Coordination of hydralazine with Cu2+ at acidic pH promotes its oxidative degradation at neutral pH
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2023
Authors
Korać Jačić, JelenaBajuk-Bogdanović, Danica

Savić, Slađana D.

Božić Cvijan, Bojana
Spasojević, Milica

MIlenković, Milica R.

Article (Published version)

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Show full item recordAbstract
Hydralazine (HL), a frequently prescribed oral antihypertensive drug, shows redox interactions with transition metals such as copper that are not fully understood. Copper may be present at high concentrations in the digestive tract and can affect oral drugs. An important parameter for such interactions is pH, which changes from acidic in the gastric juice to neutral pH in intestines. In this study, we examined interactions of HL with Cu2+ ions in conditions that mimic pH shift in the digestive tract using UV–Vis, Raman and EPR spectroscopy, cyclic voltammetry and oximetry. In the acidic solution, Cu2+ formed a stable mononuclear complex with two bidentate coordinated HL molecules. On the other hand, at neutral pH, Cu2+ initiated oxidation and degradation of HL. The degradation was more rapid in the HL-Cu2+ system that was initially prepared at acidic pH and then shifted to neutral pH. The formation of the complex at acidic pH increases the availability of Cu2+ for redox reactions after... the shift to neutral pH at which Cu2+ is poorly soluble. These results imply that the change of pH along the digestive tract may promote HL degradation by allowing the formation of the complex at gastric pH which makes Cu2+ available for subsequent oxidation of HL at neutral pH.
Keywords:
Hydralazine / Copper / Complex / Oxidative degradationSource:
Journal of Inorganic Biochemistry, 2023, 243, 112181-Publisher:
- Elsevier
Funding / projects:
- Ministry of Education, Science and Technological Development, Republic of Serbia, Grant no. 200053 (University of Belgrade, Institute for Multidisciplinary Research) (RS-200053)
- Ministry of Education, Science and Technological Development, Republic of Serbia, Grant no. 200162 (University of Belgrade, Faculty of Physics) (RS-200162)
- Ministry of Education, Science and Technological Development, Republic of Serbia, Grant no. 200146 (University of Belgrade, Faculty of Physical Chemistry) (RS-200146)
Note:
- Peer-reviewed manuscript: https://cherry.chem.bg.ac.rs/handle/123456789/5882
DOI: 10.1016/j.jinorgbio.2023.112181
ISSN: 0162-0134
WoS: 000946607300001
Scopus: 2-s2.0-85150073648
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Hemijski fakultet / Faculty of ChemistryTY - JOUR AU - Korać Jačić, Jelena AU - Bajuk-Bogdanović, Danica AU - Savić, Slađana D. AU - Božić Cvijan, Bojana AU - Spasojević, Milica AU - MIlenković, Milica R. PY - 2023 UR - http://cherry.chem.bg.ac.rs/handle/123456789/5881 AB - Hydralazine (HL), a frequently prescribed oral antihypertensive drug, shows redox interactions with transition metals such as copper that are not fully understood. Copper may be present at high concentrations in the digestive tract and can affect oral drugs. An important parameter for such interactions is pH, which changes from acidic in the gastric juice to neutral pH in intestines. In this study, we examined interactions of HL with Cu2+ ions in conditions that mimic pH shift in the digestive tract using UV–Vis, Raman and EPR spectroscopy, cyclic voltammetry and oximetry. In the acidic solution, Cu2+ formed a stable mononuclear complex with two bidentate coordinated HL molecules. On the other hand, at neutral pH, Cu2+ initiated oxidation and degradation of HL. The degradation was more rapid in the HL-Cu2+ system that was initially prepared at acidic pH and then shifted to neutral pH. The formation of the complex at acidic pH increases the availability of Cu2+ for redox reactions after the shift to neutral pH at which Cu2+ is poorly soluble. These results imply that the change of pH along the digestive tract may promote HL degradation by allowing the formation of the complex at gastric pH which makes Cu2+ available for subsequent oxidation of HL at neutral pH. PB - Elsevier T2 - Journal of Inorganic Biochemistry T1 - Coordination of hydralazine with Cu2+ at acidic pH promotes its oxidative degradation at neutral pH VL - 243 SP - 112181 DO - 10.1016/j.jinorgbio.2023.112181 ER -
@article{ author = "Korać Jačić, Jelena and Bajuk-Bogdanović, Danica and Savić, Slađana D. and Božić Cvijan, Bojana and Spasojević, Milica and MIlenković, Milica R.", year = "2023", abstract = "Hydralazine (HL), a frequently prescribed oral antihypertensive drug, shows redox interactions with transition metals such as copper that are not fully understood. Copper may be present at high concentrations in the digestive tract and can affect oral drugs. An important parameter for such interactions is pH, which changes from acidic in the gastric juice to neutral pH in intestines. In this study, we examined interactions of HL with Cu2+ ions in conditions that mimic pH shift in the digestive tract using UV–Vis, Raman and EPR spectroscopy, cyclic voltammetry and oximetry. In the acidic solution, Cu2+ formed a stable mononuclear complex with two bidentate coordinated HL molecules. On the other hand, at neutral pH, Cu2+ initiated oxidation and degradation of HL. The degradation was more rapid in the HL-Cu2+ system that was initially prepared at acidic pH and then shifted to neutral pH. The formation of the complex at acidic pH increases the availability of Cu2+ for redox reactions after the shift to neutral pH at which Cu2+ is poorly soluble. These results imply that the change of pH along the digestive tract may promote HL degradation by allowing the formation of the complex at gastric pH which makes Cu2+ available for subsequent oxidation of HL at neutral pH.", publisher = "Elsevier", journal = "Journal of Inorganic Biochemistry", title = "Coordination of hydralazine with Cu2+ at acidic pH promotes its oxidative degradation at neutral pH", volume = "243", pages = "112181", doi = "10.1016/j.jinorgbio.2023.112181" }
Korać Jačić, J., Bajuk-Bogdanović, D., Savić, S. D., Božić Cvijan, B., Spasojević, M.,& MIlenković, M. R.. (2023). Coordination of hydralazine with Cu2+ at acidic pH promotes its oxidative degradation at neutral pH. in Journal of Inorganic Biochemistry Elsevier., 243, 112181. https://doi.org/10.1016/j.jinorgbio.2023.112181
Korać Jačić J, Bajuk-Bogdanović D, Savić SD, Božić Cvijan B, Spasojević M, MIlenković MR. Coordination of hydralazine with Cu2+ at acidic pH promotes its oxidative degradation at neutral pH. in Journal of Inorganic Biochemistry. 2023;243:112181. doi:10.1016/j.jinorgbio.2023.112181 .
Korać Jačić, Jelena, Bajuk-Bogdanović, Danica, Savić, Slađana D., Božić Cvijan, Bojana, Spasojević, Milica, MIlenković, Milica R., "Coordination of hydralazine with Cu2+ at acidic pH promotes its oxidative degradation at neutral pH" in Journal of Inorganic Biochemistry, 243 (2023):112181, https://doi.org/10.1016/j.jinorgbio.2023.112181 . .