CH···O Interactions Are Not the Cause of Trends in Reactivity and Secondary Kinetic Isotope Effects for Enzymatic SN2 Methyl Transfer Reactions

Compaction mattersSN2 substitution represents an important class of reaction for both chemical and biological systems. The ability to assess enzymatic transition state structure within this class of reaction remains a major experimental challenge. Here, we comment on and compare the relative impact of compaction along the axis of reaction to the impact of an orthogonal CH{middle dot}{middle dot}{middle dot}O hydrogen bonding interaction. The latter is concluded to play a limited role in determining relative reaction rates and secondary KIEs derived from experimental structure-activity correlations.