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Structural, Kinetic, and Theoretical Studies on Models of the Zinc‐Containing Phosphodiesterase Active Center: Medium‐Dependent Reaction Mechanisms
Author(s) -
Selmeczi Katalin,
Michel Carine,
Milet Anne,
GautierLuneau Isabelle,
Philouze Christian,
Pierre JeanLouis,
Schnieders David,
Rompel Annette,
Belle Catherine
Publication year - 2007
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200700104
Subject(s) - chemistry , zinc , hydrolysis , kinetics , nuclear magnetic resonance spectroscopy , stereochemistry , reaction mechanism , transesterification , medicinal chemistry , phosphate , organic chemistry , catalysis , physics , quantum mechanics
Abstract Dinuclear zinc(II) complexes [Zn 2 (bpmp)(μ‐OH)](ClO 4 ) 2 ( 1 ) and [Zn 2 (bpmp)(H 2 O) 2 ](ClO 4 ) 3 ( 2 ) (H‐BPMP=2,6‐bis[bis(2‐pyridylmethyl)aminomethyl]‐4‐methylphenol) have been synthesized, structurally characterized, and pH‐driven changes in metal coordination observed. The transesterification reaction of 2‐hydroxypropyl p ‐nitrophenyl phosphate (HPNP) in the presence of the two complexes was studied both in a water/DMSO (70:30) mixture and in DMSO. Complex 2 was not reactive whereas for 1 considerable rate enhancement of the spontaneous hydrolysis reaction was observed. A detailed mechanistic investigation by kinetic studies, spectroscopic measurements ( 1 H, 31 P NMR spectroscopy), and ESI‐MS analysis in conjunction with ab initio calculations was performed on 1 . Based on these results, two medium‐dependent mechanisms are presented and an unusual bridging phosphate intermediate is proposed for the process in DMSO.