Determination of the microscopic acid dissociation constant of piperacillin and identification of dissociated molecular forms
For amphoteric ß-lactam antibiotics, the acid dissociation constant (pKa) is a fundamental parameter to characterize physicochemical and biochemical properties of antibiotics and to predict persistence and removal of drugs. pKa of piperacillin (PIP) is determined by potentiometric titration with a g...
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Frontiers Media S.A.
2023-04-01
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| Series: | Frontiers in Chemistry |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fchem.2023.1177128/full |
| _version_ | 1827959528788852736 |
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| author | Guoao Li Yaling Wang Yaling Wang Chengyi Sun Chengyi Sun Fei Liu |
| author_facet | Guoao Li Yaling Wang Yaling Wang Chengyi Sun Chengyi Sun Fei Liu |
| author_sort | Guoao Li |
| collection | DOAJ |
| description | For amphoteric ß-lactam antibiotics, the acid dissociation constant (pKa) is a fundamental parameter to characterize physicochemical and biochemical properties of antibiotics and to predict persistence and removal of drugs. pKa of piperacillin (PIP) is determined by potentiometric titration with a glass electrode. Electrospray ionization mass spectrometry (ESI-MS) is creatively applied to verify the reasonable pKa value at every dissociation step. Two microscopic pKa values (3.37 ± 0.06 and 8.96 ± 0.10) are identified and attributed to the direct dissociation of the carboxylic acid functional group and one secondary amide group, respectively. Different from other ß-lactam antibiotics, PIP presents a dissociation pattern where direct dissociation is involved instead of protonation dissociation. Moreover, the degradation tendency of PIP in an alkaline solution may alter the dissociation pattern or dismiss the corresponding pKa of the amphoteric ß-lactam antibiotics. This work offers a reliable determination of the acid dissociation constant of PIP and a clear interpretation of the effect of stability of antibiotics on the dissociation process. |
| first_indexed | 2024-04-09T15:53:33Z |
| format | Article |
| id | doaj.art-edefe254b60f4ce98a32ba9097d1a147 |
| institution | Directory Open Access Journal |
| issn | 2296-2646 |
| language | English |
| last_indexed | 2024-04-09T15:53:33Z |
| publishDate | 2023-04-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Chemistry |
| spelling | doaj.art-edefe254b60f4ce98a32ba9097d1a1472023-04-26T04:59:41ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462023-04-011110.3389/fchem.2023.11771281177128Determination of the microscopic acid dissociation constant of piperacillin and identification of dissociated molecular formsGuoao Li0Yaling Wang1Yaling Wang2Chengyi Sun3Chengyi Sun4Fei Liu5Beijing Key Laboratory of Water Resources and Environmental Engineering, School of water resource and Environment, China University of Geosciences (Beijing), Beijing, ChinaBeijing Municipal Research Institute of Eco-Environmental Protection, Beijing, ChinaNational Engineering Research Center for Urban Environmental Pollution Control, Beijing, ChinaBeijing Municipal Research Institute of Eco-Environmental Protection, Beijing, ChinaNational Engineering Research Center for Urban Environmental Pollution Control, Beijing, ChinaBeijing Key Laboratory of Water Resources and Environmental Engineering, School of water resource and Environment, China University of Geosciences (Beijing), Beijing, ChinaFor amphoteric ß-lactam antibiotics, the acid dissociation constant (pKa) is a fundamental parameter to characterize physicochemical and biochemical properties of antibiotics and to predict persistence and removal of drugs. pKa of piperacillin (PIP) is determined by potentiometric titration with a glass electrode. Electrospray ionization mass spectrometry (ESI-MS) is creatively applied to verify the reasonable pKa value at every dissociation step. Two microscopic pKa values (3.37 ± 0.06 and 8.96 ± 0.10) are identified and attributed to the direct dissociation of the carboxylic acid functional group and one secondary amide group, respectively. Different from other ß-lactam antibiotics, PIP presents a dissociation pattern where direct dissociation is involved instead of protonation dissociation. Moreover, the degradation tendency of PIP in an alkaline solution may alter the dissociation pattern or dismiss the corresponding pKa of the amphoteric ß-lactam antibiotics. This work offers a reliable determination of the acid dissociation constant of PIP and a clear interpretation of the effect of stability of antibiotics on the dissociation process.https://www.frontiersin.org/articles/10.3389/fchem.2023.1177128/fullacid dissociation constantpiperacillinpotentiometric titrationβ-lactam antibioticsmolecular forms |
| spellingShingle | Guoao Li Yaling Wang Yaling Wang Chengyi Sun Chengyi Sun Fei Liu Determination of the microscopic acid dissociation constant of piperacillin and identification of dissociated molecular forms Frontiers in Chemistry acid dissociation constant piperacillin potentiometric titration β-lactam antibiotics molecular forms |
| title | Determination of the microscopic acid dissociation constant of piperacillin and identification of dissociated molecular forms |
| title_full | Determination of the microscopic acid dissociation constant of piperacillin and identification of dissociated molecular forms |
| title_fullStr | Determination of the microscopic acid dissociation constant of piperacillin and identification of dissociated molecular forms |
| title_full_unstemmed | Determination of the microscopic acid dissociation constant of piperacillin and identification of dissociated molecular forms |
| title_short | Determination of the microscopic acid dissociation constant of piperacillin and identification of dissociated molecular forms |
| title_sort | determination of the microscopic acid dissociation constant of piperacillin and identification of dissociated molecular forms |
| topic | acid dissociation constant piperacillin potentiometric titration β-lactam antibiotics molecular forms |
| url | https://www.frontiersin.org/articles/10.3389/fchem.2023.1177128/full |
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