Programmable wide-range pH gradients for NMR titrations: Application to antibody–drug conjugate linker group modifications

Wallace, Matthew, Sharpe, James M., Baj, Krzysztof, Ngwube, Michael, Thirlway, Jenny, Kerigan Higgs, Patrick L., Stephenson, G. Richard, Iggo, Jonathan A., Storr, Thomas E. and Richards, Christopher J. (2025) Programmable wide-range pH gradients for NMR titrations: Application to antibody–drug conjugate linker group modifications. Analyst. ISSN 0003-2654

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Abstract

We generate pH gradients spanning more than six units in standard NMR tubes and determine all the pKa 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 pKa values of a family of vinylpyridines employed as antibody drug conjugate linkers. Our analysis reveals a strong correlation between the experimental aqueous pKa and the rate of conjugate addition of thiol nucleophiles to the vinyl group, representing a powerful predictive method.

Item Type:	Article
Faculty \ School:	Faculty of Science > School of Chemistry, Pharmacy and Pharmacology
UEA Research Groups:	Faculty of Science > Research Groups > Pharmaceutical Materials and Soft Matter Faculty of Science > Research Groups > Chemistry of Materials and Catalysis
Depositing User:	LivePure Connector
Date Deposited:	10 Jun 2025 13:30
Last Modified:	15 Jun 2025 06:30
URI:	https://ueaeprints.uea.ac.uk/id/eprint/99433
DOI:	10.1039/D5AN00406C

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