Which halogen to choose? Comparing the effects of chlorine and fluorine as bioisosteric substituents in drug design
Abstract
The effects of fluorine and chlorine on pharmaceutical systems are compared using a molecular matched pair analysis. Effects on binding constants, physicochemical properties such as lipophilicity and solubility, as well as on metabolic properties will show the differences and similarities between the elements in a medicinal context. Factors such as the difference in electronegativity, polarizability, hydrogen-bond acceptor ability, as well as conformational effects are discussed to put the differences between the elements into context, using real case studies taken from the literature.
Fields of Study & Subjects
Computational Drug Discovery Methods
Crystallography and molecular interactions
Fluorine in Organic Chemistry
Publication details
- Journal / source
- Chemical Science
- Publisher
- Royal Society of Chemistry (RSC)
- Volume
- 17
- Issue
- 5
- Pages
- 2477–2505
- Publication date
- 1 January 2026
- Language
- EN