基于核磁共振各向异性参数测定的肽液晶定向介质及其应用

NMR anisotropic parameters (including Residual dipolar coupling, RDC, Residual chemical shift anisotropy, RCSA, Residual quadrupolar coupling, RQC) have recently become dramatically important in the structural elucidation of small organic molecules due to their unique exceptionally valuable spatial and globe structural information which cannot be obtained from J-couplings and ONE from solution NMR. However, a remaining bottleneck limiting its wider use by organic and natural product chemists is the lack of a range of easily applicable aligning media for diverse organic solvents. So far, there are very few alignment media compatible with organic solvents. To address this subject, based on our previous works, we wondered whether functional peptides self-assembly liquid crystals would allow for the orientation of organic molecules and the discrimination of its enantiomers. Thus, we will search for a member of a new class of peptides bearing a phe-phe fragment due to the unit easily induces aggregation, also develop helical polyisocyanopeptides to achieve low critical concentrations and high flowability, which induced by amino acids moiety capable of forming chiral liquid crystalline phases for enantiodifferentiating. The liquid crystalline phase can be observed at lower concentrations and the completeness of the phase transition will be judged from the deuterium NMR signals. Then, we will get these kinds of functional peptides liquid crystals that are expected to be characterized by low critical concentrations, broad analytes and solvents compatibly, induced degree of order adjustable and for the compound in question and enantiodifferentiating properties. Furthermore,some well know natural produces stuctures such as Artemether will be selected as analytes to study the properties of the alignment media. To evaluate the precision and accuracy of the alignment for RDC, these parameters will be extracted by using various NMR pulses such as CLIP-HSQC, and back calculated by using the program package Mspin compare to its X-ray structures. Then the successful method of the structural analysis allows us to extend the applications to some unsolved structures. In addition, the enantiodifferentiating properties of the media also evaluated by RDC, RSCA and RQC..In a word, this ongoing study will enrich the alignment media and play an important role in expanding the applications of NMR anisotropic parameters analysis and liquid crystals NMR technology for organic molecules and have significant values in theory and application.

核磁共振各向异性参数(RDC,RCSA,RQC)携带丰富的立体结构信息，反映溶液NMR经典参数J耦合、NOE所无法展示的全局空间关系，实现分子的构型、构象分析。但是，在有机溶剂中对其检测依然是难点。本项目根据肽骨架形成液晶临界浓度低，改性位点丰富的特性，拟通过合成不同基团取代的寡肽和聚异腈肽高分子，并筛选其在各种有机溶剂中形成液晶，以氘核NMR检测形成液晶的临界浓度并评价定向排列能力，以期获得临界浓度低，分析底物兼容广，溶剂极性范围宽，定向程度可控的介质。然后以蒿甲醚等已知天然产物模式分子为参考对象，通过各种脉冲序列检测RDC并以Mspin软件计算，与晶体结构进行比较，评价检测的精度和优劣。继而开展对难于确定结构的天然产物进行解析，同时对RDC,RCSA与RQC在手性介质中的识别能力进行测定与评价。本项目的实施将实现有机分子NMR各向异性参数的简易检测，对有机分析具有较大的理论与应用价值。

核磁共振各向异性参数（RDC，RCSA，RQC）提供丰富的原子分辨率的空间结构信息，在分子结构表征中发挥重要作用。但是，缺乏检测的分析定向介质，其应用受到了严重的限制。本项目通过设计、合成不同基团改性的寡肽和聚肽高分子，并筛选其在各种有机溶剂中组装形成溶致液晶，以2H(氘核) NMR检测形成溶致液晶的最低浓度和评价定向排列能力，以期获得临界浓度低，分析底物兼容强，溶剂极性可调节，定向角度可控的溶致液晶定向介质。随后，以蒿甲醚，山道年，赤霉素等天然产物为分析对象，通过各种脉冲序列检测RDC，并以Mspin软件计算，建立基于RDC立体化学的分析方法。继而开展对难于确定结构的天然产物进行解析，同时对RDC的手性介质的相应效益进行研究。通过项目的开展，获得了多种新型的寡肽液晶定向介质，临界浓度低，背景信号弱，测定精度高，具有一定手性识别的液晶定向介质，并被用于若干天然产物的结构解析。.在JACS，德国应用化学，Chemical Science，Organic Letters, Chem. Commun.，MRC等期刊上发表系列成果，培养学生多名，组织一个核磁共振新技术国际学术研讨会，并在多个全国学术会议上交流汇报工作，多个技术培训班上进行授课。这个项目的开展，推动和加速核磁共振各向异性参数在我国的应用并推动这个领域的研究进程。.