Nickel complexes of a binucleating ligand derived from an SCS pincer

Peterson, Sonja; Helm, Monte L.; Appel, Aaron M.

doi:10.1039/c4dt02718c

Cited by 15 publications

(6 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We started our investigations by preparing a variety of easily accessible SNS complexes II in analogy to Gusev’s work (Scheme ). In addition to these simple aliphatic ligand systems, we also decided to investigate pyridine-based SNS complexes III as well as the analogous SCS complexes IV . Besides these symmetric systems, we also synthesized a variety of dissymmetric S-containing pincer ligands to access the pyridine-based complexes V – VIII within this study …”

Section: Resultsmentioning

confidence: 99%

“…Benzene-based NCN pincer-type ligands have recently attracted some interest for homogeneous Ru-catalyzed hydrogenation reactions . Analogous Ni- and Pd-based SCS complexes have been reported before, and for our screening we also tested the Ru–SCS complexes IV (entries 26 and 27). However, they did not lead to any alcohol formation under these hydrogenation conditions (higher catalyst loadings or pressures were not successful either), which is not a big surprise considering the previous observations with catalysts III , V , VI , and VII .…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

SNS-Ligands for Ru-Catalyzed Homogeneous Hydrogenation and Dehydrogenation Reactions

Schörgenhumer

Zimmermann²,

Waser

2018

Org. Process Res. Dev.

View full text Add to dashboard Cite

A detailed study of literature-known and novel S-containing pincer-type ligands for ruthenium-catalyzed homogeneous hydrogenation and dehydrogenation reactions was carried out. The scope and limitations of these catalysts were carefully investigated, and it was shown that simple bench-stable SNS−Ru complexes can be used to facilitate the hydrogenation of a variety of different substrates at a maximum H 2 pressure of 20 bar under operationally simple, easy to scale up, gloveboxfree conditions by using starting materials and reagents that do not require any special purification prior to use. It was also shown that such complexes can be used to catalyze the dehydrogenative coupling of alcohols and amines to get amides as well as for the dehydrogenative dimerization of alcohols to esters.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

SNS-Ligands for Ru-Catalyzed Homogeneous Hydrogenation and Dehydrogenation Reactions

Schörgenhumer

Zimmermann²,

Waser

2018

Org. Process Res. Dev.

View full text Add to dashboard Cite

show abstract

“…Although several nickel SCS pincer complexes have previously been reported (8)(9)(10), none exhibited an essential feature present in the active site of lactate racemase, namely a pyridinium-based pincer backbone. According to the proposed enzyme mechanism, the pyridinium group enables ligand participation in the hydride transfer reaction, which is likely impossible for a more conventional pyridine group.…”

mentioning

confidence: 99%

Nickel pincer model of the active site of lactate racemase involves ligand participation in hydride transfer

Wodrich

Scopelliti

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Lactate racemase is the first enzyme known to possess a metal pincer active site. The enzyme interconverts D-and L-lactic acid, which is important for the assembly of cell walls in many microorganisms. Here, we report a synthetic model of the active site of lactate racemase, which features a pyridinium-based SCS pincer ligand framework bound to nickel. The model complex mediates the dehydrogenation of alcohols, a reaction relevant to lactate racemization. Experimental and computational data indicate ligand participation in the dehydrogenation reaction.biomimetic chemistry | lactate racemase | nickel | pincer ligands | hydride transfer P incer complexes are widely applied in homogeneous catalysis thanks to their stability, diversity, and tunability (1-4). However, only very recently has the first pincer complex been discovered in the active site of a metalloenzyme (5-7). It was reported that lactate racemase, an enzyme responsible for the racemization of lactic acid and hence important for cell wall assembly in many microorganisms, hosts a nickel pincer cofactor (Fig. 1). The nickel center is coordinated by an SCS pincer ligand derived from a nicotinic acid mononucleotide, in addition to histidine (200) (5, 6). Based on the structure of this active site, it was proposed that the pincer ligand could reversibly capture a hydride from lactate at the carbon atom coordinated to nickel, in a manner similar to nicotinamide adenine dinucleotide in hydride transfer enzymes (Fig. 1). Nevertheless, evidence for this mechanism is still lacking.Although several nickel SCS pincer complexes have previously been reported (8-10), none exhibited an essential feature present in the active site of lactate racemase, namely a pyridinium-based pincer backbone. According to the proposed enzyme mechanism, the pyridinium group enables ligand participation in the hydride transfer reaction, which is likely impossible for a more conventional pyridine group. This hypothesis might be tested using model complexes containing either a pyridinium or a pyridine backbone. A further motivation for synthetic models of this unusual active site is the perspective of developing a new, bioinspired pincer ligand platform that enables metal ligand cooperation in catalysis (11,12). With these considerations in mind, we began investigating the biomimetic chemistry of lactate racemase. Here, we report the synthesis and characterization of a synthetic mimic of lactate racemase. Using dehydrogenation of alcohols as a model reaction, we show that the pyridinium functionality indeed facilitates hydride transfer by ligand participation. ResultsSynthesis. The pyridine-based ligand precursor (4) was synthesized from 4-chloro-3,5-dimethyl pyridine (1, Fig. 2). Oxidation of 1 by KMnO 4 gave 4-chloropyridine-3,5-dicarboxylic acid (2), which was converted to a dicarboxamide (3) by amidation. Reaction of 3 with Lawesson's reagent [2,4-bis(4-methoxyphenyl)-2,4-dithioxo-1,3,2,4-dithiadiphosphetane] yielded the ligand precursor 4 containing thioamides (13). Upon treatment o...

show abstract

“…Secondly, the C-Ni bond becomes longer upon adduct formation. In the unmodified NPN cofactor, the C-Ni bond length is within the range of 2.0-2.1 Å (PDBs: chain B of 5HUQ; chain B and chain C of 6C1W), which is slightly longer than those in small molecule SCS-type Ni pincer complexes (1.8-1.9 Å) 14, 15, 16 .…”

Section: Resultsmentioning

confidence: 93%

Irreversible inactivation of lactate racemase by sodium borohydride reveals reactivity of the nickel-pincer nucleotide cofactor

Gatreddi

Sui

Hausinger

et al. 2022

Preprint

View full text Add to dashboard Cite

The nickel-pincer nucleotide (NPN) cofactor discovered in lactate racemase from Lactiplantibacillus plantarum (LarALp) is essential for the activities of racemases/epimerases in the highly diverse LarA superfamily. Prior mechanistic studies have established a proton-coupled hydride-transfer mechanism for LarALp, but direct evidence showing that hydride attacks the C4 atom in the pyridinium ring of NPN has been lacking. Here, we show that sodium borohydride (NaBH4) irreversibly inactivates LarALp accompanied by a rapid color change of the enzyme. The drastically altered ultraviolet-visible spectra during NaBH4 titration supported hydride transfer to C4 of NPN, and the concomitant Ni loss unraveled by mass spectrometry experiments accounted for the mechanism-based inactivation. High resolution structures of LarALp revealed a substantially weakened C-Ni bond in the metastable sulfite-NPN adduct where the NPN cofactor is in the reduced state. These findings allowed us to propose a mechanism of LarALp inactivation by NaBH4 that provides key insights into the enzyme-catalyzed reaction and sheds light on the reactivity of small molecule NPN mimetics.

show abstract

Nickel complexes of a binucleating ligand derived from an SCS pincer

Cited by 15 publications

References 47 publications

SNS-Ligands for Ru-Catalyzed Homogeneous Hydrogenation and Dehydrogenation Reactions

SNS-Ligands for Ru-Catalyzed Homogeneous Hydrogenation and Dehydrogenation Reactions

Nickel pincer model of the active site of lactate racemase involves ligand participation in hydride transfer

Irreversible inactivation of lactate racemase by sodium borohydride reveals reactivity of the nickel-pincer nucleotide cofactor

Contact Info

Product

Resources

About