Biological function of metallothionein-IV. Biosynthesis and degradation of liver and kidney metallothionein in rats fed diets containing zinc or cadmium

BIOAK3RGANICCwEMISTRY

8,267-278

(1978)

267

The Relationship of Some Cop-per (II) Complexes of Facultative Tetrathioethers to the Coordination Environment in the “Blue” Copper Proteins*

MARTIN H. JONES, WILLIAM LEVASON, CHARLES A. McAULIFFE,f and STEPHEN G. MURRAY DepaHnrenrs of Chemistly, The University oj’Manchester Institu te of Science and Technology, ManchesterMdO 1QD. U.K., and Auburn University, Auburn,

Atibama 36830 and DENISE M. JOHNS

Deparnzzent of Phmmacy, Viaivezsi~ of Mmchester, ManchesterMl3 9PL. U.K. ABSTRACT The facultativepotentially tetradentatethioetherligands1,2-bis(2-methylthioetbyIthio)etbane (2,2,2), 1,3-bis(2-metbylthioethyltbio)propane (2,3,2) and 1,2-bis(3-methylthiopropykbio)etbane(3,2,3) react with copper salts to form Cu2(2,2,2)C14, Cu3
INTRODUCTION We have recently embarked on a study of open-chain tetradentate ligands which contain thioether [l-4] or selenoether donors and have characterised a number of complexes of cobalt(U), mckel(II), palladium(II), platinum(D), and rhodium(II1) with such ligands-our most notable conclusion from these studies is that metal-halogen coordination supercedes metal-ligand co-ordination in all complexes sythesised, and that, to achieve complete co-ordination of all donor atoms, dimeric or polymeric complex formation is necessary. *Part XIII [l-4] of the SeriesGoordination CornpZexes Contuining~uZti~entate *Address correspondenceto Dr. McAuliffe at the Univ. of Manchester.

0 ElsevierNorth-Holland,Inc.. 1978

Chelates.

0006-3061-75-0008-0267501.25

MARTIN H. JONES ET AL.

268

-

etry and structures of these complexes are discussedin terms of the steric demands of the ligand and the nature of the halide. The [Cu(2,3,2)(C104)] Cl04 and [Cu(3,2,3)(ClO~)]ClO4 complexes have electronic spectra which exhibit the intense 600 nm band characteristicof the “blue” copper proteins. In fact, the spectrum of [cu(2,3.2)(~04)]~04 is very similar to that of

pseudonronas aeroginosa am&. We here wish to report some complexes we have been able to isolate from solutions of copper(R) salts and the potentially tetradentate chelates 1,2-bis (2methyhhioethylthio)ethane (2,2,2), 1,3-bis(2-rnethylthioethyhhio)propane (2,3,2), and 1,2-bis(3-methylthiopropylthio)ethane (3,2,3)-l Very few tetrathioether-transition metal complexes are known, but those of copper appear to have additional significance because of the general acceptance of copper(R)-sulphur interaction in the socalled “blue” copper proteins [S-7] _ These proteins are characterised by an intense absorption baud in the 600 nm region, and it has been suggested that this band arises from a highly distorted copper co-ordination sphere imposed by the protein superstructure [8,9] in particular it has been proposed that a five-coordinated copper(R) site is involved [lo-121 _Rorabacher and co-workers [ 13 ] have recently shown that the cyclic ligand 14-ane-!Z4 (note the similarity between 14-ane-S4 and our own 3,2,3 ligand) forms a tramcomplex which exhibits an intense absorption at KW4-ane-S4XC104)21 S

CT si-_ls 144ulc-s4

CT

S

“\ /”

SF =3 3.2,3

570 mn; moreover these workers point out that since only thioether coordination (as distinct from sulphide) exists in this system it is, thus, quite likely that it is the thioether group of methionine bonded to copper(I1) which represents the vitaI coordination in the “blue” copper proteins (despite the fact that such coordination has previously been thought not to be possible) (14) It has also been suggested that, in addition to sulphur co-ordination, nitrogen and oxygen ligands are bound to the copper [ 1 1,151_ Gray and co-workers have examined the low temperature absorption, circular dichroism and magnetic circular dichroism of some blue copper proteins including iUus vemicifera stellacyanin and R ceruginosa [ 16]- Wang and co-workers have assigned charge-transfer bands in some model complexes [ 171, and Raman spectra [ 181, redox properties [191, and other model studies have recently been reported [20,21] _ We here wish to report some new complexes of non-macrocyclic tetra-thioethers. ‘Alternative nomenclature for these ligands is 2,5,8,11-tetratbiadodecane(2&L), 2,5,9,12_tetrathiatridemne (2,3,2) and 2,6,9.13-tetratbiatetradec (32,3).

SHORT COMMUNICATIONS the absorption proteins_

spectra of which correspond

269 quite well with some blue copper

EXPERIMENTAL The 2,2,2, 2,3,2, and 3,2,3 ligands were prepared as previously reported r3,41Cz+(2,2,2}Cr,_ Anhydrous cupric chloride (0.27 g, 2.0 mrnol) dissolved in anhydrous ethanol (15 cm3) was warmed to SO’? and dimethoxypropane (5 cm3) was added. To this mixture was then added the ligand (1.0 mmol) dissolved in dichloromethane(5 cma); a precipitate immediately formed. The mixture was stirred for a further 30 min and then filtered, washed with anhydrous ethanol (20 cm3), diethylether (20 cma) and dried in Y~CUO. All other chloro complexes were prepared in an analogous manner using the same molar ratios of metal sakligand. Yields 50-60% The bromo complexes were similarly prepared. Yields -80%. The perchlorate complexes could not be prepared except under the most strictly anhydrous conditions, but once isolated they are stable in air for several hours. Yields -40%. cI1RE/ The perchlorate complexes are highly explosive when heated. Attempts to prepare complexes with the 3,3,3 ligand yielded solids of variable analysis. No compleses could be isolated with anions NCS-, NOa-, F. With iodide, reduction to copper(I) occurred, but only impure complexes could be isolated_ Physical meanuements were obtained as previously described [22] . RESULTS

AND DISCUSSION

A number of points can be mentioned initially: (i) despite previous [14] statements about Cu(II)thioether co-ordination we have successfully isolated a number of such complexes with nonmacrocyclic llgands; (ii) the stoichio metries of these compounds are completely independent of molar ratios of the reactants or order of addition of reactants but depend upon ligand- and halogen-type; (iii) the visible absorption spectra would appear to offer some interesting suggestions to the current discussion on the nature of co-ordination in the “blue”copper proteins. With copper halides no CuLXa complex could be isolated and only with the 2,2,2 ligand was a Cu2LC14 species isolable. It probably has structure (I),

MARTIN H. JONES ET AL.

270

(Ix)

but a more highly polymeric four-coordinate structure (Ii) is alsopossible. Ah the halocompIexes are very Insohrble in nonpolar solvents and dissolve with almost instantaneous decomposition in polar solvents. The infrared spectrum of Cua(2,2,2)C14 in Nujol shows no evidence for chlorine bridges, but exhibits only the two v(Cu-Cl) one would expect for terminal chlorines in a fourcoordinate complex. With the ligands 2,3,2 and 3,2,3 copper(H) chloride forms CU&~CI 6 complexes, and this stoichiometry is formed by reaction of copper(H) bromide with aII three Iigands, CuaLaBra [L=2,2.2, 2,3,2, 3,2,3]. No complex with stoichiometry other than this was observed. These complexes are all very insoluble and there appears to be essentially three obvious possibilities as to the coordination around copper(III-V). We are in favor of structure (V) for the following reasons: stirring the complexes in a number of solvents in the presence of sodium perchlorate or tetraphenylborate did not lead to replacement of ionic halide (moreover, it suggests that all coordinated halides are probably quite stronglybound), and structure (IV) is discounted intuitively because it involves such an un-

rx

-

X

7

SHORT COMMUNICATIONS

271

symmetrical distribution of halides between the three copper(H) ions. Our choice is thus structure (V), and it is interesting to note that the v(Cu - Cl) region of the infrared spectra of Cua(2,3,2)a Cle and Cua(3,2,3)a Cl e are distinctly different from that of Cu,(2,2,2(C14, suggesting that in the former two complexes there is at least one more chlorine coordination site than in the latter. While it is clear that both ligand size and the nature of the halide dictate the stoichiometry of the halo-complexes, in the perchlorate complexes only one stoichiometry, CuL(ClO&, is observed, but once again one sees the important effect which ligand chain length has on the coordination environment of the copper. With the 2,3,2 and 3,2,3 ligands the infrared spectrum clearly shows the presence of two types of perchlorate ion, both coordinated and uncoordinated [23] (Table 1) and, thus, it is likely that these complexes are pentacoordinate [Cu(ligand)(ClO,+)] C104 and contain the CuS*O donor set; whereas in [Cu (2,2,2)](CIO& there is no evidence of RercNorato coordination and there exists a four-coordinate CL& donor set. The infrared spectra of [Cu(2,2,2)] (CIO& and that of [Cu(ligand)(CIOB)] ClO* complexes do not differ in absorptions due to the organic ligands, and we take this as evidence of similar l&and binding in all three complexes. We have constructed a series of molecular models which shows that the coordination of four sulphur donors in [Cu(2,2,2)] (ClO& causes quite a good deal of strain in the ligand but, more important, the hydrogens of the mejhylene groups are allowed to be in positions which block coordination of other groups above and below the coordination plane; with the longer 2,3,2 and 3,2,3 hgands the strain is released and the methylene protons are far enough away from the vacant coordination sites to allow binding of, in the examples here, a fifth ligand. (it is, perhaps, unwise to speculate too much about these factors in the dinuclear and trinuclear halide complexes, but it may be significant that theonly four-coordinate species is obtained with the 2,2,2 ligand.) The electronic spectra of these complexes (Fig. 1 and 2) are most interesting_ Firstly, the intense band CQ. 600 nm which is exhibited by the “blue” proteins, and which has been assigned to S+Cu(II) charge transfer [12, 24, 251, does not appear in the spectra of the Cua(2,2,2)C14 and Cua (ligand)aXe complexes (Fig. 1). Neither does it appear in the spectrum of the four-coordinate [Cu (2,2,2)](C104)a, but it does appear in the spectra of the pentacoordinate [Cu(ligand)(C104)]C104 complexes (Fig. 2). This may mean that the assignment of this band to S+Cu(II) charge transfer is incorrect or that there are special requirements both of coordination geometry and donor set which allow this transition to occur. For instance, mere change of geometry from fourto five-coordination (as in Cua(2,2,2)C14 to Cua(ligand)Xe) does not lead to the appearance of this band, but a change in coordination from CuSb2+ to CuS40+ in the perchlorate series does bring about the appearance of this intense band, i.e., a four-coordinate CL& donor set is insufficient in itself to produce

272

2

ti

Deep blue

Deep blue

C~(2,3,2)(ClO~)~

Cu(3,2,3)(ClO& 1.93

1125,1085,1040, 620 (C104-)

1086,620 (ClO4-)

25.9sh, 22,6, 1150, 1080,970, 18,2sh, 1S.cLsh, 620 (CIOa-‘) 8.3

1.82 26.0sh, 22.8 18.5sh, 8.6

1071 25.8sh, 22.1, 14,8, 11,7sh

1.70 25,6sh, 22.4, 20,4sh, 12,7, 10.2

a Nujol mulls. b Calculated. c e,p,r. exhibits broad singlet, line width cu. 250 G. d e.p.r. exhibits broad singlet, line width co. 450 G. c e.p.r. shows asymmetric hyperfine splitting, Al N 11 G, All N 41 G.

Bluepurple

Ct1(2,2,2)(ClO&~

Redbrown

2.03

2.03, 2,05

2.04

2.08

19.2(19,0)

2.11 22.3(22.5)

2.09 21.0(20.8)

2.08

19.0(19,8)

4,7(4.2)

3,9(3.9)

3.4(3.6)

3,8(3.6) 39.1(39.6)

MARTIN H. JONES ET AL

274 A hwmr)

cy(2.2.2lC4

___________

c

C1~~~2.3.2~2~

-_..--..-_..-SOLID

REFLECTAWCE

---_-.-

SPECTRP

-.-.-.-

CU3’2,2,2yiR~

-.-me._

Cu3(3.2.3>2%6

._,_.

_

Cu3’3,2,3)2Cr6

~-c-_-,-rL 24

m

16

I2

3

,103

CM-1

Fig. 1.

A k.aatra.er) 4

-

-

-

-

-

-

ClI(2_2,21

a$)*

.-

Cu13,2,3)K~G4)2

/-.-.--_

.--

.’ ,.”

-

___.-.-.

SPECTPA

a-

-

REFLECTEXCE

SOLI!!

_*

.

.*’

.

24

20

16

Fig. 2.

Ii?

.

8 xI03

m-1

SHORT COMh4UNICATIONS

275

the 600 nm band, but CL&O meets all the requirements of coordination number and donor set. We therefore tentatively suggest that, as far as electronic spectra2 are concerned, our [Cu(ligand)(C104)] C104 complexes show that there appear to be certain special requirements for the “blue” of the copper proteins to appear. In particular we wish to point out the very close similarity between the reflectance spectrum of [Cu(2,3,2)(C104)] C104 (Fig. 2) and that of pseudomonas aemgiizosa. While it cannot be argued that the octahedral CuS40a environment in the complexes prepared by Rorabacher and co-workersj 131 does not represent that of the “blue” proteins, what our present results show is that a Cu&O environment mirrors closely that which occurs in these proteins and thus offers support to earlier suggestions of a pentacoordinate environment [89] _ Our attempts to obtain e-p-r. data in solution were frustrated by lack of solubility; the solid state g values (Table 1) are consistent with planar or tetragonal complexes [26] _ One of us (MHJ) isgrateful to the Science Research Council for the award of a Research Studentship_

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NucL Gem_ Letts.. 12,897 (1976). (Part XII of this series). W. Levason, C. A. McAuhffe, and S. G. Murray, Inorg. &em.. submitted for publication (Part XI of this series). W. Levason, C. A. McAuliffe, and S. G. Murray, J. C. S. Dalton. 270 (1976) (Part X of this series). W. Lcvason, C. A. McAuliffe, and S. G. Murray, Inorg. aim. Acta 17,247 (1976) (part IX of this series). R. MaRin and B. G. Maimstrom, Adv. Enzymol., 33,170 (1970); R. Ma&in, inInor-

Vol. 2, G. L. Eichhom, ed., Elsevier, New York, 1973, pp. 689ff. J. Peisach, P. Aisen, and W. E. Blumberg, eds., The Biochemistry of cbpper.Academic Press, New York, 1966, p. 376-378. 7_ J_ A. Fee,Structure and Bonding 23,1(1975).

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6.

8. 9.

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Chem. Sot.

96, 5583, (1974).

z A referee has asked us to point out explicitly that the intensities of the bands in these model complexes are not known and the similarities to blue protein spectra refer only to band positions.

MARTIN H_ JONES ET AL_

276

12. V. Miskowski, S. P. W. Tang, T. G. Spiro, E. Shapiro, and T. H. Moss, Biochemistry 14, E244 (1975). 13. T. E. Jones, D. B. Rorabacher, and L. A. Ochrymowya, J. Amer. Gem Sot_. 97, 7485 (1975). 14. C. A. McAuliffe, L. M. Vallarino, and J. V. Quagliano, Inorg. them. S, 1996 (1966); hi. V. Veidis and G. J. Palenik, Uzem Comm.. 1277 (1969);M. R. Harrison and F. J. C. Rossotti, &em. &mm.. 175 (1970). 0. Sibnan, N. M. Young and P_ R. Carey,L Amex C%em_Sot. 98,744 (1976). :s L Baraeeoand C_ k McAuliffe, J_ C S_ Dalton. 948 (1972). 16. E. I. Solomon, J_ W. Hare and H. B. Gray, Prvc Nnt_ Acad_ Sci U_S_A_. 73,1389

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(1975). 25. R. J. P. WiUiams,Inorg.Chim. AC& Revs. 5,137 (1971). 26. B. A. Goodman and J. B. Raynor, Adv. Inorg. Chem Radiocbem, 13,135 (1969). Received November 30.1976: revisedMay 5. I977