胺基异构化途径:质子化和脱质子化介导的 cis-trans 相互转换的电子和结构背景
Ádám A Kelemen1,2, András Perczel1,3, Dániel Horváth1,3
1HUN-REN-ELTE Protein Modelling Research Group, Pázmány Péter sétány 1/A, H-1117 Budapest, Hungary.
The Journal of chemical physics
|October 16, 2023
概括
胺键的 cis-trans 异构化对于蛋白质折叠至关重要. 这项研究揭示了N-质子化胺的低能途径,通过水辅助的质子转移实现 cis-trans 转换.
科学领域:
- 计算化学的计算化学
- 生物物理学的生物物理.
- 蛋白质折叠的动态 蛋白质折叠的动态
背景情况:
- 氨基酸键的Cis-trans异体化显著影响蛋白质的结构和功能.
- 这种异质化可能是蛋白质折叠的速度限制步骤.
- 这种cis同位素虽然不太稳定,但在生物聚合物功能中起着至关重要的作用.
研究的目的:
- 为了研究N-甲基胺·2H2O分子系统中cis-trans异构化的能量.
- 为了阐明氨基酸键异构化的反应途径和能量障碍.
- 解释质子化状态和水分子在促进异构化中的作用.
主要方法:
- 使用结合集群单双和结合集群单双和扰乱三重 [CCSD(T] 方法进行高级理论计算.
- 确定各种胺质子状态的全部潜在能量表面f{\displaystyle f} ,ω,α) .
- 对临界点和异构化反应路径的分析.
主要成果:
- 对于中性,O-质子和N-脱质子的胺,发现了高的同质化障碍 (∼85-140 kJ mol-1),防止室温相互转换.
- 对于N-质子化胺,cis形式是最大的,具有低能量障碍 (<10kJ mol-1).
- 确定了一种新的低能途径,涉及从O-到N-质子化位点的水辅助质子转移,使转→ cis异构化能够实现,能量成本≤11.6kJ mol-1.1.
结论:
- 异构酶酶可能利用质子化胺键来促进cis-trans异构化.
- 键的N-质子化可能通过一个初始的O-质子化步骤发生,由水分子介导.
- 了解这些机制,可以了解酶催化和蛋白质动态.
相关概念视频
01:28Amides to Carboxylic Acids: Hydrolysis
3.2K
Amides can undergo either acid-catalyzed hydrolysis or base-promoted hydrolysis through a typical nucleophilic acyl substitution. Each hydrolysis requires severe conditions.
Acid-catalyzed hydrolysis:
Hydrolysis of amides under acidic conditions yields carboxylic acids. Since the reaction occurs slowly, hydrolysis requires the conditions of heat.
The mechanism begins with the protonation of the carbonyl oxygen by the acid catalyst. The protonation makes the amide carbonyl carbon more...
Acid-catalyzed hydrolysis:
Hydrolysis of amides under acidic conditions yields carboxylic acids. Since the reaction occurs slowly, hydrolysis requires the conditions of heat.
The mechanism begins with the protonation of the carbonyl oxygen by the acid catalyst. The protonation makes the amide carbonyl carbon more...
3.2K
01:29Preparation of Amides
3.0K
Amides are synthesized by treating carboxylic acids with amines in the presence of dehydrating agents like dicyclohexylcarbodiimide (DCC).
The DCC-promoted synthesis of amides begins with the protonation of DCC by carboxylic acid. The protonation makes it a better acceptor. Next, the addition of carboxylate to the protonated carbodiimide gives a reactive acylating agent.
Subsequently, the amine acts as a nucleophile that attacks the acylating agent to form a tetrahedral intermediate. In the...
The DCC-promoted synthesis of amides begins with the protonation of DCC by carboxylic acid. The protonation makes it a better acceptor. Next, the addition of carboxylate to the protonated carbodiimide gives a reactive acylating agent.
Subsequently, the amine acts as a nucleophile that attacks the acylating agent to form a tetrahedral intermediate. In the...
3.0K
01:07Preparation of 1° Amines: Hofmann and Curtius Rearrangement Overview
3.2K
In the presence of an aqueous base and a halogen, primary amides can lose the carbonyl (as carbon dioxide) and undergo rearrangement to form primary amines. This reaction, called the Hofmann rearrangement, can produce primary amines (aryl and alkyl) in high yields without contamination by secondary and tertiary amines.
3.2K
01:23Aldehydes and Ketones with Amines: Imine Formation Mechanism
5.7K
Imine formation involves the addition of carbonyl compounds to a primary amine. It begins with the generation of carbinolamine through a series of steps involving an initial nucleophilic attack and then several proton transfer reactions. The second part includes the elimination of water, as a leaving group, to give the imine.
Imines are formed under mildly acidic conditions. A pH of 4.5 is ideal for the reaction.
If the pH is low or the solution is too acidic, the reaction slows down in the...
Imines are formed under mildly acidic conditions. A pH of 4.5 is ideal for the reaction.
If the pH is low or the solution is too acidic, the reaction slows down in the...
5.7K
01:19Structure of Amines
2.6K
The hybridized nitrogen atom in amines possesses a lone pair of electrons and is bound to three substituents with a bond angle of around 108°, which is less than the tetrahedral angle of 109.5°. However, the C–N–H bond angle is slightly larger at 112°, with a carbon–nitrogen bond length of 147 pm. This carbon–nitrogen bond length of of amines is longer than the carbon–oxygen bond of alcohols (143 pm) but shorter than alkanes’...
2.6K
01:07Acid Halides to Amides: Aminolysis
2.8K
Aminolysis is a nucleophilic acyl substitution reaction, where ammonia or amines act as nucleophiles to give the substitution product. Acid halides react with ammonia, primary amines, and secondary amines to yield primary, secondary, and tertiary amides, respectively.
In the first step of the aminolysis mechanism, the amine attacks the carbonyl carbon of the acyl chloride to form a tetrahedral intermediate. In the second step, the carbonyl group is re-formed with the elimination of a chloride...
In the first step of the aminolysis mechanism, the amine attacks the carbonyl carbon of the acyl chloride to form a tetrahedral intermediate. In the second step, the carbonyl group is re-formed with the elimination of a chloride...
2.8K