Coordination and redox interactions of β-lactam antibiotics with Cu2+ in physiological settings and the impact on antibacterial activity
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2018
Authors
Božić, BojanaKorać, Jelena
Stanković, Dalibor
Stanić, Marina
Romanović, Mima
Pristov-Bogdanović, Jelena
Spasić, Snežana
Popović-Bijelić, Ana
Spasojević, Ivan
Bajčetić, Milica
Article (Published version)
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An increase in the copper pool in body fluids has been related to a number of pathological conditions, including infections. Copper ions may affect antibiotics via the formation of coordination bonds and/or redox reactions. Herein, we analyzed the interactions of Cu2+ with eight β-lactam antibiotics using UV–Vis spectrophotometry, EPR spectroscopy, and electrochemical methods. Penicillin G did not show any detectable interactions with Cu2+. Ampicillin, amoxicillin and cephalexin formed stable colored complexes with octahedral coordination environment of Cu2+ with tetragonal distortion, and primary amine group as the site of coordinate bond formation. These β-lactams increased the solubility of Cu2+ in the phosphate buffer. Ceftazidime and Cu2+ formed a complex with a similar geometry and gave rise to an organic radical. Ceftriaxone-Cu2+ complex appears to exhibit different geometry. All complexes showed 1:1 stoichiometry. Cefaclor reduced Cu2+ to Cu1+ that further reacted with molecula...r oxygen to produce hydrogen peroxide. Finally, meropenem underwent degradation in the presence of copper. The analysis of activity against Escherichia coli and Staphylococcus aureus showed that the effects of meropenem, amoxicillin, ampicillin, and ceftriaxone were significantly hindered in the presence of copper ions. The interactions with copper ions should be taken into account regarding the problem of antibiotic resistance and in the selection of the most efficient antimicrobial therapy for patients with altered copper homeostasis. © 2018 Elsevier Inc.
Keywords:
Antibiotic / Complex / Copper / EPR spectroscopy / Free radicalsSource:
Free Radical Biology and Medicine, 2018, 129, 279-285Publisher:
- Elsevier
Funding / projects:
- Molecular mechanisms of redox signalling in homeostasis: adaptation and pathology (RS-MESTD-Basic Research (BR or ON)-173014)
- Study of structure-function relationships in the plant cell wall and modifications of the wall structure by enzyme engineering (RS-MESTD-Basic Research (BR or ON)-173017)
- Strengthening of the MagBioVin Research and Innovation Team for Development of Novel Approaches for Tumour Therapy based on Nanostructured Materials (EU-FP7-621375)
Note:
- Peer-reviewed manuscript: http://cherry.chem.bg.ac.rs/handle/123456789/2940
- Supplementary material: http://cherry.chem.bg.ac.rs/handle/123456789/2941
DOI: 10.1016/j.freeradbiomed.2018.09.038
ISSN: 0891-5849
WoS: 000450298400026
Scopus: 2-s2.0-85054184646
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Hemijski fakultet / Faculty of ChemistryTY - JOUR AU - Božić, Bojana AU - Korać, Jelena AU - Stanković, Dalibor AU - Stanić, Marina AU - Romanović, Mima AU - Pristov-Bogdanović, Jelena AU - Spasić, Snežana AU - Popović-Bijelić, Ana AU - Spasojević, Ivan AU - Bajčetić, Milica PY - 2018 UR - https://cherry.chem.bg.ac.rs/handle/123456789/349 AB - An increase in the copper pool in body fluids has been related to a number of pathological conditions, including infections. Copper ions may affect antibiotics via the formation of coordination bonds and/or redox reactions. Herein, we analyzed the interactions of Cu2+ with eight β-lactam antibiotics using UV–Vis spectrophotometry, EPR spectroscopy, and electrochemical methods. Penicillin G did not show any detectable interactions with Cu2+. Ampicillin, amoxicillin and cephalexin formed stable colored complexes with octahedral coordination environment of Cu2+ with tetragonal distortion, and primary amine group as the site of coordinate bond formation. These β-lactams increased the solubility of Cu2+ in the phosphate buffer. Ceftazidime and Cu2+ formed a complex with a similar geometry and gave rise to an organic radical. Ceftriaxone-Cu2+ complex appears to exhibit different geometry. All complexes showed 1:1 stoichiometry. Cefaclor reduced Cu2+ to Cu1+ that further reacted with molecular oxygen to produce hydrogen peroxide. Finally, meropenem underwent degradation in the presence of copper. The analysis of activity against Escherichia coli and Staphylococcus aureus showed that the effects of meropenem, amoxicillin, ampicillin, and ceftriaxone were significantly hindered in the presence of copper ions. The interactions with copper ions should be taken into account regarding the problem of antibiotic resistance and in the selection of the most efficient antimicrobial therapy for patients with altered copper homeostasis. © 2018 Elsevier Inc. PB - Elsevier T2 - Free Radical Biology and Medicine T1 - Coordination and redox interactions of β-lactam antibiotics with Cu2+ in physiological settings and the impact on antibacterial activity VL - 129 SP - 279 EP - 285 DO - 10.1016/j.freeradbiomed.2018.09.038 ER -
@article{ author = "Božić, Bojana and Korać, Jelena and Stanković, Dalibor and Stanić, Marina and Romanović, Mima and Pristov-Bogdanović, Jelena and Spasić, Snežana and Popović-Bijelić, Ana and Spasojević, Ivan and Bajčetić, Milica", year = "2018", abstract = "An increase in the copper pool in body fluids has been related to a number of pathological conditions, including infections. Copper ions may affect antibiotics via the formation of coordination bonds and/or redox reactions. Herein, we analyzed the interactions of Cu2+ with eight β-lactam antibiotics using UV–Vis spectrophotometry, EPR spectroscopy, and electrochemical methods. Penicillin G did not show any detectable interactions with Cu2+. Ampicillin, amoxicillin and cephalexin formed stable colored complexes with octahedral coordination environment of Cu2+ with tetragonal distortion, and primary amine group as the site of coordinate bond formation. These β-lactams increased the solubility of Cu2+ in the phosphate buffer. Ceftazidime and Cu2+ formed a complex with a similar geometry and gave rise to an organic radical. Ceftriaxone-Cu2+ complex appears to exhibit different geometry. All complexes showed 1:1 stoichiometry. Cefaclor reduced Cu2+ to Cu1+ that further reacted with molecular oxygen to produce hydrogen peroxide. Finally, meropenem underwent degradation in the presence of copper. The analysis of activity against Escherichia coli and Staphylococcus aureus showed that the effects of meropenem, amoxicillin, ampicillin, and ceftriaxone were significantly hindered in the presence of copper ions. The interactions with copper ions should be taken into account regarding the problem of antibiotic resistance and in the selection of the most efficient antimicrobial therapy for patients with altered copper homeostasis. © 2018 Elsevier Inc.", publisher = "Elsevier", journal = "Free Radical Biology and Medicine", title = "Coordination and redox interactions of β-lactam antibiotics with Cu2+ in physiological settings and the impact on antibacterial activity", volume = "129", pages = "279-285", doi = "10.1016/j.freeradbiomed.2018.09.038" }
Božić, B., Korać, J., Stanković, D., Stanić, M., Romanović, M., Pristov-Bogdanović, J., Spasić, S., Popović-Bijelić, A., Spasojević, I.,& Bajčetić, M.. (2018). Coordination and redox interactions of β-lactam antibiotics with Cu2+ in physiological settings and the impact on antibacterial activity. in Free Radical Biology and Medicine Elsevier., 129, 279-285. https://doi.org/10.1016/j.freeradbiomed.2018.09.038
Božić B, Korać J, Stanković D, Stanić M, Romanović M, Pristov-Bogdanović J, Spasić S, Popović-Bijelić A, Spasojević I, Bajčetić M. Coordination and redox interactions of β-lactam antibiotics with Cu2+ in physiological settings and the impact on antibacterial activity. in Free Radical Biology and Medicine. 2018;129:279-285. doi:10.1016/j.freeradbiomed.2018.09.038 .
Božić, Bojana, Korać, Jelena, Stanković, Dalibor, Stanić, Marina, Romanović, Mima, Pristov-Bogdanović, Jelena, Spasić, Snežana, Popović-Bijelić, Ana, Spasojević, Ivan, Bajčetić, Milica, "Coordination and redox interactions of β-lactam antibiotics with Cu2+ in physiological settings and the impact on antibacterial activity" in Free Radical Biology and Medicine, 129 (2018):279-285, https://doi.org/10.1016/j.freeradbiomed.2018.09.038 . .