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Non‐Tethered Organometallic Phosphonate Inhibitors for Lipase Inhibition: Positioning of the Metal Center in the Active Site of Cutinase
Author(s) -
Kruithof Cornelis A.,
Dijkstra Harmen P.,
Lutz Martin,
Spek Anthony L.,
Egmond Maarten R.,
Klein Gebbink Robertus J. M.,
van Koten Gerard
Publication year - 2008
Publication title -
european journal of inorganic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.667
H-Index - 136
eISSN - 1099-0682
pISSN - 1434-1948
DOI - 10.1002/ejic.200800654
Subject(s) - cutinase , chemistry , phosphonate , pincer movement , lipase , active site , catalysis , metal , covalent bond , candida antarctica , combinatorial chemistry , stereochemistry , coordination sphere , organic chemistry , polymer chemistry , enzyme
Organometallic NCN‐pincer complexes, bearing either a p ‐nitrophenyl phosphonate ester or a phosphonic acid group directly attached to the aromatic ring of the pincer complex, were synthesized. These compounds were tested as covalent inhibitors for the lipase cutinase. In a stoichiometric reaction of the NCN‐pincer platinum phosphonate p ‐nitrophenyl ester 2 with cutinase, a 94 % conversion to the protein–pincer metal complex hybrid was obtained in 48 h. The NCN‐pincer metal phosphonic acid derivatives ( 3 , 4 ) appeared to be inactive as cutinase inhibitors. In contrast to our previous work which entails propyl tethered phosphonate esters connected to pincer metal complexes, the presented strategy allows positioning of metal complexes inside the active site of lipases. This opens up the possibility for fine‐tuning the chemical environment (second coordination sphere) around a synthetic metal center inside the pocket of an enzyme for diagnostic and catalytic purposes.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

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