Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, PA 19104, USA.
Department of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Chemistry. 2023 Jul 14;29(40):e202300696. doi: 10.1002/chem.202300696. Epub 2023 May 26.
Hydrogen bonding is a key molecular interaction in biological processes, drug delivery, and catalysis. This report describes a high throughput UV-Vis spectroscopic method to measure hydrogen bonding capacity using a pyrazinone sensor. This colormetric sensor reversibly binds to a hydrogen bond donor, resulting in a blue shift as additional equivalents of donor are added. Titration with excess equivalents of donor is used to determine the binding coefficient, ln(K ). Over 100 titrations were performed for a variety of biologically relevant compounds. This data enabled development a multiple linear regression model that is capable of predicting 95 % of ln(K ) values within 1 unit, allowing for the estimation of hydrogen bonding affinity from a single measurement. To show the effectiveness of the single point measurements, hydrogen bond strengths were obtained for a set of carboxylic acid bioisosteres. The values from the single point measurements were validated with full titrations.
氢键是生物过程、药物传递和催化中的关键分子相互作用。本报告描述了一种使用吡嗪酮传感器测量氢键结合能力的高通量紫外可见光谱法。这种比色传感器可逆地与氢键供体结合，随着额外当量的供体的加入，会发生蓝移。用过量当量的供体滴定以确定结合系数ln(K)。对多种具有生物学相关性的化合物进行了超过 100 次滴定。这些数据使我们能够开发出一个多元线性回归模型，该模型能够在 1 个单位内预测 95%的 ln(K)值，从而能够从单次测量中估算氢键亲和力。为了展示单点测量的有效性，我们获得了一组羧酸生物等排体的氢键强度。单点测量的值通过全滴定进行验证。
