探索N-和C-甲基化N-乙化的构成效应
Lucas Silva Franco1,2, Marina Amaral Alves2,3, Carlos Mauricio R Sant'Anna1,2,4
1Laboratório de Avaliação e Síntese de Substâncias Bioativas (LASSBio), Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21941-902, Brazil.
ACS omega
|May 12, 2025
概括
甲基化显著影响N-酸 (NAH) 形状,从平面结构转变为非平面结构. 这项研究揭示了N-和C-甲基化如何影响NAH衍生物,影响其电子特性和潜在的生物应用.
科学领域:
- 有机化学 有机化学
- 药用化学 医学化学
- 计算化学计算化学
背景情况:
- 在化学和药物化学中,N-酸 (NAH) 被认为是特权结构.
- 了解NAH的结构偏好对于设计具有特定生物活动的分子至关重要.
研究的目的:
- 调查N-和C-甲基化对N-酸衍生物的构造效应.
- 分析甲基化对NAH结构电子特性和平面性的影响.
主要方法:
- 使用NMR光谱 (2D技术) 合成和对四种N-酸衍生物 (4-7) 的结构特征.
- 使用密度函数理论 (DFT) 计算的理论形态分析 (CAM-B3LYP/6-31+G(d,p),C-PCM溶解模型).
- 自然键轨道 (NBO) 分析,非共价相互作用 (NCI) 分析和粉末X射线衍射.
主要成果:
- 核磁共振 (NMR) 数据证实了 (E) -二基聚合物的排他性形成.
- DFT计算显示,N-甲基化诱导了从反平面向同平面的形状转移.
- 化合物7显示了两个符合性 (反和同) 和增加偏离平面性,这是由于甲基组的固体阻碍,破坏结合.
- NBO分析和NMR化学转移与电子密度变化相关.
- NCI分析和X射线衍射证实了观察到的形状趋势.
结论:
- 甲基化显著影响N-酸衍生物的形状偏好和电子性质.
- 甲基化的立体和电子效应改变NAH平面性和结合性.
- 这些发现对NAH化合物的生物活性和分子识别特性有影响.
相关概念视频
00:52¹H NMR of Conformationally Flexible Molecules: Temporal Resolution
784
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...
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01:15¹H NMR of Conformationally Flexible Molecules: Variable-Temperature NMR
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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.
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02:11Conformations of Cyclohexane
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Cyclohexane does not exist in a planar form due to the high angle and torsional strain it would experience in the planar structure. Instead, it adopts non-planar chair and boat conformations.
The chair form is the most stable and derives its name from its resemblance to the “easy chair.” In the chair conformation, two carbon atoms are arranged out-of-plane — one above and one below, minimizing the torsional strain. In the chair form, the bond angle is very close to the ideal...
The chair form is the most stable and derives its name from its resemblance to the “easy chair.” In the chair conformation, two carbon atoms are arranged out-of-plane — one above and one below, minimizing the torsional strain. In the chair form, the bond angle is very close to the ideal...
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02:18Conformations of Ethane and Propane
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In an organic molecule, free rotation about the carbon-carbon single bond results in energetically different conformers of the molecule. Due to this rotation, called the internal rotation, ethane has two major conformations — staggered and eclipsed.
Staggered conformation is a low energy and more stable conformation with the C-H bonds on the front carbon placed at 60°dihedral angles relative to the C-H bonds on the back carbon, leading to a reduced torsional strain. In staggered...
Staggered conformation is a low energy and more stable conformation with the C-H bonds on the front carbon placed at 60°dihedral angles relative to the C-H bonds on the back carbon, leading to a reduced torsional strain. In staggered...
13.6K
02:02Chair Conformation of Cyclohexane
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The chair conformation is the most stable form of cyclohexane due to the absence of angle and torsional strain. The absence of angle strain is a result of cyclohexane’s bond angle being very close to the ideal tetrahedral bond angle of 109.5° in its chair conformer. Similarly, the torsional strain is also absent owing to the perfectly staggered arrangement of bonds.
The hydrogen atoms linked to carbons are arranged in two different axial and equatorial orientations to achieve this...
The hydrogen atoms linked to carbons are arranged in two different axial and equatorial orientations to achieve this...
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02:29Conformations of Cycloalkanes
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Adolf von Baeyer attempted to explain the instabilities of small and large cycloalkane rings using the concept of angle strain — the strain caused by the deviation of bond angles from the ideal 109.5° tetrahedral value for sp3 hybridized carbons. However, while cyclopropane and cyclobutane are strained, as expected from their highly compressed bond angles, cyclopentane is more strained than predicted, and cyclohexane is virtually strain-free. Hence, Baeyer’s theory that...
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