Generality of solvation effects on the hydrolysis rates of phosphate monoesters and their possible relevance to enzymatic catalysis.
Previous work by Kirby and co-workers revealed a significant acceleration of the rate of hydrolysis of p-nitrophenyl phosphate by added dipolar solvents such as DMSO. Activation parameters and kinetic isotope effects have been measured to ascertain the origin of this effect. The generality of this phenomenon was examined with a series of esters with more basic leaving groups. Computational analyses of the effects of desolvation of dianionic phosphate monoesters were carried out, and the possible effect of the transfer from water to the active site of alkaline phosphatase was modeled. The results are consistent with a desolvation-induced weakening of the P-O ester bond in the ground state. Other aryl phosphate esters show similar rate accelerations at high fractions of DMSO, but phenyl and methyl phosphates do not, and their hydrolysis reactions are actually slowed by these conditions.
Grzyska
Piotr K
PK
Utah State University, Department of Chemistry and Biochemistry, Logan, Utah 84322-0300, USA.
Czyryca
Przemyslaw G
PG
Golightly
Justin
J
Small
Kelly
K
Larsen
Paul
P
Hoff
Richard H
RH
Hengge
Alvan C
AC
D000469:Alkaline Phosphatase / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D002384:Catalysis; D004121:Dimethyl Sulfoxide; D004952:Esters / Q000737:chemistry; D006868:Hydrolysis; D007554:Isotopes / Q000737:chemistry; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D009943:Organophosphorus Compounds / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014867:Water / Q000737:chemistry
D004952:Esters; D007554:Isotopes; D009943:Organophosphorus Compounds; D014867:Water; D000469:Alkaline Phosphatase; D004121:Dimethyl Sulfoxide