Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Kinetics and mechanistic investigations on antiviral drug-valacyclovir hydrochloride by heptavalent alkaline permanganate.

ABSTRACT:

Abstract

Kinetics of Permanganate (MnO₄ ^-) oxidation of antiviral drug, valacyclovir hydrochloride (VCH) has been studied spectrophotometrically at a constant ionic strength of 0.1 mol dm^-3. The reaction exhibiting a 2:1 stoichiometry (MnO₄ ^-:VCH) has been studied over a wide range of experimental conditions. It was found that the rate enhancement was associated with an increase in concentrations of alkali, reductant and temperature. A plausible mechanism involving an intermediate Mn(VII)-VCH complex (C) was expected and rate law is derived accordingly. Calculated activation parameters also supported the anticipated mechanism.

Graphic abstract

Supplementary information

The online version contains supplementary material available at 10.1007/s12039-021-01969-4.

SUBMITTER: Tuwar SM

PROVIDER: S-EPMC8565177 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Kinetics and mechanistic investigations on antiviral drug-valacyclovir hydrochloride by heptavalent alkaline permanganate.

Tuwar Suresh M SM Hanabaratti Rohini M RM

Journal of chemical sciences (Bangalore, India) 20211103 4

<h4>Abstract</h4>Kinetics of Permanganate (MnO4 -) oxidation of antiviral drug, valacyclovir hydrochloride (VCH) has been studied spectrophotometrically at a constant ionic strength of 0.1 mol dm-3. The reaction exhibiting a 2:1 stoichiometry (MnO4 -:VCH) has been studied over a wide range of experimental conditions. It was found that the rate enhancement was associated with an increase in concentrations of alkali, reductant and temperature. ...[more]

PMID: 34751205

Similar Datasets

H/D Exchange Processes in Flavonoids: Kinetics and Mechanistic Investigations.

Project description:Several classes of flavonoids, such as anthocyanins, flavonols, flavanols, and flavones, undergo a slow H/D exchange on aromatic ring A, leading to full deuteration at positions C(6) and C(8). Within the flavanol class, H-C(6) and H-C(8) of catechin and epicatechin are slowly exchanged in D2O to the corresponding deuterated analogues. Even quercetin, a relevant flavonol representative, shows the same behaviour in a D2O/DMSOd6 1:1 solution. Detailed kinetic measurements of these H/D exchange processes are here reported by exploiting the time-dependent changes of their peak areas in the 1H-NMR spectra taken at different temperatures. A unifying reaction mechanism is also proposed based on our detailed kinetic observations, even taking into account pH and solvent effects. Molecular modelling and QM calculations were also carried out to shed more light on several molecular details of the proposed mechanism.

| S-EPMC8229540 | biostudies-literature

Monitoring the heat-induced structural changes of alkaline phosphatase by molecular modeling, fluorescence spectroscopy and inactivation kinetics investigations.

Project description:The heat induced conformational changes of calf alkaline phosphatase (ALP) were analyzed using different methods, based on fluorescence spectroscopy, molecular modeling and inactivation studies. Experimental studies were conducted in buffer solution in the temperature range between 25 and 70 °C. Molecular dynamic (MD) simulation provided details on thermally induced changes in ALP structure, highlighting that heating favored the hydrophobic exposure and important alteration of the catalytic site above 60 °C. Additional information to MD data were obtained by using different fluorescence spectroscopy methods, which revealed a complex mechanism of thermal denaturation. Therefore, the emissive properties indicated an unfolding of ALP at temperatures below 60 °C, whereas at higher temperatures, the polypeptides chains fold leading to a higher exposure of Trp residues. In order to establish a structure-function relationship, the results were correlated with inactivation studies of ALP in buffer at pH 9.0. The inactivation data were fitted using a first-order kinetic model, resulting in an activation energy value of 207.26 ± 21.68 kJ · mol(-1).

| S-EPMC4573144 | biostudies-literature

Oxidation of Cefalexin by Permanganate: Reaction Kinetics, Mechanism, and Residual Antibacterial Activity.

Project description:The oxidation of cefalexin (CFX), a commonly used cephalosporin antibiotic, was investigated by permanganate (PM) in water. Apparent second-order rate constant of the reaction between CFX and PM was determined to be 12.71 ± (1.62) M-1·s-1 at neutral pH. Lower pH was favorable for the oxidation of CFX by PM. The presence of Cl- and HCO₃- could enhance PM-induced oxidation of CFX, whereas HA had negligible effect on CFX oxidation by PM. PM-induced oxidation of CFX was also significant in the real wastewater matrix. After addition of bisulfite (BS), PM-induced oxidation was significantly accelerated owing to the generation of Mn(III) reactive species. Product analysis indicated oxidation of CFX to three products, with two stereoisomeric sulfoxide products and one di-ketone product. The thioether sulfur and double bond on the six-membered ring were the reactive sites towards PM oxidation. Antibacterial activity assessment indicated that the activity of CFX solution was significantly reduced after PM oxidation.

| S-EPMC6222860 | biostudies-literature

Mechanistic Investigations Support Liver Safety of Ubrogepant.

Project description:Small-molecule calcitonin gene-related peptide (CGRP) receptor antagonists have demonstrated therapeutic efficacy for the treatment of migraine. However, previously investigated CGRP receptor antagonists, telcagepant and MK-3207, were discontinued during clinical development because of concerns about drug-induced liver injury. A subsequent effort to identify novel CGRP receptor antagonists less likely to cause hepatotoxicity led to the development of ubrogepant. The selection of ubrogepant, following a series of mechanistic studies conducted with MK-3207 and telcagepant, was focused on key structural modifications suggesting that ubrogepant was less prone to forming reactive metabolites than previous compounds. The potential for each drug to cause liver toxicity was subsequently assessed using a quantitative systems toxicology approach (DILIsym) that incorporates quantitative assessments of mitochondrial dysfunction, disruption of bile acid homeostasis, and oxidative stress, along with estimates of dose-dependent drug exposure to and within liver cells. DILIsym successfully modeled liver toxicity for telcagepant and MK-3207 at the dosing regimens used in clinical trials. In contrast, DILIsym predicted no hepatotoxicity during treatment with ubrogepant, even at daily doses up to 1000 mg (10-fold higher than the approved clinical dose of 100 mg). These predictions are consistent with clinical trial experience showing that ubrogepant has lower potential to cause hepatotoxicity than has been observed with telcagepant and MK-3207.

| S-EPMC8312697 | biostudies-literature

Mechanistic investigations on six bacterial terpene cyclases.

Project description:The products obtained by incubation of farnesyl diphosphate (FPP) with six purified bacterial terpene cyclases were characterised by one- and two-dimensional NMR spectroscopic methods, allowing for a full structure elucidation. The absolute configurations of four terpenes were determined based on their optical rotary powers. Incubation experiments with 13C-labelled isotopomers of FPP in buffers containing water or deuterium oxide allowed for detailed insights into the cyclisation mechanisms of the bacterial terpene cyclases.

| S-EPMC5082573 | biostudies-literature

Structural and mechanistic investigations of protein S-glycosyltransferases.

Project description:Attachment of sugars to nitrogen and oxygen in peptides is ubiquitous in biology, but glycosylation of sulfur atoms has only been recently described. Here, we characterize two S-glycosyltransferases SunS and ThuS that selectively glycosylate one of five Cys residues in their substrate peptides; substitution of this Cys with Ser results in a strong decrease in glycosylation activity. Crystal structures of SunS and ThuS in complex with UDP-glucose or a derivative reveal an unusual architecture in which a glycosyltransferase type A (GTA) fold is decorated with additional domains to support homodimerization. Dimer formation creates an extended cavity for the substrate peptide, drawing functional analogy with O-glycosyltransferases involved in cell wall biosynthesis. This extended cavity contains a sharp bend that may explain the site selectivity of the glycosylation because the target Cys is in a Gly-rich stretch that can accommodate the bend. These studies establish a molecular framework for understanding the unusual S-glycosyltransferases.

| S-EPMC8688163 | biostudies-literature

Kinetics of Direct Reaction of Vanadate, Chromate, and Permanganate with Graphene Nanoplatelets for Use in Water Purification.

Project description:Oxometalates of vanadium(V), chromium(VI), and manganese(VII) have negative impacts on water resources due to their toxicity. To remove them, the kinetics of 0.04 mM oxometalates in natural and synthetic water were studied using graphene nanoplatelets (GNP). The GNP were dispersible in water and formed aggregates >15 µm that could be easily separated. Within 30 min, the GNP were covered with ~0.4 mg/g vanadium and ~1.0 mg/g chromium as Cr(OH)3. The reaction of 0.04 mM permanganate with 50 mg of GNP resulted in a coverage of 10 mg/g in 5 min, while the maximum value was 300 mg/g manganese as Mn2O3/MnO. TEM showed a random metal distribution on the surfaces; no clusters or nanoparticles were detected. The rate of disappearance in aerated water followed a pseudo second-order adsorption kinetics (PSO) for V(V), a pseudo second-order reaction for Cr(VI), and a pseudo first-order reaction for Mn(VII). For Cr(VI) and Mn(VII), the rate constants were found to depend on the GNP mass. Oxygen sorption occurred with PSO kinetics as a parallel slow process upon contact of GNP with air-saturated water. For thermally regenerated GNP, the rate constant decreased for V(V) but increased for Cr(VI), while no effect was observed for Mn(VII). GNP capacity was enhanced through regeneration for V(V) and Cr(VI); no effect was observed for Mn(VII). The reactions are well-suited for use in water purification processes and the reaction products, GNP, decorated with single metal atoms, are of great interest for the construction of sensors, electronic devices, and for application in single-atom catalysis (SAC).

| S-EPMC10819118 | biostudies-literature

Mechanistic investigations of unsaturated glucuronyl hydrolase from Clostridium perfringens.

Project description:Experiments were carried out to probe the details of the hydration-initiated hydrolysis catalyzed by the Clostridium perfringens unsaturated glucuronyl hydrolase of glycoside hydrolase family 88 in the CAZy classification system. Direct (1)H NMR monitoring of the enzymatic reaction detected no accumulated reaction intermediates in solution, suggesting that rearrangement of the initial hydration product occurs on-enzyme. An attempt at mechanism-based trapping of on-enzyme intermediates using a 1,1-difluoro-substrate was unsuccessful because the probe was too deactivated to be turned over by the enzyme. Kinetic isotope effects arising from deuterium-for-hydrogen substitution at carbons 1 and 4 provide evidence for separate first-irreversible and overall rate-determining steps in the hydration reaction, with two potential mechanisms proposed to explain these results. Based on the positioning of catalytic residues in the enzyme active site, the lack of efficient turnover of a 2-deoxy-2-fluoro-substrate, and several unsuccessful attempts at confirmation of a simpler mechanism involving a covalent glycosyl-enzyme intermediate, the most plausible mechanism is one involving an intermediate bearing an epoxide on carbons 1 and 2.

| S-EPMC4036275 | biostudies-literature

Mechanistic investigations on Pinnick oxidation: a density functional theory study.

Project description:A computational study on Pinnick oxidation of aldehydes into carboxylic acids using density functional theory (DFT) calculations has been evaluated with the (SMD)-M06-2X/aug-pVDZ level of theory, leading to an important understanding of the reaction mechanism that agrees with the experimental observations and explaining the substantial role of acid in driving the reaction. The DFT results elucidated that the first reaction step (FRS) proceeds in a manner where chlorous acid reacts with the aldehyde group through a distorted six-membered ring transition state to give a hydroxyallyl chlorite intermediate that undergoes a pericyclic fragmentation to release the carboxylic acid as a second reaction step (SRS). 1H NMR experiments and simulations showed that hydrogen bonding between carbonyl and t-butanol is unlikely to occur. Additionally, it was found that the FRS is a rate-determining and thermoneutral step, whereas SRS is highly exergonic with a low energetic barrier due to the Cl(III) → Cl(II) reduction. Frontier molecular orbital analysis, intrinsic reaction coordinate, molecular dynamics and distortion/interaction analysis further supported the proposed mechanism.

| S-EPMC7062072 | biostudies-literature

Chalcone Scaffolds Exhibiting Acetylcholinesterase Enzyme Inhibition: Mechanistic and Computational Investigations.

Project description:This study was aimed to perform the mechanistic investigations of chalcone scaffold as inhibitors of acetylcholinesterase (AChE) enzyme using molecular docking and molecular dynamics simulation tools. Basic chalcones (C1-C5) were synthesized and their in vitro AChE inhibition was tested. Binding interactions were studied using AutoDock and Surflex-Dock programs, whereas the molecular dynamics simulation studies were performed to check the stability of the ligand-protein complex. Good AChE inhibition (IC50 = 22 ± 2.8 to 37.6 ± 0.75 μM) in correlation with the in silico results (binding energies = -8.55 to -8.14 Kcal/mol) were obtained. The mechanistic studies showed that all of the functionalities present in the chalcone scaffold were involved in binding with the amino acid residues at the binding site through hydrogen bonding, π-π, π-cation, π-sigma, and hydrophobic interactions. Molecular dynamics simulation studies showed the formation of stable complex between the AChE enzyme and C4 ligand.

| S-EPMC9145706 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data