Guanidinium groups act as general-acid catalysts in phosphoryl transfer reactions: a two-proton inventory on a model system.
Cleavage/transesterification of phosphodiesters is catalyzed by various acidic groups in solution and with enzymes. General-acid catalysts can transfer protons to the developing phosphorane intermediate, resulting in a monoprotic-monoanionic intermediate, giving the so-called "triester mechanism". Using a proton inventory on a model compound (1) possessing an intramolecular hydrogen bond between a phosphodiester and a guanidinium group, we find that two protons move in the rate-determining step for cleavage/transesterification. In contrast, HPNP shows a single-proton inventory and is a substrate well accepted to react with the movement of only one proton at the transition state. We therefore propose a mechanism for 1 that involves general-acid catalysis by the guanidinium group. This leads one to conclude that other, more acidic groups, such as ammonium and imidazolium, would also act as general-acid catalysts.
Piatek
Anna M
AM
Department of Chemistry and Biochemistry, The University of Texas at Austin, Austin, Texas 78712, USA.
Gray
Mark
M
Anslyn
Eric V
EV
D002384:Catalysis; D019791:Guanidine / Q000737:chemistry*; D007700:Kinetics; D008958:Models, Molecular; D010755:Organophosphates / Q000737:chemistry*; D009943:Organophosphorus Compounds / Q000737:chemistry; D010753:Phosphoranes / Q000737:chemistry; D011522:Protons; D014867:Water / Q000737:chemistry
C436487:2-(hydroxypropyl)-4-nitrophenyl phosphate; D010755:Organophosphates; D009943:Organophosphorus Compounds; D010753:Phosphoranes; D011522:Protons; D014867:Water; D019791:Guanidine