Stopped-flow nuclear magnetic resonance spectroscopy

Grimaldi, John J.; Baldo, John H.; McMurray, C.H.; Sykes, Brian D.

doi:10.1021/ja00777a006

Cited by 48 publications

(22 citation statements)

References 3 publications

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“…These requirements also reduce the possible range of applications of NMR for the study of fast nonequilibrium processes. Nevertheless, the potential advantages of integrating stopped‐flow methods with NMR have already been described early on in the development of NMR …”

Section: Introductionmentioning

confidence: 99%

Applications of dissolution dynamic nuclear polarization in chemistry and biochemistry

Zhang

Hilty

2018

Magnetic Reson in Chemistry

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Sensitivity of detection is one of the most limiting aspects when applying NMR spectroscopy to current problems in the molecular sciences. A number of hyperpolarization methods exist for increasing the population difference between nuclear spin Zeeman states and enhance the signal-to-noise ratio by orders of magnitude. Among these methods, dissolution dynamic nuclear polarization (D-DNP) is unique in its capability of providing high spin polarization for many types of molecules in the liquid state. Originally proposed for biomedical applications including in vivo imaging, applications in high resolution NMR spectroscopy are now emerging. These applications are the focus of the present review. Using D-DNP, a small sample aliquot is first hyperpolarized as a frozen solid at low temperature, followed by dissolution into the liquid state. D-DNP extends the capabilities of liquid state NMR spectroscopy towards shorter timescales and enables the study of nonequilibrium processes, such as the kinetics and mechanisms of reactions. It allows the determination of intermolecular interactions, in particular based on spin relaxation parameters. At the same time, a challenge in the application of this hyperpolarization method is that spin polarization is nonrenewable. Substantial effort has been devoted to develop methods for enabling rapid correlation spectroscopy, the measurement of time-dependent signals, and the extension of the observable time window. With these methods, D-DNP has the potential to open new application areas in the chemical and biochemical sciences.

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Section: Introductionmentioning

confidence: 99%

Applications of dissolution dynamic nuclear polarization in chemistry and biochemistry

Zhang

Hilty

2018

Magnetic Reson in Chemistry

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“…Whilst the IR/quench techniques allowed us to determine a wide range of protodeboronation kinetics, n = 0 to 5, Scheme 2, they did not provide the key insights that NMR spectroscopy can. These aspects led us to explore application of the two general techniques to monitor relatively fast irreversible reactions by NMR: rapid-injection, [30][31][32][33][34][35] and stopped-flow, [36][37][38][39][40][41][42][43] Figure 1. The primary difference between the two techniques lies in the way they mix the analytes.…”

Section: Resultsmentioning

confidence: 99%

Stopped‐Flow ¹⁹F NMR Spectroscopic Analysis of a Protodeboronation Proceeding at the Sub‐Second Time‐Scale

et al. 2021

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In‐situ NMR spectroscopic analysis of homogeneous reactions is an essential tool for mechanistic analysis in organic and organometallic chemistry. However, rapid non‐equilibrium reactions, that are initiated by mixing, require specialized approaches. We report herein on a study of the factors that ensure quantitative results in a recently‐developed technique for stopped‐flow NMR spectroscopy. The influence of some of the key parameters on quantitation is studied by 19F NMR spectroscopic analysis of the kinetics and activation parameters for the base‐catalyzed protodeboronation of highly‐reactive polyfluorinated arylboronic acids, with half‐lives as low as 0.1 seconds. The effects of spin relaxation, pre‐magnetization, heat‐transfer versus reaction enthalpy, and mixing‐efficiency are analyzed in detail. We also compare and contrast choice of pulse angle, interscan delay, and use of pseudo real‐time by interleaving, as means to achieve an optimal balance between temporal resolution and sensitivity.

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“…Here the important consideration is that the spectral acquisition time must be long enough so that either (1) the observed line widths are not broadened (AT > Tz*) or (2) the resolution is sufficient to follow the chemical shift changes 6 involved (1/AT << 6), for the two types of measurements, respectively. Of course the condition l / Tl* << 6 must also hold if chemical shift changes are being followed.…”

Section: Resultsmentioning

confidence: 99%

Stopped flow Fourier transform nuclear magnetic resonance spectroscopy. Application to the .alpha.-chymotrypsin-catalyzed hydrolysis of tert-butyl-L-phenylalanine

Grimaldi¹,

Sykes²

1975

J. Am. Chem. Soc.

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A stopped flow Fourier transform nuclear magnetic resonance spectrometer capable of monitoring reactions with half-times as short as 1 sec is described. By utilizing the Fourier difference spectroscopy technique described by Ernst, this spectrometer (1) can be used to detect the weak resonances of reacting species in the presence of a strong solvent resonance and (2) allows the signal averaging of transients obtained at the same time after mixing in successive transients. Various pulse sequences for obtaining stopped flow FT spectra are given and stopped flow FT nuclear magnetic resonance is used to measure the a-chymotrypsin hydrolysis of L-phenylalanine tert-butyl ester. The capabilities of stopped flow FT nuclear magnetic resonance are discussed in detail.The development of Fourier transform (FT) techniques in nuclear magnetic resonance (nmr) spectroscopy has focused attention on the possibility of using nmr to follow time-dependent phenomena such as irreversible chemical reactions or chemically induced dynamic nuclear polarizat i~n . ' -~ Obviously, having the nmr spectrum of a reaction mixture including reactants, intermediates, and products a t several times during a reaction would provide a very powerful tool for elucidating reaction mechanisms. We have previously described the construction of a stopped flow nmr spectrometer and its use to study the acid-catalyzed dissociation of Ni(NH3)(H20)52+ I and conformational changes produced in Concanavalin A by the binding of Mn2+, Ca2+, and a-methy1-D-mannoside.2 Both of these reactions involved following a single resonance, thereby allowing the observation of reactions with very short half-times by sacrificing the requirement to observe the complete spectrum. W e have also used FT nmr methods to follow the relatively slow cleavage of cell wall tetrasaccharide by l y s o~y r n e .~ In the present paper we describe the application of stopped flow Fourier transform nmr techniques to the achymotrypsin-catalyzed hydrolysis of the tert-butyl ester of p phenylalanine (PABE). Through this application we are able to assess the capabilities and limitations of stopped flow FT nmr. The success of this technique depends on overcoming two practical problems of FT nmr. First, under most reaction conditions, a strong solvent resonance will create dynamic range problems and will interfere with the observation of the much weaker resonances of the reacting species. This is especially true for biochemical reactions which are normally studied in water. Second, a lock system which is not affected by pushing and mixing is needed to allow averaging of transients. These two problems were simultaneously solved in the present application by using the Fourier transform difference spectroscopy technique described by Ernst6 The basis of this technique is that in the presence of one very strong resonance such as water, the free induction decay (FID) can be approximated by a single carrier frequency which is modulated by the difference frequencies between the strong resonance and each weak res...

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Stopped-flow nuclear magnetic resonance spectroscopy

Cited by 48 publications

References 3 publications

Applications of dissolution dynamic nuclear polarization in chemistry and biochemistry

Applications of dissolution dynamic nuclear polarization in chemistry and biochemistry

Stopped‐Flow ¹⁹F NMR Spectroscopic Analysis of a Protodeboronation Proceeding at the Sub‐Second Time‐Scale

Stopped flow Fourier transform nuclear magnetic resonance spectroscopy. Application to the .alpha.-chymotrypsin-catalyzed hydrolysis of tert-butyl-L-phenylalanine

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Stopped-flow nuclear magnetic resonance spectroscopy

Cited by 48 publications

References 3 publications

Applications of dissolution dynamic nuclear polarization in chemistry and biochemistry

Applications of dissolution dynamic nuclear polarization in chemistry and biochemistry

Stopped‐Flow 19F NMR Spectroscopic Analysis of a Protodeboronation Proceeding at the Sub‐Second Time‐Scale

Stopped flow Fourier transform nuclear magnetic resonance spectroscopy. Application to the .alpha.-chymotrypsin-catalyzed hydrolysis of tert-butyl-L-phenylalanine

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Stopped‐Flow ¹⁹F NMR Spectroscopic Analysis of a Protodeboronation Proceeding at the Sub‐Second Time‐Scale