阐明氨基电荷状态对多 (β-氨基) 降解的作用,使用永久电荷的类似物
Mara K Kuenen1, Keelin S Reilly2, Rachel A Letteri1
1Department of Chemical Engineering, University of Virginia, Charlottesville, Virginia 22903, United States.
ACS macro letters
|October 4, 2023
概括
聚β氨基 (PBAE) 的降解是依赖pH的. 合成聚β四元氨基 (PBQAEs) 揭示了脱质胺加速PBAE水解,为聚合物寿命提供了新的控制.
科学领域:
- 聚合物化学 聚合物化学
- 材料科学 材料科学 材料科学
- 生物材料工程 生物材料工程
背景情况:
- 聚β氨基 (PBAE) 具有可调性降解和pH依赖性质,使其在基因疗法和热凝等应用中具有价值.
- PBAE的pH取决于溶解率和水解率,由可质子胺控制,使预测性降解模型的开发复杂化.
- 了解控制PBAE降解的精确机制对于为特定应用量身定制它们的寿命至关重要.
研究的目的:
- 阐明聚合物电荷状态和溶液pH在聚β氨基 (PBAE) 降解中的不同作用.
- 为进行比较性降解研究,开发一类新型的聚合物,即具有pH独立的阴离子电荷的聚-β四元氨基 (PBQAEs).
- 确定影响PBAE水解速率的其他因素,超出溶液pH值.
主要方法:
- 合成聚-β-四方氨基 (PBQAEs) 通过修改PBAE结构以额外的甲基组来实现永久的阴阳电荷.
- 在各种pH条件下对PBAE和PBQAE进行比较的水解研究.
- 降解动力学的分析,以区分pH值和聚合物电荷对水解速率的影响.
主要成果:
- 无论是PBAE还是PBQAE,都表现出加快的水解与增加的pH.
- 在任何给定的pH值下,PBAE的降解速度比PBQAE更快,这种差异在基本条件下最为显著.
- 这些发现表明,PBAE中的脱胺氨基组积极加速水解过程,独立于散装溶液的pH.
结论:
- 在PBAE中氨基基群的存在和质子化状态显著影响其降解动力学.
- 脱胺胺作为PBAE水解的催化剂,为调整聚合物降解速率提供了额外的机制.
- 这项研究提供了对PBAE和其他pH敏感聚合物的降解机制的关键见解,为改进设计和应用铺平了道路.
更多相关视频
相关概念视频
01:21Basicity of Aliphatic Amines
5.9K
Amines can behave as Brønsted–Lowry bases by accepting a proton from the acid to form corresponding conjugate acids. Due to a lone pair of nonbonding electrons, aliphatic amines can also act as Lewis bases by forming a covalent bond with an electrophile.
To measure the basicity of amines, two conventions are generally used. The first defines Kb as the basicity constant for the deprotonation reaction of water by the amine, as presented in Figure 1. Conventionally, lower Kb indicates...
To measure the basicity of amines, two conventions are generally used. The first defines Kb as the basicity constant for the deprotonation reaction of water by the amine, as presented in Figure 1. Conventionally, lower Kb indicates...
5.9K
01:25Basicity of Heterocyclic Aromatic Amines
6.1K
Heterocyclic amines, where the N atom is a part of an alicyclic system, are similar in basicity to alkylamines. Interestingly, the heterocyclic amine having a nitrogen atom as part of an aromatic ring has much less basicity than its corresponding alicyclic counterpart. For this reason, as presented in Figure 1, piperidine (pKb = 2.8) is significantly more basic than pyridine (pKb = 8.8).
6.1K
01:28Amides to Carboxylic Acids: Hydrolysis
3.3K
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...
3.3K
01:19Amines to Amides: Acylation of Amines
2.5K
Various carboxylic acid derivatives (such as acid chlorides, esters, and anhydrides) can be used for the acylation of amines to yield amides. The reaction requires two equivalents of amines. The first amine molecule functions as a nucleophile and attacks the carbonyl carbon to produce a tetrahedral intermediate. This is followed by the loss of the leaving group and restoration of the C=O bond.
Next, the second equivalent of amine serves as a Brønsted base and deprotonates the quaternary...
Next, the second equivalent of amine serves as a Brønsted base and deprotonates the quaternary...
2.5K
01:18Basicity of Aromatic Amines
7.2K
The basicity of aromatic amines is much weaker than that of aliphatic amines due to the involvement of the lone pair of electrons over the N atom in resonance with the aryl rings. Generally, the electron-donating ability of any substituents on the aryl ring of aromatic amines increases the basicity of the amine by increasing electron density, and hence the availability of lone pair on the nitrogen. On the other hand, electron-withdrawing functional groups on the aryl ring of amines decrease the...
7.2K
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