J-modulated ADEQUATE (JM-ADEQUATE) experiment for accurate measurement of carbon–carbon coupling constants

Kövér, Katalin E.; Forgó, Péter

doi:10.1016/j.jmr.2003.09.015

Cited by 46 publications

(36 citation statements)

References 39 publications

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“…We have recorded ω 1 -refocused J-modulated 1,1-ADEQUATEs using BIPs with scaling factors of 5, 10 and 20 and have not observed any deviations of line shapes or coupling constants (except the normal scatter of values). Larger scaling factors lead -as observed previously 23 -to increasing relaxation and therefore, a balance between precision of the coupling constant and signal intensity has to be found.…”

Section: Resultsmentioning

confidence: 81%

“…multiplet structure/intensity. As proposed recently, 23,24 we chose smoothed chirp pulses 25 (500 µs, 60 kHz sweep width) for all inversion 180°and composite smoothed chirp pulses 26 (2 ms total duration, 1 : 2:1, 500 µs, 1 ms, 500 µs, 60 kHz sweep width) for all refocusing pulses including the refocusing pulse in the J-modulation spin echo ( Fig. 2(a)).…”

Section: Resultsmentioning

confidence: 99%

“…22 The achievable precision of 13 C-13 C coupling constants using this approach is, however, strongly limited by the number of t 1 increments and the size of the coupling constant. It was clearly shown by Köver et al 23 that by introducing a J-modulated spin echo after the INEPTtransfer of the ω 1 -refocused ADEQUATE sequence, scaling of couplings can be achieved thus significantly improving obtainable precision (see Fig. 1).…”

Section: Introductionmentioning

confidence: 99%

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J‐modulated ADEQUATE experiments using different kinds of refocusing pulses

Thiele¹,

Bermel²

2007

Magnetic Reson in Chemistry

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Owing to the recent developments concerning residual dipolar couplings (RDCs), the interest in methods for the accurate determination of coupling constants is renascenting. We intended to use the J-modulated ADEQUATE experiment by Kövér et al. for the measurement of (13)C - (13)C coupling constants at natural abundance. The use of adiabatic composite chirp pulses instead of the conventional 180 degrees pulses, which compensate for the offset dependence of (13)C 180 degrees pulses, led to irregularities of the line shapes in the indirect dimension causing deviations of the extracted coupling constants. This behaviour was attributed to coupling evolution, during the time of the adiabatic pulse (2 ms), in the J-modulation spin echo. The replacement of this pulse by different kinds of refocusing pulses indicated that a pair of BIPs (broadband inversion pulses), which behave only partially adiabatic, leads to correct line shapes and coupling constants conserving the good sensitivity obtained with adiabatic pulses.

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Section: Resultsmentioning

confidence: 81%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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J‐modulated ADEQUATE experiments using different kinds of refocusing pulses

Thiele¹,

Bermel²

2007

Magnetic Reson in Chemistry

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“…Table 1. Carbon-carbon coupling constants of 1, in Hz, determined from in-and antiphase spectra of the isotropic and aligned sample Using the same sample, spectrometer, and identical experimental time, a 1 H-detected J-modulated IPAP-INADEQUATE experiment combining the existing Jmodulated INADEQUATE experiments 10,11 yielded S/N ratio of 8 : 1 (no window function in F 1 , data not shown). General reasons for such a good performance of the 13 C-detected INADEQUATE were discussed previously.…”

Section: Resultsmentioning

confidence: 98%

“…The determination of n J CC coupling constants is however non trivial, as partial cancellation of closely spaced antiphase lines produces an apparent splitting that is larger than the true coupling constant. 11,20,21 The use of inverse FT methods 22,23 in the analysis of antiphase doublets is also problematic. These methods rely on significant presence of the signal after the zero crossing, which is difficult to achieve in noise INADEQUATE cross peaks containing small coupling constants.…”

Section: Resultsmentioning

confidence: 99%

¹³C‐detected IPAP‐INADEQUATE for simultaneous measurement of one‐bond and long‐range scalar or residual dipolar coupling constants

Jin

Uhrı́n

2007

Magnetic Reson in Chemistry

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The sensitivity of cryoprobes, which are rapidly becoming available, means that the measurement of coupling constants involving 13C, 13C pairs at the natural abundance of 13C can now, in principle, be done by using tens rather then hundreds of milligrams of compounds. However, a robust method that would yield reliable values of small long-range carbon--carbon coupling constants is still missing. In this Communication, we describe a novel 13C-detected incredible natural-abundance double-quantum transfer experiment (INADEQUATE) experiment for simultaneous correlation of one-bond and long-range 13C- 13C pairs and the measurement of both types of coupling constants in 13C natural abundance samples. This method yields accurate values of one-bond and long-range coupling constants by manipulation of pure phase in-phase (IP) and antiphase (AP) doublets, and is referred to as 13C-detected IPAP-INADEQUATE. It is illustrated by the measurement of interglycosidic (3)J(CCOC) coupling constants in a disaccharide molecule providing important information about the conformation of the glycosidic linkage. Owing to the simplicity of INADEQUATE spectra the carbon-carbon coupling constants are particularly suitable for studies of partially oriented molecules through the measurement of carbon-carbon residual dipolar couplings (RDCs). An example of this approach is presented. We expect the method to find a variety of applications in the conformational analysis of small molecules, determination of diastereoisomers and enantiomers, and studies of molecules in aligned media.

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Advances in NMR‐Based Characterization of Drug Substances, Impurities, Degradants, and Drug Metabolites

Saurí

Reibarkh

Williamson

et al. 2021

Burger's Medicinal Chemistry and Drug Discovery

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In the approximately 70 years since the first reports of experiments that led to what is now known as nuclear magnetic resonance or NMR spectroscopy, the technique has become the cornerstone of molecular structure characterization. From the isolation of strychnine to the confirmation of its complex structure in a total synthesis reported by Woodward consumed a century and a half. In contrast, using a modern 600 MHz NMR instrument equipped with a 1.7 mm MicroCryoProbe™, that task can now be accomplished in 24 hours, including the acquisition of 15 N chemical shift information on a few milligrams of sample. Such is the magnitude of the advances that have been made in the discipline. This article is not intended to make NMR spectroscopists out of a practicing medicinal chemistry; rather, the article is intended to acquaint the reader with recent advances in NMR techniques that are making it possible to successfully and unequivocally characterize ever increasingly more complex structures being synthesized in the laboratory as potential drug candidates or isolated from nature. Our goal was to augment the NMR knowledge of the medicinal chemist, better equipping him or her to more effectively interact with the NMR spectroscopy staff at the chemist's facility. The article begins with a discussion of new experimental methods that allow the acquisition of broadband decoupled 1 H NMR spectra that resemble an 1 H‐decoupled 13 C spectrum, with every proton resonance reduced to a singlet. Pure‐shift heteronuclear shift correlation methods are described next, followed by new long‐range heteronuclear chemical shift correlation experiments and then hyphenated techniques to identify components of complex, overlapped proton homonuclear spin systems. Techniques are also described for the unequivocal identification of vicinal neighbor carbon resonances that can be invaluable when dealing with complex impurities or degradation products. Covariance NMR data processing methods that allow 2D NMR experiments to be treated as large numerical matrices that can be manipulated using matrix algebraic operations are briefly discussed. Finally, anisotropic NMR methods are considered, which afford investigators the means of orthogonally verifying chemical structure constitution and configuration without investigator bias that often can lead to erroneously assigned structures. The latter eventuality, of course, can slow development timelines or could potentially have devastating patent protection consequences and regulatory implications.

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J-modulated ADEQUATE (JM-ADEQUATE) experiment for accurate measurement of carbon–carbon coupling constants

Cited by 46 publications

References 39 publications

J‐modulated ADEQUATE experiments using different kinds of refocusing pulses

J‐modulated ADEQUATE experiments using different kinds of refocusing pulses

¹³C‐detected IPAP‐INADEQUATE for simultaneous measurement of one‐bond and long‐range scalar or residual dipolar coupling constants

Advances in NMR‐Based Characterization of Drug Substances, Impurities, Degradants, and Drug Metabolites

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J-modulated ADEQUATE (JM-ADEQUATE) experiment for accurate measurement of carbon–carbon coupling constants

Cited by 46 publications

References 39 publications

J‐modulated ADEQUATE experiments using different kinds of refocusing pulses

J‐modulated ADEQUATE experiments using different kinds of refocusing pulses

13C‐detected IPAP‐INADEQUATE for simultaneous measurement of one‐bond and long‐range scalar or residual dipolar coupling constants

Advances in NMR‐Based Characterization of Drug Substances, Impurities, Degradants, and Drug Metabolites

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¹³C‐detected IPAP‐INADEQUATE for simultaneous measurement of one‐bond and long‐range scalar or residual dipolar coupling constants