NDLI: Acylglucuronide in alkaline conditions: migration vs. hydrolysis

Content Provider	Springer Nature Link
Author	Di Meo, Florent Steel, Michele Nicolas, Picard Marquet, Pierre Duroux, Jean Luc Trouillas, Patrick
Copyright Year	2013
Abstract	This work rationalizes the glucuronidation process (one of the reactions of the phase II metabolism) for drugs having a carboxylic acid moiety. At this stage, acylglucuronides (AG) metabolites are produced, that have largely been reported in the literature for various drugs (e.g., mycophenolic acid (MPA), diclofenac, ibuprofen, phenylacetic acids). The competition between migration and hydrolysis is rationalized by adequate quantum calculations, combing MP2 and density functional theory (DFT) methods. At the molecular scale, the former process is a real rotation of the drug around the glucuconic acid. This chemical-engine provides four different metabolites with various toxicities. Migration definitely appears feasible under alkaline conditions, making proton release from the OH groups. The latter reaction (hydrolysis) releases the free drug, so the competition is of crucial importance to tackle drug action and elimination. From the theoretical data, both migration and hydrolysis appear kinetically and thermodynamically favored, respectively.
Starting Page	2423
Ending Page	2432
Page Count	10
File Format	PDF
ISSN	16102940
Journal	Journal of Molecular Modeling
Volume Number	19
Issue Number	6
e-ISSN	09485023
Language	English
Publisher	Springer-Verlag
Publisher Date	2013-02-19
Publisher Place	Berlin, Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Acylglucuronides Alkaline hydrolysis DFT Kinetics Migration Thermodynamics Computer Applications in Chemistry Molecular Medicine Computer Application in Life Sciences Characterization and Evaluation of Materials Theoretical and Computational Chemistry
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Physical and Theoretical Chemistry Computational Theory and Mathematics Catalysis Inorganic Chemistry Computer Science Applications

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Mechanisms and kinetics of thiotepa and tepa hydrolysis: DFT study

DFT study of the hydrolysis reaction in atranes and ocanes: the influence of transannular bonding

A density functional theory study on peptide bond cleavage at aspartic residues: direct vs cyclic intermediate hydrolysis

Exohedral and endohedral adsorption of alkaline earth cations in BN nanocluster

Can Satraplatin be hydrated before the reduction process occurs? The DFT computational study

A theoretical study on the hydrolysis mechanism of carbon disulfide

Computational benchmark for calculation of silane and siloxane thermochemistry

Fluorination of BC3 nanotubes: DFT studies

DFT calculation of the electronic properties of fluorene-1,3,4-thiadiazole oligomers

Acylglucuronide in alkaline conditions: migration vs. hydrolysis

Similar Documents

Mechanisms and kinetics of thiotepa and tepa hydrolysis: DFT study

DFT study of the hydrolysis reaction in atranes and ocanes: the influence of transannular bonding

A density functional theory study on peptide bond cleavage at aspartic residues: direct vs cyclic intermediate hydrolysis

Exohedral and endohedral adsorption of alkaline earth cations in BN nanocluster

Can Satraplatin be hydrated before the reduction process occurs? The DFT computational study

A theoretical study on the hydrolysis mechanism of carbon disulfide

Computational benchmark for calculation of silane and siloxane thermochemistry

Fluorination of BC3 nanotubes: DFT studies

DFT calculation of the electronic properties of fluorene-1,3,4-thiadiazole oligomers

Acylglucuronide in alkaline conditions: migration vs. hydrolysis