DOI: 10.1021/acscatal.0c04360
氧化还原酶是一类重要酶，约占已知酶总数量的四分之一。由于氧化还原酶特有的催化性能，例如优异的活性和对映选择性以及温和的反应条件，而被广泛的应用于化学合成、制药、生物降解等领域。然而大多数氧化还原酶催化的生物转化过程依赖于辅酶NAD(P)+/NAD(P)H（氧化态/还原态）作为电子转移的载体。尽管辅酶广泛存在于生物体内，由于其等计量比地参与酶催化反应和昂贵的价格，NAD(P)H的循环再生吸引了大量的研究工作。60多年来，NAD(P)H再生的方法主要有生物催化、化学法、电催化、光催化、均相催化以及非均相催化。大多数的文献报道都基于紫外光谱（340 nm），以NAD(P)H收率作为评价反应和催化剂的指标。对于生物催化的NAD(P)H再生过程，由于酶本身天然的高选择性，此时收率等同于转化率，这种评价方法是合理的。然而非酶法的再生过程通常会伴随1,2-, 1,6-NAD(P)H和NAD2 dimer以及NAD(P)H分解产物的生成(Scheme 1)，在这种情况下，上述仅通过收率评价反应和催化剂性能的方法会错过重要的信息，即实际的产物分布和转化率（包括碳平衡），通常会导致不严谨、不可靠的研究结论。因此本工作旨在揭示NADH在负载型金属催化剂上再生反应过程中的产物分布和实际转化率，指出现有研究过程中的潜在问题，为日后该领域的研究提供分析手段和理论基础。本文考察了NADH在Pt/SiO2, Pt/C和Pt/MgO上的再生反应，通过课题组建立的产物分析新方法（Chemical Communications, 56 (2020) 1231），检测了反应进程中的真实产物分布（Fig. 1a-c），首次报道了NAD+转化率，并通过以此得到的TOF构建了NADH再生反应活性与载体表面等电点的联系（Fig. 1d）。结果表明，在反应条件下（pH=7）溶剂化效应导致载体表面产生电荷差异，表现为Pt/SiO2表面带负电，增强了对NAD+分子参与反应且带正电的nicotinamide ring (+1)部分的静电吸附，从而获得更高的局部浓度和反应可能性/活性，而Pt/MgO上则反之。通过紫外计算得到的“收率”与真实收率、转化率均有显著差别（see Graphical Abstract），由此可见，在大多数文献中，仅报道收率（甚至是包含NADH同分异构体及dimer的总收率）并不合理，可能会导致错误的研究结论。
我们通过对即时产物分布的系统分析，NADH、NAD+（Fig. 2a, b）的稳定性实验以及副产物的合成与定性（1H NMR），进而提出了NAD+在负载型Pt催化剂表面还原生成NADH的反应路径（Fig. 2c）。本工作通过实验揭示了NADH在负载型Pt催化剂上再生中的真实产物分布、转化率和反应路径，同时探讨了催化剂性质和反应活性的构效关系，为未来催化剂设计提供思路。文章指出了该领域研究工作存在的潜在问题，为辅酶再生实验数据的正确报道方式提出了新思考。
该工作得到了英国The Royal Society International Collaboration Award (ICAR1180317)的支持。The Wang Group at Lancaster University (UK).
Lancaster University is consistently in the UK top 10 in three main league tables and has been named International University of the Year 2020 by The Times and The Sunday Times Good University Guide.Xiaodong Wang is currently a Senior Lecturer (Associate Professor) in Chemical Engineering at Lancaster University (UK). Prior to this, he was a Lecturer (Assistant Professor) in Chemical Engineering at the University of Aberdeen (UK), Postdoctoral Research Associate at Heriot-Watt University (UK), where he also obtained his PhD (2014). He completed both MSc and BEng studies in Chemical Engineering at Tianjin University (China).Research in The Wang Group ranges from reaction engineering, renewable energy and chemicals to materials, where heterogeneous catalysis is the core discipline. The Group has been funded mainly by The Engineering and Physical Sciences Research Council (and The UK Catalysis Hub), The Royal Society, The Carnegie Trust for the Universities of Scotland and Industry, with total research income (as PI) of over £1 million pounds.Xiaodong has been the author of over 40 publications in peer-reviewed journals including Chem, Joule and ACS Catalysis etc. The Group’s recent work focuses on the innovative use of heterogeneous catalysts (e.g., supported metals) in enzymatic transformations via cofactor NAD(P)H regeneration. A list of representative publications on this line of research can be seen below:[1] Saba, T., Li, J., Burnett, J. W. H., Howe, R. F., Kechagiopoulos, P. N., & Wang, X. (2021). NADH regeneration: a case study of Pt-catalyzed NAD+ reduction with H2. ACS Catalysis, 11(1), 283–289.[2] Jones, W., Burnett, J. W. H., Shi, J., Howe, R. F., & Wang, X. (2020). Improving photocatalytic energy conversion via NAD(P)H. Joule, 4(10), 2055–2059.[3] Burnett, J. W. H., Howe, R. F., & Wang, X. (2020). Cofactor NAD(P)H regeneration: how selective are the reactions? Trends in Chemistry, 2(6), 488–492.[4] Zhang, S., Shi, J., Chen, Y., Huo, Q., Li, W., Wu, Y., Sun, Y., Zhang, Y., Wang, X., & Jiang, Z. (2020). Unraveling and manipulating of NADH oxidation by photo-generated holes. ACS Catalysis, 10(9), 4967–4972.[5] Saba, T., Burnett, J. W. H., Li, J., Kechagiopoulos, P. N., & Wang, X. (2020). A facile analytical method for reliable selectivity examination in cofactor NADH regeneration. Chemical Communications, 56(8), 1231–1234.[6] Wang, X., Saba, T., Yiu, H. H. P., Howe, R. F., Anderson, J. A., & Shi, J. (2017). Cofactor NAD(P)H regeneration inspired by heterogeneous pathways. Chem, 2(5), 621–654.[7] Wang, X., & Yiu, H. H. P. (2016). Heterogeneous catalysis mediated cofactor NADH regeneration for enzymatic reduction. ACS Catalysis, 6(3), 1880–1886.The Group is recruiting in 2021, please get in touch. Xiaodong’s contact details are available here: https://www.lancaster.ac.uk/engineering/about/people/xiaodong-wang
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