【作者】 庞涛涛；

【导师】 杜黎明；

【作者基本信息】 山西师范大学 ， 无机化学， 2015， 博士

【摘要】 杯芳烃作为第三代超分子主体化合物，凭着自身特殊的识别能力，近年来引起了众多科学家的广泛关注，并为构造新奇的主体化合物提供了很好的平台，它的空腔内还可以包合很多客体分子，形成了新的功能化目标分子。其中最重要的一类水溶性杯芳烃衍生物-磺化杯芳烃，结构更加富有柔性，在包合分子时会迎合分子尺寸而获得众多的包合物，本论文合成了三种常见的磺化杯芳烃，以此为基础，利用多种检测手段，研究了磺化杯芳烃和多种客体分子之间的包合行为，并探讨了包合物形成机理，并以此为契机，将磺化杯芳烃强包合作用拓展到毒性分子的包合上，为提高药物分子利用率和解毒功能提供了理论基础。本论文重点讨论以下几部分：第一部分简单阐述了超分子化学的发展史，讨论了杯芳烃及其杯芳烃上缘和下缘衍生物的研究进展，重点探讨磺化杯芳烃为主体的超分子识别阴离子、阳离子以及有机分子的进展，评价了这些主体化合物在分子识别和组装方面所取得的研究成果，同时提出了本论文研究的主要内容。第二部分选用2种不同N-取代的色氨酸衍生物：N-叔丁氧羰基-L-色氨酸和N-苯氧羰基-L-色氨酸，利用荧光滴定法系统研究了它们和3种磺化杯芳烃主体化合物的包合行为和包合模式，并提出叔丁基和苯基位阻效应的假设，运用1HNMR和密度泛函理论再次证实了包合机理，从主体空腔和客体结构探讨了分子选择性包合及它们的热力学起源，并且证明了荧光光谱数据所提出的假设是成立的。结果表明它们之间的包合均是由焓变引起的包合比为1:1的包合行为。根据两种客体结构中的不同官能团位阻的理论，叔丁基的位阻应该比苄基的大，按这样的理论N-叔丁氧羰基-L-色氨酸会比N-苄氧羰基-L-色氨酸与磺化杯芳烃的包合程度会弱得多，而荧光实验却得出完全相反的结论，N-叔丁氧羰基-L-色氨酸比N-苄氧羰基-L-色氨酸与磺化杯芳烃的荧光猝灭程度要强，那么包合程度自然也要强的多。这样我们提出了不可能在叔丁基和苄基部位进行包合，可能会是在其它基团部位发生包合的假设。在对热力学起源进行研究的过程中，磺化杯[n]芳烃可以更好的包合N-Boc-L-trp客体分子，这一客体选择性主要是由焓变所作的贡献。而磺化杯芳烃空腔尺寸并不一样，空腔尺寸越大，与客体之间的包合能力就越强，这是空腔匹配效应带来的结果，两种色氨酸衍生物客体与SCnA之间的包合常数随着主体空腔的增大而增大，主体选择性包合能力为：SC4A﹤SC6A﹤SC8A。第三部分利用制备好的磺化杯芳烃修饰电极，采用循环伏安法，扫描速度为0.1V/s，富集电压为+0.6V，对色氨酸进行了测定，对色氨酸分子识别最好的修饰电极为磺化杯[4]芳烃，其次是磺化杯[6]芳烃，最后是磺化杯[8]芳烃。线性范围为1×10-7～1×10-5mol·L-1，检出限为3×10-8mol·L-1，我们重点研究磺化杯[4]芳烃键合在金电极上对色氨酸的超分子电化学识别行为，为了更加清晰地了解色氨酸在磺化杯[4]芳烃键合的金电极上的电化学行为，通过扫描电镜，傅里叶变换红外光谱，循环伏安法等手段均获得磺化杯[4]芳烃修饰的半胱胺金电极是测定色氨酸的最佳基底。从电化学阻抗谱中获知磺化杯[4]芳烃修饰电极对色氨酸测定有着更低的检出限和更高的灵敏度。磺化杯[4]芳烃与色氨酸之间的键合作用比磺化杯[6]芳烃和磺化杯[8]芳烃之间的要强，究其原因，是由于空腔匹配效应和电荷作用以及疏水作用等相互作用而导致的结果，核磁实验证明SC4A空腔尺寸与色氨酸空间匹配效应是最好的，SC4A刚性结构正好满足了色氨酸分子可以进入其空腔内，而SC6A和SC8A结构比SC4A更柔韧，与分子键合时构象变化之多，反而不如后者结合稳定。同时色氨酸中的–NH2+与磺化杯芳烃的–SO3之间的电荷作用对它们的键合也起了必不可少的作用，这些影响直接导致SC4A和色氨酸之间的极化作用能力也提高，因而电化学阻抗也随之增强。第四部分采用电化学方法对秋水仙碱与磺化杯芳烃相互作用进行研究，磺化杯芳烃和秋水仙碱都具有电化学活性，而二者相互作用引起秋水仙碱峰电流下降，峰电位正移，说明二者形成的包合物并没有电化学活性，秋水仙碱的峰电流的降低值与加入的磺化杯[4]芳烃的浓度在一定范围内呈现良好的线性关系，测得二者之间的包合数为1，并且有很高的包结常数和低的检出限，通过紫外光谱的研究再次证实包结比为1:1，根据现象推测二者发生包合的部位可能是在苯基，并通过能量最低原理分子模型模拟结果得以验证。秋水仙碱的增溶实验和模拟细胞膜透过实验得出磺化杯[4]芳烃对秋水仙碱具有很好的增溶作用，并在十二烷基磺酸钠胶束的模拟细胞膜的实验中，得出秋水仙碱可以从磺化杯[4]芳烃和秋水仙碱的包合物中释放出来，并进入胶束疏水内部，由此推断磺化杯[4]芳烃可以考虑用作秋水仙碱的药物载体。第五部分将制备的三种磺化杯芳烃修饰电极分别测定L-酪氨酸，发现L-酪氨酸峰电流值有很明显的变化，氧化峰电位也随着空腔尺寸的变小，明显向更负的方向移动，降低了氧化峰电位，使得氧化过程更容易进行，能够加快酪氨酸在电极表面上的电子传递速率，电化学活性也随之增强。即该修饰电极对L-酪氨酸氧化反应的催化能力也在增强。通过实验分析该电极有着很好的选择性和稳定性，当用于测定不同pH下不同浓度的酪氨酸时，有着很好的线性范围、低的检测限和高的灵敏度，建立了一种准确、快速、灵敏的电化学测定酪氨酸的方法。通过荧光光谱以及核磁手段和计算模拟研究了磺化杯芳烃和酪氨酸的包合行为，实验结果表明，主体磺化杯芳烃分子和客体酪氨酸之间均是以1:1的化学计量比包合的，包合作用主要是来自于C-H…π或者π…π相互作用导致的有利的焓变所引起的，同时伴随着小的不利的熵变，同时，磺化杯芳烃空腔尺寸并不一样，空腔尺寸越大，磺化杯芳烃与客体之间的包合能力就越强，这是空腔匹配效应带来的结果，通过1HNMR结果推测，酪氨酸的苯酚单元进入了磺化杯[4]芳烃空腔内，酪氨酸客体分子穿插进入空腔内部，则磺化杯[6]芳烃可能以两种方式包合酪氨酸，而酪氨酸却以横卧的方式在磺化杯[8]芳烃空腔上部稳定存在。我们猜测在磺化杯芳烃修饰电极和酪氨酸之间的作用是外包合效应，而荧光光谱中的包合作用是内包合作用，由此看来，超分子主体对客体分子的包合方式会因体系的改变而改变。更多还原

【Abstract】 Calixarenes, as the third generation of host molecules, have attracted considerable attention in host-guest chemistry because of their excellent recognition ability. Calixarenes with specific functions have been studied extensively as a platform for constructing novel host compounds. These host molecules have a cavity-shaped structure that can hold a guest molecule and create specific affinity to a target molecule by introducing various functional groups. Studies have investigated p-sulfonated calix[n]arenes, which have flexible and often defined cavities that bind positively charged species. One of the most important water-soluble calixarene derivatives-sulfonated calixarenes, they will cater to the molecular size and access to many of the inclusion compound because of more flexible structure. We synthesized three kinds of p-sulfonated calixarenes and took this as the foundation and discussed the inclusion behavior and the inclusion complex formation mechanism between sulfonation calixarene and various guest molecules by means of various methods in this paper. Taking advantage of this strong inclusion ability, p-sulfonated calixarenes were used to the inclusion toxic molecules. The results show p-sulfonated calixarenes could improve the utilization rate ofdrug molecules and provide a theoretical basis for detoxificationfunction. This thesis focuses on following parts:The first part briefly discusses the history of supramolecularchemistry and the research progress of up and lower edge ofcalixarene and the calixarene derivatives. It focuses on thesupramolecular recognition progress of sulfonated calixarenes withthe cation, anion and organic molecules guest. It evaluated theresearch in the hosts with molecular recognition and assemblyaspects. At the same time, it put forward the main contents of thisthesis.The second part studies the inclusion behavior and bonding typeof two kinds of N-substituted derivatives of tryptophan:N-[(tert–butoxy) carbonyl]-tryptophan (N-Boc-L-trp) andN-carbobenzoxy\-tryptophan (Z-trp-OH) with three kinds of sulfonatedcalixarene host compounds by fluorescence titration system, and putforward the hypothesis of the tert butyl and phenyl steric effect.1HNMR and density functional theory results reconfirmed theinclusion mechanism. It discusses molecular selective inclusion andtheir thermodynamics origin from the cavity sizes of hosts andstructures of guests. It is proved that the hypothesis was true. Theresults show the inclusion behavior caused by the inclusion ratio of1:1and rise from enthalpy change. According to the steric hindrancetheory of the different functional groups, Steric hindrance of thetert-butyl group of N-[(tert–butoxy) carbonyl]-tryptophan should bebigger than the phenyl group of N-carbobenzoxy-tryptophan, then theinclusion degree of N-[(tert–butoxy) carbonyl]-tryptophan with sulfonated calixarene will be much weaker thanN-carbobenzoxy-tryptophan with sulfonated calixarene. But thefluorescent experiment reaches the opposite conclusion, Whensulfonated calixarenes add to the guests, the fluorescence quenchingof N-[(tert–butoxy) carbonyl]-tryptophan are much bigger thanN-carbobenzoxy-tryptophan. So the inclusion degree naturally ismuch stronger. We propose that the inclusion are impossiblehappened in the tert butyl and benzyl position, the inclusion may beoccur in other groups of the guest. From the investigation ofthermodynamic origin, p-sulfonated calix [n] arene intend to includeN-[(tert–butoxy) carbonyl]–tryptophan. The guest molecular selectivewas mainly determined by the enthalpy contribution. The cavity sizeof every sulfonated calixarene is not the same. The larger is the cavitysize, the stronger is the inclusion ability of sulfonated calixarene bycavity matching effect. The binding constant between SCnA host andtwo tryptophan derivatives guest increases with the increasing of thecavity of the hosts, the host selective inclusion capacity: SC4A <SC6A <SC8A.The third part depicts that the tryptophan were determined byprepared sulfonating calixarene modified electrode, using cyclicvoltammetry, scanning speed is0.1V/s, the enrichment of voltage of+0.6V, the best molecule recognition of the tryptophan wasp-sulfonated calix [4] arene, followed by p-sulfonated calix [6] arene,finally sulfonated calix [8] arene. The linear range is1×10-7～1×10-5mol·L-1, and the detection limit is3×10-8mol·L-1. In order to moreclearly understand the tryptophan electrochemical behavior onsulfonated calix[n]arene modified gold electrode, the next section focuses on the research of supramolecular electrochemicalrecognition of tryptophan behavior on a p-sulfonated calix[4]arenemodified gold electrode. From EIS results, SC4A-cysteamine-goldelectrode showed the highest sensitivity, in terms of variation of Zreal value versus tryptophan concentration. The proposed methodcan also be used to detect tryptophan in real samples withsatisfactory results. The higher tryptophan sensitivity of SC4Acompared with SC6A and SC8A can be explained by their differencesin SCnA structures. SC4A rigid structure just meet the tryptophanmolecules, and permit tryptophan enter the inner part of the cavity.While SC6A and SC8A structure is more flexible than the SC4A and themolecular conformation often changes as they interacted with otherguests, the interaction in the tryptophan–SC4A complex was morestabilized than that in the tryptophan-SC6A (SC8A) complex.Molecular modeling calculation reconfirmed EIS results and indicatedthat the electrostatic interaction and the structural matching effectwere the dominant stabilizing factors for the host-guest complexes ofthe tryptophan and SCnA. At the same time charge interaction onbonding between the tryptophan–NH2+and sulfonated calixarenes–SO3also plays an indispensable rolet. These effects directly lead topolarization ability between SC4A and the tryptophan also increasing,thus the electrochemical impedance increases.The fourth part discusses the interaction of sulfonatedcalixarenes with colchicine using the electrochemical methods.Results show sulfonated calixarenes and colchicine both haveelectrochemical activity. When they interacted, the peak currentdecreased and the peak potential shifted positively, the phenomenon show the complex has no electrochemical activity. The reductionvalue of the peak current of colchicine shows a good linearrelationship with increasing sulfonated calix [4] arene concentrationswithin a certain range which confirmed that the1:1ratio complexassembly formed. The results showed a wide linear concentrationrange, low detection limit and high selectivity. UV spectrum resultsreconfirmed the inclusion ratio of1:1and presumably the inclusionsite may be in the phenyl ring. It was verified through the simulationresults of the lowest energy molecular model. The sulfonated calix [4]arene has good effects on solubilization of colchicine through theexperiment of colchicine solubilization and simulated cell membraneexperiments. The colchicine can be released from the sulfonatedcalix [4] arene and colchicines complex in sodium dodecyl sulfonatemicelle simulated cell membrane experiments, and entered into themicellar’s hydrophobic interior, which considered as a drug carrierwith colchicine.The fifth part discusses three sulfonated calixarene modifiedelectrode will be prepared to determine L-tyrosine. Not only thecurrent peak has obvious differences, the oxidation peak potentialsobviously move to more negative direction with cavity size smaller.The oxidation peak potential reduces, which makes the oxidationprocess easier, thus the electrochemical activity increases withaccelerating tyrosine electron transport rate on the surface of theelectrode. The modified electrode shows good catalytic ability of L-tyrosine oxidation reaction. The electrode has good selectivity andstability for the determination of tyrosine, there is a good linear rangeand low detection limit and high sensitivity at different concentrations under different pH. It established an accurate, fast,sensitive electrochemical method for the determination of tyrosine.The fluorescence spectra and1HNMR methods and computersimulation discuss p-sulfonated calix[n]arenes and tyrosine inclusionbehavior. P-sulfonated calix[n]arenes and tyrosine are all in thestoichiometric ratio of1:1subject-guest inclusion. The inclusion ismainly favorable enthalpy change caused by C-H…π or π…πinteraction of the p-sulfonated calix[n]arenes and tyrosine,accompanied by the unfavorable entropy of small change. The largeris the size of the cavity, the stronger the inclusion ability betweenp-sulfonated calix[n]arenes and guest. According to the results of1HNMR and cavity matching effect, presumably, the phenol unit oftyrosine enter into p-sulfonated calix[4]arene cavity, and the guesttyrosine molecule vertically penetrate into the cavity of p-sulfonatedcalix[6]arene in two different inclusion ways, tyrosine stably exists bythe way of lying on p-sulfonated calix[8]arene upper cavity. In view ofthis, the inclusion way of sulfonated calixarenes modified electrodeand sulfonated calixarenes solution with guest tyrosine is different,and supramolecular inclusion mode will change because of thechange of system.更多还原