scholarly journals Tuning the stability of alkoxyisopropyl protection groups

2019 ◽  
Vol 15 ◽  
pp. 746-751
Author(s):  
Zehong Liang ◽  
Henna Koivikko ◽  
Mikko Oivanen ◽  
Petri Heinonen
Keyword(s):  
Hydroxy Group ◽  
Relative Rate ◽  
Hplc Method ◽  
Alkoxy Group ◽  
Protecting Groups ◽  
Hydronium Ion ◽  
Silyl Groups ◽  
Relative Rate Constants ◽  
The Stability ◽  
Ph Range

Five different 2-alkoxypropan-2-yl groups are introduced as acid-labile protecting groups for the 5’- and 3’-hydroxy groups of a 2’-deoxynucleoside. All studied protecting groups were readily introduced with good to excellent yields using the appropriate enol ether as a reagent and 0.5 to 1 mol % p-toluenesulfonic acid as a catalyst. The protected compounds could be purified by silica gel column chromatography without degradation. The compatibility of these protecting groups in parallel use with benzoyl and silyl groups was verified. The stabilities of the different alkoxy acetal protecting groups were compared by following the kinetics of their hydrolysis at 25.0 °C in buffered solutions through an HPLC method. In the pH range 4.94 to 6.82 the hydrolysis reactions are of first order in the hydronium ion. The rate of hydrolysis correlates with the electron-donating or electron-withdrawing ability of the corresponding alkoxy group. The studied 2-alkoxypropan-2-yl groups and the relative rate constants for their cleavage from the 5’-hydroxy group of 2’-deoxythymidine were: cyclohexyloxy (k rel = 7.7), isopropoxy (7.4), methoxy (1), benzyloxy (0.6) and 2,2,2-trifluoroethyloxy (0.04). The attachment of the same groups to the 3’-hydroxy group are from 1.3 to 1.9-fold more stable. The most reactive of these acetone-based acetal groups are faster removed than a dimethoxytrityl group, and they are easier to cleave completely in solution. The structural variation allows steering of the stability and lipophilicity of the compounds in some range.

Bridgehead free radical stability. The decomposition of t-butylperoxyesters of the 1-adamantyl, 1-bicyclo[2•2•2]octyl, and 1-norbornyl systems

1968 ◽  
Vol 46 (19) ◽  
pp. 3099-3103 ◽  
Author(s):  
Leonard B. Humphrey ◽  
Bruce Hodgson ◽  
Richard E. Pincock
Keyword(s):  
Free Radicals ◽  
Free Radical ◽  
Relative Rate ◽  
First Order ◽  
Carbonium Ion ◽  
Carbonium Ions ◽  
Radical Decomposition ◽  
Out Of Plane ◽  
Relative Rate Constants ◽  
The Stability

The t-butylperoxyesters of 1-adamantyl, 1-bicyclo[2•2•2]octyl, and 1-norbornyl carboxylic acids thermally undergo first order, free radical decomposition in cumene with relative rate constants at 80° of 1.0, 0.07, and 0.001 respectively. As measures of the stability of the derived bridgehead free radicals, the rates span a range much narrower than that for carbonium ion formation at these strained positions. The results are consistent with suggestions that free radicals have smaller force constants for out-of-plane bending than do the corresponding carbonium ions.

Schiff base equilibria. II. Beryllium complexes of N-n-butylsalicylideneimine and the hydrolysis of the Be2+ ion

1965 ◽  
Vol 18 (5) ◽  
pp. 651 ◽  
Author(s):  
RW Green ◽  
PW Alexander
Keyword(s):  
Aqueous Solution ◽  
Schiff Base ◽  
Complex Formation ◽  
Distribution Coefficient ◽  
Dilute Aqueous Solution ◽  
The Stability ◽  
Ph Range ◽  
Hydrolysis Of ◽  
Beryllium Complexes ◽  
Equilibria In Aqueous Solution

The Schiff base, N-n-butylsalicylideneimine, extracts more than 99.8% beryllium into toluene from dilute aqueous solution. The distribution of beryllium has been studied in the pH range 5-13 and is discussed in terms of the several complex equilibria in aqueous solution. The stability constants of the complexes formed between beryllium and the Schiff base are log β1 11.1 and log β2 20.4, and the distribution coefficient of the bis complex is 550. Over most of the pH range, hydrolysis of the Be2+ ion competes with complex formation and provides a means of measuring the hydrolysis constants. They are for the reactions: Be(H2O)42+ ↔ 2H+ + Be(H2O)2(OH)2, log*β2 - 13.65; Be(H2O)42+ ↔ 3H+ + Be(H2O)(OH)3-, log*β3 -24.11.

scholarly journals Investigations of ternary complexes of Co(II) and Ni(II) with thiodiacetate anion and 1,10-phenanthroline or 2,2’-bipyridine in aqueous solutions

2014 ◽  
Vol 13 (1) ◽  
Author(s):  
Dariusz Wyrzykowski ◽  
Joanna Pranczk ◽  
Dagmara Jacewicz ◽  
Aleksandra Tesmar ◽  
Bogusław Pilarski ◽  
...  
Keyword(s):  
Aqueous Solutions ◽  
Substitution Reactions ◽  
Experimental Conditions ◽  
Kinetic Measurements ◽  
Hydroxo Complexes ◽  
Binary Complexes ◽  
Vis Spectroscopy ◽  
Potentiometric Titration Method ◽  
The Stability ◽  
Ph Range

AbstractA potentiometric titration method (PT) and a stopped-flow kinetic technique monitored by a UV−Vis spectroscopy have been used to characterize the stability of series of Co(II)- and Ni(II)-thiodiacetato complexes, M(TDA), in the presence of 1,10-phenanthroline (phen) or 2,2’-bipyridine (bipy) in aqueous solutions. The stability constants of the binary (1:1), ternary (1:1:1) as well as the resulting hydroxo complexes were evaluated and compared to the corresponding oxydiacetate complexes. Based on the species distribution as a function of pH the relative predominance of the species in the system over a pH range was discussed. Furthermore, the kinetic measurements of the substitution reactions of the aqua ligands to phen or bipy in the coordination sphere of the binary complexes M(TDA) were performed in the 288–303 K temperature range, at a constant concentration of phen or bipy and at seven different concentrations of the binary complexes (0.2–0.5 mM). The kinetic stability of the M(TDA) complexes was discussed in relation to the experimental conditions and the kind of the auxiliary ligands (phen/bipy). Moreover, the influence of the type of primary ligand (thiodiacetate/oxydiacetate) on the substitution rate of the auxiliary ligands was also compared.

scholarly journals An Investigation into the Adsorption of Aniline from Aqueous Solution Using H-Beta Zeolites and Copper-Exchanged Beta Zeolites

2005 ◽  
Vol 23 (3) ◽  
pp. 255-266 ◽  
Author(s):  
J. O'Brien ◽  
T. Curtin ◽  
T.F. O'Dwyer
Keyword(s):  
Aqueous Solution ◽  
Adsorption Process ◽  
Zeolite Beta ◽  
Langmuir Model ◽  
Beta Zeolite ◽  
Copper Leaching ◽  
Beta Zeolites ◽  
The Stability ◽  
Ph Range ◽  
Adsorbent Materials

Zeolite beta, a large-pore zeolite, was investigated in this study with a view to examining it as a potential adsorbent for the removal of aniline from aqueous solutions. Two different metal-loaded zeolites were prepared by exchanging H-beta zeolite (SiO2/Al2O3 = 75:1) with copper. The influence of exchanged copper on the uptake level was assessed. The effect of varying the silica-to-alumina ratio of the H-beta zeolite on the aniline uptake level was also examined, using three different H-beta zeolites with ratios of 25:1, 75:1 and 150:1 as adsorbents. The sorption experiments indicated an uptake level of ca. 110–120 mg/g for each zeolite and this level was also adsorbed by the copper-modified H-beta zeolites (SiO2/Al2O3 = 75:1). In all cases, the adsorption process followed the Langmuir model for adsorption and the level of aniline adsorbed was largely unaffected by a change in temperature or the presence of extra framework copper. The stability of the exchanged copper on these zeolites was then examined by measuring the quantity of copper leached from each zeolite into solution as a function of pH. Minimum copper leaching was observed in the pH range 5–11. This provided a stable pH working range for the adsorbent materials.

Kinetics of the successive chlorination of 1,2-dichloroethane in the liquid phase

1969 ◽  
Vol 22 (6) ◽  
pp. 1177 ◽  
Author(s):  
DS Caines ◽  
RB Paton ◽  
DA Williams ◽  
PR Wilkinson
Keyword(s):  
Liquid Phase ◽  
Rate Constants ◽  
Relative Rate ◽  
Stirred Tank ◽  
Continuous Stirred Tank Reactor ◽  
Alternative Pathways ◽  
Tank Reactor ◽  
Relative Rate Constants ◽  
Continuous Stirred Tank ◽  
Kinetics Of

Liquid 1,2-dichloroethane has been chlorinated by dissolved chlorine to a succession of chloroethanes up to the ultimate hexachloroethane. The results of both batch and continuous stirred tank reactor systems have been analysed by computer techniques to give a set of relative rate constants from which one can predict the product composition for a given chlorine uptake, the aim in this work being to optimize the production of tetrachloroethanes. An unusual feature of the kinetics is that 1,1,1,2- and 1,1,2,2-tetrachloroethanes provide alternative pathways between 1,1,2-trichloroethane and pentachloroethane.

scholarly journals Kinetic study of the photochemical changes of (ZZ)-bilirubin IX α bound to human serum albumin. Demonstration of (EZ)-bilirubin IX α as an intermediate in photochemical changes from (ZZ)-bilirubin IX α to (EZ)-cyclobilirubin IX α

1985 ◽  
Vol 226 (1) ◽  
pp. 251-258 ◽  
Author(s):  
S Itoh ◽  
S Onishi
Keyword(s):  
Human Serum Albumin ◽  
Serum Albumin ◽  
Kinetic Study ◽  
Human Serum ◽  
Photochemical Reaction ◽  
Relative Rate ◽  
Significant Preference ◽  
Geometrical Isomers ◽  
Relative Rate Constants

The present study was performed to elucidate why the photochemical reaction of (ZZ)-bilirubin bound to human serum albumin is singularly selective, and only one of the two (EZ)- and (ZE)-bilirubins, the (ZE)-isomer, is produced. In a kinetic study of the photochemical reaction in vitro, the sum of the relative rate constants of photochemical transformation of (EZ)-bilirubin into both (EZ)-cyclobilirubin and (ZZ)-bilirubin, with a significant preference for the former, was proved to be considerably larger than that of the transformation of (ZZ)-bilirubin into (EZ)-bilirubin. Therefore only one of the geometrical isomers, namely (ZE)-bilirubin, is apparently formed. It was concluded that (EZ)-bilirubin photochemically undergoes (EZ)-cyclization, i.e. structural photoisomerization, while bound to its high-affinity site on human serum albumin, and is an intermediate in the transformation of (ZZ)-bilirubin into (EZ)-cyclobilirubin.

Formulation and Stability Test of Lip Cream Preparation of Kenop Flower Ethanol Extract (Gomphrena globosa L.)

2021 ◽  
Vol 3 (2) ◽  
Author(s):  
Mevi Irianti Tonapa ◽  
Rani Dewi Pratiwi ◽  
Elsye Gunawan
Keyword(s):  
Ph Value ◽  
Ethanol Extract ◽  
Stability Test ◽  
Gomphrena Globosa ◽  
Homogeneous Composition ◽  
Semi Solid ◽  
The Stability ◽  
Ph Range ◽  
Average Dispersion ◽  
Brown Color

Kenop Flower (Gomphrena globosa L.) is used in the manufacture of lip cream because contains betacyanin pigments that function as color pigments. This study aims to determine the physical quality and stability of the lip cream preparation of the ethanol extract of kenop flower (Gomphrena globosa L.). This research was conducted experimentally, including the manufacture of lip cream formulations with ethanol extract of kenop flower (Gomphrena globosa L.) with a concentration of 10%. The results of the physical examination test for lip cream preparations for all preparations have a distinctive vanilla aroma with a semi-solid texture, F0 has ivory white color and F1-F3 has a brown color. The preparations had a homogeneous composition, average pH 6-7, had good greasing power, 5.0-5.8 average dispersion and 60.33-66.67 seconds average adhesion. The stability test carried out on day 28 found that all preparations were stable, had a distinctive vanilla aroma with a semi-solid texture, F0 had ivory white color and F1-F3 had a brown color. The preparation has a homogeneous composition; the average pH is 6-7. Where the lip cream formulas F1 and F3 decreased the pH value on the 28th day from 7 to 6 but tended to be stable and in the pH range that matched the lip pH. And there is no phase separation in all formulas.

A New, Rapid and Simple RP-HPLC Method for Stability Quantification of a Protease Inhibitor in Tablets

2021 ◽  
Author(s):  
Rochele Cassanta Rossi ◽  
Josué Guilherme Lisbôa Moura ◽  
Vanessa Mossmann ◽  
Patrícia Weimer ◽  
Pedro Eduardo Fröehlich
Keyword(s):  
Quality Control ◽  
Protease Inhibitor ◽  
Degradation Products ◽  
Gradient Elution ◽  
Hplc Method ◽  
Array Detector ◽  
Forced Degradation ◽  
Control Analysis ◽  
Quality Control Laboratory ◽  
The Stability

Abstract Fosamprenavir calcium is a protease inhibitor widely used in the treatment and prevention of human immunodeficiency virus and acquired immunodeficiency syndrome. This protease inhibitor serves as a prodrug of amprenavir, offering better oral bioavailability. Although this drug was approved by the FDA in 2003, there are few methods established for quantifying the stability for quality control analysis of fosamprenavir-coated tablets. The purpose of the study was to develop and validate a method for determining the stability of fosamprenavir-coated tablets (Telzir®) that may be applied by any quality control laboratory. Chromatographic separation was performed using a Vertical RP-18 column programmed to run a gradient elution with sodium acetate buffer and acetonitrile. Flow rate was 1.2 mL min−1 for a total run time of 15 min. Ultraviolet detection was set at 264 nm and the use of a photodiode array detector in scan mode allowed selectivity confirmation by peak purity evaluation. The analyte peak was found to be adequately separated from degradation products generated during forced degradation studies. Thus, the proposed method was found to accurately indicate stability and was sufficient for routine quantitative analysis of fosamprenavir in coated tablets without interference from major degradation products and excipients.

scholarly journals Linking Aromatic Hydroxy Metabolic Functionalization of Drug Molecules to Structure and Pharmacologic Activity

Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2119 ◽  
Author(s):  
Babiker El-Haj ◽  
Samrein Ahmed ◽  
Mousa Garawi ◽  
Heyam Ali
Keyword(s):  
Benzene Ring ◽  
Hydroxy Group ◽  
Water Solubility ◽  
Parent Drug ◽  
Drug Action ◽  
Alkoxy Group ◽  
Drug Molecules ◽  
Drug Classes ◽  
Pharmacologic Activity ◽  
Hydroxy Groups

Drug functionalization through the formation of hydrophilic groups is the norm in the phase I metabolism of drugs for the modification of drug action. The reactions involved are mainly oxidative, catalyzed mostly by cytochrome P450 (CYP) isoenzymes. The benzene ring, whether phenyl or fused with other rings, is the most common hydrophobic pharmacophoric moiety in drug molecules. On the other hand, the alkoxy group (mainly methoxy) bonded to the benzene ring assumes an important and sometimes essential pharmacophoric status in some drug classes. Upon metabolic oxidation, both moieties, i.e., the benzene ring and the alkoxy group, produce hydroxy groups; the products are arenolic in nature. Through a pharmacokinetic effect, the hydroxy group enhances the water solubility and elimination of the metabolite with the consequent termination of drug action. However, through hydrogen bonding, the hydroxy group may modify the pharmacodynamics of the interaction of the metabolite with the site of parent drug action (i.e., the receptor). Accordingly, the expected pharmacologic outcome will be enhancement, retention, attenuation, or loss of activity of the metabolite relative to the parent drug. All the above issues are presented and discussed in this review using selected members of different classes of drugs with inferences regarding mechanisms, drug design, and drug development.

RECOMBINATION OF OPPOSITELY CHARGED AQUEOUS CLUSTER IONS USING ELECTROSTATICALLY MERGED ION BEAMS

1996 ◽  
Vol 03 (01) ◽  
pp. 655-660 ◽  
Author(s):  
B. PLASTRIDGE ◽  
K.A. COWEN ◽  
D.A. WOOD ◽  
M.H. COHEN ◽  
J.V. COE
Keyword(s):  
Rate Constants ◽  
Cluster Size ◽  
Collision Energy ◽  
Relative Rate ◽  
Center Of Mass ◽  
Cluster Ions ◽  
Charged Cluster ◽  
Relative Rate Constants ◽  
Oppositely Charged ◽  
Electrostatic Quadrupole

A new method for studying cluster-cluster interactions is introduced which involves merging mass-selected beams of oppositely charged cluster ions with an electrostatic quadrupole deflector. Recombination is monitored by measuring the rate of fast neutral production. Relative rate constants have been measured for the reaction of H 3O+( H 2 O )n+ OH −( H 2 O )m as a function of cluster size (m=n=0–3), which display a pronounced enhancement with clustering. Relative rate constants have also been measured as a function of center-of-mass collision energy for a heavily clustered reaction (n=3, m=3) and a lightly clustered reaction (n=1, m=0) revealing that clustering produces a dramatic change in the reaction mechanism.

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