Os(VIII)-catalyzed and uncatalyzed oxidation of biotin by chloramine-T in alkaline medium: Comparative mechanistic aspects and kinetic modeling

Sodium N-chloro-p-toluenesulfonamide (chloramine-T or CAT) is the prominent member of aromatic sulfonyl haloamines and has received considerable attention as a mild oxidant for several organic compounds. d-Biotin, a member of the B-vitamin family, is an essential nutrient in human nutrition as is commonly referred to as Vitamin H. Controlled oxidation of biotin to biotin sulfoxide forms a very important synthetic route in biochemical reactions. Optimum conditions have been developed for the oxidation of biotin to biotin sulfoxide. Literature survey has revealed that no attention has been paid towards the controlled oxidation of biotin to biotin sulfoxide by N-haloamines from the kinetic and mechanistic view points. This prompted us to undertake the title investigation. The kinetics of Os(VIII) catalyzed and uncatalyzed oxidation of biotin by CAT have been studied in NaOH medium at 303 K under identical experimental conditions. The stoichiometry (1:1) and the oxidation product (biotin sulfoxide) are the same for Os(VIII) catalyzed and uncatalyzed reactions. Biotin sulfoxide was confirmed by GC-MS analysis. In Os(VIII) catalyzed oxidation, the rate law is -dCAT/dt = kCATOs(VIII)/NaOH but it takes the form -dCAT/dt = kCATBiotin x/NaOH -y for uncatalyzed reaction, where x and y are less than unity. The reaction was subjected to changes in: (a) concentration of added reduction product of CAT, p-toluenesulfonamide, (b) ionic strength, (c) dielectric permittivity and (d) halide ions effect in both the cases. Proton inventory studies made in a mixture of H 2O-D 2O indicated the participation of OH - ion in the formation of transition state. The reaction fails to initiate polymerization of acrylonitrile. Activation parameters for the composite reaction were deduced from Arrhenius plots. In case of uncatalyzed reactions, the reaction constants involved in the proposed scheme were deduced. Under the identical set of experimental conditions, the kinetics of Os(VIII) catalyzed oxidation of biotin by CAT in alkaline medium has been compared with uncatalyzed reactions, revealing that the catalyzed reactions are eight fold faster than the uncatalyzed reactions. Hence, Os(VIII) acts as an efficient catalyst for the oxidation of biotin by CAT in alkaline medium. The catalytic constant (K C) has been calculated at different temperatures and the values of activation parameters with respect to catalyst have been evaluated from the plots of log K C versus 1/T. Some spectroscopic evidence for the formation of 1:1 complex between oxidant and Os(VIII) has been obtained. CH 3C 6H 4SO 2NHCl has been postulated as the reactive oxidizing species in both the cases. The observed experimental results have been explained by plausible mechanisms and the related rate laws have been deduced for both catalyzed and uncatalyzed reactions. © 2006 Elsevier B.V. All rights reserved

Mechanistic Investigations of Oxidation of Some Dipeptides by Sodium N-chloro-p-toluenesulfonamide in Alkaline Medium:A Kinetic Study

The kinetics of oxidation of five dipeptides (DPP) viz., glycylglycine (Gly-Gly), L-alanyl-L-alanine (Ala-Ala), L-valyl-L-valine (Val-Val), L-leucyl-L-leucine (Leu-Leu) and phenylglycyl-phenylglycine (Phg-Phg) by sodium N-chloro-p-toluenesulfonamide or chloramine-T (CAT) in NaOH medium was studied at 308 K. The reactions follow identical kinetics for all the dipeptides, being first-order dependence each on [CAT]o, [DPP]o and fractional-order on [OH−]. Addition of p-toluenesulfonamide or halide ions (Cl− or Br−) has no significant effect on the rate of reaction. The reaction rate was found to increase with increase in ionic strength of the medium. The solvent isotope effect was studied using D2O. The activation parameters for the reaction were computed from Arrhenius plots. Equilibrium and decomposition constants were evaluated. The oxidation products of the dipeptides were identified as their corresponding aldehydes. An isokinetic relationship was observed with β=352 K, indicating that enthalpy factors control the reaction rate. CH3C6H4SO2NCl− of the oxidant has been postulated as the reactive oxidizing species. Under comparable experimental conditions, the rate of oxidation of the dipeptides increases in the order:Phg-Phg>Ala-Ala>Val-Val>Leu-Leu>Gly-Gly. The kinetics of oxidation of the dipeptides have also been compared with those of their corresponding monomer amino acids. The observed results have been explained by a plausible mechanism and the related rate law has been deduced

Oxidation of some catecholamines by sodium N-chloro-p-toluenesulfonamide in acid medium: A kinetic and mechanistic approach

The kinetics of the oxidation of five catecholamines viz., dopamine (A), L-dopa (B), methyldopa (C), epinephrine (D) and norepinephrine (E) by sodium N-chloro-p-toluenesulfonamide or chloramine-T (CAT) in presence of HClO 4 was studied at 30 ± 0.1 °C. The five reactions followed identical kinetics with a first-order dependence on CAT o, fractional-order in substrate o, and inverse fractional-order in H +. Under comparable experimental conditions, the rate of oxidation of catecholamines increases in the order D > E > A > B > C. The variation of ionic strength of the medium and the addition of p-toluenesulfonamide or halide ions had no significant effect on the reaction rate. The rate increased with decreasing dielectric constant of the medium. The solvent isotope effect was studied using D 2O. A Michaelis-Menten type mechanism has been suggested to explain the results. Equilibrium and decomposition constants for CAT-catecholamine complexes have been evaluated. CH 3C 6H 4SO 2NHCl of the oxidant has been postulated as the reactive oxidizing species and oxidation products were identified. An isokinetic relationship is observed with β = 361 K, indicating that enthalpy factors control the reaction rate. The mechanism proposed and the derived rate law are consistent with the observed kinetics. © Central European Science Journals. All rights reserved

Ru(III)​-​catalyzed oxidation of some amines by chloramine-​T in hydrochloric acid medium: Mechanistic aspects and kinetic modeling

A review. The kinetics of oxidn. of five amines viz., ethylenediamine (EDA)​, diethylenetriamine (DETA)​, triethylenetetramine (TETA)​, aminoethylpiperazine (AEP) and isophoronediamine (IPDA) by sodium N-​chloro-​p-​toluenesulfonamide or chloramine-​T (CAT) in the presence of HCl and Ru(III) chloride was studied at 303 K. The five reactions followed identical kinetics and the exptl. rate law is rate = k[CAT]​0[amine]​x0[H+]​y[Ru(III)​]​z, where x, y and z are fractions. A variation of the ionic strength or dielec. const. of the medium and the addn. of halide ions and p-​toluenesulfonamide had no significant effect on the rate of the reaction. The solvent isotope effect has been studied in D2O medium. The activation parameters have been evaluated from the Arrhenius plots. Under comparable exptl. conditions, the rate of oxidn. of amines increases in the order: AEP > TETA > DETA > EDA > IPDA. An isokinetic relationship is obsd. with β = 377 K, indicating enthalpy as a controlling factor. Oxidn. products were identified. CH3C6H4SO2+NH2Cl of the oxidant has been postulated as the reactive oxidizing species. Further, the kinetics of Ru(III)​-​catalyzed oxidn. of these amines have been compared with unanalyzed reactions (in the absence of Ru(III) catalyst) and found that the catalyzed reactions are 2-​3-​fold faster. The catalytic const. (KC) was also calcd. for each amine at different temps. from the plots of log KC against 1​/T, values of activation parameters with respect to the catalyst have been evaluated. The obsd. results have also been explained by a plausible mechanism and the related rate law has been deduced

Ruthenium catalyzed oxidative conversion of isatins to anthranilic acids: Mechanistic study

Oxidation of isatins (isatin, 5-methylisatin, 5-bromoisatin, and 5-nitroisatin) to their corresponding anthranilic acids was performed with sodium N-bromo-p-toluenesulfonamide or bromamine-T (BAT) as an oxidant and ruthenium trichloride (Ru(III)) as a catalyst in HCl medium at 30 +/- 0.1 degrees C. The four reactions follow identical kinetics with a first-order dependence each on [BAT](o) and [Ru(III)], zero-order on [Isatin], and inverse fractional-order on [H(+)]. Activation parameters have been deduced for the composite reaction. The rates satisfactorily correlate with the Hammett U relationship and the reaction constant p is -0.36 signifies that the electron donating groups accelerate the reaction while the electron withdrawing groups retard the rate. An isokinetic relationship is observed with beta = 360 K, indicating that enthalpy factors control the reaction rate. Oxidation products of isatins were identified as their corresponding anthranilic acids by GC-MS analysis and the yields were found to be > 90%. Under similar experimental conditions, the kinetics of Ru(III)-catalyzed oxidation of isatins with BAT has been compared with that of uncatalyzed reactions, revealing that the catalyzed reactions are three to fourfold faster. The observed results have been explained by a plausible mechanism and the related rate law has been deduced. The method adopted for the oxidation of isatins to anthranilic acids in the present work offers several advantages and can be scaled up to industrial operation. (c) 2008 American Institute of Chemical Engineers

Ru(III)-catalysed oxidation of some N-heterocycles by chloramine-T in hydrochloric acid medium: A kinetic and mechanistic study

The kinetics of the ruthenium(III) chloride (Ru(III))-catalysed oxidation of five N-heterocycles (S) viz. imidazole (IzlH), benzimidazole (BzlH), 2-hydroxybenzimidazole (2-HyBzlH), 2-aminobenzimidazole (2-AmBzlH) and 2-phenylbenzimidazole (2-PhBzlH) by sodium-N-chloro-p-toluenesulfonamide (chloramine-T; CAT) in the presence of HCl has been studied at 313 K. The oxidation reaction follows the identical kinetics for all the five N-heterocycles and obeys the rate law, rate = k CAT0 S 0 x H+y Ru(III)z, where x, y and z are less than unity. Addition of p-toluenesulfonamide (PTS) retards the reaction rate. Variation of ionic strength of the medium and the addition of halide ions show negligible effect on the rate of the reaction. The rate was found to increase in D2O medium and showed positive dielectric effect. The reaction products are identified. The rates are measured at different temperatures for all substrates and the composite activation parameters have been computed from the Arrhenius plots. From enthalpy-entropy relationships and Exner correlations, the calculated isokinetic temperature (β) of 392 K is much higher than the experimental temperature (313 K), indicating that, the rate has been under enthalpy control. Relative reactivity of these substrates are in the order: 2-HyBzlH > 2-AmBzlH > BzlH > IzlH > 2-PhBzlH. This trend may be attributed to resonance and inductive effects. Further, the kinetics of Ru(III)-catalysed oxidation of these N-heterocycles have been compared with uncatalysed reactions (in the absence of Ru(III) catalyst) and found that the catalysed reactions are 16-20 times faster. The catalytic constant (KC) was also calculated for each substrate at different temperatures. From the plots of log KC versus 1/T, values of activation parameters with respect to the catalyst have been evaluated. H2O+Cl has been postulated as the reactive oxidizing species. The reaction mechanism and the derived rate law are consistent with the observed experimental results. © 2004 Elsevier B.V. All rights reserved

Catalysis and mechanistic studies of ruthenium and osmium on synthesis of anthranilic acids

Ruthenium, osmium and ruthenium + osmium catalyzed synthetic methodology was developed for the synthesis of anthranilic acids from indoles in good to excellent yields using bromamine-B in alkaline acetonitrile-water (1 : 1) at 313 K. Detailed catalysis studies of ruthenium, osmium and the mixture of both were carried out for the synthetic reactions. The positive synergistic catalytic activity of Ru(III) + Os(VIII) was observed to a large extent with the activity greater than the sum of their separate catalytic activities. Detailed kinetic and mechanistic investigations for each catalyzed reactions were carried out. The kinetic pattern and mechanistic picture of each catalyzed reaction were found to be different for each catalyst and to obey the underlying rate laws

Integrated analyses of single-cell atlases reveal age, gender, and smoking status associations with cell type-specific expression of mediators of SARS-CoV-2 viral entry and highlights inflammatory programs in putative target cells

The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, creates an urgent need for identifying molecular mechanisms that mediate viral entry, propagation, and tissue pathology. Cell membrane bound angiotensin-converting enzyme 2 (ACE2) and associated proteases, transmembrane protease serine 2 (TMPRSS2) and Cathepsin L (CTSL), were previously identified as mediators of SARS-CoV2 cellular entry. Here, we assess the cell type-specific RNA expression of ACE2, TMPRSS2, and CTSL through an integrated analysis of 107 single-cell and single-nucleus RNA-Seq studies, including 22 lung and airways datasets (16 unpublished), and 85 datasets from other diverse organs. Joint expression of ACE2 and the accessory proteases identifies specific subsets of respiratory epithelial cells as putative targets of viral infection in the nasal passages, airways, and alveoli. Cells that co-express ACE2 and proteases are also identified in cells from other organs, some of which have been associated with COVID-19 transmission or pathology, including gut enterocytes, corneal epithelial cells, cardiomyocytes, heart pericytes, olfactory sustentacular cells, and renal epithelial cells. Performing the first meta-analyses of scRNA-seq studies, we analyzed 1,176,683 cells from 282 nasal, airway, and lung parenchyma samples from 164 donors spanning fetal, childhood, adult, and elderly age groups, associate increased levels of ACE2, TMPRSS2, and CTSL in specific cell types with increasing age, male gender, and smoking, all of which are epidemiologically linked to COVID-19 susceptibility and outcomes. Notably, there was a particularly low expression of ACE2 in the few young pediatric samples in the analysis. Further analysis reveals a gene expression program shared by ACE2(+)TMPRSS2(+) cells in nasal, lung and gut tissues, including genes that may mediate viral entry, subtend key immune functions, and mediate epithelial-macrophage cross-talk. Amongst these are IL6, its receptor and co-receptor, IL1R, TNF response pathways, and complement genes. Cell type specificity in the lung and airways and smoking effects were conserved in mice. Our analyses suggest that differences in the cell type-specific expression of mediators of SARS-CoV-2 viral entry may be responsible for aspects of COVID-19 epidemiology and clinical course, and point to putative molecular pathways involved in disease susceptibility and pathogenesis

Kinetics of oxidation of pantothenic acid by chloramine-T in perchloric acid and in alkaline medium catalyzed by OsO4: A mechanistic approach

Kinetics of oxidation of pantothenic acid (PA) by sodium N-chloro-p-toluenesulfonamide or chloramine-T (CAT) in the presence of HClO 4 and NaOH (catalyzed by OsO4) has been investigated at 313 K. The stoichiometry and oxidation products are same in both media; however, their kinetic patterns were found to be different. In acid medium, the rate shows first-order dependence on |CAT|o, fractional-order dependence on |PA|o, and inverse fractional-order on |H+|. In alkaline medium, the rate shows first-order dependence each on |CAT| o and |PA|o and fractional-order dependence on each of |OH-| and |OsO4|. Effects of added p-toluenesulfonamide and halide ions, varying ionic strength, and dielectric constant of medium as well as solvent isotope on the rate of reaction have been investigated. Activation parameters were evaluated, and the reaction constants involved in the mechanisms have been computed. The proposed mechanisms and the derived rate laws are consistent with the observed kinetics. © 2005 Wiley Periodicals, Inc