基质DOTA衍生物的计算研究:对结构,稳定性和放松性的洞察
Niharika Keot1, Manabendra Sarma1
1Department of Chemistry, Indian Institute of Technology Guwahati, Assam 781039, India.
The journal of physical chemistry. A
|September 29, 2025
概括
分子动力学模拟表明,DOTA衍生物HMDOTA-SS和T为Gd3+化提供了增强的稳定性和更快的水交换,改善了MRI对比剂.
科学领域:
- 无机化学 无机化学 有机化学
- 计算化学计算化学
- 生物物理化学 生物物理化学
背景情况:
- 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) 是MRI对比剂中Gd3+化的一个关键配体.
- 了解带协调和稳定性对于开发先进的MRI药物至关重要.
研究的目的:
- 研究带有DOTA,HMDOTA-SS和T连接体的兰坦化物复合物的协调行为和热力学稳定性.
- 探索温度和连接物结构对复杂稳定性和水交换率的影响.
- 为了阐明影响MRI应用的零场分裂 (ZFS) 的磁结构相关性.
主要方法:
- 使用了经典和初始分子动力学模拟.
- 模拟在一个温度范围 (25,45,65°C) 的水溶液中进行.
- 分析包括辐射分布函数,结合能,水交换率 (kex298) 和零场分裂 (ZFS).
主要成果:
- 在SAP和TSAP异构体之间观察到温度依赖的变化,在更高的温度下稳定性增加与波动减少相关.
- 兰他尼德的收缩影响了辐射分布的功能.
- 绑定能量遵循了趋势[Ln(T) ]- > [Ln(HMDOTA-SS) ]- > [Ln(DOTA) ]-,表明T和HMDOTA-SS.的稳定性优越.
- HMDOTA-SS和T连接物加速了水交换率,这是由于固态阻碍和改变的旋转动力学.
- 增加Gd-O(w) 键长度调节轴向ZFS (D),特别是在水损失时.
结论:
- 与DOTA相比,T和HMDOTA-SS体表现出增强的热力学稳定性和有利的水交换特性.
- 连接体设计显著影响复杂的稳定性,水动力学和与MRI对比剂相关的电子放松.
- 这些发现为设计下一代高放松度MRI对比剂提供了宝贵的见解.
相关概念视频
02:30Chirality in Nature
16.7K
Chirality is the most intriguing yet essential facet of nature, governing life’s biochemical processes and precision. It can be observed from a snail shell pattern in a macroscopic world to an amino acid, the minutest building block of life. Most of the snails around the world have right-coiled shells because of the intrinsic chirality in their genes. All the amino acids present in the human body exist in an enantiomerically pure state, except for glycine - the sole achiral amino acid.
16.7K
02:05Prochirality
4.8K
The concept of prochirality leads to the nomenclature of the individual faces of a molecule and plays a crucial role in the enantioselective reaction. It is a concept where two or more achiral molecules react to produce chiral products. A typical process is the reaction of an achiral ketone to generate a chiral alcohol. Here, the achiral reactant reacts with an achiral reducing agent, sodium borohydride, to generate an equimolar mixture of the chiral enantiomers of the product. For example, an...
4.8K
02:33Stereoisomerism of Cyclic Compounds
10.9K
In this lesson, we delve into the role of ring conformation and its stability, which determines the spatial arrangement and, consequently, the molecular symmetry and stereoisomerism of cyclic compounds. 1,2-Dimethylcyclohexane is used as a case study to evaluate the possible number of stereoisomers. Here, given the multiple (n = 2) chiral centers, there are 2n = 4 possible configurations that lack a plane of symmetry, as the ring skeleton exists in a non-planar chair conformation. In addition,...
10.9K
02:24Properties of Enantiomers and Optical Activity
21.2K
It is essential to understand the difference between chiral and achiral interactions and the implications thereof in optical activity and their applications. Just as our feet, which are chiral, interact uniquely with chiral objects, such as a pair of shoes, but identically with achiral socks, enantiomers of a molecule exhibit different properties only when they interact with other chiral media. An example of a significant implication from this facet is the phenomenon known as optical activity,...
21.2K
02:30Stability of Substituted Cyclohexanes
14.7K
This lesson discusses the stability of substituted cyclohexanes with a focus on energies of various conformers and the effect of 1,3-diaxial interactions.
The two chair conformations of cyclohexanes undergo rapid interconversion at room temperature. Both forms have identical energies and stabilities, each comprising equal amounts of the equilibrium mixture. Replacing a hydrogen atom with a functional group makes the two conformations energetically non-equivalent.
For example, in...
The two chair conformations of cyclohexanes undergo rapid interconversion at room temperature. Both forms have identical energies and stabilities, each comprising equal amounts of the equilibrium mixture. Replacing a hydrogen atom with a functional group makes the two conformations energetically non-equivalent.
For example, in...
14.7K
01:28Stability of Conjugated Dienes
4.1K
Introduction
A comparison of the enthalpies of hydrogenation of dienes reveals that conjugated dienes release less heat on hydrogenation, rendering them more stable than their nonconjugated analogs.
A comparison of the enthalpies of hydrogenation of dienes reveals that conjugated dienes release less heat on hydrogenation, rendering them more stable than their nonconjugated analogs.
4.1K