Hydrogen Bonding Parameters by Rapid Colorimetric Assessment: Evaluation of Structural Components Found in Biological Ligands and Organocatalysts

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...

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Bibliographic Details
Published in:Chemistry : a European journal 2023-07, Vol.29 (40), p.e202300696-n/a
Main Authors: Roenfanz, Hanna F., Paniak, Thomas J., Berlin, Cameron B., Tran, Van, Francisco, Karol R., Lassalas, Pierrik, Devas, Anisha, Landes, Olivia, Rosenberger, Avalon, Rotella, Madeline E., Ballatore, Carlo, Kozlowski, Marisa C.
Format: Article
Language:English
Subjects:
bioisoteres
Biological activity
Carboxylic acids
Catalysis
Chemistry
colorimetric sensors
Colorimetry
Colorimetry - methods
Drug delivery
Equivalence
Hydrogen Bonding
Hydrogen bonds
Ligands
Molecular interactions
organocatalysts
Regression models
Titration
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Summary: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(Keq). 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(Keq) 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. A high throughput UV‐Vis method to measure hydrogen bonding capacity is disclosed using over 100 compounds of biological and catalytic relevance. A multiple linear regression model enables estimation of hydrogen bonding affinity from a single measurement using ∼2 mg of analyte that was showcased with a set of carboxylic acid bioisosteres.
ISSN:0947-6539
1521-3765
1521-3765
DOI:10.1002/chem.202300696