Influence of the Chelate Ligand Structure on the Amide Methanolysis Reactivity of Mononuclear Zinc Complexes

Abstract

Zinc complexes of three new amide-appended ligands have been prepared and isolated. These complexes, [(dpppa)Zn](ClO4)2 (4(ClO4)2; dpppa = N-((N,N-diethylamino)ethyl)-N-((6-pivaloylamido-2-pyridyl)methyl)-N-((2-pyridyl)methyl)amine), [(bdppa)Zn](ClO4)2 (6(ClO4)2; bdppa = N,N-bis((N,N-diethylamino)ethyl)-N-((6-pivaloylamido-2-pyridyl)methyl)amine), and [(epppa)Zn](ClO4)2 (8(ClO4)2; epppa = N-((2-ethylthio)ethyl)-N-((6-pivaloylamido-2-pyridyl)methyl)-N-((2-pyridyl)methyl)amine), have been characterized by X-ray crystallography (4(ClO4)2 and 8(ClO4)2), 1H and 13C NMR, IR, and elemental analysis. Treatment of 4(ClO4)2 or 8(ClO4)2 with 1 equiv of Me4NOH.5H2O in methanol-acetonitrile (5:3) results in amide methanolysis, as determined by the recovery of primary amine-appended forms of the chelate ligand following removal of the zinc ion. These reactions proceed via the initial formation of a deprotonated amide intermediate ([(dpppa-)Zn]ClO4 (5) and [(epppa-)Zn]ClO4 (9)) which in each case has been isolated and characterized (1H and 13C NMR, IR, elemental analysis). Treatment of 6(ClO4)2 with Me4NOH.5H2O in methanol-acetonitrile results in the formation of a deprotonated amide complex, [(bdppa-)Zn]ClO4 (7), which was isolated and characterized. This complex does not undergo amide methanolysis after prolonged heating in a methanol-acetonitrile mixture. Kinetic studies and construction of Eyring plots for the amide methanolysis reactions of 4(ClO4)2 and 8(ClO4)2 yielded thermodynamic parameters that provide a rationale for the relative rates of the amide methanolysis reactions. Overall, we propose that the mechanistic pathway for these amide methanolysis reactions involves reaction of the deprotonated amide complex with methanol to produce a zinc methoxide species, the reactivity of which depends, at least in part, on the steric hindrance imparted by the supporting chelate ligand. Amide methanolysis involving a zinc complex supported by a N2S2 donor chelate ligand (3(ClO4)2) is more complicated, as in addition to the formation of a deprotonated amide intermediate free chelate ligand is present in the reaction mixture.

Divalent Nickel, Cobalt and Iron Complexes of an Amide‐Appended N2S2 Ligand: Synthesis, Characterization and Reactivity with Hydroxide Anion

“…[16,18] This reaction proceeds through the initial formation of a depronated amide complex, [(bmppa -)Zn]ClO 4 , which subsequently undergoes reaction with methanol to produce the reactive species for amide cleavage. [18] (1) in that intense vibrations found in the region of ca. 1600-1635 cm -1 for 1, which include the ν(CO amide ) vibration, are not present in the spectrum of 4.…”

“…[16][17][18] The reaction pathway for amide cleavage in these systems was found to involve the initial formation of a (deprotonated amide)zinc complex which subsequently undergoes reaction with methanol to produce a reactive complex for amide methanolysis. The products generated in these amide methanolysis reactions are a zinc complex of a primary amine-appended chelate ligand, methyl trimethylacetate, and 1 equiv.…”

“…of Me 4 NClO 4 . [16][17][18] The research described herein examines how the amide methanolysis reactivity of divalent metal complexes of an amide-appended N 2 S 2 ligand is influenced by the nature of the metal center. This work has some relevance to peptide deformylase, as we have examined the structural, spectroscopic, and amide cleavage reactivity properties of Ni II [16,18] To the best of our knowledge, this is the first direct comparison of amide cleavage reactivity in structurally related complexes of these metal ions.…”

“…[16][17][18] The research described herein examines how the amide methanolysis reactivity of divalent metal complexes of an amide-appended N 2 S 2 ligand is influenced by the nature of the metal center. This work has some relevance to peptide deformylase, as we have examined the structural, spectroscopic, and amide cleavage reactivity properties of Ni II [16,18] To the best of our knowledge, this is the first direct comparison of amide cleavage reactivity in structurally related complexes of these metal ions. Findings of this study include: (1) similar to the chemistry of [(bmppa)Zn](ClO 4 ) 2 , the Ni II and Co II analogs form deprotonated amide complexes upon treatment with hydroxide anion, whereas the Fe II analog decomposes to yield free bmppa ligand and unidentified iron species; and (2) of the non-zinc metals only the (deprotonated amide)Co II complex reacts with methanol to yield amide methanolysis products, albeit in lower yield than the zinc analog.…”

Coenzyme Q Functionalized CdTe/ZnS Quantum Dots for Reactive Oxygen Species (ROS) Imaging

“…Recently, we investigated in detail the amide methanolysis reactivity of zinc complexes of amide‐appended N 4 , N 3 S, and N 2 S 2 donor ligands in the presence of hydroxide anion in methanol 16–18. The reaction pathway for amide cleavage in these systems was found to involve the initial formation of a (deprotonated amide)zinc complex which subsequently undergoes reaction with methanol to produce a reactive complex for amide methanolysis.…”