Cupric Ion-Catalyzed Hydrolysis of Penicillins: Mechanism and Site of Complexation

Cressman, William A.; Sugita, Edwin T.; Doluisio, James T.; Niebergall, Paul J.

doi:10.1002/jps.2600581210

Cited by 48 publications

(17 citation statements)

References 11 publications

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“…Coordination occurring to the carboxylate group is indicated because esterification of this group decreases the rate enhancement by a factor of about 5 Â 10 3 . It has been suggested that Cu(II) ions coordinate to the 6-acylamino side-chain and the b-lactam carbonyl group [73]. However, replacement of the acylamino side-chain by the more basic amino group has little effect upon the binding constant and the rate enhancement for the hydroxide ion-catalyzed hydrolysis for 6-aminopenicillanic acid is very similar to that for benzylpenicillin.…”

Section: Metal Ion-catalyzed Hydrolysismentioning

confidence: 99%

Structure and Reactivity of β‐Lactams

Page

2010

Amino Acids, Peptides and Proteins in Organic Chemistry

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Section: Metal Ion-catalyzed Hydrolysismentioning

confidence: 99%

Structure and Reactivity of β‐Lactams

Page

2010

Amino Acids, Peptides and Proteins in Organic Chemistry

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“…However, this mechanism of action can be interfered with by β‐lactamase enzymes, which catalyze hydrolysis of the antibiotics to biologically inactive products 2–4. Hydrolysis of β‐ lactams is also promoted by transition metal ions, such as Cu II , Zn II , Co II , and Ni II 5–16. Cu II ions, which are present in the human body as free ions or coordinatively bound to proteins, enzymes, and other bioligands, can interact with β‐lactam antibiotics to form different complexes 17–20.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Many experimental works have reported the formation of Cu II –penicillin complexes and proposed different modes of complexation 5–7. 9, 10, 23–26 It has been suggested that copper coordinates to the nitrogen atom of the 6‐amido side chain (see Scheme for atom numbering) and to the oxygen atom of the β‐lactam carbonyl group (see A in Scheme ) 5. Nevertheless, NMR studies23 and the fact that replacement of the 6‐amido side chain by the more basic amino group, or by hydrogen, has little effect on the binding constant of the Cu II – penicillin complex or on the enhancement of the hydrolysis rate by the metal ion, seem to indicate that this mode of binding does not occur 7.…”

Section: Introductionmentioning

confidence: 99%

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A Theoretical Analysis of the Coordination Modes of Cu^IIwith Penicillins: Activation of the β‐Lactam CN Bond

et al. 2005

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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.

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“…by pH, chemical structure, ionic strength, presence of carbohydrates and heavy metal contaminants (5)(6)(7)(8)(9).…”

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confidence: 99%

The use of evaporative cooling to extend the shelf life of reconstituted oral penicillin solutions

Dzuda

Morton

1993

J Clin Pharm Ther

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The relationship between temperature and the degradation of reconstituted penicillin solutions was evaluated. In all cases storage at temperatures of 25 degrees C or less was sufficient to maintain penicillin stability within acceptable pharmacopoeial limits for 5 days. In addition, the relationship between humidity and dry bulb temperature was examined in order to assess the use of evaporative cooling in lowering the temperature of penicillin solutions in those areas of the country where temperatures commonly exceed 25 degrees C. The results of this study suggest that, with the use of evaporative cooling, penicillin solutions can be maintained in a stable state for a 5-day period without the need for refrigeration.

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Cupric Ion-Catalyzed Hydrolysis of Penicillins: Mechanism and Site of Complexation

Cited by 48 publications

References 11 publications

Structure and Reactivity of β‐Lactams

Structure and Reactivity of β‐Lactams

A Theoretical Analysis of the Coordination Modes of Cu^IIwith Penicillins: Activation of the β‐Lactam CN Bond

The use of evaporative cooling to extend the shelf life of reconstituted oral penicillin solutions

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Cupric Ion-Catalyzed Hydrolysis of Penicillins: Mechanism and Site of Complexation

Cited by 48 publications

References 11 publications

Structure and Reactivity of β‐Lactams

Structure and Reactivity of β‐Lactams

A Theoretical Analysis of the Coordination Modes of CuIIwith Penicillins: Activation of the β‐Lactam CN Bond

The use of evaporative cooling to extend the shelf life of reconstituted oral penicillin solutions

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A Theoretical Analysis of the Coordination Modes of Cu^IIwith Penicillins: Activation of the β‐Lactam CN Bond