ピコリナミドとニコチナミドにおけるアミド回転障壁:NMRとアビイニシオ研究
Ryan A Olsen1, Lisa Liu, Nima Ghaderi
1Department of Chemistry, University of California-Riverside, Riverside, CA 92521, USA.
Journal of the American Chemical Society
|August 14, 2003
まとめ
ピコリナミドやニコチナミドのようなピリジンカルボキシアミドには,異なるアミド回転障壁があります. ダイナミックな核磁気共振とアビニシオ計算では,ステリック相互作用と電子効果による異なるエネルギーが明らかになる.
科学分野:
- 薬用化学 薬用化学について
- 物理有機化学 物理有機化学
- コンピューティング・ケミストリー
背景:
- ピリジンカルボキシアミドは,鉄による腎臓損傷の減少と放射線感受性を含む多様な薬理学的な作用を示します.
- カーボキシアミド分子は,生物学的活性分子に多く存在し,アミド結合の回転がそれらの機能において重要な役割を果たします.
研究 の 目的:
- ピリジン・カルボキシアミド・レジオアイソマー,特にピコリナミドとニコチナミド間のアミド結合の回転におけるエネルギー差異を調査する.
- 実験的および計算的方法を使用して,観測されたエネルギー変化に寄与する要因を解明する.
主な方法:
- 動的核磁共振 (NMR) スペクトロスコピーは,アミドの回転障壁を測定するために使用されました.
- Ab initio計算を行い,回転障壁をモデル化し,要因を分析しました.
主要な成果:
- ニコチナミドは,ピコリナミド (18.3 ± 0.4 kcal / mol と +1.3 ± 1.0 cal / mol K) に比べて,より低いアクティベーションエンタルピー (12.9 ± 0.3 kcal / mol) と負のアクティベーションエントロピー (-7.7 ± 0.9 cal / mol K) を示した.
- 計算の結果は,実験データと密接に一致し,ステリック変異,π電子提供,および分子内水素結合を ~5.4 kcal/molのエンタルピー差の主要な要因として特定しました.
結論:
- ピコリナミドとニコチナミドの間のアミド回転には,重要なエネルギー差があり,その構成上の好み,そして潜在的にその生物学的活動に影響を与えます.
- この研究は,これらのピリジンカルボキシアミドの詳細なエネルギープロファイルを提供し,関連する薬剤の設計に役立ちます.
さらに関連する動画
関連する概念動画
¹H NMR of Conformationally Flexible Molecules: Temporal Resolution
At room temperature, the chair conformer of cyclohexane undergoes rapid ring flipping between two equivalent chair conformers at a rate of approximately 105 times per second. These two chair conformers are in equilibrium. The rapid ring flipping results in the interconversion of the axial proton to an equatorial proton and an equatorial to the axial proton. Such interconversions are too rapid and cannot be detected on the NMR timescale. Hence, the NMR spectrometer cannot distinguish between the...
¹³C NMR: Distortionless Enhancement by Polarization Transfer (DEPT)
When proton-coupled carbon-13 spectra are simplified by a broadband proton decoupling technique, structural information about the coupled protons is lost. Distortionless enhancement by polarization transfer (DEPT) is a technique that provides information on the number of hydrogens attached to each carbon in a molecule. While the DEPT experiment utilizes complex pulse sequences, the pulse delay and flip angle are specifically manipulated. The resulting signals have different phases depending on...
¹H NMR Chemical Shift Equivalence: Enantiotopic and Diastereotopic Protons
Replacing each alpha-hydrogen in chloroethane by bromine (or a different functional group) yields a pair of enantiomers. Such protons are called prochiral or enantiotopic and are related by a mirror plane. Enantiotopic protons are chemically equivalent in an achiral environment. Because most proton NMR spectra are recorded using achiral solvents, enantiotopic hydrogens yield a single signal.
In chiral compounds such as 2-butanol, replacing the methylene hydrogens at C3 produces a pair of...
In chiral compounds such as 2-butanol, replacing the methylene hydrogens at C3 produces a pair of...
¹H NMR of Conformationally Flexible Molecules: Variable-Temperature NMR
The axial and equatorial protons in cyclohexane can be distinguished by performing a variable-temperature NMR experiment. In this process, except for one proton, the remaining eleven protons are replaced by deuterium. The deuterium substitution avoids the possible peak splitting caused by the spin-spin coupling between the adjacent protons. The remaining proton flips between the axial and equatorial positions.
NMR Spectroscopy Of Amines
In proton NMR spectroscopy, primary amines and secondary amines showcase their N–H protons as a broad signal in the chemical shift range between δ 0.5 and 5 ppm. The exact position in this range depends on several factors, including sample concentration, hydrogen bonding, and the type of solvent used. Since amine protons undergo fast proton exchange in solution, the protons are labile and therefore do not participate in any splitting with adjacent protons. Thus, the observed peak is broad and...
Other Nuclides: 31P, 19F, 15N NMR
Many organic, inorganic, and biological molecules contain spin-half nuclei such as nitrogen-15, fluorine-19, and phosphorus-31. As a result, NMR studies of these nuclei have found extensive applications in chemical and biological research.
While fluorine-19 and phosphorous-31 have high natural abundances (100%) and positive gyromagnetic ratios, nitrogen-15 has a low natural abundance and a negative gyromagnetic ratio. However, nitrogen-15 is still preferred over nitrogen-14 (which has a high...
While fluorine-19 and phosphorous-31 have high natural abundances (100%) and positive gyromagnetic ratios, nitrogen-15 has a low natural abundance and a negative gyromagnetic ratio. However, nitrogen-15 is still preferred over nitrogen-14 (which has a high...


