受限空间能够从根本上改变内部分子的化学和物理性质，在生物成像、传感以及有机合成等领域展现出巨大的应用潜力。目前受限空间已经被越来越多地应用于调节内部的催化反应，从而实现反应加速，提高反应选择性或者分子的稳定性。因此，对于受限空间内限域效应的作用机理以及反应分子机理进行研究，对其蓬勃发展具有非常重要的推动作用。然而，目前对于受限空间的研究仍存在一些挑战，如常规表征方法难以直接在纳米尺度进行表征，不能直接获取受限空间内分子的结构信息，并且难以实现空间内分子的连续、动态监测。质谱（mass spectrometry, MS）是获取分子结构信息的最有效工具之一。常压电喷雾质谱（electrospray mass spectrometry, ESI MS）技术能在不进行样品预处理的情况下，在毫秒到亚毫秒时间尺度上捕获不同极性和分子量的瞬态中间体，并获取其结构信息。同时能够以极低的样品消耗量为前提实现样品的连续检测，从而有利于反应动力学和反应机理的研究。基于此，本报告开展基于常压质谱的受限空间内催化反应研究，分别针对受限空间内、受限空间电极上、以及材料表面上的化学反应进行监测和研究，主要工作包括如下三部分：

1. 受限空间内吲哚阳离子自由基环化反应研究

  针对受限空间内的反应独特的反应研究，本工作以吲哚阳离子自由基环化反应为模型，采用原位纳升电喷雾质谱法（nano-electrospray mass spectrometry, nanoESI-MS）对受限空间中的反应进行了研究。实验结果表明，受限空间较体相能够显著地加快反应速率。进一步的实验和理论结果表明，造成反应加速的原因主要是nanopipette受限空间内表面能够使得Ru(II)配合物聚集从而通过配体-金属电荷转移（ligand-to-metal charge transfer, LMCT）产生具有较低HOMO-LUMO间隙的活性阳离子自由基。最后，基于原位nanoESI-MS获取的中间体信息，推导出了包含 [4 + 2]环加成和分子内脱氢在内的反应机理。该工作有利于人们对受限空间内独特的催化反应的更深层次的理解。

2. 受限空间内单核一价铜催化点击反应研究

  针对受限空间内电极上的特殊反应活性，开展了Cu(I)催化叠氮化物和炔烃的1,3-偶极环加成反应的研究。本工作利用nanoESI-MS和Cu电极皮摩尔级阳极腐蚀的固有电化学能力来原位生成Cu(I)作为催化剂，并对反应进行评估和分子机理的研究。Nanopipette内表面丰富的Si-O^-能够在无外源性催化剂配体加入的条件下，通过静电相互作用稳定Cu(I)。通过原位nanoESI-MS以及同位素标记实验，捕获并鉴定了大量反应中间体，并确定了质子性溶剂水在该类反应中的作用。进而，基于获得的反应中间体信息，推导出受限空间内无配体单核Cu(I)催化叠氮化物和炔烃的1,3-偶极环加成反应的机理。该工作为点击反应的机理研究提供了新的思路，并有望进一步拓展受限空间在催化反应领域的应用。

3. 光敏化半导体受限表面催化氧化选择性研究

  针对材料表面的反应行为，我们以光敏化半导体表面催化氧化含有杂原子（X=N, Cl）的有机物为例开展研究。该类无色有机化合物可以得到C-N偶联产物或者降解产物，但其选择性仍需进一步研究。本工作以TiO₂表面催化氧化含有杂原子的4-氯苯-1,2-二胺为例，结合常压电喷雾质谱在线反应监测和多种光谱表征手段对该反应的选择性反应机制以及分子反应机理进行研究。4-氯苯-1,2-二胺在可见光照射下，在TiO₂表面主要发生C-N偶联反应，造成该结果的原因是反应过程中表面缺陷氧空位的生成。氧空位通过调节O₂活化同时降低反应中间体生成的能垒，诱导C-N偶联产物的选择性以及高效生成。该工作有利于推动光敏化半导体表面催化氧化反应的进一步发展。

  The chemical and physical properties of molecules could be fundamentally changed in confined space, which has been increasingly used to regulate internal catalytic reactions, including reaction acceleration, improvements on reaction selectivity or molecular stability. Therefore, it is significant to study the mechanism of the confinement effect and the molecular mechanism in confined space. However, there are still some challenges: Conventional characterization methods are difficult to directly obtaining the structural information of molecules in the confined space. In addition, characterize reactions in confined space, even hard to realize continuous and dynamic monitoring of molecules in the confined space. Mass spectrometry (MS) is one of the most effective tools for obtaining structural information. Electrospray mass spectrometry (ESI MS) can provide structural information of different polarities and molecular weights in a milli- to submilliseconds without sample pretreatment. Especially, the continuous sample detection can be obtained on the premise of extremely low sample consumption, which is conducive to the study of reaction kinetics and reaction mechanism. Therefore, the reactions in the confined spaces, on the electrodes and on surface of catalysts have been examined by ESI MS. The corresponding works are shown as follows:

1. Studies of Indole Cation-Radical Cyclization in Confined spaces

  Reactions in confined space exhibit unique reactivity, but how the confinement effect affects the reactions is still unclear. In this work, indole cation radical cyclization reaction was selected as a model to study the reaction in confined space by nano-electrospray mass spectrometry (nanoESI-MS). As demonstrated, confined space can significantly accelerate the reactions compared with the bulk phase. As demonstrated by both experimental and theoretical studies, the acceleration of the reaction was mainly attributed to the aggregation of Ru(II) complexes aggregate on the inner surface of nanopipette, which generated active cationic radicals with a low HOMO-LUMO gap through LMCT. Finally, the reaction mechanism including [4 + 2] cycloaddition and intramolecular dehydrogenation was proposed. This work provided a deeper understanding of unique catalytic reactions in confined spaces.

2. Studies of ligand-free mononuclear copper(I)-catalyzed azide–alkyne cycloaddition in confined spaces

  The copper(I)-catalyzed azide–alkyne cycloaddition in confined space was further studied by mass spectrometry. Upon electrospray, Cu(I) catalyst was in situ generated by corrosion of Cu electrode, and the reaction was online examined by MS. As demonstrated, the abundant Si-O^- on the inner surface of nanopipette can stabilize Cu(I) through electrostatic interaction without the addition of exogenous catalyst ligands. In situ nanoESI-MS and isotope labeling experiments were used to characterize reaction intermediates, and the role of protic solvent water in the reaction was also studied. Finally, the mechanism of 1, 3-dipole cycloaddition of azides and alkynes catalyzed by mononuclear Cu(I) without ligands in confined space is proposed. This work provides a new pathway to study the mechanism of click reactions and is expected to further expand the application of confined space in catalytic reactions.

3. Studies of ligand-free mononuclear copper(I)-catalyzed azide–alkyne cycloaddition in confined spaces

  To examine the reactions on surface of catalyst, the catalytic oxidation of heteroatom-containing (X=N, Cl) colorless organics on photosensitized semiconductors was selected as the model. As reported, C-N coupling products or degradation products can be employed, while the mechanism of selectivity is still unclear. In this work, catalytic oxidation of heteroatom-containing 4-chlorobenzene-1,2-diamine on TiO₂ surface was examined, and the selectivity was studied in combination with MS detections and spectral analysis. As resulted, the C-N coupling reaction mainly occurs on TiO₂ surface under visible light irradiation, which was initiated by the formation of oxygen vacancy during the reaction process. By regulating O₂ activation and reducing the energy barrier, oxygen vacancy promoted the selective and efficient C-N coupling reaction. This work is conducive to the further development of catalytic oxidation reactions on photosensitized semiconductor surface.