Vanadium Compounds - American Chemical Society

Chapter 4

Structural and Functional Models for Biogenic Vanadium Compounds

Downloaded by PURDUE UNIV on August 29, 2014 | http://pubs.acs.org Publication Date: December 10, 1998 | doi: 10.1021/bk-1998-0711.ch004

D. Rehder, M . Bashirpoor, S. Jantzen, H. Schmidt, M. Farahbakhsh, and H. Nekola Chemistry Department, University of Hamburg, D-20146 Hamburg, Germany

Model compounds are described for the following biogenic vanadium systems: (i) Vanadate-ionophore interaction; (ii) vanadate-dependent haloperoxidases; (iii) vanadium-nitrogenase; (iv) vanadium-thiolate re dox interaction; (v) alkyne-reductase and isonitrile-reductase/ligase activities of nitrogenases. The complexes model the coordination sphere (or part of it) of the active site in biogenic vanadium systems, and some of them are also functional mimics for biological systems and also catalyze industrially relevant reactions. Thus, penta-coordinate aminoalcohol and Schiff base complexes with NO donor sets mimic peroxidase activity and catalyze the peroxidation of thioethers, and isonitrile complexes model active intermediates of in vivo (by nitrogenases) and in vitro C-C coupling reactions. Dinitrogenvanadium complexes undergo reductive protonation of nitrogen to ammonia. 4

Although the biological role of vanadium had already been recognized at the beginning of this century, its establishment as a bio-metal is of more recent nature. As an analog of phosphate, vanadate inhibits or stimulates a variety of phosphate metabolizing enzymes and thus possibly attains a general role in the majority if not all of the living organisms. This role includes its insulin-mimetic effect, which may be traced back to the inhibition of a tyrosine kinase or tyrosine phosphatase. In its physiologically relevant forms, vanadium occurs in the oxidation states +V (anionic mainly as dihydrogen vanadate, although some oligovanadates are also active), +IV [mainly as the vanadyl(2+) cation] and +III (as a cationic aqua complex or, at physiological pH, stabilized by ligands). Vanadium(III) is the main form present in those marine organisms that accumulate vanadium from sea water, viz. certain sea squirts and fan worms. A terrestrial organism, the fly agaric toad stool, contains a molecular non-oxo vanadium(IV) complex - called amavadin - of unknown function. In addition, vanadium is the active center of two enzymes: a haloperoxidase, containing V ( V 0 ) , and an alternative nitrogenase with medium-valent vanadium. v

60

3+

©1998 American Chemical Society In Vanadium Compounds; Tracey, A., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1998.

61 A Decavanadate Sandwiched by Cryptand-2,2,2 Vanadate inhibits or stimulates a variety of phosphorylation enzymes. It also inhibits the inositoltriphosphate-induced C a release. The potentially active forms of vanadate are monovanadate, divanadate, tetra- and decavanadate. The physiological effects of decavanadate are particularly noteworthy, since kinetically rather stable decavanadate should not be present at physiological vanadium concentrations and in the reducing intracellular medium. Once administered or formed, however, e.g. at vanadate accumulating cell sites, it may be stabilized towards hydrolysis and reduction by embodiment into ionophores. We have shown that cryptands, which are commonly considered to model biogenic ionophores, can protect decavanadate by forming sandwich-like contact ion pairs as shown in Figure 1 for the interaction between a centrosymmetric dihydrogendecavanadate and two diprotonated cryptands C222 (7). There are no hydrogen bonding interactions between anion and cations. The protons on the decavanadate are bound to the C-site u -oxo ions, the protons in the cryptands are trapped in the cavities formed by the 2 Ns and the 4 Os pointing towards the anion.


2+

2

+

Figure 1. [C222(H ) ]2[H Vio028] may be considered to model the stabilization of decavanadate by ionophores under physiological conditions. 2

2

Two Enzymes with Vanadium in Their Active Center To this date, two vanadium-dependent enzymes have been found in nature: Vanadatedependent haloperoxidases are present in a variety of brown see weeds, but have also been isolated from red algae, a lichen and, more recently, from a primitive fungus. In the active enzyme, vanadium is in the +V state in an environment dominated by oxygen functions. The reduced (V ) form is inactive. The second enzyme is an alternative nitrogenase, containing vanadium instead of the more common molybdenum. Vanadium-nitrogenases from free-living nitrogen-fixing bacteria such as Azotobacter contain vanadium as a constituent of an iron-vanadium-sulfur cluster in an oxidation state between II to IV (XANES evidence). In this contribution, we will address model complexes of the two enzymes, models which mainly mimic the coordination environment but, in several instances, also the function of these enzymes, and which should provide deeper insight into the structure/function synergism of biological catalysts - to the benefit of, inter alia, related in vitro processes. In several cases, the relation between in vivo and in vitro processes will we pointed out. w

In Vanadium Compounds; Tracey, A., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1998.

62 The Peroxidation of Halides and Sulfides. The structure of a chloroperoxidase from the mold Curvularia inaequalis has recently been resolved by X-ray structure analysis (2, 3). In the native form, vanadium is in a trigonal-bipyramidal array in a 0 N donor set (Figure 2), where the only covalent link is provided by of a histidine residue. The 0 N donor set is retained in the peroxo form, but the geometry changes to tetragonal pyramidal. First results of an X-ray diffraction analysis of bromoperoxidase from the knobbed wrack (Ascophyllum nodosum) points into the same direction (4), although earlier X-ray absorption studies have suggested a somewhat different coordination environment, including a short V - 0 single bond typical of an alkoxide bonded to vanadium, possibly provided by serine (5). The peroxidases oxidize halide to hypohalide, which in turn generates halogenated hydrocarbons. The overall mechanism (6) is represented in Figure 3. The primary product is a peroxovanadium compound, verified by an X-ray structure analysis of the peroxoenzyme (3) (Figure 2). Halide is then oxidized and reacts with a hydrocarbon or, if no substrate hydrocarbon is available, produces singlet oxygen. 4


4

Ari O(Gly)

Ari

Figure 2. Vanadium site in vanadate-dependent peroxidase, native [left, (2)] and peroxo form [right, (3)], according to X-ray diffraction. Selected structural models are shown in Figure 4. The compounds constitute an 0 N or 0 N donor set and contain, in the case of 1, 3 and 4, a labile ligand. The selection has been carried out so as to demonstrate the versatility of vanadium complexes with respect to coordination number and coordination geometry, essential requisites for catalytic activity. Thus, 1 is tetragonal-pyramidal, 2 distorted trigonalbipyramidal, and 3 and 4 octahedral/tetragonal-pyramidal (7-9). Compound 2 in Fig. 4, with a coordination geometry in-between tetragonal-pyramidal and trigonal-bipyramidal (7), perhaps is closest to the structure of the active center of the vanadate-dependent haloperoxidases (cf. Figure 2). Further, compound 2 is a functional model, as is complex 4. In either case, the intermediately formed peroxo complex, identified by V N M R spectroscopy, catalyzes the bromination of organic substrates (such as acetanilide, phenol red, trimethoxybenzene) under mildly acidic conditions. Ethanolamine complexes of the kind represented by compound 4 in Figure 4 also catalyze the oxidation by peroxide of organic sulfides to sulfoxides (8) (Figure 5). Several interme4

5

5 1



63

Figure 3. Mechanism of haloperoxidation by peroxovanadium as proposed by Pecoraro et al. (6). X (X = halogen) stands for Enz-X , V O - X , H X O or X . The peroxo intermediate has recently been structurally characterized (3). +

+

+

3

diates containing the oxidizing agent (H2O2) or the substrate (methyl-phenyl-sulfide or sulfoxide) coordinated to vanadium have been detected (Figure 5). If there is a center of chirality in the catalyst, one of the sulfoxide enantiomers is formed in excess.

Figure 4. Models for the vanadium site in peroxidases. A dashed line (cf. 1, 3 and 4) represents a weak bond. The supporting ligands are Schiff bases (1-3) or diethanolamine (4). 2 and 4 have also been shown to be active in the oxidation (by peroxide) of thioethers.



64

Figure 5. Enantioselective peroxidation of thioethers by 4, and intermediates. The vanadyl group itself can act as an oxidation reagent. This is demonstrated by the reaction between VOCl (thf) and o-mercaptoaniline (9), Figure 6, part of which is oxidized to the disulfide, and part of which coordinates to the center to form a labile complex 5. Reaction of 5 with hydroxynaphthaldehyde yields the non-oxo enamine complex 6, where vanadium is in a highly distorted trigonal prismatic array. 2

thf\|iyci + 3

thf" ^ C l

HS

2

P

®

+2

CHi

H N' 2

|

^2H20, 2H+

Figure 6. Formation of a non-oxo vanadium complex with SNO coordination. The twist angle between the two trigonal planes spanned by the two sets of S, O and N amounts to 69°. The two planes are inclined towards each other by 28.6°.



65 The Fixation of Nitrogen, and the Oxidation of Thiolate. Compound 6 in Figure 6 presents a few features which are also relevant for the V site in vanadium nitrogenase, namely the coordination of sulfur, the coordination of an enamine nitrogen, and the absence of an oxo group. So far, no crystal structure has been reported for a vanadium-nitrogenase, but there is much evidence that the active site of the iron-vanadium cofactor is built in essentially the same manner as the active site in the iron-molybdenum cofactor of the structurally characterized Mo nitrogenase (10). The immediate environment of vanadium hence contains three sulfides (which link vanadium to three irons in one half of the M-cluster of the iron-vanadium protein, Figure 7), the enamine nitrogen from a histidine, and the vicinal carboxylate and alkoxide of homocitrate. As for the molybdenum analog, vanadium nitrogenase exhibits concomitant hydrogenase activity, and alkyne-, alkene and isonitrile-reductase/ligase activities. The formation of the Z-isomer of ethylene if alkyne reduction is carried out in deuterated water, clearly indicates that the substrate alkyne is coordinated to and activated by a metal site - possibly vanadium - prior to reductive protonation. CH COOH r

X

5—FCS—V—OJ (CH ) -COOH 2

Reactions:

2

(1) Nitrogenase and Hydrogenase Activity: +

+

N + 14H + 12^

2NH4 + 3H

2

2

(2) Alkyne Reductase Activity: +

+ 2H + 2e~ (3) Isonitrile Reductase Activity RN=C + 6H 2 x

+

+

+ 6e~

1 + 8H + 8e „

*

H x

H c=C'

RNH2

+ Chk

+ 2RNH

2

Figure 7. Plausible structure of the vanadium site in vanadium nitrogenase, and some reactions which are catalyzed by nitrogenases. In order to model thio-ligation to vanadium, we have synthesized a variety of vanadium(II, III and IV) complexes with thiolates and thioether (sulfide) ligands (77-,


66 n

m

13). Compound 6 in Fig.6 is an example for V™ Selected V and V complexes are shown in Figure 8: A mixed thiolato/sulfide coordination to V is realized by complex 7, which can be oxidized reversibly to the V analog at -0.37 V (relative to SCE). A second ligand giving rise to a X V L arrangement in an octahedral array, providing two reactive cisoid positions for the two X ligands, is the V complex 8. The two chlorines can be substituted in salt metathesis reactions. Compound 9 finally, a dinuclear V complex bridged by thiophenolate, contains one replaceable chlorine at each vanadium center. n

m

2

4

n


ffl

Figure 8. Thiolate and sulfide coordination to vanadium(II and III) centers. Vanadium nitrogenase is not the only biogenic case for vanadium-sulfur coordination. Vanadate and vanadyl have been shown to interact with the sulfhydryl of cysteinyl residues in proteins, and there is at least one reported case, where the inhibition of an enzyme (viz. glyceraldehyde 3-phosphate dehydrogenase) can be traced back to a redox reaction between cysteine and vanadium (14). We have modeled such a reaction by the interaction of vanadyl chloride with the tetradentate dithiolate-diamine ligand shown in Figure 9 (11, 12). Three concomitant processes can be observed in this reaction: First, part of the ligand is oxidized to a heterocycloeicosane containing two disulfide groups. Part of the vanadium precursor looses its oxo function in this process. Second, an amide is formed by deprotonation of one of the amine functions. Third, the trianionic ligand thus generated coordinates to vanadium, forming an asymmetrically oxo-bridged, dinuclear vanadium complex, 10, with formally V and V There are additional interesting features in this complex, such as a hydrogen-bonding interaction between the amine hydrogen in one half of the molecule to the thiolate sulfur in the other half. m

v

Coming back to vanadium-nitrogenase: Apart from the thio coordination, another main point in the coordination environment of vanadium is homocitrate. Its simultaneous coordination via vicinal alkoxide and carboxylate can be modeled by appropriate ligands, benzilate in our case, as shown in Figure 10 (75). The starting material is the vanadyl complex 11 with the double Schiffbase salen. 11 is converted to the trans-dichloro complex 12. This type of reaction can quite generally be applied to vanadyl complexes containing ONNO or ONO donor sets. In the latter case, the cisdichloro complex forms. 12 reacts with dilithiumbenzilate to the non-oxo V™ complex 13, with benzilate occupying cis positions. 13 can be reversibly oxidized (+0.920 V) and reduced (-0.338 V; vs. SCE).



67

Figure 10. Generation of a complex with vicinal carboxylate-alkoxide coordination. The complexes 6-10 and 13 model part of the structure of the vanadium site in nitrogenase; they are, however, inactive as fiinctional models (as is the isolated cofactor by itself). Functional models - dinitrogen complexes of vanadium - can be generated as shown in Figure 11: The starting material is THF-stabilized VC1 which, in the presence of lithium or sodium and an oligodentate phosphine, is reduced to a chlorophosphinevanadium(II) (14) and a mixed valence Y complex (15). In the presence of dinitrogen and catalytic amounts of naphthalene, the reduction proceeds to the formation of mono- and bis(dinitrogen) complexes of V" , the latter in the cis and trans 3

m

1


68 (16) conformation. These anionic complexes are stabilized by close contact ion-pair interaction with the alkaline metal ion. Addition of proton-active substances such as HC1 converts one of the four nitrogens to ammonia. A small amount of hydrazine is also formed - as by the native enzyme. The electrons for the reduction of nitrogen stem from the vanadium center, which is recovered in the +11 or +III state. The structures of the complexes have been verified by V N M R spectroscopy of the N-enriched compounds in solution, by L i N M R spectroscopy and, for p = dppe and N a as the counter ion, by X-ray diffraction analysis (76). 5 1

15

7

+

2


15 thf

j,

c l

Cl

i. Cl

^thf

+

L

i N +

2

+

P "" n

\

©

CI .

(naphthalene)

P

( P = n-dentate phosphine) n

. Y '* • *' ^ I jjf N H

yn/ni p + n

1

6

+

1.5 N 2 (+N H5+) + N H 4 2

Figure 11. Dinitrogenvanadium complexes. Synthesis and protonation. The dashed arrows connect intermediates which can be isolated if no redox catalyst (naphthalene) is added. L i can be replaced by Na. P represents an oligodentate phosphine. n

Reductive Protonation of Alkynes and Reductive C-C Coupling of Isonitriles. As mentioned previously (cf. Figure 7), the nitrogenases can also reduce other unsaturated substrates. Thus, acetylene is converted to ethylene (and further to ethane by vanadiumnitrogenase), and isonitrile is converted to methane and primary amine. In a side reaction, C-C coupling, accompanied by the formation of ethylene is observed along with the generation of primary amine. The nitrogenases hence attain an alkyne-reductase activity and an isonitrile-reductase plus -ligase activity (77). As in N fixation, the activation of the unsaturated substrate is probably connected with its coordination to a metal center. Whether this is iron or the hetero metal - V or Mo - is still under debate. There are good arguments for assuming that the hetero metal plays the decisive role. Hence, to model these additional activities of nitrogenases, we have synthesized several compounds which indicate that (i) alkynes and isonitriles do coordinate to low-valent vanadium, (ii) isonitriles undergo reductive C-C coupling when attached to vanadium, and (iii) coordinated alkynes produce alkenes with ET/H* or H . Examples of complexes and their reactions are given in Figure 12: The V-alkyne complex 17 (18), when treated successively with hydride and protons, yields styrene, and the vMsonitrile complex 18 2

2


69 m

(79) reacts in the presence of small amounts of water to form the V alkyne complex 19 [see ref (20) for the Nb analog]. A similar vanadium complex has been shown to split off a Z-olefin when treated with hydrogen under slightly elevated pressure (21). These reactions are, of course, also of relevance for the in vitro catalysis of reductive coupling and protonation reactions carried out by certain vanadium-based catalysts (22). R

-\.? Downloaded by PURDUE UNIV on August 29, 2014 | http://pubs.acs.org Publication Date: December 10, 1998 | doi: 10.1021/bk-1998-0711.ch004

R'

C

C

8 17

\ & O

C N

NR R

18

\ r • •

\CJ

C

R

N

«

Q

19

N

R

R

Figure 12. Reactions modeling alkyne-reductase and isonitrile-lyase activities of nitro genases. Acknowledgment. This work was supported by the Deutsche Forschungsgemeinschaft and the Fonds der Chemischen Industrie. Literature Cited (1) Farahbakhsh, M.; Schmidt, H.; Rehder, D. Chem. Ber./Recueil 1997, 130, 1123. (2) Messerschmidt, A.; Wever, R., Proc. Natl. Acad. Sci. U.S.A. 1996, 93, 392. (3) Messerschmidt, A.; Prade, L.; Wever, R. Biol. Chem. 1997, 378, 309. (4) Weyand, M. Ph. D. Thesis, Gesellschaft für Biotechnologische Forschung Braunschweig, 1996. (5) Arber, J.M.; de Boer, E.; Garner, C.D.; Hasnain, S.S.; Wever, R. Biochemistry 1989, 28, 7968. (6) Colpas, G.J.; Hamstra, B.J.; Kampf, J.W.; Pecorao, V.L. J. Am. Chem. Soc. 1996, 118, 3469. (7) Bashirpoor, M.; Schmidt, H.; Schulzke, C.; Rehder, D. Chem. Ber./Recueil 1997, 130, 651. (8) Schmidt, H.; Bashirpoor, M.; Rehder, D. J. Chem. Soc., Dalton Trans. 1996, 3865. (9) Farahbakhsh, M.; Nekola, H.; Schmidt, H.; Rehder, D. Chem. Ber./Recueil 1997, 130, 1129. (10) Chan, M.M.; Kim, J.; Rees, D.C. Science 1993, 792. (11) Tsagkalidis, W.; Rehder, D. J. Bioinorg. Chem. 1996, 1, 507. (12) Tsagkalidis, W.; Rodewald, D.; Rehder, D. Inorg. Chem. 1995, 34, 1943. (13) Tsagkalidis, W.; Rodewald, D.; Rehder, D. J. Chem. Soc., Chem. Commun. 1995, 165 (14) Banabe, J.E.; Echegoyen, L.A.; Pastrona, B.; Martinez-Maldonado, M. J. Biol. Chem. 1987, 262, 9555. (15) Vergopoulos, V.; Jantzen, S.; Rodewald, D.; Rehder, D. J. Chem. Soc., Chem. Commun. 1995, 377.


70


(16) Gailus, H.; Woitha, C.; Rehder, D., J. Chem. Soc., Dalton Trans. 1994, 3471. (17) Miller, R.W. In Biology and Biochemistry of Nitrogen Fixation; Dilworth, M.J.; Glenn, A.R., Eds; Elsevier: Amsterdam, 1991, pp 9-36. (18) Gailus, H.; Maelger, H. Rehder, D. J. Organomet. Chem. 1994, 465, 181. (19) Böttcher, C.; Rodewald, D.; Rehder, D. J. Organomet. Chem. 1995, 496, 43. (20) Collazo, C.; Rodewald, D.; Schmidt, H.; Rehder, D. Organometallics 1996, 15, 4884. (21) Protasiewicz, J.D.; Lippard, S.J., J. Am. Chem. Soc. 1991, 113, 6564. (22) Rehder, D.; Gailus, H. Trends Organomet. Chem. 1994, 1, 397.


Vanadium Compounds - American Chemical Society

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