Structure elucidation capabilities on typical pharmaceutical drugs by new nuclear magnetic resonance technology: a 400 MHz high-temperature superconducting power-driven magnet NMR system

Elipe, Maria Victoria Silva; Donovan, Neil; Krull, Robert; Pooke, D.; Colson, Kimberly L.

doi:10.1080/10739149.2018.1516226

Cited by 6 publications

(25 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, we have tested a 400 MHz cryogen-free power-driven high-temperature superconducting (HTS) magnet NMR system with standard electronics using a Bruker Nanobay console and BBFO probe to determine the capability of the instrument for reaction monitoring. We proved that the NMR data is comparable to standard commercial cryogenic 400 MHz magnet NMR systems. , Because liquid cryogens are not required and because of the smaller footprint of this HTS magnet NMR system, we have been able to install it directly in a chemistry laboratory, integrating it with other analytical instrumentation that is available for immediate use by scientists. An important reason for this colocation is to have the NMR tool inside the same chemistry fume hood where the reactors are housed.…”

Section: Introductionmentioning

confidence: 74%

“…Recent technological developments of high-temperature superconducting (HTS) devices have provided power-driven magnets operating at temperatures of 10–30 K using mechanical cryocoolers for cooling power. Recently, we compared a 400 MHz HTS power-driven magnet NMR system to a standard LTS NMR system with the focus on demonstrating its capability in structure elucidation for typical APIs in the pharmaceutical industry, , commonly done in deuterated solvents. As we demonstrated, the data acquired using the HTS magnet with standard electronics was similar to that using LTS magnets.…”

Section: Resultsmentioning

confidence: 99%

“…An air-cooled chiller (Huber Unichiller 040T, Offenburg, Germany) provides water cooling to the power supply. The shims used in the HTS magnet are passive ferromagnetic shims instead of the typical active superconducting shims found in standard commercial cryogen-bath magnets, providing field uniformity of order one part per million over the sample zone, which is sufficient for conventional electric shimstacks to be employed for further shimming. , The NMR console is an AVANCE III HD NMR (Bruker BioSpin, Billerica, MA). The probe is a 5 mm Bruker multinuclear broadband fluorine observe (BBFO) ( 1 H on the outer coil, inner coil tunable from 109 Ag– 19 F, coil length 24 mm).…”

Section: Experimental Sectionmentioning

confidence: 99%

“…The shimstack is a Bruker orthogonal shim system-3 (BOSS3) with 38 shims. Additional information on this NMR system can be found in two previous publications with details of the electrical requirements and a footprint of the instrument. , …”

Section: Experimental Sectionmentioning

confidence: 99%

“…We proved that the NMR data is comparable to standard commercial cryogenic 400 MHz magnet NMR systems. 11,12 Because liquid cryogens are not required and because of the smaller footprint of this HTS magnet NMR system, we have been able to install it directly in a chemistry laboratory, integrating it with other analytical instrumentation that is available for immediate use by scientists. An important reason for this colocation is to have the NMR tool inside the same chemistry fume hood where the reactors are housed.…”

Section: ■ Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Application of the New 400 MHz High-Temperature Superconducting (HTS) Power-Driven Magnet NMR Technology for Online Reaction Monitoring: Proof of Concept with a Ring-Closing Metathesis (RCM) Reaction

Elipe

Cherney

Krull

et al. 2020

Org. Process Res. Dev.

Self Cite

View full text Add to dashboard Cite

Monitoring chemical reactions by nuclear magnetic resonance (NMR) is an established and valuable approach for process understanding, robustness, scalability, and control in the pharmaceutical industry. Understanding speciation, reaction rates, and reaction completion times provides information on how to improve a chemical process, leading to increased quality and quantity of the desired product. An important consideration for online monitoring is to have an NMR instrument colocated with a chemical reactor. The standard commercial medium-to high-field NMR instruments are normally installed in isolated locations due to facility and safety restrictions. Low-field NMR instruments suffer from low resolution and sensitivity, requiring chemometric analysis for medium to complex chemical structures. Reactions are typically monitored using NMR tubes and deuterated solvents. Therefore, reaction analysis may not provide the same kinetic information as when the reaction occurs in a reactor at a larger scale. To overcome these factors, we have tested a prototype NMR instrument with a 400 MHz cryogen-free power-driven high-temperature superconducting (HTS) magnet installed in a chemistry laboratory fume hood for online monitoring of reactions. We have tested the HTS NMR system with a ring-closing metathesis (RCM) reaction of diethyl diallyl malonate with Grubbs 2nd Gen catalyst in a reactor with a protonated solvent. The reaction was monitored online with a Bruker InsightMR flow cell, and data was acquired in automation, yielding a kinetic time-course of the transformation and reaction rate values. This work demonstrates that NMR instruments with HTS magnets can be integrated into the chemistry laboratory with other equipment and are a valuable tool for reaction monitoring under typical reaction conditions and in protonated solvents.

show abstract

Section: Introductionmentioning

confidence: 74%

Section: Resultsmentioning

confidence: 99%

Section: Experimental Sectionmentioning

confidence: 99%

Section: Experimental Sectionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Application of the New 400 MHz High-Temperature Superconducting (HTS) Power-Driven Magnet NMR Technology for Online Reaction Monitoring: Proof of Concept with a Ring-Closing Metathesis (RCM) Reaction

Elipe

Cherney

Krull

et al. 2020

Org. Process Res. Dev.

Self Cite

View full text Add to dashboard Cite

show abstract

Anisotropic NMR data acquisition with a prototype 400 MHz cryogen‐free NMR spectrometer

Silva Elipe,

Ndukwe,

Navarro‐Vázquez

2023

Magnetic Reson in Chemistry

Self Cite

View full text Add to dashboard Cite

High‐temperature superconducting (HTS) materials have recently been incorporated into the construction of HTS cryogen‐free magnets for nuclear magnetic resonance (NMR) spectroscopy. These HTS NMR spectrometers do not require liquid cryogens, thereby providing significant cost savings and facilitating easy integration into chemistry laboratories. However, the optimal performance of these HTS magnets against standard cryogen NMR magnets must be evaluated, especially with demanding modern NMR applications such as NMR in anisotropic media. The stability of the HTS magnets over time and their performance with complex pulse sequence experiments are the main unknown factors of this new technology. In this study, we evaluate the utility of our prototype 400 MHz cryogen‐free power‐driven HTS NMR spectrometer, installed in the fumehood of a chemistry laboratory, for stereochemical analysis of three commercial natural products (artemisinin, artemether, and dihydroartemisinin) via measurement of anisotropic NMR data, in particular, residual dipolar couplings. The accuracy of measurement of the anisotropic NMR data with the HTS magnet spectrometer is evaluated through the CASE‐3D fitting protocol, as implemented in the Mestrenova‐StereoFitter software program.

show abstract

Cryogen‐free 400‐MHz nuclear magnetic resonance spectrometer as a versatile tool for pharmaceutical process analytical technology

Silva Elipe,

Ndukwe,

Murray

2024

Magnetic Reson in Chemistry

Self Cite

View full text Add to dashboard Cite

The discovery of new ceramic materials containing Ba‐La‐Cu oxides in 1986 that exhibited superconducting properties at high temperatures in the range of 35 K or higher, recognized with the Nobel Prize in Physics in 1987, opened a new world of opportunities for nuclear magnetic resonance (NMRs) and magnetic resonance imaging (MRIs) to move away from liquid cryogens. This discovery expands the application of high temperature superconducting (HTS) materials to fields beyond the chemical and medical industries, including electrical power grids, energy, and aerospace. The prototype 400‐MHz cryofree HTS NMR spectrometer installed at Amgen's chemistry laboratory has been vital for a variety of applications such as structure analysis, reaction monitoring, and CASE‐3D studies with RDCs. The spectrometer has been integrated with Amgen's chemistry and analytical workflows, providing pipeline project support in tandem with other Kinetic Analysis Platform technologies. The 400‐MHz cryofree HTS NMR spectrometer, as the name implies, does not require liquid cryogens refills and has smaller footprint that facilitates installation into a chemistry laboratory fume hood, sharing the hood with a process chemistry reactor. Our evaluation of its performance for structural analysis with CASE‐3D protocol and for reaction monitoring of Amgen's pipeline chemistry was successful. We envision that the HTS magnets would become part of the standard NMR and MRI spectrometers in the future. We believe that while the technology is being developed, there is room for all magnet options, including HTS, low temperature superconducting (LTS) magnets, and low field benchtop NMRs with permanent magnets, where utilization will be dependent on application type and costs.

show abstract

Structure elucidation capabilities on typical pharmaceutical drugs by new nuclear magnetic resonance technology: a 400 MHz high-temperature superconducting power-driven magnet NMR system

Cited by 6 publications

References 13 publications

Application of the New 400 MHz High-Temperature Superconducting (HTS) Power-Driven Magnet NMR Technology for Online Reaction Monitoring: Proof of Concept with a Ring-Closing Metathesis (RCM) Reaction

Application of the New 400 MHz High-Temperature Superconducting (HTS) Power-Driven Magnet NMR Technology for Online Reaction Monitoring: Proof of Concept with a Ring-Closing Metathesis (RCM) Reaction

Anisotropic NMR data acquisition with a prototype 400 MHz cryogen‐free NMR spectrometer

Cryogen‐free 400‐MHz nuclear magnetic resonance spectrometer as a versatile tool for pharmaceutical process analytical technology

Contact Info

Product

Resources

About