E-xper inien t a/ Procedure Ozone adsorbed on silica gel at - 78 C was passed very slowly between - 5 0 - 60 'C through a solution of Br2 in CFCI, with a stream of argon. until the brown color of the bromine in solution had almost disappeared. The lemon-ycl- low solid was freed from solvent and ozone under vacuum and dissolved in ii

little CH,CI, at - 78 C. The undissolved colorless bromine oxide was removed by low-temperature centrifugation When the orange solution wiis cooled to - 90 C. Br,O, crystallized in needles of the same color. Raman spectrum (solid. krypton ion laser. 647.0 nm). i. = 156. 167 m. sh. 325 OJ BrOZ) s. 387 w. 449 v(Br0Br) s. 588 v(Br0Br) s. X49 v(Br0,) s. 890 v,,.(BrOL) M cm ~ ' . Crystal structure analysis: o =1186.6(2), h =762.9(1). = 869.3(2) pm. /j =106.4(1) . T = -145 C. P2,'c. Z = 8, / i = 20Xcm-'. 3029 measured reflections in the range 11 = 2 -35 . + / I , + k , + I, 2800 unique reflections. R,,, = 0.020. 2302 re- flections with 12 3a(/). R = 0.046. R, = 0.039. Further details of the crystal structure investization may be obtained from the Fachinformationstentrum Karlsruhe. Gesellschaft fur wissenschaftlich-technische Information mbH. D- 76344 Eg_pen~tein-Leopoldshafen (FRG), on quoting the depositor! number CSD-57429. thc names of the authors. and thc journal citation.

Received: June 5. 1993 [Z61261E] German version: Anpew. Chew. 1993. /05. I734

Fig. 1. The structure of' Br-0-BrO, I . (ORTEP plot. thermal ellipsoids at 50% probability level). Distances [pm] and angles 1 I : Brl-011 184.9(5). Brl- 0 1 2 161.1(5), Brl-013 162.0(5), Br2-011 184.9(5). Br3-021 186.0(5). Br3-022 161.0(4). Br3-023 160.5(4). Br4-021 184.1(4). 81-2...Br4 299.5(1): 011-Brl- 0 1 2 103.0(?). 0 1 I-Brl-013 103.2(2), 012-BrI-013 106.4(3), Brl-011-Br2 I1 1.2(2l.Oll-Br3-022 103.5(2). 021-Br3-023 102 X(2). 022-Br3-023 108.8(2). Br3-021-BI-4 1 I l l ( ? ) . 011-BrZ- ' .Br4 175.9(2). 021-Br4...BrZ 86.4(2).

few covalent bromates like O,BrONO, ,[Ih1 O,BrOCIO, ," 'I and C,F,BrO,~lS1 are known. Crystal structure analyses of these compounds have not yet been reported.

The new bromine oxide 1 has bond lengths and bond angles in accord with the formula Br-0-BrO,. that is, 1 has Br" in a pyramidal environment with two short Br=O bonds and an angled Br-0-Br unit. The two crystallographically different but chemically identical molecules both have a syn conformation. Of particular note are the dimers of 1 in the crystalline solid with a Br . . . Br distance of 29931) pm. This distance i s even somewhat shorter than the intramolecular Br . . . Br distance of 305.0(1) pm. The directionality of this interaction is also indicated by the angles in the -0-Br t . . Br- 0- bridge, which are 175.9(2) and 86.4(2)".

A comparison between the structural data of 1 and those of the compound recently described as Br-O-BrO,'"' re- veals a striking resemblance. The latter was prepared with the discharge method and characterized by EXAFS as BrO- BrO, . The EXAFS method determines fairly accurate bond lengths only if multiple scattering effects can be excluded or if they are properly considered. Moreover, the determination of the number of neighboring backscatterers (which is gener- ally not very accurate) becomes impossible if perhaps poly- morphic products or even product mixtures are investigated. A comparison of the Raman spectra also fails to decide if we have identical or different products. If we restrict ourselves to the prominent bands above 400 cm-'. 1 absorbs at 449, 588. and 849 cm- ' . The postulated r'I1 BrOBrO, absorbs at 453, 582. and 842 cm- ' . If it is assumed that the local C,, symmetry of the BrO, part of the molecule dominates the Raman spectrum, the spectra of the compounds could be indeed very similar. The detection of BrO, among the hy- drolysis products is only meaningful for a uniform product. The existence of BrOBrO, is therefore questionable.

None of our experiments resulted in a product with a prominent Raman band at G = 205 cm - I . Theoccurrenceof this band had been the main argument for the existence of a bromine oxide formulated as O,Br-BrO,, which should now be regarded as a totally hypothetical

For the colorless residual bromine oxide, which precipi- tates on dissolution in CH,CI,, we have as yet not found a suitable solvent. Its Raman spectrum shows it to be a new compound, and it seems to be more strongly oxidized, since the colorless-residue/Br,O, ratio increases with increasing ozonization time. Its lack of coloration excludes the presence of a hypobromite group. We refrain from speculating about i t s structure a t this point.[191 At any rate, if Br-0-BrO, 1 is the first traceable product during ozonization, it is fascinat- ing to think that it might have been formed by a bimolecular reaction Br, + 0, + BrzO,.

H. Davy, Pliilos. li-uns. 1811. 155. H. S. P. Miiller. H. Willner, Inorg Chem. 1992. 31. 2527 2534. K . M. Tobias. M. Jansen. Z. Anorg. ANp. Chen?. 1987, 550. 16 26. A. Simon. H. Borrmann, Anyew. Chmi. 1988. (00. 1386- 138%: Aiigcw. Cherii. / i i / . Ed. ERR/. 1988, 27, 1339 A. Rehr. M. Jansen. lnorg. Cheiii. 1 9 2 . 31. 4740-4742 C. Campbell. J. P. M. Jones. J. J. Turner. J . C'hcr i i . Socc Clioii. Coiiiinitn.

1968. 888-889. W. Levason. J. S. Ogden. M. D. Spicer. N. A. Young. J. Am. U i c v i i . .So.. 1990. 112, 1019-1022. R . Schwarz, M. Schmeisser, Cizeiii. Bw. 1937. 70. 1163- 1166. M. Schmeisser, K. Joerger, Angi,a.. C/iwii. 1959. 71. 523-~524. J.-L. Pascal. J. Potier, J . C/icwi. Soc. Cheiii. Cwiiiinin. 1973, 446- 447. T. R. Gilson, W. Levason. J. S. Ogden. M. D. Spicer. N. A. Young. J. Am. Cheiii. Soc. 1992. f 14, 5469 - 5470. D. D. DesMarteau, Inorg. Cliein. 1968, 7. 434-437. K. Seppelt. Chew. Em. 1973, 160, 157 -164. B. Piilter. D. Lentz. H. Pritrkow, K. Seppel~, A n p r . U i i w 1981. Y3, 1095-1096: Angew. Cliem. / n t . Ed. Engl. 1981. 20. 1036 1037. M. Schmeisser. L. Taglinger. Chrvii. Bw. 1961. Y4. 1533 -1539. C. J. Schack. K. 0. Christe. R. D. Wilson. I i iorg. Chain. 1971. 10. 1078 1081. C. J. Schack. K. 0. Christe. Inorg. Cheni. 1974. 13, 2378 2381 W. Breuer. H. J. Frohn. Z. Anorg. Allg. Chem. 1993. 619. 209 214. M Schmeisser. K . Brindle, Arb. h o r g . Ciiern. Rudiochein. 1963.5.41 89. A summary ofearher work on (Br20$)>. (Br308)l and ( B r 0 3 ) \ . None of these bromine oxides is characterized unambiguously.

1341.

Double Lewis Acid Activation in Phosphate Diester Cleavage"" By Mark Wall, Rosemary C. Hynes, and Jik Chin*

It has recently been shown that a number of important enzymes that hydrolyze phosphate diesters are activated by two metal ions. They include 3'-5' exonuclease from DNA polymerase'll as well as RNase H from HIV reverse tran- scriptase.['] In order to investigate the cooperativity between adjacent metal ions for cleaving phosphate diesters, we com- pared the reactivities of a simple mononuclear and a simple dinuclear copper (11) complex, using 2-[bis(2-benzimidazolyl- methyl)aminomethyl]-4,6-dimethylphenol (HL-1) and 2,6- bis[bis( 2-benzimidazolylmethyl)aminomethyl]-4-methylphe- no1 (HL-2), which are mono- and dinucleating ligands respectively (Fig. 1).[31 Here we report on the reactivity of the

[*I Prof. J. Chin, M. Wall, Dr R. C. Hynes Department of Chemistry. McGill University X01 Sherbrooke Street West. Montreal. Quebec H3A 2K6 (Canada) Telefax: Int. code + (514)398-3797

[**I Financial support was provided by the National Science and Engineering Council of Canada and the US Army Research Office.

Q Q Q

HL 1 HL 2

i,o*2 - 0-P

' O Y - C H ,

HPNP H d

Fig. 1. Structures of HL-I, HL-2, and HPNP.

mononuclear copper (11) complex 1 and the dinuclear copper (11) complex 2 for cleaving 2-hydroxypropyl-p-nitro- phenylphosphate (HPNP).

[(L-l)CuCl] 1

[(L-2)CU2C1,1CI 2

There is considerable interest in developing catalysts that hydrolyze RNA. Many artificial enzymes that hydrolyze RNA or simple RNA models (e.g. HPNP) have been report- ed to date. They include nonmetallic compounds,141 as well as mononuclear transition metal['] complexes and Ian- thanide complexes.16] In nature there are many DNases and RNases that are activated by two metal ions. Crystal struc- tures reveal that both 3'-5' exonuclease"] and RNase H from HIV reverse transcriptasel21 contain two metal ions at the active site. There is evidence that the Tetrahymena ribozyme is also activated by two metal ions.171 Site-directed mutagen- esis may shed some light into the role of each metal ion in the enzymes. However, it would be easier to evaluate whether two metals could be better than one as catalysts in simple chemical systems rather than in complex biological systems. Interestingly, 2 is more reactive than 1 for cleaving HPNP. The pseudo first-order rate constants for cleavage of HPNP

Fig. 2. View of cation in 3 (ORTEP ell~psoids at the 50% probability level). Selected bond lengths [A] and angles["]: Cul -Cu2 3.670(4), 0 2 - 0 3 2.496(18); N2 - Cul -N4 152.8(6), N7-Cu2- N9 91. I .

(50 yM) catalyzed by 1 or 2 (1 mM) at 25 "C and pH 7 are 4 . 0 ~ 10-ss - l and 2.1 x 10-3s-1, respectively. The dinucle- ar 2 cleaves HPNP by intramolecular transesterification rather than by oxidation. The products of the cleavage of HPNP catalyzed by 2, as detected by 'H and 31P NMR, are p-nitrophenol and the cyclic phosphate.

To gain some insight into the mechanistic role of the din- uclear complex in cleaving HPNP we obtained a crystal structure of dibenzyl phosphate (DBP) coordinated to the copper complex 3.18] The crystal structure reveals that both oxygen atoms of the phosphate diester are coordinated to metal centers of the dinuclear complex to form a bridged structure (Fig. 2). The distance between the two metal cen- ters in 3 (3.67 A) is comparable to that in 3'-5' exonuclease (3.8 A) and HIV RNase H (4 A). We propose that the key to the reactivity of 2 for cleaving HPNP is double Lewis acid activation of the phosphate diester (Fig. 3). Double Lewis

Fig. 3. Proposal for the mechanism of double Lewis acid activation for

CH,

HPNP cleavage. I

acid activation should be particularly effective for cleaving phosphate diesters bound to a nucleophile (for instance, RNA or HPNP).I9I Single Lewis acid activation in combina- tion with intramolecular metal hydroxide activation has been shown to be effective for hydrolyzing phosphate di- esters not bound to a nucleophile (dimethyl phosphate, bis(p-nitrophenyl)phosphate).["] Intramolecular metal-hy- droxide activation should not provide much rate-accelera- tion for cleaving phosphate diesters that are already bound to a nucleophile.

(I(L~)CU,(DBP)I(C~O,)~ 3

Over the years, many elegant dinuclear metal complexes with bridging carboxylates or phosphates have been synthe- sized as spectroscopic models for dimetallic enzymes." In contrast, functional models of dimetallic enzymes are scarce. Dinuclear 2 is not only more reactive for cleaving HPNP than mononuclear 1, but also significantly more reactive than previously reported nonmetallic catalysts,[4e1 and than mononuclear transition metal c ~ m p l e x e s ~ ~ ~ ] and lanthanide compIexes.*6c*dl

E-xperimental Procedure Compound 3 wds prepared by adding sodium dibenzyl phosphate (10 pmol) to an ethanolic solution of HL-2 (10 ymol) and Cu(CIO,), (20 pmol). The crude product was recrystallized from ethanol by slow evaporation to yield thin greenish plates. The cleavage of the barium(n) salt of HPNP was followed by monitoring the increase in the visible absorbance at 400 nrn caused by release ofthey-nitrophe- nolate ion. In a typical kinetic expenment, 5 mL of a 0.01 M stock solution of HPNP in water was added to 1 mL of a solution of 1 or 2 (0.5 to 1 mM) at 25 "C and pH 7.0. The rate constants were obtained by fitting the first three half-lives of the reaction to a first-order rate low (correlation coefficient > 0.996). Each kinetic run was reproducible to within 3% error. The pH of the reaction solu- tion did not change appreciably during the course of the hydrolysis as a result of the buffering effect of the metal complex solution. In water, the coordinated

1634 0 VCH VerlagsgeseNschaf~ mbH, 0-69451 Wernherm, 1993 0570-0833/93/1iil-i634 $ iO.OO+.ZSjO Angen. Chem. In1 Ed. Engl. 1993, 32, N o ii

chloride atoms are replaced by solvent molecules. Potentiometric titration re- veals that the plc, values of the two bound water molecules in [(L-2)Cu2- (H,0)J3+ are 6.7 and 7.2. The pK, value of the bound water molecule in [(L-l)Cu(H20)]+ is 6.6.

Received: June 23, 1993 [Z 6160 IE] German version: Angew. Chem. 1993, 105. 1696

111 L. S. Beese. T. A. Steitz. EMBO J. 1991, 10, 25. [2] J. F. Davies. 2. Hostomska, Z. Hostomsky. S. R. Jordan, D. A. Mathews,

[3] P. B. Hilde, D. W Stephan, Inorg. Chem. 1987, 26, 749. [4] a) J. Smith, K. Ariga. E. V. Anslyn. J. Am. Chem. SOF. 1993,115.362; b) R.

Breslow. M. Labelle, ihid. 1986, 108, 2655; c) B. Barbier, A. Brack, ihrd. 1992, 114. 351 1; d) M. W. Gobel, J. W. Bats, G. Diirner, Angen. Chem. 1992, 104, 21 7; Angrw. Chrm. 1111. Ed. Engl. 1992, 31, 207; e) V. Jubian, R. P. Dixon, A. Hamilton, J. Am. Chem. Soc. 1992. 114, 1120.

[ 5 ] a) J Chin. Aec. Chem. Res. 1991. 25, 145; b) M. K. Stern, J. K. Bashkin. E. D. Sall. J . Am. Chem. Soc. 1990, 112, 5357; c) W. R. Farkas, Biorhim. Bmp/rjs. A ~ I U 1968. 155, 401 ; d) M. Sundaralingam, J. R. Rubin, J. F. Cannon, In[. J. Quuntutn Chrm. Quuntum Biol. Symp. 1984, 11, 355; e) Y. Matsumoto, M. Komiyama. J. Chem. Soc. Chem. Commun. 1990, 1050; f ) .1. J. Butzow. G. L. Eichhorn, Biopol.vmers 1965, 3, 95. g) R. Breslow, D. L. Huang, E. Anslyn. Proc. N u f l . Acad. Sci. USA 1989, 86, 1746.

[6] a) G. L. Eichhorn, J. J. Butzow. Biopolymers 1965,3, 79; b) J. R. Morrow, L. A. Buttrey, V. M. Sheiton, K. A. Berback, J. Am. Chem. Sou. 1992,114, 1903; c) R. Breslow, D. L. Huang, Proc. Nut/. Acud. Sc;. USA 1991, 88, 4080. d) J. R. Morrow. L. A. Buttrey, K. A. Berback, Inorg. Chem. 1992, 31. 16.

Scienw 1991. 252, 88.

[7] T. Cech (University of Colorado). private communication. [ S ] Crystal structural data of 3: triclinic, Pi. u =14.402(3), b = 15.635(3).

c=15.634(3)A. a = 94.819(17). /1=96.546(16), y=117.213(12)', V = 3073.3(10) A3. 2 = 2; 6681 measured reflections, 2931 with I > 2.5 o(/), 322 refined parameters. R = 0.089. Futher details of the crystal structure investigation may be obtained from the Fachinformationszentrum Karls- ruhe. Gesellschaft fur wissenschaftlich-technische Information mbH, D-76344 Eggenstein-Leopoldshafen (FRG), on quoting the depository number CSD-57635, the names of the authors, and the journal citation.

[9] The difference in the reactivlty of 1 and 2 may also be in part due to the difference in the equilibrium constant for coordination of the substrate to the catalysts.

[lo] a) J H. Kim. J. Chin, J . Am. Chon. Soc. 1992,114,9792; b) B. K. Takasaki. J. H. Kim, E. Rubin, J. Chin, ihid. 1993,115, 1157 ;~ ) J. H. Kim, J. Britten, J . Chin. ihid. 1993, 115, 3618; d) J. Chin, M. Banaszczyk, V. Jubian, X. Zou. ihid. 1989. 111. 186.

[ l l ] a) K . Schepers, B. Bremer. B. Krebs, G. Henkel, E. Althaus, B. Mosel, W. Muller-Warmuth. Angew. Chem. 1990, 102, 582; Angeii.. Chem. Int. Ed. EngI. 1990, 29. 531. b) S. Uhlenbrock, B. Krebs ;hid. 1992, 104, 1631 and 1992.31. 1647. c) M. Suzuki, H. Kanatomi. I. Murase. Chem. Letr. 1983, 185: d) W. H. Armstrong, A. Spool, G. C. Papaefthymiou, R. B. Frankel, S. 1. Lippard, J. Am. Chem. Soc. 1984, 106,4632.

How "Innocent" Are Pentane-2,4-dione- bis(S-alkylisothiosemicarbazonato) Ligands in Biomimetic Fe" and Fe'" Complexes?** By Ulrich KnoJ Thomas Weyhermiiller, Thomas Wolter, Karl Wieghardt,* Eckhard Bill, Christian Butzlaff, and Alfred X. Trautwein

In recent years a few square-pyramidal and octahedral ironfrv) complexes have been isolated and structurally char- acterized." - 3 1 Complexes of this type have been studied in detail, as compounds with iron in the + I V oxidation state have been shown by spectroscopy to be intermediates in the

[*] Prof Dr. K. Wieghdrdt, DipLChem. U. Knof, Dipl.-Chem. T, Weyhermuller. Dipl.-Chem. T. Wolter Lehrstuhl fur Anorganische Chemie I der UniversitHt Postfaach 102 148, D-44780 Bochum (FRG) Telefax: Int. code + (234)7094-201 Dr. E. Bill. Dip1 -Phys. C. Butzlaff, Prof. Dr. A. X. Trautwein Institut fur Physik der Medizinischen UniversitHt Ratzeburger Allee 160, D-23538 Liibeck (FRG)

Deutsche Forschungsgemeinschaft. [**I This work was funded by the Fonds der Chemischen Industrie and the

catalytic cycle of iron-containing heme peroxidase~.'~] Nota- bly all structurally characterized iron(1v) model complexes to date have the t:g low-spin configuration with a triplet ground state (S = 1 ) regardless of the coordination number at the iron(iv) center (five or six).'' '1

Inspired by the work of Gerbeleu et al. and Leovac et who showed that the trianionic pentane-2,4-dione- bis(S-alkylisothiosemicarbazonate), a porphyrin-like, four- coordinate ligand L3 -, can form stable square-pyramidal iron(1v) complexes [Fe"(L")X] (X = Cl, Br, I , NCO, NCSC3"]) and [(Fe1vL)2(p-O)],13b1 we determined the crystal structure of the S-methyl derivative [Fe'"(L")I] (1, Scheme 1 and Fig. 1, top). The structure is very similar to the

l n

g: -, ' H , C - b

H L -I

[LFe"X]

X = le ( n = 0) .CI

&" ( n = O )

X = PPh, 6

H,C - N a 7

L

[ LFeXJ Clod) [AsPh,][LFe(CN),]. CH,CI,. H,O 8

Scheme 1. Synthesized square-pyramidal (a) and octahedral (b) iron complex- es 1-8.

analogous S-ethyl complex.[3a3 '1 The iodide ion in 1 was then exchanged for the biomimetic ligands, thiophenolate and N-methylimidazole, as well as 2,4,6-trichlorophenolate and triphenylphosphane, to form 2-5 (Scheme 1). The new five- coordinate complexes 2-5 were isolated as analytically pure species; as expected they have an S = 1 ground state (see Table 1).

We then noticed that the reaction of [(Fe'VL),(p-O)][3b1 in CHCI, with a large excess of PPh, or N-methylimidazole gave the octahedral complexes 6 and 7 after the addition of some aqueous HClO, [Eq. (a)]. Treatment of 1 with KCN in

[(LFe'v)z(p-O)] + 4 X + 2H' - 2[FeL(X),]' + H,O (a)

6 : X = PPh, 7: X = CH,-C,H,N, (in CH,CI,)

a two-phase CH,Cl,/H,O mixture, followed by addition of [AsPhJCl, gave black crystals of 8, the structure of which has been determined by X-ray crystallography (Fig. 1 bot-

The complexes 6 and 7 can also be obtained from solutions of 4 and 5 in CH2Cl, with an excess of PPh, or N-methylim-

Angeic.. Chm~. In,. Ed. End. 1993, 32, No. 11 0 VCH Verlugsgesellschaft mbH, 0-69451 Weinheim, 1993 0570-0833193jlfll-1635 $10.00+ ,2510 1635