Enzyme inhibition by fluoro compounds.

Abeles, Robert H.; Alston, Theodore A.

doi:10.1016/s0021-9258(17)44813-7

Cited by 79 publications

(21 citation statements)

References 83 publications

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“…PLP-dependent decarboxylases are also susceptible to α-(1′-halo)vinyl-α-amino acid MBIs. , One example is d -(1-chlorovinyl)glycine ( 393 ), which inhibited the alanine racemase from Escherichia coli B. , Similarly, (1-fluorovinyl)glycine ( 394 ), an MBI of Escherichia coli B alanine racemase, also inhibited Salmonella typhimurium tryptophan synthase. Compound 395 is an inhibitor of lysine decarboxylase from the Gram-negative bacterium Hafnai alvei .…”

Section: Fluorinated Aminesmentioning

confidence: 99%

“…300 PLP-dependent decarboxylases are also susceptible to α-(1′halo)vinyl-α-amino acid MBIs. 301,302 One example is D-(1chlorovinyl)glycine (393), which inhibited the alanine racemase from Escherichia coli B. 285,303 glycine (394), an MBI of Escherichia coli B alanine racemase, also inhibited Salmonella typhimurium tryptophan synthase.…”

Section: Metabolism Of β-Fluorinatedmentioning

confidence: 99%

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Metabolic and Pharmaceutical Aspects of Fluorinated Compounds

et al. 2020

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The applications of fluorine in drug design continue to expand, facilitated by an improved understanding of its effects on physicochemical properties and the development of synthetic methodologies that are providing access to new fluorinated motifs. In turn, studies of fluorinated molecules are providing deeper insights into the effects of fluorine on metabolic pathways, distribution, and disposition. Despite the high strength of the C–F bond, the departure of fluoride from metabolic intermediates can be facile. This reactivity has been leveraged in the design of mechanism-based enzyme inhibitors and has influenced the metabolic fate of fluorinated compounds. In this Perspective, we summarize the literature associated with the metabolism of fluorinated molecules, focusing on examples where the presence of fluorine influences the metabolic profile. These studies have revealed potentially problematic outcomes with some fluorinated motifs and are enhancing our understanding of how fluorine should be deployed.

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Section: Fluorinated Aminesmentioning

confidence: 99%

Section: Metabolism Of β-Fluorinatedmentioning

confidence: 99%

Metabolic and Pharmaceutical Aspects of Fluorinated Compounds

et al. 2020

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“…33 In bio-inorganic and medicinal chemistry, the formation of intermolecular X-HÁ Á ÁF-C (X = O, N) hydrogen bridges is significantly important because of the binding nature of the fluorinated compounds to enzyme active sites. [34][35][36][37][38] In spite of the fact that fluorine containing organic molecules have great importance in a number of fields, the study of intramolecular HB involving organic fluorine is limited owing to the fact that it hardly ever accepts intramolecular HB [39][40][41][42][43][44][45] This is also substantiated by a report by Dunitz and co-workers entitled ''organic fluorine hardly ever accepts hydrogen bonds''. [46][47][48][49] However, there are very few reports of the involvement of organic fluorine in the HB in the solution state.…”

Section: Introductionmentioning

confidence: 99%

Intramolecular hydrogen bonds involving organic fluorine in the derivatives of hydrazides: an NMR investigation substantiated by DFT based theoretical calculations

Mishra

Suryaprakash

2015

Phys. Chem. Chem. Phys.

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The rare examples of intramolecular hydrogen bonds (HB) of the type the N-H∙∙∙F-C, detected in a low polarity solvent in the derivatives of hydrazides, by utilizing one and two-dimensional solution state multinuclear NMR techniques, are reported. The observation of through-space couplings, such as, (1h)JFH, and (1h)JFN, provides direct evidence for the existence of intra-molecular HB. Solvent induced perturbations and the variable temperature NMR experiments unambiguously establish the presence of intramolecular HB. The existence of multiple conformers in some of the investigated molecules is also revealed by two dimensional HOESY and (15)N-(1)H HSQC experiments. The (1)H DOSY experimental results discard any possibility of self or cross dimerization of the molecules. The derived NMR experimental results are further substantiated by Density Function Theory (DFT) based Non Covalent Interaction (NCI), and Quantum Theory of Atom in Molecule (QTAIM) calculations. The NCI calculations served as a very sensitive tool for detection of non-covalent interactions and also confirm the presence of bifurcated HBs.

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“…In addition, organouorine molecules have enormous importance due to their applicability as biomaterials and agrochemicals, in molecular imaging, 23,24 crystal engineering [25][26][27] and also in functional materials design. 28 The bio-origin of the medicinal and bio-inorganic properties of uorinated compounds is a consequence of the binding nature of uorine to enzyme active sites [29][30][31][32][33] through intermolecular hydrogen bonded bridges of the type X-H/F-C (X ¼ O, N). Nevertheless there are very few reports on the participation of organic uorine in HBs in the solution state.…”

Section: Introductionmentioning

confidence: 99%

Organic fluorine involved intramolecular hydrogen bonds in the derivatives of imides: NMR evidence corroborated by DFT based theoretical calculations

Mishra

Suryaprakash

2015

RSC Adv.

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The rare occurrence of the intramolecular Hydrogen bonds (HBs) of the type N−H•••F−C are detected in the derivatives of imides in a low polarity solvent by using multi-dimensional and multinuclear NMR experiments. The observation of 1h JFH, 2h JFN, and 2h JFF, where the spin magnetization is transmitted through-space among the interacting NMR active nuclei, provided the strong and unambiguous evidence for the existence of intra-molecular HB. The variation of chemical shifts of labile protons on physical conditions, such as, solvent dilution and systematic alteration of temperature confirmed the presence of weak interactions through intramolecular HBs in all the investigated fluorine substituted molecules. The self or cross dimerization of molecules is unequivocally discarded by the analysis of the rates of diffusion obtained using pseudo-two dimensional DOSY experiments. The Density Function Theoretical (DFT) calculations based on Quantum Theory of Atoms in Molecules (QTAIM) and Non Covalent Interaction (NCI), are in close agreement with the NMR experimental findings.

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Enzyme inhibition by fluoro compounds.

Cited by 79 publications

References 83 publications

Metabolic and Pharmaceutical Aspects of Fluorinated Compounds

Metabolic and Pharmaceutical Aspects of Fluorinated Compounds

Intramolecular hydrogen bonds involving organic fluorine in the derivatives of hydrazides: an NMR investigation substantiated by DFT based theoretical calculations

Organic fluorine involved intramolecular hydrogen bonds in the derivatives of imides: NMR evidence corroborated by DFT based theoretical calculations

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