title: Anomeric Effects in Sulfamides.
abstract: Sulfamides, together with their simpler sulfonamide analogs, are common functional groups in a significant number of biologically active compounds. This is partly due to their unique electronic structure and conformational behavior, which mimics the tetrahedral intermediate involved in many proteases, esterases, and related enzymes. Here, the origin of these unique structural elements are analyzed in the context of a coupled, double anomeric effect using DFT calculations, including conformational scans, and NBO analysis. It is shown that these coupled interactions can be implicitly parametrized in MM3* type force fields using the quantum-guided molecular mechanics (Q2MM) method, yielding accurate force field parameters for molecular mechanics studies of sulfamides and sulfonamides.
authors.affiliation: Department of Chemistry and Biochemistry, University of Notre Dame , Notre Dame, Indiana 46556, United States.
authors.forename: Eric
authors.initials: E
authors.lastname: Hansen
authors.affiliation: Pharmaceutical Technology and Development, AstraZeneca , Pepparedsleden 1, SE-431 83 Mölndal, Sweden.
authors.forename: Elaine
authors.initials: E
authors.lastname: Limé
authors.affiliation: Pharmaceutical Technology and Development, AstraZeneca , Pepparedsleden 1, SE-431 83 Mölndal, Sweden.
authors.forename: Per-Ola
authors.initials: PO
authors.lastname: Norrby
authors.affiliation: Department of Chemistry and Biochemistry, University of Notre Dame , Notre Dame, Indiana 46556, United States.|Lab of Computational Chemistry and Drug Design, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School , Shenzhen 518055, China.
authors.forename: Olaf
authors.initials: O
authors.lastname: Wiest