(5) Co(1)-N(1) Co(2)-O(4) Co(2)-O(7) Co(2)-N(4)

1.895(4) 1.893(4) 2.027(5) 1.909(4) 1.897(4) 2.024(5)

O(1)-Co(1)-O(3) O(3)-Co(1)-O(5) O(2)-Co(1)-O(5) O(1)-Co(1)-N(2) O(5)-Co(1)-N(2) O(1)-Co(1)-N(1) O(5)-Co(1)-N(1) O(2)-Co(1)-N(1) O(2)-Co(2)-N(4) O(2)-Co(2)-O(4) O(6)-Co(2)-N(4) O(5)-Co(2)-N(3) O(4)-Co(2)-N(3) O(5)-Co(2)-N(4) O(4)-Co(2)-N(4)

88.37(18) 175.17(18) 94.11(18) 86.96(8) 88.3(2) 173.9(2) 88.8(2) 88.1(2) 94.4(2) 89.72(18) 88.14(8) 172.74(8) 86.72(8) 92.29(8) 170.53(9)

O(1)-Co(1)-O(2) O(2)-Co(1)-O(3)

82.64(17) 89.45(18)

O(2)-Co(1)-N(2) O(2)-Co(1)-N(1) O(3)-Co(1)-N(1) O(3)-Co(1)-N(2) O(2)-Co(2)-O(7) O(2)-Co(2)-O(1) O(7)-Co(2)-O(1) O(2)-Co(2)-O(4) O(7)-Co(2)-O(4) O(2)-Co(2)-N(4) O(7)-Co(2)-N(4) N(3)-Co(2)-N(4)

177.5(2) 92.6(2) 87.76(19) 88.2(2) 94.15(18) 82.95(16) 92.84(18) 89.72(18) 175.90(18) 94.4(2) 91.3(2) 88.0(2)

to attempt a quantitative discussion of the temperature-dependent magnetic susceptibility data. Ideally, such data should be supplemented by complementary techniques, such as variabletemperature and variable-field magnetic circular dichroism; however, access to such techniques was not available so we have attempted to interpret the susceptibility data in terms of the minimum number of parameters which are physically meaningful.

Dicobalt Hydroxamates and Model Hydrolases

Inorganic Chemistry, Vol. 40, No. 23, 2001 5967

Table 9. Infrared Spectral Data for Complexes 1-4 in Selected Solventsa medium

2

3

KBr

1

1669 1670 1618 1634 1630 1606 1559 CH2Cl2 1664 1663 1614 1626 1624 1613 1603 1553 1552 1557 acetone 1669 1667 1617 1629 1632 1604 1550 1548 1554 methanol 1666 1667 1627 1628 1610 1604 1560 1560 1562 a

4

assgnt

urea 1636 bidentate bridging acetate 1592,1610 (sh) coord hydroxamate monodentate acetate urea 1624 bidentate bridging acetate monodentate hydroxamate 1610 coord hydroxamate 1558 monodentate acetate urea 1634 bidentate bridging acetate 1591, 1609 coord hydroxamate 1559 monodentate acetate urea 1627 bidentate bridging acetate 1582 coord hydroxamate H-bonded acetate 1554 monodentate acetate

All values in cm-1.

Figure 5. Susceptibility and effective magnetic moment per dimer vs temperature of complex [Co2(µ-H2O)(µ-OAc)2(OAc)2(tmen)2] (1). The solid lines represent the best fit with the following parameters: J ) -0.7 cm-1; D ) 45 cm-1, g| ) 2.9; g⊥ ) 2.5.

Complexes 1-3 were magnetically characterized by measuring the temperature dependence of their molar susceptibilities in the temperature range 4.4-310 K; the results for 4 were not reproducible. The behavior of the three complexes differs remarkably. While 3 shows a distinct maximum in χM at 15 K, 1 and 2 exhibit more or less a paramagnetic hyperbola. For all three compounds, the magnetic moment/dimer at room temperature is much higher than the spin-only value. In the case of 2, the value increases on cooling from 7.61 µB at 300 K to 7.79 µB at 140 K followed by a decrease to 6.16 µB at 4.5 K. The effective magnetic moments of 1 and 3 decrease with decreasing temperature from 7.17 µB at 300 K to 4.08 µB at 4.6 K and from 7.20 µB at 300 K to 1.77 µB at 4.4 K, respectively. The temperature dependencies of the magnetic susceptibilities and effective magnetic moments of 1-3 are shown in Figures 5-7, respectively. The magnetic data were interpreted in terms of the Hamiltonian: Here the first term is the isotropic exchange interaction

between two Co(II) ions, the next two terms are due to the local field splitting, and the last two terms are the Zeeman perturbation. The orbital contribution to the exchange interaction together with the biquadratic exchange and anisotropic exchange interactions have all been neglected. Calculations were performed on

Figure 6. Susceptibility and effective magnetic moment per dimer vs temperature of complex [Co2(µ-OAc)3(urea)(tmen)2][OTf] (2).

Figure 7. Susceptibility and effective magnetic moment per dimer vs temperature of complex [Co2(µ-OAc)2(µ-AA)(urea)(tmen)2][OTf] (3). The solid lines represent the best fit with the following parameters: J ) -3.6 cm-1; D ) 45 cm-1; g| ) 3.0; g⊥ ) 2.6.

a coupled basis, and the details are given elsewhere.24The principal values of the magnetic susceptibility were calculated from the usual expression:

χu ) NkT

[ [

∂2 ∂Hu2

ln

∑i exp

- Ei(Hu) kT

]]

u ) xl ylz

Here Ei are the energy levels of the system in the external magnetic field. Finally, the powder average susceptibility is calculated as

1 χaν ) (χx + χy + χz) 3 The experimental magnetic properties of 1 as well as the calculated values of the magnetic susceptibility and effective magnetic moment are presented in Figure 5 (best-fit parameters are shown in the caption). The calculated value of the local axial zero field splitting parameter for 1 of D ) 45 cm-1 is typical of high-spin Co(II). The small value of the isotropic exchange interaction (J ) -0.7 cm-1) indicates a very weak antiferromagnetic interaction consistent with the structure of 1 containing bridging acetate groups which do not provide a good pathway for superexchange. Due to this small value of the (24) Ostrovski, S. M. Private Communication.

5968 Inorganic Chemistry, Vol. 40, No. 23, 2001

Brown et al.

Table 10. Spectroscopic Data for CoIII2 and CoIIICoII Dinuclear Homo- and Mixed-Valence Complexes IR carbonyl freq, cm-1

complex [CoIIICoII(µ-OH)(µ-OAc)2(OAc)(urea)(tmen)2][OTf] (10) [CoIII2(µ-OH)(µ-OAc)2(OAc)(urea)(tmen)2][OTf][OAc] (11) [CoIIICoII(µ-H2O)(µ-OH)(µ-OAc)(OAc)2(tmen)2][OAc] (6) [CoIII2(µ-OH)(µ-OAc)2(OAc)2(tmen)2][OTf]

(7)

[CoIII2(µ-OH)(OH)(µ-OAc)2(OAc)(tmen)2][OTf] (8) [CoIIICoII(µ-OH)(µ-OAc)2(µ-AA)(urea)(tmen)2][OTf][OAc] (12)

isotropic exchange parameter, the excited states with M ) (1 are very close in energy to the antiferromagnetic ground state and their thermal population is significant even at very low temperatures. Thus, at T ) 4.5 K, the effective magnetic moment of 1 is about 4 µB. In contrast, the best-fit parameters for 3 give a J value of -3.6 cm-1 indicating a stronger antiferromagnetism than in 1 in accord with the presence of the bridging hydroxamate group although the analogous nickel complex shows a weak ferromagnetic interaction (J ) 4.09 cm-1).17 Unfortunately, the magnetic properties of complex 2 cannot be explained within the framework of the above pure spin model. An analysis based on a model which takes into account a strong orbital contribution of Co(II) is in progress. Dicobalt(III) Complexes 7-9. Oxidation of aqueous solutions of cobalt(II) in the presence of various ligands yields a range of µ-hydroxo and µ-peroxo complexes, for example, [L4Co(µ-OH)(µ-O2)CoL4]3+ (L ) NH3, tn, tren, trien).25Dihydroxoand trihydroxo-bridged dinuclear complexes together with mixed-valency Co(II)/Co(III) complexes have also been reported.26 In view of the difficulty in assessing the protonation state of the bridging ligand in dinuclear metalloenzymes as mentioned in the Introduction, it was decided to attempt the synthesis of model dicobalt(III) complexes with bridging hydroxo groups by oxidation of the model dicobalt(II) complexes, 1-3 especially, since it was noted that, on prolonged exposure to air, pink solutions of 1 and 2 turned reddish-brown, indicating aerial oxidation. Oxidation of solutions of the above complexes was attempted with a variety of oxidants such as Ce(SO4)2, HNO3, air, and H2O2, but only with H2O2 were reproducible results obtained and only in the case of the oxidation of 1 and 3 were crystals obtained suitable for a structure determination, yielding complexes 7-9. Oxidation of 1 with H2O2. The dicobalt hydrolase model, 1, reacted vigorously with hydrogen peroxide to give three products, one brown and two green, depending on the amount of hydrogen peroxide used. Addition of only a few drops of H2O2 to 1 in methanol gave after workup a brown complex 6 characterized by IR and UV-visible (Table 10). Its proposed structure shown in Scheme 1 of a mixed Co(II)/Co(III) bridged dimer. Excess of hydrogen peroxide added to a solution of 1 in methanol under nitrogen gave a green solution. Removal of solvent and treatment of the resulting green oil with diethyl ether and ethyl acetate gave two crystalline products, 8 and 7, suitable for X-ray crystallography (Figures 8 and 9, respectively). Crystallographic data and selected bond lengths and angles are given in Tables 1, 6, and 7, respectively. (25) Fallab, S.; Mitchel, P. R. AdV. Inorg. Bioinorg. Mech. 1984, 3, 311377. (26) Chaudhuri, P.; Querback, J.; Wieghardt, K.; Nuber, B.; Weiss, J. J. Chem. Soc., Dalton Trans. 1990, 271-278.

1670, 1618, 1560 (KBr) 1664, 1614, 1556 (CH2Cl2) 1669, 1619, 1559 (KBr) 1665, 1615, 1554 (CH2Cl2) 1631, 1548 (KBr) 1624, 1556, 1711 (CH2Cl2) 1651, 1645, 1606, 1570 (KBr) 1655, 1645, 1604, 1568 (CH2Cl2) 1632, 1576 (KBr) 1614, 1564,1554 (CH2Cl2) 1670, 1633, 1607 (KBr)

UV/vis spectral data: λmax, nm (, cm-1 M-1) (CH2Cl2)