Synthetic Analogues of the Active Site of the A-Cluster of Acetyl Coenzyme A Synthase/CO Dehydrogenase:  Syntheses, Structures, and Reactions with CO

Abstract

Two metallosynthons, namely (Et 4 N) 2 [Ni(NpPepS)] (1) and (Et 4 N) 2 [Ni(PhPepS)] (2) containing carboxamido-N and thiolato-S as donors have been used to model the bimetallic M p -Ni d subsite of the A-cluster of the enzyme ACS/CODH. A series of sulfurbridged Ni/Cu dinuclear and trinuclear complexes (3-10) have been synthesized to explore their redox properties and affinity of the metal centers toward CO. The structures of (Et 4 N) 2 (8), and [Ni(dppe)Ni(PhPepS)]•CH 2 Cl 2 (10•CH 2 Cl 2 ) have been determined by crystallography. The Ni d mimics 1 and 2 resist reduction and exhibit no affinity toward CO. In contrast, the sulfur-bridged Ni center (designated Ni C ) in the trinuclear models 5-8 are amenable to reduction and binds CO in the Ni(I) state. Also, the sulfurbridged Ni C center can be removed from the trimers (5-8) by treatment with 1,10-phenanthroline much like the "labile Ni" from the enzyme. The dinuclear Ni-Ni models 9 and 10 resemble the Ni p -Ni d subsite of the A-cluster more closely and only the modeled Ni p site of the dimers can be reduced. The Ni(I)-Ni(II) species display EPR spectra typical of a Ni(I) center in distorted trigonal bipyramidal and distorted tetrahedral geometries for 9 red and 10 red , respectively. Both species bind CO and the CO-adducts 9 red -CO and 10 red -CO display strong ν co at 2044 and 1997 cm -1 , respectively. The reduction of 10 is reversible. The CO-affinity of 10 in the reduced state and the ν co value of 10 red -CO closely resemble the CO-bound reduced A-cluster (ν co = 1996 cm -1 ).

Bisamidate and Mixed Amine/Amidate NiN2S2 Complexes as Models for Nickel-Containing Acetyl Coenzyme A Synthase and Superoxide Dismutase: An Experimental and Computational Study

“…In one of the trimers in the asymmetric unit, all of the Ni-S distances in the NiS 4 plane refine to the same value by coincidence, while in the second molecule the two independent Ni-S distances are slightly different. In both molecules of the asymmetric unit, the Ni-S bond lengths in the NiS 4 plane are similar to those reported by us14 and others 16b,19b,c,21. Conversely, while the Ni-S bond lengths in the NiN 2 S 2 planes are similar to ({Ni(ema)} 2 Ni),16b where ema = N,N ’-ethylenebis-2-mercaptoacetamide, they are significantly lower than the 6,5,6 chelated bis[Ni II N,N ’-ethylenebis(3-mercaptopropionamide)]Ni II trimer complex14 and the 6,5,5 chelating ring complex reported by Holm 21b…”

“…Since the elucidation of the ACS crystal structure, considerable effort has been directed toward modeling the dinuclear nickel active site (Ni p -Ni d site), and several labs have reported on various aspects of the dinuclear Ni-Ni site 14–21. Unfortunately, attempts to synthesize discrete dinuclear ACS models often leads to the formation of trinuclear or multinuclear complexes, although some success has been achieved using phosphine ligands 16,19–21. Recently, binuclear Ni complexes containing a methylnickel moiety have been reported by Riordan and coworkers 24.…”

Dinuclear nickel complexes modeling the structure and function of the acetyl CoA synthase active site

“…The order of the addition of the substrates, Me, CO, and CoA, to the active site is also controversial, and several mechanisms have been proposed on the basis of biological and computational studies (12)(13)(14). On the other hand, synthetic studies that probe the reaction mechanisms are limited in number, although various thiolato-bridged dinuclear nickel complexes have been reported as A-cluster models (15)(16)(17)(18)(19)(20)(21)(22)(23).…”

Aromatic Versus Heteroradialene Character in Extended Thiophloroglucinol Ligands and their Trinuclear Nickel(II) Complexes

“…[108][109][110][111][112][113] The CS resonances in the thiophloroglucinol systems shift from about 189 to about 155 ppm on complexation, whereas the CO resonances in the phloroglucinol systems shift from about 185 to about 170 ppm. [108][109][110][111][112][113] The CS resonances in the thiophloroglucinol systems shift from about 189 to about 155 ppm on complexation, whereas the CO resonances in the phloroglucinol systems shift from about 185 to about 170 ppm.…”

“…Comparisons for the evaluation of the change in the heteroradialene character in the thiophloroglucinol ligands on complexation are limited, as the chemical shifts for the mononuclear Ni II thiosalen complexes are not assigned if provided at all. [108][109][110][111][112][113] The CS resonances in the thiophloroglucinol systems shift from about 189 to about 155 ppm on complexation, whereas the CO resonances in the phloroglucinol systems shift from about 185 to about 170 ppm. This much Scheme 3.…”