Pálla Tamás, Mazák Károly, Alkhazragee Dania Mohammed, Balogh György Tibor, Noszál Béla, Mirzahosseini Arash
Department of Pharmaceutical Chemistry, Semmelweis University, Hőgyes Endre utca 9, 1092 Budapest, Hungary.
Center for Pharmacology and Drug Research & Development, Semmelweis University, 1085 Budapest, Hungary.
Int J Mol Sci. 2024 Nov 27;25(23):12727. doi: 10.3390/ijms252312727.
The accurate determination of acid/base constants (proton dissociation constants-p, or equivalently protonation constants-log) is essential for the physicochemical characterization of new molecules, especially in drug design and development, as these parameters thoroughly influence the pharmacokinetics and pharmacodynamics of drug action. While pH/potentiometric titration remains the gold standard method for determining acid/base constants, spectroscopic techniques-particularly nuclear magnetic resonance spectroscopy (as NMR/pH titrations)-have emerged as powerful alternatives for specific challenges in analytical chemistry, providing also information on the structure and site of protonation. In this study, we performed a comprehensive meta-analysis of protonation constants reported in the literature, measured using both potentiometry and NMR titrations. Our analysis compiled the available literature data and assessed the agreement between the two methods, taking into consideration various experimental conditions, such as temperature and ionic strength. The results provide insights into the reliability and applicability of NMR titrations compared with potentiometry, offering guidance for selecting appropriate methodologies in drug design.
准确测定酸/碱常数（质子解离常数-p，或等效的质子化常数-log）对于新分子的物理化学表征至关重要，尤其是在药物设计和开发中，因为这些参数会全面影响药物作用的药代动力学和药效学。虽然pH/电位滴定法仍然是测定酸/碱常数的金标准方法，但光谱技术——特别是核磁共振光谱法（如NMR/pH滴定）——已成为解决分析化学中特定挑战的有力替代方法，同时还能提供有关质子化结构和位点的信息。在本研究中，我们对文献报道的质子化常数进行了全面的荟萃分析，这些常数通过电位滴定法和NMR滴定法测量。我们的分析汇总了现有的文献数据，并考虑了温度和离子强度等各种实验条件，评估了这两种方法之间的一致性。结果提供了与电位滴定法相比NMR滴定法的可靠性和适用性的见解，为药物设计中选择合适的方法提供了指导。
