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A Theoretical Analysis of the Coordination Modes of Cu II with Penicillins: Activation of the β‐Lactam CN Bond
Author(s) -
Campomanes Pablo,
Menéndez M. Isabel,
López Ramón,
Sordo Tomás L.
Publication year - 2005
Publication title -
chemphyschem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.016
H-Index - 140
eISSN - 1439-7641
pISSN - 1439-4235
DOI - 10.1002/cphc.200400280
Subject(s) - chemistry , carboxylate , lactam , bond length , crystallography , molecule , stereochemistry , hydrolysis , tetrahedron , computational chemistry , crystal structure , organic chemistry
The interaction of Cu II with 6‐formylamino‐3α‐carboxypenam and 6‐acetylamino‐3α‐carboxypenam was investigated by means of DFT calculations with the UB3LYP functional. Nine different modes of complexation between Cu II and 6‐formylamino‐ 3 α‐carboxypenam were located. When two water molecules directly bonded to Cu II are included in the calculations on 6‐acetylamino‐3α‐carboxypenam as penicillin model, only six Cu II (H 2 O) 2 –6‐acetylamino‐3α‐carboxypenam complexes ( 1 S – 6 S ) are found. In solution the four most stable complexes obtained from our calculations, 6 S , 1 S , 2 S , and 3 S , exhibit Cu II in square‐planar coordination with at least one bond to the carboxylate group, in agreement with experimental evidence. Complexes 6 S , 1 S , and 3 S were previously suggested by available experimental evidence. In three of the most stable complexes ( 6 S , 2 S , and 3 S ) the β‐lactam CN bond is remarkably activated and displays CN bond lengths similar to those found in some tetrahedral intermediates located for the hydrolysis of 2‐azetidinones. This suggests that these kinds of complexes belong to the reaction coordinate for the degradation of β ‐lactam antibiotics in the presence of Cu II .