Penicillins

Ismalaj, Ermal; Borggraeve, Wim M. De

doi:10.1016/b978-0-12-818655-8.00141-4

Cited by 2 publications

(2 citation statements)

References 258 publications

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“…In bicyclic structures, the amide stabilization is attenuated by a third bonding partner, which creates a trigonal pyramidal (sp 3 ) nitrogen geometry. The reduced amide resonance conferred by these bicyclic systems affords increased carbonyl electrophilicity and higher intrinsic reactivity to nucleophiles and nucleophile-containing enzymes such as transpeptidases, β-lactamases, and metallo-β-lactamases ( Green et al, 1965 ; Morin et al, 1969 ; Sweet and Dahl, 1970 ; Glover and Rosser, 2012 ; Szostak et al, 2015 ; Ismalaj, 2022 ).…”

Section: Structural Platforms and β-Lactam Classesmentioning

confidence: 99%

“…Considering the trigonal pyramid, defined by the nitrogen (i.e., the apex) and its three bond-pair substituents (i.e., the base) ( Figure 3 ), the distortion from a planar (sp 2 ) amide can be defined by a parameter known as the Woodward height ( h -Woodward) ( Ernest et al, 1978 ; Lang et al, 1978 ; Woodward, 1980 ; Meng et al, 2021 ; Ismalaj, 2022 ). Monocyclic monobactams, having an essentially planar geometry at nitrogen, tend to be the least reactive of the β-lactams with negligible h -Woodward values ( Diaz et al, 2002 ).…”

Section: Structural Platforms and β-Lactam Classesmentioning

confidence: 99%

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The Chemical Relationship Among Beta-Lactam Antibiotics and Potential Impacts on Reactivity and Decomposition

Turner

Muraoka

Bedenbaugh³

et al. 2022

Front. Microbiol.

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Beta-lactam antibiotics remain one of the most commonly prescribed drug classes, but they are limited by their propensity to cause hypersensitivity reactions (e.g., from allergy to anaphylaxis) as well as by the emergence of bacteria with a myriad of resistance mechanisms such as β-lactamases. While development efforts continue to focus on overcoming resistance, there are ongoing concerns regarding cross-contamination of β-lactams during manufacturing and compounding of these drugs. Additionally, there is a need to reduce levels of drugs such as β-lactam antibiotics in waste-water to mitigate the risk of environmental exposure. To help address future development of effective remediation chemistries and processes, it is desired to better understand the structural relationship among the most common β-lactams. This study includes the creation of a class-wide structural ordering of the entire β-lactam series, including both United States Food and Drug Association (US-FDA)-approved drugs and experimental therapies. The result is a structural relational map: the “Lactamome,” which positions each substance according to architecture and chemical end-group. We utilized a novel method to compare the structural relationships of β-lactam antibiotics among the radial cladogram and describe the positioning with respect to efficacy, resistance to hydrolysis, reported hypersensitivity, and Woodward height. The resulting classification scheme may help with the development of broad-spectrum treatments that reduce the risk of occupational exposure and negative environmental impacts, assist practitioners with avoiding adverse patient reactions, and help direct future drug research.

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