Journal of Medicinal Chemistry· 2015Q1
A Survey of the Role of Noncovalent Sulfur Interactions in Drug Design
- 771citations
- Q1SCImago
- 2015year
Short summary
Electron-deficient sulfur atoms, with positive electrostatic potential, can interact with oxygen, nitrogen, and pi-systems, influencing molecular conformation and offering underappreciated applications in drug design.
AI-generated from the title and abstract; the full text is not read.
Key points
- Electron-deficient sulfur atoms exhibit positive electrostatic potential, facilitating interactions with electron donors.
- These interactions can influence molecular conformation, analogous to hydrogen bonding.
- Applications of these sulfur interactions in drug design are currently underutilized.
- The phenomenon is rooted in the interaction with low-lying sigma-star orbitals of C-S bonds.
AI-generated from the title and abstract; the full text is not read.
Abstract
Electron deficient, bivalent sulfur atoms have two areas of positive electrostatic potential, a consequence of the low-lying σ* orbitals of the C-S bond that are available for interaction with electron donors including oxygen and nitrogen atoms and, possibly, π-systems. Intramolecular interactions are by far the most common manifestation of this effect, which offers a means of modulating the conformational preferences of a molecule. Although a well-documented phenomenon, a priori applications in drug design are relatively sparse and this interaction, which is often isosteric with an intramolecular hydrogen-bonding interaction, appears to be underappreciated by the medicinal chemistry community. In this Perspective, we discuss the theoretical basis for sulfur σ* orbital interactions and illustrate their importance in the context of drug design and organic synthesis. The role of sulfur interactions in protein structure and function is discussed and although relatively rare, intermolecular interactions between ligand C-S σ* orbitals and proteins are illustrated.
The authors' abstract, as published at the source. Journal of Medicinal Chemistry, 2015 · DOI ↗
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Field: Physical and Theoretical Chemistry
Physical and Theoretical ChemistryChemistry