Kinetics of ligand exchange in solution: a quantitative mass spectrometry approach

Duez, Quentin; Tinnemans, Paul; Elemans, Johannes A. A. W.; Roithová, Jana

doi:10.1039/d3sc03342b

Cited by 3 publications

(8 citation statements)

References 63 publications

(80 reference statements)

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“…Regardless of the time delay, the kinetics with which the precursors of S 1A and S 1B react in solution are strikingly different (Figure 6b). The relative concentrations of S 1A and S 1A–D5 almost immediately reach the equilibrium, which indicates a short half‐life of S 1A (MS‐observed rate k MS >0.5 s −1 , see Equations S1 and S2 and ref [38] …”

Section: Resultsmentioning

confidence: 98%

“…Delayed reactant labeling (DRL) experiments provide a quantitative connection between the solution kinetics and ESI‐MS [37,38] . The reaction mixture is spiked with an isotopically labeled reagent after a time delay, leading to the generation of the labeled reaction intermediates.…”

Section: Resultsmentioning

confidence: 99%

“…Delayed reactant labeling (DRL) experiments provide a quantitative connection between the solution kinetics and ESI-MS. [37,38] The reaction mixture is spiked with an isotopically labeled reagent after a time delay, leading to the generation of the labeled reaction intermediates. Since the isotopically labeled and unlabeled ions share the same ionization efficiency, their relative abundance in the mass spectrum directly reports on the relative concentration of their precursors in solution, enabling the determination of quantitative kinetic data.…”

Section: Detection Of the Intermediates In The Eschenmoser Coupling R...mentioning

confidence: 99%

“…The relative concentrations of S 1A and S 1A-D5 almost immediately reach the equilibrium, which indicates a short halflife of S 1A (MS-observed rate k MS > 0.5 s À 1 , see Equations S1 and S2 and ref. [38] ). Hence, S 1A is either in a fast equilibrium with the reactants or reacts rapidly towards the following reaction intermediates.…”

Section: Detection Of the Intermediates In The Eschenmoser Coupling R...mentioning

confidence: 99%

“…[6,[28][29][30][31] We coupled mass detection with ion mobility spectrometry to detect the presence of isomers [32][33][34] and used ion spectroscopy to characterize the structure of the reaction intermediates. [35,36] Details about reaction kinetics in solution were gathered using delayed reactant labeling, [31,37,38] and flow chemistry. [39] Combining all results from the individual methods provides a comprehensive view of the reaction mechanism and reveals the autocatalytic behavior of the ECR reaction.…”

Section: Introductionmentioning

confidence: 99%

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Autocatalysis in Eschenmoser Coupling Reactions

Duez,

Marek,

Váňa

et al. 2023

Chemistry A European J

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The Eschenmoser coupling reaction (ECR) of thioamides with electrophiles is believed to proceed via thiirane intermediates. However, little is known about converting the intermediates into ECR products. Previous mechanistic studies involved external thiophiles to remove the sulfur atom from the intermediates. In this work, an ECR proceeding without any thiophilic agent or base is studied by electrospray ionization‐mass spectrometry. ESI‐MS enables the detection of the so‐far elusive polysulfide species Sn, with n ranging from 2 to 16 sulfur atoms, proposed to be the key species leading to product formation. Integrating observations from ion mobility spectrometry, ion spectroscopy, and reaction monitoring via flow chemistry coupled with mass spectrometry provides a comprehensive understanding of the reaction mechanism and uncovers the autocatalytic nature of the ECR reaction.

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Section: Resultsmentioning

confidence: 98%

Section: Resultsmentioning

confidence: 99%

Section: Detection Of the Intermediates In The Eschenmoser Coupling R...mentioning

confidence: 99%

Section: Detection Of the Intermediates In The Eschenmoser Coupling R...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Autocatalysis in Eschenmoser Coupling Reactions

Duez,

Marek,

Váňa

et al. 2023

Chemistry A European J

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Competing Mechanisms in Palladium-Catalyzed Alkoxycarbonylation of Styrene

Mehara,

Anania,

Kočovský

et al. 2024

ACS Catal.

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Palladium-catalyzed carbonylation is a versatile method for the synthesis of various aldehydes, esters, lactones, or lactams. Alkoxycarbonylation of alkenes with carbon monoxide and alcohol produces either saturated or unsaturated esters as a result of two distinct catalytic cycles. The existing literature presents an inconsistent account of the procedures favoring oxidative carbonylation products. In this study, we have monitored the intermediates featured in both catalytic cycles of the methoxycarbonylation of styrene PhCH�CH 2 as a model substrate, including all short-lived intermediates, using mass spectrometry. Comparing the reaction kinetics of the intermediates in both cycles in the same reaction mixture shows that the reaction proceeding via alkoxy intermediate [Pd II ]-OR, which gives rise to the unsaturated product PhCH�CHCO 2 Me, is faster. However, with an advancing reaction time, the gradually changing reaction conditions begin to favor the catalytic cycle dominated by palladium hydride [Pd II ]-H and alkyl intermediates, affording the saturated products PhCH 2 CH 2 CO 2 Me and PhCH(CO 2 Me)CH 3 preferentially. The role of the oxidant proved to be crucial: using p-benzoquinone results in a gradual decrease of the pH during the reaction, swaying the system from oxidative conditions toward the palladium hydride cycle. By contrast, copper(II) acetate as an oxidant guards the pH within the 5−7 range and facilitates the formation of the alkoxy palladium complex [Pd II ]-OR, which favors the oxidative reaction producing PhCH�CHCO 2 Me with high selectivity. Hence, it is the oxidant, rather than the catalyst, that controls the reaction outcome by a mechanistic switch. Unraveling these principles broadens the scope for developing alkoxycarbonylation reactions and their application in organic synthesis.

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Quantitative Online Monitoring of an Immobilized Enzymatic Network by Ion Mobility–Mass Spectrometry

Duez,

van de Wiel,

van Sluijs

et al. 2024

J. Am. Chem. Soc.

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The forward design of in vitro enzymatic reaction networks (ERNs) requires a detailed analysis of network kinetics and potentially hidden interactions between the substrates and enzymes. Although flow chemistry allows for a systematic exploration of how the networks adapt to continuously changing conditions, the analysis of the reaction products is often a bottleneck. Here, we report on the interface between a continuous stirred-tank reactor, in which an immobilized enzymatic network made of 12 enzymes is compartmentalized, and an ion mobility− mass spectrometer. Feeding uniformly 13 C-labeled inputs to the enzymatic network generates all isotopically labeled reaction intermediates and products, which are individually detected by ion mobility−mass spectrometry (IMS−MS) based on their mass-to-charge ratios and inverse ion mobilities. The metabolic flux can be continuously and quantitatively monitored by diluting the ERN output with nonlabeled standards of known concentrations. The real-time quantitative data obtained by IMS−MS are then harnessed to train a model of network kinetics, which proves sufficiently predictive to control the ERN output after a single optimally designed experiment. The high resolution of the time-course data provided by this approach is an important stepping stone to design and control sizable and intricate ERNs.

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Kinetics of ligand exchange in solution: a quantitative mass spectrometry approach

Abstract: Complex speciation and exchange kinetics of labile ligands are critical parameters for understanding the reactivity of metal complexes in solution. We present a novel approach to determine ligand exchange parameters...

Cited by 3 publications

References 63 publications

Autocatalysis in Eschenmoser Coupling Reactions

Autocatalysis in Eschenmoser Coupling Reactions

Competing Mechanisms in Palladium-Catalyzed Alkoxycarbonylation of Styrene

Quantitative Online Monitoring of an Immobilized Enzymatic Network by Ion Mobility–Mass Spectrometry

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