溶剂效应和取代基效应对2-(2-氨基苯基)苯并噻唑光谱性质及激发态分子内质子转移的影响

合成了多种2-(2-氨基苯基)苯并噻唑(APBT)氨基氢原子被供电子及吸电子基团取代的衍生物, 并用紫外光谱﹑荧光光谱等方法和密度泛函理论(DFT)计算研究了溶剂效应和取代基效应对衍生物的光谱性质及激发态分子内质子转移(ESIPT)的影响规律. 结果表明, 相比于非极性溶剂环己烷, 随溶剂极性的增加及APBT-溶剂分子间氢键的形成, APBT的紫外-可见最大吸收峰和荧光最大发射峰均发生了一定程度的红移, 并对APBT的ESIPT产生了影响. 在APBT分子的氨基氮原子上引入不同的吸电子或斥电子取代基, 对氮原子的电荷性质有较大的影响. 在环己烷溶剂中, 甲基取代后的APBT仅有单重荧光发射峰, 体系未发生ESIPT过程; 而COCH₂Cl等吸电子基团能促进APBT的ESIPT, 其荧光发射光谱出现了明显的双重峰, 表明体系发生了激发态分子内质子转移反应. 量子化学的理论计算较好地验证了光谱实验结果.     

纳米腔限制环境下2-(2-羟苯基)苯并噻唑的质子转移

采用稳态和瞬态荧光法对2-(2-羟苯基)苯并噻唑(HBT)与七元瓜环(CB7)的超分子作用及CB7分子纳米腔限制作用对HBT激发态质子转移(ESIPT)过程进行了研究,并采用Benesi-Hildebrand方程对荧光数据进行处理,以确定超分子复合物的组成比.结果表明,在N,N-二甲基甲酰胺(DMF)和二氯甲烷溶液中,CB7与HBT的作用均形成化学计量比为1∶1的主客体复合物,HBT的质子转移对溶剂很敏感,CB7的加入,使HBT的荧光寿命降低,量子产率增大.在DMF溶液中,CB7的加入促进了酚氧负离子的形成,而在二氯甲烷溶液中,CB7的加入限制了HBT的激发态质子转移.结构优化计算表明,CB7与HBT能形成化学计量比为1∶1的复合物.     

七元瓜环纳米腔限制环境下2-(3-乙酰胺基-2-吡啶基)苯并咪唑的激发态质子转移

以荧光发射光谱,1H NMR谱及量子化学计算研究了2-(3-乙酰胺基-2-吡啶基)苯并咪唑(2-3Am2PyBI)质子转移过程及其与七元瓜环超分子(CB7)的包合作用,考察了乙酰基取代基效应及CB7的包合作用对2-3Am2PyBI质子转移过程的影响.结果表明:乙酰基取代促进了质子转移过程;2-3Am2PyBI阳离子构型更易与CB7发生包合作用;在特定溶液pH值条件下,摩尔比法荧光光谱实验表明超分子包合作用抑制了2-3Am2PyBI的激发态质子转移过程;Benesi-Hildebrand方程拟合得到,超分子体系的包合比为1∶1;1H NMR测试进一步表明2-3Am2PyBI以苯环部分进入CB7的空腔,同时,以量化计算与荧光实验结合,从理论与实验方面共同验证了2-3Am2PyBI的质子转移异构体.     

八元瓜环超分子作用下2-(2-氨基-3-吡啶基)苯并咪唑的质子转移

利用荧光发射光谱、 紫外吸收光谱和核磁共振氢谱(¹H NMR)研究了八元瓜环(CB8)与2-(2-氨基-3-吡啶基)苯并咪唑(2-A3PyBI)的超分子相互作用及其对2-A3PyBI分子内质子转移过程的影响. 结果表明, 在水溶液中2-A3PyBI具有双重荧光发射峰, 分别对应其2种质子转移异构体. 固定pH值下的荧光滴定实验表明主客体包合比为1:2, 2-A3PyBI进入CB8空腔后促进了其分子内激发态质子转移过程. 同时, ¹H NMR结果表明2-A3PyBI的苯环部分进入了CB8空腔.     

光谱法研究七元瓜环作用下2-(2-羟苯基)咪唑并[1,2-a]吡啶的质子转移

采用荧光发射光谱法、瞬态荧光光谱法和紫外-可见光谱法考察了七元瓜环(CB7)与2-(2-羟苯基)咪唑并[1,2-a]吡啶(HPIP)的相互作用,结果表明二者发生了相互作用.瞬态荧光光谱结果表明,CB7的加入使荧光寿命下降而量子产率逐渐增加,在1,4-二氧六环溶液中,CB7的加入限制了HPIP的质子转移过程,而在环己烷溶液中则有利于HPIP的激发态质子转移.采用Benesi-Hildebrand方程对所测数据进行了线性拟合,结果表明形成了化学计量比为1∶1的复合物.     

一个新的七元环吡咯-吡啶氢键分子激发态分子内质子转移的理论研究

运用含时密度泛函理论(TD-DFT)方法和以环己烷为溶剂的可极化连续模型(PCM),研究了2-[2-(1 H-pyrrol-2-yl)-cyclopent-1-enyl]-pyridine(7-HB)发生激发态分子内质子转移(ESIPT)的反应机制.结果表明,7-HB分子被光激发到Franck-Condon区域后,在第一光学亮态(S_1)上会发生一个超快的从Normal(N)式到Tautomer(T)式的质子转移反应,其反应的能垒仅有0.05eV.此外,在相同计算水平下,还研究了7-HB分子的吸收和发射光谱,所得结果与实验数据吻合得很好.     

2-(2-氨基苯基)苯并噻唑与四苯基卟啉及四苯基锌卟啉的荧光共振能量转移

采用紫外光谱和荧光光谱法研究了四氢呋喃溶液中2-(2-氨基苯基)苯并噻唑(APBT)与四苯基卟啉(TPP)、四苯基锌卟啉(ZnTPP)之间的相互作用。结果表明,APBT可作为能量供体分子分别与能量受体分子TPP或ZnTPP构成荧光共振能量转移(FRET)体系,APBT的作用将使TPP和ZnTPP的荧光增强。在此FRET体系中,APBT与TPP及ZnTPP作用的分子结合比分别为2∶1和3∶1,能量转移效率分别为0.180 3和0.137 5,能量转移临界距离分别为3.76和3.44 nm,供体-受体分子间距离分别为4.31和3.88 nm。     

2-(3-巯基-2-吡啶基)苯并咪唑分子内质子转移及溶剂化效应

在B3LYP/6-31G(d,p)和TD B3LYP/6-31++G(d,p)//CIS/6-31G(d,p)水平上,研究了2-(3-巯基-2-吡啶基)苯并咪唑(MPyBI)在气相和七种溶剂(环己烷、苯、三氯甲烷、乙醇、乙腈、二甲亚砜和水)中基态和激发态的分子内质子转移(GSIPT和ESIPT)过程.在基态势能面的研究中发现,该化合物存在分子内双质子转移,其中分步的双质子转移在动力学上具有优势.同时对激发态质子转移势能面及激发态转移过程中的光物理现象进行了研究,结果表明该化合物存在快速的无能垒的激发态分子内质子转移,随着溶剂极性的增强,可以降低基态过渡态的能垒,改变硫醇式与硫酮式互变异构体的比例,从而灵敏地控制荧光的强度.     

生色团连接的苯骈三氮唑衍生物的激发态分子内质子转移

用从头算和密度泛函理论研究了对硝基二苯乙烯作为生色团连接的2-(2-羟基-苯基)-苯骈三氮唑的衍生物2-羟基-5-[对硝基-二苯乙烯基-氧亚甲基]-苯基-(2H-苯骈三氮唑)(C1)和4′-硝基-3,4-二[2-羟基-(2H-苯骈三氮唑)-苄氧基]-二苯乙烯(C2)发生激发态分子内质子转移(ESIPT)的可能性.系统研究了C1和C2发生ESIPT的互变异构体的基态与激发态的性质变化,包括相关的键长、键角等结构参数,Mulliken电荷和偶极矩,前线轨道以及势能曲线.计算结果表明,对于C1来讲,酮式(keto)的基态(K)不存在稳定结构,因此发生基态分子内质子转移(GSIPT)可能性很小.酮式的激发态(K*)的氢键强度要远强于烯醇式(enol)的激发态(E*)的氢键强度.分子在光致激发后,质子供体所带负电荷减小而质子受体所带负电荷增加.在K*,HOMO→LUMO的电子跃迁导致电子密度从"酚环"向质子化杂环转移.E*→K*跃迁只需要克服较小的能垒(约41 kJ.mol-1).计算结果表明C1发生ESIPT的可能性很大.C2由于具有高能量,其具有基态的单质子转移特征的异构体EK(同时含烯醇E与酮K结构)、具有基态的双质子转移特征的异构体2K(含有双酮结构),以及具有双酮结构特征的激发态2K*均无法获得它们的稳定结构,因此,基态分子内单或双质子转移和激发态分子内双重质子转移发生的可能性极小.然而,由于双烯醇式的激发态(2E*)和EK的激发态(EK*)存在稳定结构,且2E*→EK*跃迁具有低能垒,因此C2有可能发生激发态分子内单重质子转移.本文进一步计算了两个分子的紫外-可见吸收光谱与荧光发射光谱,获得了具有较大斯托克位移的ESIPT的荧光发射峰.     

盐酸巴马汀与葫芦[7]脲的相互作用及荧光增敏机理探讨

采用荧光光谱法和核磁共振技术(1H NMR)研究了葫芦[7]脲(CB[7])与盐酸巴马汀(PAL)之间的超分子作用,无荧光的CB[7]可以与弱荧光的PAL相互作用形成1∶1的主客体包结配合物,同时产生强大的荧光发射,其包结稳定常数K=1.18×105 L.mol-1。热力学常数△G、△H和△S计算结果说明反应是焓变驱动。分子模型通过高斯密度泛函理论计算。在能量最小化结构中,PAL分子中含甲氧基的异喹啉部分进入CB[7]的疏水空腔,形成内包结物。苯环和异喹啉环的二面角从23.37°变为-8.09°。从而确定了PAL在CB[7]存在下产生强大的荧光发射的主要因素。此外,1H NMR研究和分子模型计算推导出了主客体之间相互作用的机理,确定了包结配合物的形成过程。     

A Cucurbit[8]uril 2:2 Complex with a Negative pKa Shift

A viologen derivative carrying a benzimidazole group ( V-P-I ²⁺; viologen–phenylene–imidazole V-P-I ) can be dimerized in water using cucurbit[8]uril (CB[8]) in the form of a 2:2 complex resulting in a negative shift of the guest pK_a, by more than 1 pH unit, contrasting with the positive pK_a shift usually observed for CB-based complexes. Whereas 2:2 complex protonation is unclear by NMR, silver cations have been used for probing the accessibility of the imidazole groups of the 2:2 complexes. The protonation capacity of the buried imidazole groups is reduced, suggesting that CB[8] could trigger proton release upon 2:2 complex formation. The addition of CB[8] to a solution containing V-P- I ³⁺ indeed released protons as monitored by pH-metry and visualized by a coloured indicator. This property was used to induce a host/guest swapping, accompanied by a proton transfer, between V-P-I ³⁺ ⋅ CB[7] and a CB[8] complex of 1-methyl-4-(4-pyridyl)pyridinium. The origin of this negative pK_a shift is proposed to stand in an ideal charge state, and in the position of the two pH-responsive fragments inside the two CB[8] which, alike residues engulfed in proteins, favour the deprotonated form of the guest molecules. Such proton release triggered by a recognition event is reminiscent of several biological processes and may open new avenues toward bioinspired enzyme mimics catalyzing proton transfer or chemical reactions.     

Proton transfer in hydrogen-bonded pyridine/acid systems: the role of higher aggregation

In this work the role of higher molecular aggregation in the proton transfer processes within hydrogen bond (H-bond) is investigated. The H-bonded complex consisting of 4-cyanopyridine (CyPy) with trichloroacetic acid (TCA) has been studied in the solutions of acetonitrile, carbon tetrachloride, chloroform and dichloroethane as solvent by FTIR spectroscopy and quantum chemical DFT calculations. In order to illustrate the effect of increasing H-bond strength FTIR investigations have also been performed on solutions of CyPy with H(2)O, acetic-, trifluoroacetic- and methanesulfonic acids. Proton states in the H-bond have been monitored using vibrational CyPy ring modes in FTIR spectra. The stabilization of the CyPy/TCA complex in its protonated form upon increasing polarity of the solvent has been evidenced. It was shown that formation of the CyPy/(TCA)(2) aggregates in the solutions favors the proton transfer process. An X-ray diffraction study has been performed on a single 1 : 2 co-crystal of pyridine/3,5-dinitrobenzoic acid. The H-bond motif found in this system exhibits the same connectivity by strong hydrogen bonds N-H(+)[dot dot dot]O(-) and O-H[dot dot dot]O as that in the CyPy/(TCA)(2) complex predicted by DFT calculation. Certain discrepancies are observed in C-H[dot dot dot]O connectivity only. The networks of H-bonds in both assemblies differ from those usually pictured for 1 : 2 base/carboxylic acid complexes in the literature.     

Chemistry of the phenoxathiins and isosterically related heterocycles. XXXVII The synthesis and molecular structure of benzo[2, 3]naphtho[5, 6, 7-ij][1, 4]dithiepin and its 1-oxide

Benzo[2, 3]naphtho[5, 6, 7-ij][1, 4]dithiepin was prepared by the condensation of the disodium salt of 1, 2-dimercaptobenzene with 1-chloro-8-nitronaphthalene. The structure was established by nmr and mass spectroscopy. A small quantity of benzo[2, 3]naphtha[5, 6, 7,ij][1, 4]dithiepin 1-oxide was also isolated. The structure was initially established by mass spectrometry. The proton spectrum was totally assigned using a combination of proton zero quantum coherence (ZQCOSY) and proton-carbon heteronuclear chemical shift correlation (HC-COSY) techniques, which also allowed the unequivocal assignment of the protonated carbon resonances. An X-ray crystal structure of the 1-oxide irrefutably confirmed the structure. The crystal was triclinic and the space group was Pl, and the data refined to a final R = 0.0353. The molecule was shown to be folded about the axis passing through the two sulfur atoms with a dihedral angle of 109.00°.     

The effect of hydrogen bonding on the excited-state proton transfer in 2-(2'-hydroxyphenyl)benzothiazole: a TDDFT molecular dynamics study

The dynamics of the excited-state proton transfer (ESPT) in a cluster of 2-(2'-hydroxyphenyl)benzothiazole (HBT) and hydrogen-bonded water molecules was investigated by means of quantum chemical simulations. Two different enol ground-state structures of HBT interacting with the water cluster were chosen as initial structures for the excited-state dynamics: (i) an intramolecular hydrogen-bonded structure of HBT and (ii) a cluster where the intramolecular hydrogen bond in HBT is broken by intermolecular interactions with water molecules. On-the-fly dynamics simulations using time-dependent density functional theory show that after photoexcitation to the S(1) state the ESPT pathway leading to the keto form strongly depends on the initial ground state structure of the HBT-water cluster. In the intramolecular hydrogen-bonded structures direct excited-state proton transfer is observed within 18 fs, which is a factor two faster than proton transfer in HBT computed for the gas phase. Intermolecular bonded HBT complexes show a complex pattern of excited-state proton transfer involving several distinct mechanisms. In the main process the tautomerization proceeds via a triple proton transfer through the water network with an average proton transfer time of approximately 120 fs. Due to the lack of the stabilizing hydrogen bond, intermolecular hydrogen-bonded structures have a significant degree of interring twisting already in the ground state. During the excited state dynamics, the twist tends to quickly increase indicating that internal conversion to the electronic ground state should take place at the sub-picosecond scale.     

Supramolecular Host‐Inhibited Excited‐State Proton Transfer and Fluorescence Switching of the Anti‐Cancer Drug,Topotecan

The effect of cucurbit[7]uril (CB[7]) nano‐caging on the photophysical properties, particularly excited‐state proton transfer (ESPT) reaction, of an eminent anti‐cancer drug, topotecan (TPT), is demonstrated through steady‐state and time‐resolved fluorescence measurements. TPT in water (pH 6) exists exclusively as the cationic form (C) in the ground state. However, the drug emission mainly comes from the excited‐state zwitterionic form (Z*) of TPT, and is attributed to water‐assisted ESPT between the 10‐hydroxyl group and water, which leads to the transformation of C* to Z* of TPT. In the presence of CB[7], it is found that selective encapsulation of the C form of TPT results in the formation of a 1:1 inclusion complex (CB[7]:TPT), and the ESPT process is inhibited by this encapsulation process. As a result, C* becomes the dominant emitting species in the presence of CB[7] rather than Z*, and fluorescence switching takes place from green to blue. Time‐resolved studies also support the existence of CB[7]‐encapsulated cationic species as the major emitting species in the presence of the macrocyclic host. Semi‐empirical quantum chemical calculations are employed to gain insight into the molecular picture of orientation of TPT in the inclusion complex. It is clearly seen from the optimised structure of 1:1 CB[7]:TPT inclusion complex that both 10‐hydroxyl and 9‐dimethylaminomethylene groups of TPT lie partly inside the cavity, and thereby inhibit the excited‐state transformation of C* to Z* by the ESPT process. Finally, controlled release of the drug is achieved by means of fluorescence switching by introducing NaCl, which is rich in cells, as an external stimulus.     

铂配合物cis-[Pt(NH_3)_2(4-mepy)Cl]NO_3与甲基-谷胱甘肽作用的NMR研究

使用质子核磁共振方法测定了新的抗癌活性配合物cis－[Pt（NH3）2（4－mepy）Cl]＋与甲基-谷胱甘肽（GS－Me）的反应及其动力学．结果表明Pt与GS－Me间形成1：1加合物．为了解结合部位，对Pt－GS－Me配合物进行pH滴定，由GS－Me的质子核磁共振谱对pH的依赖关系判断Gs－Me只通过S原子与Pt配位，而氨基和羧基不参与配位反应．由配体吡啶环质子核磁共振随时间的变化，提出了两步反应机制：首先GS－Me通过S原子与Pt配位，然后由于S配位的高度反位效应使反应的NH3活动化．通过1HNMR方法测定了第一步反应的速率常数k＝0．017L·mol－1·s－1（pH3．1）和k＝0．013L·mol－1·s－1（pH7．2）．     

Computational analysis of the proton translocation from Asp96 to schiff base in bacteriorhodopsin

The potential energy change during the M --> N process in bacteriorhodopsin has been evaluated by ab initio quantum chemical and advanced quantum chemical calculations following molecular dynamics (MD) simulations. Many previous experimental studies have suggested that the proton transfer from Asp96 to the Schiff base occurs under the following two conditions: (1) the hydrogen bond between Thr46 and Asp96 breaks and Thr46 is detached from Asp96 and (2) a stable chain of four water molecules spans an area from Asp96 --> Schiff base. In this work, we successfully reproduced the proton-transfer process occurring under these two conditions by molecular dynamics and quantum chemical calculations. The quantum chemical computation revealed that the proton transfer from Asp96 to Shiff base occurs in two-step reactions via an intermediate in which an H(3)O(+) appears around Ala215. The activation energy for the proton transfer in the first reaction was calculated to be 9.7 kcal/mol, which enables fast and efficient proton pump action. Further QM/MM (quantum mechanical/molecular mechanical) and FMO (fragment molecular orbital) calculations revealed that the potential energy change during the proton transfer is tightly regulated by the composition and the geometry of the surrounding amino acid residues of bacteriorhodopsin. Here, we report in detail the Asp96 --> Schiff base proton translocation mechanism of bacteriorhodopsin. Additionally, we discuss the effectiveness of combining quantum chemical calculations with truncated cluster models followed by advanced quantum chemical calculations applied to a whole protein to elucidate its reaction mechanism.     

Theoretical studies on pyridoxal 5'-phosphate-dependent transamination of alpha-amino acids

Density functional methods have been applied to investigate the irreversible transamination between glyoxylic acid and pyridoxamine analog and the catalytic mechanism for the critical [1,3] proton transfer step in aspartate aminotransferase (AATase). The results indicate that the catalytic effect of pyridoxal 5'-phosphate (PLP) may be attributed to its ability to stabilize related transition states through structural resonance. Additionally, the PLP hydroxyl group and the carboxylic group of the amino acid can shuttle proton, thereby lowering the barrier. The rate-limiting step is the tautomeric conversion of the aldimine to ketimine by [1,3] proton transfer, with a barrier of 36.3 kcal/mol in water solvent. A quantum chemical model consisting 142 atoms was constructed based on the crystal structure of the native AATase complex with the product L-glutamate. The electron-withdrawing stabilization by various residues, involving Arg386, Tyr225, Asp222, Asn194, and peptide backbone, enhances the carbon acidity of 4'-C of PLP and Calpha of amino acid. The calculations support the proposed proton transfer mechanism in which Lys258 acts as a base to shuttle a proton from the 4'-C of PLP to Calpha of amino acid. The first step (proton transfer from 4'-C to lysine) is shown to be the rate-limiting step. Furthermore, we provided an explanation for the reversibility and specificity of the transamination in AATase.     

Cucurbituril binding of trans-[{PtCl(NH3)2}2(micro-NH2(CH2)8NH2)]2+ and the effect on the reaction with cysteine

The effect of encapsulation by cucurbiturils Q[7] and Q[8] on the rate of reaction of the anti-cancer dinuclear platinum complex trans-[{PtCl(NH3)2}2(micro-NH2(CH2)8NH2)]2+ with the model biological nucleophiles glutathione and cysteine has been examined by NMR spectroscopy. It was expected that the octamethylene linking chain would fold inside the cucurbituril host and hence position the reactive platinum centres close to the cucurbituril portals, and thereby, confer resistance to degradation by biological nucleophiles. The upfield shifts of the resonances from the methylene protons in the linking ligand observed in 1H NMR spectra of the platinum complex upon addition of either Q[7] or Q[8] indicate that the cucurbituril is positioned over the linking ligand, with the Pt(II) centres projecting out of the portal. Furthermore, the relative changes in chemical shift of the methylene resonances suggest that the octamethylene linking chain folds within the cucurbituril cavity, particularly in Q[8]. Simple molecular models, based on the observed relative changes in chemical shift, could be constructed that were consistent with the proposed folding of the linking ligand within the cucurbituril cavity. Encapsulation by Q[7] was found to reduce the rate of reaction of the platinum complex with glutathione. Encapsulation by Q[7] and Q[8] was also found to reduce the rate of reaction of the platinum complex with cysteine, with Q[8] slowing the reaction to a greater extent than Q[7], consistent with the inferred encapsulation geometries. Encapsulation of dinuclear platinum complexes within the cucurbituril cavity may provide a novel way of reducing the reactivity and degradation of these promising chemotherapeutic agents with blood plasma proteins.