Copper(II)-catalysed hydrolysis of an unactivated amide. Application of the groves' rule to the hydrolysis of acrylamide

Duerr, Brook F.; Czarnik, Anthony W.

doi:10.1039/c39900001707

Cited by 11 publications

(6 citation statements)

References 18 publications

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“…The rate of amide hydrolysis, in which the limiting step is believed to be breakdown of the tetrahedral intermediate [64] , may depend critically upon stereoelectronic constraints of the metal and the carbonyl ligand [64] , [68] , a nearby amino acid side chain for proton transfer to the leaving amide nitrogen [66] , as well as the identity of the attacking nucleophile. Hence, post-translational modifications, familial mutations, binding partner or receptor interactions in vivo , or formation low molecular weight oligomeric species may modulate such a process.…”

Section: Discussionmentioning

confidence: 99%

Alzheimer's Aβ Peptides with Disease-Associated N-Terminal Modifications: Influence of Isomerisation, Truncation and Mutation on Cu2+ Coordination

2010

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BackgroundThe amyloid-β (Aβ) peptide is the primary component of the extracellular senile plaques characteristic of Alzheimer's disease (AD). The metals hypothesis implicates redox-active copper ions in the pathogenesis of AD and the Cu2+ coordination of various Aβ peptides has been widely studied. A number of disease-associated modifications involving the first 3 residues are known, including isomerisation, mutation, truncation and cyclisation, but are yet to be characterised in detail. In particular, Aβ in plaques contain a significant amount of truncated pyroglutamate species, which appear to correlate with disease progression.Methodology/Principal FindingsWe previously characterised three Cu2+/Aβ1–16 coordination modes in the physiological pH range that involve the first two residues. Based upon our finding that the carbonyl of Ala2 is a Cu2+ ligand, here we speculate on a hypothetical Cu2+-mediated intramolecular cleavage mechanism as a source of truncations beginning at residue 3. Using EPR spectroscopy and site-specific isotopic labelling, we have also examined four Aβ peptides with biologically relevant N-terminal modifications, Aβ1[isoAsp]–16, Aβ1–16(A2V), Aβ3–16 and Aβ3[pE]–16. The recessive A2V mutation preserved the first coordination sphere of Cu2+/Aβ, but altered the outer coordination sphere. Isomerisation of Asp1 produced a single dominant species involving a stable 5-membered Cu2+ chelate at the amino terminus. The Aβ3–16 and Aβ3[pE]–16 peptides both exhibited an equilibrium between two Cu2+ coordination modes between pH 6–9 with nominally the same first coordination sphere, but with a dramatically different pH dependence arising from differences in H-bonding interactions at the N-terminus.Conclusions/SignificanceN-terminal modifications significantly influence the Cu2+ coordination of Aβ, which may be critical for alterations in aggregation propensity, redox-activity, resistance to degradation and the generation of the Aβ3–× (× = 40/42) precursor of disease-associated Aβ3[pE]–x species.

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Section: Discussionmentioning

confidence: 99%

Alzheimer's Aβ Peptides with Disease-Associated N-Terminal Modifications: Influence of Isomerisation, Truncation and Mutation on Cu2+ Coordination

2010

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“…The hydrolysis of unactivated peptide bonds is exceptionally slow at physiological pH (the half-life of a typical peptide bond is 7-350 years at neutral pH and 25°C) [25,26,27], although this can be efficiently catalyzed by enzymes [28,29]. To understand the mechanism of these remarkable hydrolysis reactions, and to mimic enzymatic processes, many studies have been carried out over several decades using a variety of model complexes of Cu(II) [7,8,9,30,31,32,33,34,35 (recent papers)], Zn(II) [22,34,35], Ni(II) [34,35], Pd(II) [10,11,12,13,14,15,16,17], Pt(II) [10,17,18], Co(III) [36, 37, 38 (recent papers)] and Ce(IV) [21,23]. However, the hydrolysis of unactivated peptides promoted by substitution-labile bivalent metal complexes such as Ni(II), Cu(II) and Zn(II) is generally too slow for detailed kinetic studies.…”

Section: Introductionmentioning

confidence: 99%

“…However, the hydrolysis of unactivated peptides promoted by substitution-labile bivalent metal complexes such as Ni(II), Cu(II) and Zn(II) is generally too slow for detailed kinetic studies. Therefore, activated amides have often been used to investigate reaction mechanisms, instead of peptides themselves [4,5,30,31,32,33,34,35,36,37,38,39,40,41].…”

Section: Introductionmentioning

confidence: 99%

Copper(II)-cis,cis-1,3,5-triaminocyclohexane complex-promoted hydrolysis of dipeptides: kinetic, speciation and structural studies

et al. 2002

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The hydrolysis of glycylglycine (GylGly), glycyl-L-leucine (GlyLeu), L-leucylglycine (LeuGly) and glycyl-DL-serine (GlySer) promoted by a copper(II)- cis, cis-1,3,5-triaminocyclohexane complex [Cu(II)TACH] was investigated at 70 degrees C and pH 7-10, using HPLC. The observed pseudo-first-order rate constants (k(obs)) and rate enhancing factors (REF) were as follows: 4.1x10(-3 )h(-1)(REF=23) for GylGly, 1.6x10(-3 )h(-1)(REF=21) for GlyLeu, 5.1x10(-3 )h(-1)(REF=64) for LeuGly and 9.2x10(-2 )h(-1)(REF=47) for GlySer [pH 8.1, dipeptide 2 mM, copper(II) 2 mM and TACH 2 mM]. Based on the pH dependence and dipeptide concentration dependence of the initial rates and speciation of the Cu(II)-TACH-dipeptide system at 25 degrees C and I=0.1, the reactions proceed via the formation of a ternary complex [Cu(TACH)(dipeptide)](+) as an intermediate followed by OH(-)-dependent and OH(-)-independent paths to give amino acid(s). GylGly, GlyLeu and LeuGly preferred the OH(-)-dependent path, while GlySer preferred the OH(-)-independent path. The latter can be explained by the intramolecular attack of the amide carbonyl group coordinated with its oxygen atom by the OH group in the serine residue. The X-ray crystal structure of [Cu(TACH)(GlyGly)]BPh(4).MeOH confirmed that GlyGly coordinates to copper(II) ion with its terminal amino N and amide O atoms. The crystal structures of [Cu(TACH)(Gly)]BPh(4) and [Cu(2)(TACH)(2)(OH)(2)](ClO(4))(2).NaClO(4).H(2)O are also reported.

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“…that can serve as nucleophiles. A number of investigators have concluded that nucleophilic attack by metalhydroxo species is at least partially responsible for observations of metal ion-catalyzed amide hydrolysis (Buckingham et al, 1970;Duerr and Czarnik, 1990;Takasaki et al, 1993). Mechanism 2 is also observed in systems where the metal ion coordinates a side group of the substrate that can serve as an intramolecular nucleophile (Sigman and Jorgensen, 1972;Groves and Baron, 1989;Koike et al, 1995).…”

Section: Amide and Anilide Hydrolysis: Catalysis And Inhibition By Di...mentioning

confidence: 99%

Hydrolysis of Naptalam and Structurally Related Amides: Inhibition by Dissolved Metal Ions and Metal (Hydr)Oxide Surfaces

Huang

Stone

1999

J. Agric. Food Chem.

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In metal ion-free solutions, the secondary amide naptalam hydrolyzes more rapidly as the pH is decreased; intramolecular nucleophilic attack by a carboxylate side group is very likely involved. Millimolar levels of dissolved Cu(II) and Zn(II) inhibit hydrolysis between pH 3.6 and pH 6.5. Metal ion-naptalam complex formation is important since addition of the competitive ligand citrate lessens the inhibitory effect. The metal (hydr)oxide surfaces Al(2)O(3) and FeOOH inhibit naptalam hydrolysis to a lesser degree; inhibition is proportional to the extent of naptalam adsorbed. Secondary amides (propanil, salicylanilide, and N-1-naphthylacetamide) and tertiary amides (N-methyl-N-1-naphthylacetamide, furalaxyl, and N, N-diethylsalicylamide) that lack carboxylate side groups do not hydrolyze within 45 days of reaction, even when millimolar Cu(II) concentrations are present. Tertiary amides possessing carboxylate side groups (N,N-diethyl-3,6-difluorophthalamic acid and N, N-dimethylsuccinamic acid) do hydrolyze but are insensitive to the presence or absence of Cu(II). The inhibitory effect is believed to occur via metal coordination of (1) the carbonyl group of naptalam, which induces deprotonation of the amide group and makes the substrate less reactive toward nucleophilic attack; (2) the free carboxylate group of naptalam, which blocks intramolecular nucleophilic attack; or (3) a combination of the two.

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Copper(II)-catalysed hydrolysis of an unactivated amide. Application of the groves' rule to the hydrolysis of acrylamide

Cited by 11 publications

References 18 publications

Alzheimer's Aβ Peptides with Disease-Associated N-Terminal Modifications: Influence of Isomerisation, Truncation and Mutation on Cu2+ Coordination

Alzheimer's Aβ Peptides with Disease-Associated N-Terminal Modifications: Influence of Isomerisation, Truncation and Mutation on Cu2+ Coordination

Copper(II)-cis,cis-1,3,5-triaminocyclohexane complex-promoted hydrolysis of dipeptides: kinetic, speciation and structural studies

Hydrolysis of Naptalam and Structurally Related Amides: Inhibition by Dissolved Metal Ions and Metal (Hydr)Oxide Surfaces

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