A theoretical analysis of the coordination modes of CuII with penicillins: activation of the beta-lactam C-N bond.
The interaction of CuII with 6-formylamino-3alpha-carboxypenam and 6-acetylamino-3alpha-carboxypenam was investigated by means of DFT calculations with the UB3LYP functional. Nine different modes of complexation between CuII and 6-formylamino-3alpha-carboxypenam were located. When two water molecules directly bonded to CuII are included in the calculations on 6-acetylamino-3alpha-carboxypenam as penicillin model, only six CuII(H2O)2-6-acetylamino-3alpha-carboxypenam complexes (1S-6S) are found. In solution the four most stable complexes obtained from our calculations, 6S, 1S, 2S, and 3S, exhibit CuII in square-planar coordination with at least one bond to the carboxylate group, in agreement with experimental evidence. Complexes 6S, 1S, and 3S were previously suggested by available experimental evidence. In three of the most stable complexes (6S, 2S, and 3S) the beta-lactam C-N bond is remarkably activated and displays C-N 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 beta-lactam antibiotics in the presence of CuII.
Campomanes
Pablo
P
Departamento de Química Fisica y Analitica, Facultad de Química, Universidad de Oviedo C/Julián Clavería 8, 33006 Oviedo, Principado de Asturias, Spain.
Menéndez
M Isabel
MI
López
Ramón
R
Sordo
Tomás L
TL
D000890:Anti-Infective Agents / Q000737:chemistry*; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002627:Chemistry, Physical; D003300:Copper / Q000737:chemistry*; D006860:Hydrogen Bonding; D008956:Models, Chemical; D008958:Models, Molecular; D008962:Models, Theoretical; D008968:Molecular Conformation; D015394:Molecular Structure; D009584:Nitrogen / Q000737:chemistry; D010406:Penicillins / Q000737:chemistry*; D012984:Software; D013696:Temperature; D013816:Thermodynamics; D014867:Water / Q000737:chemistry; D047090:beta-Lactams / Q000737:chemistry
D000890:Anti-Infective Agents; D010406:Penicillins; D047090:beta-Lactams; D014867:Water; D003300:Copper; D009584:Nitrogen