Interaction of N-acetylmethionine with a non-C2-symmetrical platinum diamine complex

Williams, Katherine M.; Chapman, Donald J.; Massey, Sondra R.; Haare, Carrie

doi:10.1016/j.jinorgbio.2005.07.010

Cited by 8 publications

(16 citation statements)

References 23 publications

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“…A 1 H NMR spectrum acquired ~45 minutes later showed new resonances; two singlets at 2.41 and 2.42 ppm were observed; these singlets were ~0.4 ppm downfield of the singlet observed for unreacted SeMet (Figure 1). A downfield shift of similar magnitude has been previously observed for S -CH 3 resonances of Met upon coordination of the Met to platinum via the sulfur atom,[9, 20, 21] and similar shifts were observed with previous complexes of platinum with selenomethionine. [16, 17] Thus, the singlets were assigned to the CH 3 resonance of [Pt(dien)(SeMet- Se )] 2+ .…”

Section: Resultssupporting

confidence: 84%

“…[9, 20] Since there are relatively few crystal structures of platinum(II) selenomethionine complexes, we instead examined models of energy-minimized [Pt(Me 4 en)(Met- S,N )] + structures with both the R and the S stereochemistries at the sulfur atom. The energy-minimized structure with the R stereochemistry had a twist-boat conformation for the six-membered chelate ring that formed, as this conformation avoided steric clashes of the Se -CH 3 group with the methyl groups of the Me 4 en ligand.…”

Section: Resultsmentioning

confidence: 99%

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Reaction of platinum(II) diamine and triamine complexes with selenomethionine

Williams

Dudgeon

Chmely

et al. 2011

Inorganica Chimica Acta

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We have reacted [Pt(dien)Cl]Cl, [Pt(en)(D2O)2]2+, and [Pt(Me4en)(D2O)2]2+ [Me4en = N,N,N′,N′-tetramethylethylenediamine] with selenomethionine (SeMet). When [Pt(dien)Cl]Cl is reacted with SeMet, [Pt(dien)(SeMet-Se)]2+ is formed; two Se-CH3 resonances are observed due to the different chiralities at the Se atom upon platination. In a reaction of [Pt(dien)Cl]Cl with an equimolar mixture of SeMet and Met, the SeMet product forms more quickly though a slow equilibrium with approximately equal amounts of both products is reached. [Pt(Me4en)(D2O)2]2+ reacts with SeMet to form [Pt(Me4en)(SeMet-Se)(D2O)]2+ initially but forms [Pt(Me4en)(SeMet-Se,N)]+ ultimately. One stereoisomer of the chelate, assigned to the R chirality at the Se atom, dominates within the first few minutes of reaction. [Pt(en)(D2O)2]2+ forms a variety of products depending on reaction stoichiometry; when one equivalent or less of SeMet is added, the dominant product is [Pt(en)(SeMet-Se,N)]+. In the presence of excess SeMet, [Pt(en)(SeMet-Se)2]2+ is the dominant initially, but displacement of the en ligand occurs leading to [Pt(SeMet-Se,N)2] as the eventual product. Displacement of the en ligand from [Pt(en)(SeMet-Se,N)]+ does not occur. In reactions of K2PtCl4 with two equivalents of SeMet, [Pt(SeMet-Se,N)2] is formed, and three sets of resonances are observed due to different chiralities at the Se atoms. Only the cis geometric isomers are observed by 1H and 195Pt NMR spectroscopy.

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Section: Resultssupporting

confidence: 84%

Section: Resultsmentioning

confidence: 99%

Reaction of platinum(II) diamine and triamine complexes with selenomethionine

Williams

Dudgeon

Chmely

et al. 2011

Inorganica Chimica Acta

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“…[17, 22] Molecular mechanics studies have indicated that steric clashes would be present in cis -[PtA 2 (Met- S ) 2 ] 2+ complexes when the A 2 ligand is bulky. [17] Such bulk does not prevent coordination of a second guanine.…”

Section: Introductionmentioning

confidence: 99%

Effects of amine ligand bulk and hydrogen bonding on the rate of reaction of platinum(II) diamine complexes with key nucleotide and amino acid residues

Sandlin

Whelan

Bradley

et al. 2012

Inorganica Chimica Acta

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NMR spectroscopy has been used to observe the effects of the amine ligand on the rate of reaction of platinum diamine and triamine complexes with DNA and protein residues. Whereas [Pt(dien)Cl]Cl and [Pt(dien)(D2O)]2+ have been known to react faster with thioether residues such as N-AcMet than with 5′-GMP, we found that [Pt(Me4en)(D2O)2]2+ appeared to react faster with 5′-GMP. To quantitatively assess the factors influencing the rates of reaction, rate constants at pH 4 were determined for the reactions of [Pt(en)(D2O)2]2+ [en = ethylenediamine] and [Pt(Me4en)(D2O)2]2+ with N-AcMet, N-AcHis, 5′-GMP, and Guo (guanosine). In each case the less bulky complex ([Pt(en)(D2O)2]2+) reacts more quickly than does the bulkier [Pt(Me4en)(D2O)2]2+, as expected. Both complexes reacted faster with 5′-GMP; however, analysis of the rate constants suggests that the [Pt(en)(D2O)2]2+ complex favors reaction with 5′-GMP due to hydrogen bonding with the 5′-phosphate, whereas [Pt(Me4en)(D2O)2]2+ disfavors reaction with N-AcMet due to steric clashes. Bulk had relatively little effect on the rate constant with N-AcHis, suggesting that peptides or proteins that coordinate via His residues would not have their reactivity affected by bulky diamine ligands.

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“…Molecular mechanics calculations suggested severe steric clashes in a 2:1 N-AcMet:Pt complex. Later work with [Pt(N,N-diethylethylenediamine)(D 2 O) 2 ] 2+ indicated only one geometric isomer of the observed sulfur-oxygen chelate, namely the one with the sulfur atom trans to the diethyl nitrogen [7]. Thus, coordination of a methionine sulfur atom cis to a bulky amine nitrogen is apparently slowed considerably.…”

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confidence: 99%

“…Finally, steric clashes between the carrier ligands and the entering ligand would be more likely for Me 5 dien than dien. Our previous studies have indicated that steric clashes are relevant to the types of N-AcMet adducts that form in platinum(II) diamine complexes [6, 7]. Studies from Canovese et al utilized a dien derivative with ethyl groups cis to the entering ligand position, and there was a noticeable selectivity for smaller nucleophiles [12]; thus, severe steric clashes between the methyl groups of Me 5 dien and the methionine ligand seems to be a reasonable explanation for our findings.…”

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A bulky platinum triamine complex that reacts faster with guanosine 5′-monophosphate than with N-acetylmethionine

Sandlin

Starling

Williams

2010

Journal of Inorganic Biochemistry

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A bulky platinum triamine complex, [Pt(Me 5 dien)(NO 3 )]NO 3 (Me 5 dien = N,N,N′,N′,N″ -pentamethyldiethylenetriamine) has been prepared and reacted in D 2 O with N-acetylmethionine (NAcMet) and guanosine 5′-monophosphate (5′-GMP); the reactions have been studied using 1 H NMR spectroscopy. Reaction with 5′-GMP leads to two rotamers of [Pt(Me 5 dien)(5′-GMP-N7)] + . Reaction with N-AcMet leads to formation of [Pt(Me 5 dien)(N-AcMet-S)] + . When a sample with equimolar mixtures of [Pt(Me 5 dien)(D 2 O)] 2+ , 5′-GMP, and N-AcMet was prepared, [Pt(Me 5 dien)(5′-GMP-N7)] + was the dominant product observed throughout the reaction. This selectivity is the opposite of that observed for a similar reaction of [Pt(dien)(D 2 O)] 2+ with 5′-GMP and N-AcMet. To our knowledge, this is the first report of a platinum(II) triamine complex that reacts substantially faster with 5′-GMP than with N-AcMet; the effect is most likely due to steric clashes between the methyl groups of the Me 5 dien ligand and the N-AcMet. Keywordsnuclear magnetic resonance; ligand binding; anticancer drug; platinum Cisplatin and its analogs are known to form 1,2-intrastrand cross-links with guanine that lead to DNA distortion and are considered responsible for cytotoxicity. However, reaction with proteins, especially at methionine residues, occurs readily [1,2]. Protein adducts could be responsible for toxicity or resistance [3]. Previous small molecule studies have shown that [Pt (dien)Cl]Cl (dien = diethylenetriamine) reacts faster both with methionine (Met) [4] and with S-methylglutathione [5] than with guanosine 5′-monophosphate (5′-GMP).We previously found that bulk on a platinum diamine compound can affect the N-AcMet adducts that can form. [Pt(N,N,N′,N′ -tetramethylethylenediamine)(D 2 O) 2 ] 2+ reacts with NAcMet in only a 1:1 ratio even when excess N-AcMet is present, forming a chelate via the sulfur and carboxylate oxygen atoms [6]. Molecular mechanics calculations suggested severe steric clashes in a 2:1 N-AcMet:Pt complex. Later work with [Pt(N,N-diethylethylenediamine) (D 2 O) 2 ] 2+ indicated only one geometric isomer of the observed sulfur-oxygen chelate, namely the one with the sulfur atom trans to the diethyl nitrogen [7]. Thus, coordination of a methionine sulfur atom cis to a bulky amine nitrogen is apparently slowed considerably. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Replacement of the amine hydrogens of dien with methyl groups would have several possible effects. First, a difference in observed trans effect would be possible, as Me 5 dien has an a methyl group on the N tr...

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Interaction of N-acetylmethionine with a non-C2-symmetrical platinum diamine complex

Cited by 8 publications

References 23 publications

Reaction of platinum(II) diamine and triamine complexes with selenomethionine

Reaction of platinum(II) diamine and triamine complexes with selenomethionine

Effects of amine ligand bulk and hydrogen bonding on the rate of reaction of platinum(II) diamine complexes with key nucleotide and amino acid residues

A bulky platinum triamine complex that reacts faster with guanosine 5′-monophosphate than with N-acetylmethionine

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