Four- and five-coordinate cobalt(II) thiolate complexes: models for the catalytic site of alcohol dehydrogenase

Abstract

Sir:The catalytic zinc in liver alcohol dehydrogenase (LADH) is coordinated by two cysteines, a histidine, and a water molwule.'s2 There is a controversy whether the substrate displaces the water molecule with the zinc remaining four-coordinate or whether the substrate binds without displacement of H20 to give a five-coordinate intermediate ~t a t e .~~~.~ Many spectroscopic studies relating to this mechanistic question have been made on the cobalt-substituted LADH, whose structure and activity are quite similar to the native zinc e n~y m e .~.~ Spectroscopic evidence supporting five-coordinate intermediate states comes from the proposed relationship of the zero-field splitting of Co(I1) complexes with coordination number and from I7O relaxation ~t u d i e s .~ Electronic spectroscopy provides a major argument against the five-coordinate states: there are no significant differences in the extinction coefficients of the ligand field bands in the spectrum of the cobalt enzyme upon transition from the initial tetrahedral state to the proposed five-coordinate intermediate states. 6 We report the synthesis and structure determination of a series of bis(thio1ate)cobalt complexes, which are spectroscopic models for the catalytic center in LADH.The reaction of Co(SR), (SR = S-2,4,6-i-Pr3C6H2 or S-2,6i-Pr,C6H3)7 with 2 equiv of pyridine or 1-methylimidazole in CH3CN gives C O ( S R )~L~ complexes in high yield.8s9 [Co(S-2,4,6-i-Pr,C6H,),(py),] (1) was previously shown to have a distorted tetrahedral structure by X-ray diffra~tion.~ The structure of 1 closely reproduces the [ (cy~-S)~Zn(imid)(his)] coordination unit of the structurally characterized imidazole inhibited enzyme; in both structures the rings of the nitrogen donor ligands are nearly orthogonal. lo When bidentate ligands such as bipyridine or phenanthroline are substituted for the monodentate nitrogen bases, five-coordinate complexes of formulation [Co(SR),(L)(CH,CN)] (L = bpy, phen) are obtained." The X-ray crystal structure of [Co(S-2,6-i-Pr2C6H3),(bpy)(CH3CN)] (2) reveals it to be monomeric with a distorted trigonal-bipyramidal geometry (Figure l ) . l 2 The two thiolates occupy equatorial positions, the bpy ligand spans an axial-equatorial edge and the CH3CN, which comes from the solvent, occupies an axial position. Well-characterized examples of five-coordinate Co(I1) complexes are limited in number.When the same reaction was performed with a less sterically hindered thiolate ligand, the resultant complex is a dimer, [Co-(S-2,3,5,6-Me4C6H),(bpy)], (3) (Figure l).I3 The cobalt ions are five-coordinate with an asymmetric dithiolate bridge.14 The difference in the nuclearity of compounds 2 and 3 reflects the reduced tendency of the more steric thiolates to bridge metal centers.I5 The structures of 2 and 3 also indicate the tendency of cobalt to become five coordinate.Complexes 1 and 2 and their respective derivatives are monomeric four-and five-coordinate complexes with very similar ligand sets. They should make a good test case for spectroscopic methods tha...

A retroviral Cys-Xaa2-Cys-Xaa4-His-Xaa4-Cys peptide binds metal ions: spectroscopic studies and a proposed three-dimensional structure.

“…coefficients for these bands of -500 M-1cm-1 are most consistent with a tetrahedral site (62). This conclusion is supported by recent studies of four-and five-coordinate complexes of Co2+ with nitrogen and sulfur ligands (63,64). The spectrum also includes charge transfer bands indicative of metal-cysteinate coordination.…”

2-Carboxy-9-dihydroxymethyl-1,10-phenanthroline Complexes of Cobalt(II) and Copper(II)

“…The variation in the bond lengths is due to the coordination of the carboxyl O21 atom which causes the metal center to shift towards N1, effectively shortening the M--N1 bond while lengthening M--N10. The N1--Co--N10 bond angles of 75 ° are smaller than those in bidentate phenanthroline species (Boys et al, 1984;Corwin, Fikar & Koch, 1987) but similar to those for phenanthroline-containing macrocycles (Hanton & Raithby, 1980). The total bite angle for the ligand is 150 °.…”

Molecular dynamics simulations of alcohol dehydrogenase with a four‐ or five‐coordinate catalytic zinc ion

“…Crystallographic and spectroscopic data showing that binding to zinc of certain bidentate inhibitors is fivecoordinate 14,15 have been taken as evidence in favor of these suggestions. Furthermore, spectroscopic studies of metal-substituted alcohol dehydrogenase have indicated that several binary and ternary complexes may be five-coordinate [6][7][8][15][16][17][18][19][20] , although other spectroscopic investigations contradict these results [21][22][23][24][25] . The kinetic evidence is also scattered and has been taken to favor fourcoordination 1,26 , as well as five-coordination 6,7,9,11,27 , of zinc in the catalytically productive ternary complexes.…”