Hydrogen-Deuterium (H-D) Exchange Reaction of Warfarin in D2O Solution

Tode, Chisato; Takeuchi, Atsuko; Iwakawa, Seigo; Tatsumi, Akitoshi; Sugiura, Makiko

doi:10.1248/cpb.57.653

Cited by 7 publications

(11 citation statements)

References 10 publications

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“…Meanwhile, the new resonance at δ =6.15 ppm gradually diminished and eventually became undetectable. The chemical resonance at δ =6.15 ppm that emerged during the early phase of the deuteration process is likely to arise from the C−HD proton, and broadening is likely to result from the quadrupolar effect of deuterium . Thus, the distinctive deuteration process provided direct evidence of our hypothesis of keto–enol tautomerism of the carbonyl α‐hydrogen of ALA.…”

Section: Resultsmentioning

confidence: 99%

“…According to the mechanism of keto–enol tautomerism, hydrogen/deuterium exchange of carbonyl α‐hydrogen (H5) may undergo successive CH 2 →CHD→CD 2 steps (Scheme ). Therefore, the rate constants of the two steps ( k 1 for the first step; k 2 for the second step) can be calculated by fitting the plot of the observed carbonyl α‐hydrogen (H5) versus time, according to Equation (1) (derivation details are given in the Experimental Section) .

true [CH_{2}]_{obs} = 2 \exp (- k_{1} t) + {k_{1} / (k_{2} - k_{1})} {\exp (- k_{1} t) - \exp (- k_{2} t)}

…”

Section: Resultsmentioning

confidence: 99%

“… Successive hydrogen/deuterium exchange of the carbonyl α‐hydrogen. The first step CH 2 →CHD ( k 1 ) was from compound 1 to compound 4, while the second step CHD→CD 2 ( k 2 ) was from compound 5 to compound 8 …”

Section: Resultsmentioning

confidence: 99%

“…The H/D exchange of the carbonyl α‐hydrogen of ALA was regarded as the successive reaction of CH 2 →CHD→CD 2 . The first step rate constant was defined as k 1 , and the second step rate constant was defined as k 2 .…”

Section: Methodsmentioning

confidence: 99%

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Encapsulation of AGE‐Breaker Alagebrium by Cucurbit[7]uril Improved the Stability of Both Its Carbonyl α‐Hydrogen and Thiazolium C2‐Hydrogen

Ding

Yin

et al. 2016

Chemistry An Asian Journal

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As determined by both H NMR and UV/Vis spectroscopic titration, ESI-MS, isothermal titration calorimetry, and DFT molecular modeling, advanced glycation end products (AGE) breaker alagebrium (ALA) formed 1:1 guest-host inclusion complexes with cucurbit[7]uril (CB[7]), with a binding affinity, K , in the order of magnitude of 10 m , thermodynamically driven by both enthalpy (ΔH=-6.79 kcal mol ) and entropy (TΔS=1.21 kcal mol ). For the first time, a dramatic inhibition of keto-enol tautomerism of the carbonyl α-hydrogen of ALA has been observed, as evidenced by over an order of magnitude decrease of both the first step rate constant, k , and the second step rate constant, k , during hydrogen/deuterium exchange in D O. Meanwhile, as expected, the reactivity of C2-hydrogen was also inhibited significantly, with an upshift of 2.09 pK units. This discovery will not only provide an emerging host molecule to modulate keto-enol tautomerism, but also potentially lead to a novel supramolecular formulation of AGE-breaker ALA for improved stability and therapeutic efficacy.

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Section: Resultsmentioning

confidence: 99%

true [CH_{2}]_{obs} = 2 \exp (- k_{1} t) + {k_{1} / (k_{2} - k_{1})} {\exp (- k_{1} t) - \exp (- k_{2} t)}

…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Encapsulation of AGE‐Breaker Alagebrium by Cucurbit[7]uril Improved the Stability of Both Its Carbonyl α‐Hydrogen and Thiazolium C2‐Hydrogen

Ding

Yin

et al. 2016

Chemistry An Asian Journal

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“…Isotope-enriched chemicals have alleviated signal overlaps by shifting mass-to-charge ratio in mass spectroscopy (MS) [1][2][3][4] or vibrational frequencies in infrared or Raman spectroscopy. [5][6][7] Likewise, nuclear magnetic resonance (NMR) spectra have been clarified by altering J-coupling splitting patterns and chemical shifts using isotope enrichment.…”

Section: Introductionmentioning

confidence: 99%

Deuterium Naturally Present in Solvent and Site-Specific Isotope Population of Deuterium-Enriched Solute

Hwang¹,

Han

Kim³

2013

Bulletin of the Korean Chemical Society

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As the concentration of aqueous CD 3 OH solutions was decreased, the OD peaks in 2 H NMR spectra grew relative to the CD 3 peaks. Isotope impurity for OH groups of CD 3 OH and deuterium naturally present in water contributed to the OD peaks. Using these peak area data, the site-specific isotope populations of isotope enriched chemicals were measured. In addition, the method using both 1 H and 2H NMR spectroscopy was demonstrated with neat CD 3 OH to measure the site-specific isotope populations. The results indicate that although it represents only ~0.015% of hydrogen isotopes, the deuterium naturally present in solvents cannot be ignored, especially when the concentration of deuterium-enriched solutes is varied. Proton/deuteron exchange between methyl and methyl/hydroxyl groups was confirmed to be negligible, while that among hydroxyl groups was detectable.

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Preparation and characterization of a new solid form of praziquantel, an essential anthelmintic drug. Praziquantel racemic monohydrate

Salazar-Rojas

Maggio

Kaufman

2020

European Journal of Pharmaceutical Sciences

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Hydrogen-Deuterium (H-D) Exchange Reaction of Warfarin in D2O Solution

Abstract: Two kinds of diastereomers exist for a cyclic hemiketal due to two chiral centers.

Cited by 7 publications

References 10 publications

Encapsulation of AGE‐Breaker Alagebrium by Cucurbit[7]uril Improved the Stability of Both Its Carbonyl α‐Hydrogen and Thiazolium C2‐Hydrogen

Encapsulation of AGE‐Breaker Alagebrium by Cucurbit[7]uril Improved the Stability of Both Its Carbonyl α‐Hydrogen and Thiazolium C2‐Hydrogen

Deuterium Naturally Present in Solvent and Site-Specific Isotope Population of Deuterium-Enriched Solute

Preparation and characterization of a new solid form of praziquantel, an essential anthelmintic drug. Praziquantel racemic monohydrate

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