Syntheses with stable isotopes: Pyridine‐<sup>15</sup>N

Whaley, Thomas W.; Ott, Donald G.

doi:10.1002/jlcr.2590100212

Cited by 31 publications

(33 citation statements)

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“…44,45,46 [Tp Ph,Me ZnOH] was a gift of H. Vahrenkamp (Freiburg, Germany). It was synthesized and characterized by 1 H NMR as described previously by Ruf et al 32 …”

Section: Methodsmentioning

confidence: 99%

Intrinsic Proton-Donating Power of Zinc-Bound Water in a Carbonic Anhydrase Active Site Model Estimated by NMR

et al. 2011

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Using liquid state NMR spectroscopy we have estimated the proton donating ability of Zn-bound water in organometallic complexes designed as models for the active site of the metalloenzyme carbonic anhydrase (CA). This ability is important for the understanding of the enzyme reaction mechanism. The desired information was obtained by 1H and 15N NMR at 180 K of solutions of [TpPh,MeZnOH] (1, TpPh,Me = tris(2-methyl, 4-phenyl pyrazolyl) hydroborate) in CD2Cl2, in the absence and presence of the proton donors (C6F5)3BOH2 (aquatris(pentafluorophenyl)boron) and Col-H+ (2,4,6-trimethylpyridine-H+). Col-H+ forms a strong OHN hydrogen bond with 1, where the proton is located closer to nitrogen than to oxygen. (C6F5)3BOH2 - which exhibits a pKa value of 1 in water - also forms a strong hydrogen bond with 1, where the proton is shifted slightly across the hydrogen bond center towards the Zn-bound oxygen. Finally, a complex between Col and (C6F5)3BOH2 was identified, exhibiting a zwitterionic OHN hydrogen bond where H is entirely shifted to nitrogen. The comparison with complexes of Col with carboxylic acids studied previously suggests that, surprisingly, the Zn-bound water exhibits in an aprotic environment a similar proton donating ability as a carboxylic acid characterized in water by a pKa of 2.2 ± 0.6. This value is much smaller than the value of 9 found for [Zn(OH2)6]2+ in water, and those between 5 and 8 reported for different forms of CA. Implications for the biological function of CA are discussed.

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“…44,45,46 [Tp Ph,Me ZnOH] was a gift of H. Vahrenkamp (Freiburg, Germany). It was synthesized and characterized by 1 H NMR as described previously by Ruf et al 32 …”

Section: Methodsmentioning

confidence: 99%

Intrinsic Proton-Donating Power of Zinc-Bound Water in a Carbonic Anhydrase Active Site Model Estimated by NMR

et al. 2011

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“…After that, the cyclization proceeds, and the labeled 15 N‐pyridine derivative is formed (Figure ). The reactions shown in Figures and clearly indicate that preparation of 15 N‐pyridine derivatives would become challenging using the method described in Whaley and Ott (because a sophisticated precursor would be required), whereas the Zincke salt–based approach allows for straightforward 15 N‐enrichment using a non‐labeled biomolecule, e.g., nicotinamide (vitamin B3) shown in Figure .…”

Section: Resultsmentioning

confidence: 99%

“…Moreover, demonstration that the presented approach works for preparation of 15 N‐Py (in addition to the previously reported 15 N‐nicotinamide preparation) opens the road for future 15 N‐enrichment of more‐complex pyridine derivatives using this relatively straightforward approach. The key synthetic results and their comparison with the method described in Whaley and Ott are provided in Table .…”

Section: Resultsmentioning

confidence: 99%

A versatile synthetic route to the preparation of ¹⁵N heterocycles

Чуканов

Kidd

Kovtunova

et al. 2019

Labelled Comp Radiopharmac

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A robust medium‐scale (approximately 3 g) synthetic method for 15N labeling of pyridine (15N‐Py) is reported based on the Zincke reaction. 15N enrichment in excess of 81% was achieved with approximately 33% yield. 15N‐Py serves as a standard substrate in a wide range of studies employing a hyperpolarization technique for efficient polarization transfer from parahydrogen to heteronuclei; this technique, called SABRE (signal amplification by reversible exchange), employs a simultaneous chemical exchange of parahydrogen and a to‐be‐hyperpolarized substrate (e.g., pyridine) on metal centers. In studies aimed at the development of hyperpolarized contrast agents for in vivo molecular imaging, pyridine is often employed either as a model substrate (for hyperpolarization technique development, quality assurance, and phantom imaging studies) or as a co‐substrate to facilitate more efficient hyperpolarization of a wide range of emerging contrast agents (e.g., nicotinamide). Here, the produced 15N‐Py was used for the feasibility study of spontaneous 15N hyperpolarization at high magnetic (HF) fields (7 T and 9.4 T) of an NMR spectrometer and an MRI scanner. SABRE hyperpolarization enabled acquisition of 2D MRI imaging of catalyst‐bound 15N‐pyridine with 75 × 75 mm2 field of view (FOV), 32 × 32 matrix size, demonstrating the feasibility of 15N HF‐SABRE molecular imaging with 2.4 × 2.4 mm2 spatial resolution.

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“…15 N‐pyridine and 1‐ 15 N‐nicotinamide used as SABRE substrates were synthesized according to the procedures described in the literature (for details of synthesis of 15 N‐pyridine see Supporting Information) . 600 μL [D 4 ]MeOH mixtures: 1 m solution of 15 N‐Py and 50 m m of Ir(COD)(IMes)Cl, 0.1 m solution of 15 N‐Py and 5 m m of Ir(COD)(IMes)Cl or 0.1 m solution of 15 N‐NA and 5 m m Ir(COD)(IMes)Cl, were used for MRI experiments.…”

Section: Experimental Designmentioning

confidence: 99%

¹⁵N MRI of SLIC‐SABRE Hyperpolarized ¹⁵N‐Labelled Pyridine and Nicotinamide

Svyatova

Skovpin

Чуканов

et al. 2019

Chemistry A European J

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Magnetic Resonance Imaging (MRI) is a powerful non‐invasive diagnostic method extensively used in biomedical studies. A significant limitation of MRI is its relatively low signal‐to‐noise ratio, which can be increased by hyperpolarizing nuclear spins. One promising method is Signal Amplification By Reversible Exchange (SABRE), which employs parahydrogen as a source of hyperpolarization. Recent studies demonstrated the feasibility to improve MRI sensitivity with this hyperpolarization technique. Hyperpolarized 15N nuclei in biomolecules can potentially retain their spin alignment for tens of minutes, providing an extended time window for the utilization of the hyperpolarized compounds. In this work, we demonstrate for the first time that radio‐frequency‐based SABRE hyperpolarization techniques can be used to obtain 15N MRI of biomolecule 1‐15N‐nicotinamide. Two image acquisition strategies were utilized and compared: Single Point Imaging (SPI) and Fast Low Angle SHot (FLASH). These methods demonstrated opportunities of high‐field SABRE for biomedical applications.

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Syntheses with stable isotopes: Pyridine‐¹⁵N

Abstract: The acid‐catalyzed condensation of either 2‐ethoxy‐3,4‐dihydro‐2H‐pyran or pentanedial (glutaraldehyde) with ammonium‐15N chloride in the presence of methylene blue is a convenient one‐step synthesis of pyridine‐15N.

Cited by 31 publications

References 1 publication

Intrinsic Proton-Donating Power of Zinc-Bound Water in a Carbonic Anhydrase Active Site Model Estimated by NMR

Intrinsic Proton-Donating Power of Zinc-Bound Water in a Carbonic Anhydrase Active Site Model Estimated by NMR

A versatile synthetic route to the preparation of ¹⁵N heterocycles

¹⁵N MRI of SLIC‐SABRE Hyperpolarized ¹⁵N‐Labelled Pyridine and Nicotinamide

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Syntheses with stable isotopes: Pyridine‐15N

Abstract: The acid‐catalyzed condensation of either 2‐ethoxy‐3,4‐dihydro‐2H‐pyran or pentanedial (glutaraldehyde) with ammonium‐15N chloride in the presence of methylene blue is a convenient one‐step synthesis of pyridine‐15N.

Cited by 31 publications

References 1 publication

Intrinsic Proton-Donating Power of Zinc-Bound Water in a Carbonic Anhydrase Active Site Model Estimated by NMR

Intrinsic Proton-Donating Power of Zinc-Bound Water in a Carbonic Anhydrase Active Site Model Estimated by NMR

A versatile synthetic route to the preparation of 15N heterocycles

15N MRI of SLIC‐SABRE Hyperpolarized 15N‐Labelled Pyridine and Nicotinamide

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Syntheses with stable isotopes: Pyridine‐¹⁵N

A versatile synthetic route to the preparation of ¹⁵N heterocycles

¹⁵N MRI of SLIC‐SABRE Hyperpolarized ¹⁵N‐Labelled Pyridine and Nicotinamide