Wallace Matthew, Sharpe James M, Baj Krzysztof, Ngwube Michael, Thirlway Jenny, Kerigan Higgs Patrick L, Stephenson G Richard, Iggo Jonathan A, Storr Thomas E, Richards Christopher J
School of Chemistry, Pharmacy and Pharmacology, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, UK.
Department of Chemistry, University of Liverpool, Crown Street, Liverpool, L69 7ZD, UK.
Analyst. 2025 Jun 2. doi: 10.1039/d5an00406c.
We generate pH gradients spanning more than six units in standard NMR tubes and determine all the p values of polyprotic compounds in single 20 minutes chemical shift imaging (CSI) NMR experiments. The modest demands of our method in terms of sample quantity and preparation time allow it be performed as part of the routine characterisation and optimisation of organic molecules during synthesis campaigns. As proof of concept, we measure the p values of a family of vinylpyridines employed as antibody drug conjugate linkers. Our analysis reveals a strong correlation between the experimental aqueous p and the rate of conjugate addition of thiol nucleophiles to the vinyl group, representing a powerful predictive method.
我们在标准核磁共振管中生成了跨越六个以上单位的pH梯度，并在单次20分钟的化学位移成像（CSI）核磁共振实验中测定了多质子化合物的所有p值。我们的方法对样品量和制备时间的要求不高，因此可以作为合成过程中有机分子常规表征和优化的一部分来进行。作为概念验证，我们测量了用作抗体药物偶联物连接子的一系列乙烯基吡啶的p值。我们的分析揭示了实验测得的水相p值与硫醇亲核试剂向乙烯基加成共轭物的速率之间存在很强的相关性，这代表了一种强大的预测方法。
