手性TN双自由基的设计合成及动态核极化性能研究

发布时间：2018-06-27 21:28

本文选题：双自由基 + 电子顺磁共振　；参考：《天津医科大学》2017年硕士论文

【摘要】：目的:近年来,由三芳基甲基(trityl,T)自由基和氮氧(nitroxide,N)自由基组成的一类杂化型TN双自由基受到了广泛关注。该类双自由基具有独特的物理化学性质,在诸多领域呈现很强的应用前景,如生物分子结构领域的自旋标记物,氧化还原探针以及动态核极化(DNP)试剂等。DNP是一种增强核磁共振灵敏性的有效方法,结合魔角旋转固态核磁技术已被广泛应用于膜蛋白质、淀粉样蛋白、功能化多孔材料和纳米颗粒等的结构动力学研究。类似于氮氧双自由基,TN双自由基的自旋-自旋相互作用是其最重要的理化性质之一,也是决定其DNP性能的关键因素。诸多研究表明,双自由基的自旋-自旋相互作用受多因素影响,如两自旋电子间连接链的属性(长度、刚柔性),自由基部分的构象,环境因素(温度、溶剂)等。因此,理论上可通过改变上述条件调控TN双自由基的自旋-自旋相互作用强弱,进而开发性能更佳的TN双自由基,增强其应用潜质。本人所在的课题组在TN双自由基的自旋-自旋相互作用调控及其高场DNP应用方面已经开展了深入研究,提出了调控其自旋-自旋相互作用的两种方法:1)改变两个自由基之间连接链的属性;2)TN双自由基与环糊精之间的主-客体超分子相互作用。在本工作中,我们阐述了利用自由基的手性调控TN双自由基自旋-自旋相互作用强弱的方法,并研究了自旋-自旋相互作用强弱对DNP性能的影响。方法:本课题首先以L-脯氨酸和外消旋化合物2,2,5,5-四甲基-3-氨基-吡咯烷-1-氧自由基为原料通过酰胺缩合得到两个非对映异构体NP1和NP2;光学纯氮氧自由基NP1和NP2与外消旋trityl自由基(CT-03,M/P构型)共价偶联后分别得到双自由基的两个非对映异构体混合物TNT和TNL。采用制备HPLC方法得到了TNT的两个光学纯非对映异构体TNT_1和TNT_2。随后,采用EPR技术研究了温度和溶剂对TNT和TNL及TNT_1和TNT_2的自旋-自旋相互作用的影响,用于揭示氮氧自由基和trityl自由基部分对其交换相互作用的影响。在此基础上,进一步考察了TNT和TNL的手性对其DNP增强性质的影响。结果:合成得到了双自由基的两个非对映异构体混合物TNT和TNL;TNT经HPLC制备分离得到了相应的两个非对映异构体TNT_1和TNT_2。采用上述方法研究了双自由基TNT和TNL及TNT_1和TNT_2的手性对其自旋-自旋相互作用的影响,也考察了TNT和TNL的手性对其DNP增强性质的影响。研究结果表明:1)室温条件下,双自由基TNT和TNL的EPR谱图呈现较大差别;EPR谱图模拟表明,TNT可用单组分进行模拟,其交换相互作用(J)为421 G;相反,TNL仅能通过双组分进行模拟,其J值分别为12 G(88%)和171 G(12%);2)溶剂对双自由基TNT和TNL的自旋交换相互作用有显著影响,且双自由基的交换相互作用与溶剂的介电常数呈负相关;3)温度对双自由基TNT和TNL的自旋-自旋相互作用影响较大,低温下TNT和TNL有相似的偶极相互作用,但交换相互作用明显不同;4)TNT_1和TNT_2的自旋-自旋相互作用存在一定差异,温度及溶剂对其自旋-自旋相互作用有适度影响;5)双自由基TNT和TNL的DNP增强效果展现出明显不同,表明相对弱的自旋-自旋相互作用有利于DNP增强效应。结论:1)TNT和TNL的差异证实氮氧自由基部分的手性对TN双自由基自旋-自旋相互作用及DNP增强有显著影响;2)TNT_1和TNT_2的对比研究证明trityl自由基部分的M/P构型对其自旋-自旋相互作用的影响较小;3)研究还证实双自由基太强的交换相互作用对双自由基的DNP增强效果不利。该研究对双自由基自旋-自旋相互作用的调控及开发性能更佳的DNP极化试剂提供了新思路和新方法,有望拓展TN双自由基在磁共振和磁性材料领域的潜在应用。
[Abstract]:Objective: in recent years, a class of hybrid TN double radicals, composed of three aryl methyl (trityl, T) free radicals and nitroxide (N) free radicals, has been widely concerned. This kind of double radical has unique physical and chemical properties, and presents a strong application foreground in many fields, such as spin markers in the field of biomolecular structure, redox The probe and the dynamic nuclear polarization (DNP) reagents, such as.DNP, are an effective method to enhance the sensitivity of nuclear magnetic resonance. The solid-state nuclear magnetic technique combined with the magic angle rotation has been widely used in the structural dynamics of membrane protein, amyloid, functionalized porous materials and nanoparticles. It is similar to the double radicals of nitrogen oxygen and the spin of the TN double radical. Spin interaction is one of the most important physical and chemical properties and a key factor in determining its DNP properties. Many studies have shown that the spin spin interaction of the double radicals is influenced by many factors, such as the properties of the two spin electrons (length, rigid flexibility), the conformation of the free radical part, the environmental factors (temperature, solvent), etc. In view of the above conditions, the spin spin interaction of TN double radicals can be regulated by changing the above conditions, and then the TN double radical with better performance can be developed to enhance the potential of its application. The research group I was located in the spin spin interaction of the TN double free radical and the high field DNP application side have been studied in depth, and the regulation and control have been put forward. Two methods of spin spin interaction: 1) change the properties of the chain between the two free radicals; 2) the interaction between the principal guest supramolecular interaction between the TN double radical and the cyclodextrin. In this work, we expound the method of using the chiral radicals to regulate the spin spin interaction of the TN double radicals and study the spin self. The effect of spin interaction strength on the performance of DNP. Methods: first of all, two non enantiomers NP1 and NP2 were obtained by amidation of L- proline and racemic compound 2,2,5,5- four methyl -3- amino pyrrolidine -1- oxygen radical, and optical pure nitrogen oxygen free radical NP1 and NP2 and racemic trityl free radical (CT-03, M/P configuration). Two non enantiomer mixtures TNT and TNL. with double free radicals were obtained after valence coupling, and two optically pure non enantiomers TNT_1 and TNT_2. were obtained by HPLC method. The effects of temperature and solvent on the spin self spin interaction of TNT and TNL, TNT_1 and TNT_2 were investigated by EPR technology, which was used to reveal the nitrogen and oxygen self. The effects of the radical and trityl radicals on their exchange interactions. On this basis, the effects of the chirality of TNT and TNL on their DNP enhancement properties were further investigated. Results: the synthesis of two non enantiomer mixtures of TNT and TNL with double radicals was synthesized, and TNT was separated by HPLC to obtain the corresponding two non enantiomers TNT_1 and TNT_2. has been used to study the effects of the chiral on the spin spin interaction of the two free radicals TNT and TNL, TNT_1 and TNT_2, and the effect of the chirality of TNT and TNL on its DNP enhancement. The results show that: 1) the EPR spectra of the dual radicals TNT and TNL are quite different at room temperature; EPR spectrum simulation shows that A single component is used to simulate the exchange interaction (J) is 421 G; on the contrary, the TNL can only be simulated by two components, and the J values are 12 G (88%) and 171 G (12%); 2) the solvent has a significant influence on the spin exchange interaction of the double free radical TNT and TNL, and the exchange interaction of the double radicals is negatively correlated with the dielectric constant of the solvent; 3) temperature The spin spin interaction of two free radicals TNT and TNL has great influence. At low temperature, TNT and TNL have similar dipole interactions, but the exchange interaction is obviously different. 4) there is a certain difference in spin spin interaction between TNT_1 and TNT_2, temperature and solvent have a moderate effect on its spin spin interaction; 5) D of TNT and TNL of double free radicals. The enhanced effect of NP shows a distinct difference, indicating that the relatively weak spin spin interaction is beneficial to the DNP enhancement effect. Conclusion: 1) the difference between TNT and TNL confirms that the chirality of the nitrogen and oxygen radicals has a significant influence on the spin spin interaction of the TN double radicals and the enhancement of DNP; and the contrast between TNT_1 and TNT_2 proves M/ of the trityl radical part. The P configuration has little effect on its spin spin interaction; 3) the study also confirmed that the strong exchange interaction of the double radicals is unfavorable to the DNP enhancement of the double radicals. This study provides new ideas and new methods for the regulation of spin spin interaction of the double radicals and the better development of DNP polarization reagents. It is expected to expand the TN double self. Potential applications in the field of magnetic resonance and magnetic materials.
【学位授予单位】：天津医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O621.146

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