Epimerization of Benzylpenicilloic Acid in Alkaline Media

Ghebre-Sellassie, Isaac; Hem, Stanley L.; Knevel, Adelbert M.

doi:10.1002/jps.2600730135

Cited by 36 publications

(20 citation statements)

References 9 publications

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“…In previous work with benzylpenicilloic acid, a slow conversion between epimers has been noted in aqueous solution at pH 8.7 [29]. In this case, the conversion from 5R,6R-benzylpenicilloic acid to 5S,6R-benzylpenicilloic acid was found to occur over a 5 day period.…”

Section: Nmr and Molecular Modeling Studies Of Warfarin Conversionmentioning

confidence: 71%

Stability of warfarin solutions for drug–protein binding measurements: Spectroscopic and chromatographic studies

Moser

Kingsbury

Hage

2006

Journal of Pharmaceutical and Biomedical Analysis

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Warfarin is commonly used in drug-protein binding studies as a displacement marker for Sudlow site I on the protein human serum albumin (HSA). This study examined the stability of aqueous warfarin solutions prepared for such experiments. This was investigated using NMR spectroscopy and affinity chromatography. It was found by 1H NMR that warfarin underwent a slow first-order conversion in aqueous solution. The rate of this reaction increased with temperature, giving rate constants at pH 7.4 of 0.0086 h(-1) at 25 degrees C and 0.041 h(-1) at 37 degrees C. It was concluded from further 1H and 13C NMR studies, along with molecular modeling, that this process involved the conversion of the minor cyclic hemiketal form of warfarin to its major cyclic hemiketal. This reaction had a small but measurable effect on the binding of R- and S-warfarin to HSA, as demonstrated by HPLC using an immobilized HSA affinity column. From this work, general guidelines were developed concerning the usable lifetimes for warfarin that is prepared in aqueous solutions for studies of drug-protein binding.

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Section: Nmr and Molecular Modeling Studies Of Warfarin Conversionmentioning

confidence: 71%

Stability of warfarin solutions for drug–protein binding measurements: Spectroscopic and chromatographic studies

Moser

Kingsbury

Hage

2006

Journal of Pharmaceutical and Biomedical Analysis

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“…The observation of penicilloic acid and hydrolyzed meropenem binding to SPM‐1 is of potential clinical relevance. Previous studies have shown that penicilloic acids are competitive inhibitors of serine β‐lactamases23 and MBLs 24. Although the levels of inhibition by penicilloic acids are much less than those for the intact β‐lactams, given the high concentration of β‐lactams used clinically, it is possible that β‐lactamase inhibition by PAs is relevant.…”

mentioning

confidence: 99%

¹⁹F‐NMR Reveals the Role of Mobile Loops in Product and Inhibitor Binding by the São Paulo Metallo‐β‐Lactamase

et al. 2017

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Resistance to β‐lactam antibiotics mediated by metallo‐β‐lactamases (MBLs) is a growing problem. We describe the use of protein‐observe 19F‐NMR (PrOF NMR) to study the dynamics of the São Paulo MBL (SPM‐1) from β‐lactam‐resistant Pseudomonas aeruginosa. Cysteinyl variants on the α3 and L3 regions, which flank the di‐ZnII active site, were selectively 19F‐labeled using 3‐bromo‐1,1,1‐trifluoroacetone. The PrOF NMR results reveal roles for the mobile α3 and L3 regions in the binding of both inhibitors and hydrolyzed β‐lactam products to SPM‐1. These results have implications for the mechanisms and inhibition of MBLs by β‐lactams and non‐β‐lactams and illustrate the utility of PrOF NMR for efficiently analyzing metal chelation, identifying new binding modes, and studying protein binding from a mixture of equilibrating isomers.

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“…Penicillin is not stable in acidic and alkaline conditions [23,24] and prone to bring b-lactam ring opening, which will result in inactivation of NaBP drug. In this part, the effects of pH value on NaBP and its SERS spectrum were studied.…”

Section: The Influence Of Ph Value On Nabp and Its Sers Spectrummentioning

confidence: 99%

Rapid monitoring of benzylpenicillin sodium using Raman and surface enhanced Raman spectroscopy

Jiang

Qin

Yin

et al. 2015

Spectrochimica Acta Part A: Molecular and Biomolecular Spectros

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Epimerization of Benzylpenicilloic Acid in Alkaline Media

Cited by 36 publications

References 9 publications

Stability of warfarin solutions for drug–protein binding measurements: Spectroscopic and chromatographic studies

Stability of warfarin solutions for drug–protein binding measurements: Spectroscopic and chromatographic studies

¹⁹F‐NMR Reveals the Role of Mobile Loops in Product and Inhibitor Binding by the São Paulo Metallo‐β‐Lactamase

Rapid monitoring of benzylpenicillin sodium using Raman and surface enhanced Raman spectroscopy

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Epimerization of Benzylpenicilloic Acid in Alkaline Media

Cited by 36 publications

References 9 publications

Stability of warfarin solutions for drug–protein binding measurements: Spectroscopic and chromatographic studies

Stability of warfarin solutions for drug–protein binding measurements: Spectroscopic and chromatographic studies

19F‐NMR Reveals the Role of Mobile Loops in Product and Inhibitor Binding by the São Paulo Metallo‐β‐Lactamase

Rapid monitoring of benzylpenicillin sodium using Raman and surface enhanced Raman spectroscopy

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Product

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¹⁹F‐NMR Reveals the Role of Mobile Loops in Product and Inhibitor Binding by the São Paulo Metallo‐β‐Lactamase