Structure-activity relationships for unimolecular reactions of peroxy radicals, RO2, at atmospheric temperatures

2020 ◽  
Author(s):  
Luc Vereecken ◽  
Giang H. T. Vu ◽  
Hue M. T. Nguyen
Keyword(s):  
Ring Closure ◽  
Specific Rate ◽  
Extensive Literature ◽  
Peroxy Radicals ◽  
Unimolecular Reactions ◽  
Radical Site ◽  
Critical Step ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Wide Range

<p>The oxidation of most organic matter emitted to the atmosphere proceeds by radical reaction steps, where peroxy radicals, ROO<sup>•</sup>, are critical intermediates formed by addition of O<sub>2</sub> molecules to carbon-based radicals. The chemistry of these RO<sub>2</sub> radicals in high-NOx conditions is well-known, forming alkoxy radicals and NO<sub>2</sub>. In low-NOx and pristine conditions, the RO<sub>2</sub> radicals react with HO<sub>2</sub> and other R'O<sub>2</sub> radicals, but can have a sufficiently long lifetime to also undergo unimolecular reactions. Hydrogen atom migration, forming a hydroperoxide (-OOH) and a new peroxy radical site after addition of an additional O<sub>2</sub> on the newly formed radical site, has been studied extensively in some compounds, such as isoprene where it was shown to be the a critical step in OH radical regeneration. RO<sub>2</sub> ring closure reactions have likewise been studied, where for β-pinene it has been shown to be a critical step governing the yield of the decomposition products such as acetone and nopinone.</p><p>Despite the interest in RO<sub>2</sub> unimolecular reactions, and the potential impact on atmospheric chemistry, no widely applicable structure-activity relationships (SARs) have been proposed to allow systematic incorporation of such unimolecular reactions in gas phase atmospheric kinetic models. In this work, we present a series of systematic theoretical predictions on the site-specific rate coefficients for such reactions for a wide range of molecular substitutions. Combined with extensive literature data this allows for the formulation of a SAR for RO<sub>2</sub> unimolecular reactions, covering aliphatic, branched, and unsaturated RO<sub>2</sub> with oxo, hydroxy, hydroperoxy, nitrate, carboxylic acid, and ether substitutions.</p><p>The predictions are compared to experimental and theoretical data, including multi-functionalized species. Though some molecular classes are well represented in the training set (e.g. aliphatic RO<sub>2</sub>), other classes have little data available and additional work is needed to enhance and validate the reliability of the SAR. Direct experimental data is scarce for all RO<sub>2</sub> classes. The fastest H-migrations are found to be for unsaturated RO<sub>2</sub>, with the double bond outside the H-migration TS ring. Ring closure of unsaturated RO<sub>2</sub> are likewise fast if the product radical carbon is exocyclic to the newly formed peroxide ring.</p>

scholarly journals Structure-Activity Relationships for the Anaesthetic and Analgaesic Properties of Aromatic Ring-Substituted Ketamine Esters

Molecules ◽  
2020 ◽  
Vol 25 (12) ◽  
pp. 2950
Author(s):  
Ivaylo V. Dimitrov ◽  
Martyn G. Harvey ◽  
Logan J. Voss ◽  
James W. Sleigh ◽  
Michael J. Bickerdike ◽  
...  
Keyword(s):  
Electronic Properties ◽  
Benzene Ring ◽  
Aromatic Ring ◽  
Alkyl Esters ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Wide Range ◽  
Powerful Electron ◽  
Electron Withdrawing Substituents

A series of benzene ring substituted ketamine N-alkyl esters were prepared from the corresponding substituted norketamines. Few of the latter have been reported since they have not been generally accessible via known routes. We report a new general route to many of these norketamines via the Neber (oxime to α-aminoketone) rearrangement of readily available substituted 2-phenycyclohexanones. We explored the use of the substituents Cl, Me, OMe, CF3, and OCF3, with a wide range of lipophilic and electronic properties, at all available benzene ring positions. The 2- and 3-substituted compounds were generally more active than 4-substituted compounds. The most generally acceptable substituent was Cl, while the powerful electron-withdrawing substituents CF3 and OCF3 provided fewer effective analogues.

scholarly journals Novel Azolylalkyloxy Compounds with Antipicornaviral Activity

1995 ◽  
Vol 6 (4) ◽  
pp. 245-254 ◽  
Author(s):  
M. D. Abel ◽  
A. D. Cameron ◽  
C. M. Ha ◽  
C. A. Koski ◽  
H. T. Luu ◽  
...  
Keyword(s):  
Vitro Activity ◽  
In Vitro Activity ◽  
Optimal Length ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Wide Range ◽  
Highly Effective ◽  
Qualitative Structure

A novel series of azolylalkyloxy compounds was designed, synthesized and evaluated for antipicornaviral activity. Several of the compounds exhibited in vitro activity comparable to that of Disoxarll. An investigation of qualitative structure-activity relationships indicated that the optimal length of the alkyI chain is six or seven carbon atoms, with seven being marginally superior. The effect of different azole moieties on activity was relatively small, with 3-methylisoxazole and 4-methylthiazole being most effective. The nature of the oxy substituent was found to be extremely important for antipicornaviral activity. The 2-dibenzofuryl group proved to be the most effective oxy substituent for this class of compounds. Compounds 11 and 22, combining dibenzofuran with 3-methylisoxazole and 4-methylthiazole, respectively, were highly effective in vitro against a wide range of human rhinoviruses as well as several enteroviruses.

Importance of isomerization reactions for the OH radical regeneration from the photo-oxidation of isoprene investigated in the atmospheric simulation chamber SAPHIR

2020 ◽  
Author(s):  
Anna Novelli ◽  
Luc Vereecken ◽  
Birger Bohn ◽  
Hans-Peter Dorn ◽  
Georgios Gkatzelis ◽  
...  
Keyword(s):  
Oh Radicals ◽  
Oh Radical ◽  
Peroxy Radicals ◽  
Atmospheric Conditions ◽  
Unimolecular Reactions ◽  
Model Calculations ◽  
Hydrogen Shift ◽  
Wide Range ◽  
Regeneration Efficiency ◽  
Simulation Chamber

<p>Theoretical, laboratory and chamber studies have shown fast regeneration of hydroxyl radical (OH) in the photochemistry of isoprene largely due to previously disregarded unimolecular reactions which were previously thought not to be important under atmospheric conditions. Based on early field measurements, nearly complete regeneration was hypothesized for a wide range of tropospheric conditions, including areas such as the rainforest where slow regeneration of OH radicals is expected due to low concentrations of nitric oxide (NO). In this work the OH regeneration in the isoprene oxidation is directly quantified for the first time through experiments covering a wide range of atmospheric conditions (i.e. NO between 0.15 and 2 ppbv and temperature between 25 and 41°C) in the atmospheric simulation chamber SAPHIR. These conditions cover remote areas partially influenced by anthropogenic NO emissions, giving a regeneration efficiency of OH close to one, and areas like the Amazonian rainforest with very low NO, resulting in a surprisingly high regeneration efficiency of 0.5, i.e. a factor of 2 to 3 higher than explainable in the absence of unimolecular reactions. The measured radical concentrations were compared to model calculations and the best agreement was observed when at least 50% of the total loss of isoprene peroxy radicals conformers (weighted by their abundance) occurs via isomerization reactions for NO lower than 0.2 parts per billion (ppbv). For these levels of NO, up to 50% of the OH radicals are regenerated from the products of the 1,6 α-hydroxy-hydrogen shift (1,6-H shift) of Z-δ-RO<sub>2 </sub>radicals through photolysis of an unsaturated hydroperoxy aldehyde (HPALD) and/or through the fast aldehyde hydrogen shift (rate constant ~10 s<sup>-1</sup> at 300K) in di-hydroperoxy carbonyl peroxy radicals (di-HPCARP-RO<sub>2</sub>), depending on their relative yield. The agreement between all measured and modelled trace gases (hydroxyl, hydroperoxy and organic peroxy radicals, carbon monoxide and the sum of methyl vinyl ketone, methacrolein and hydroxyl hydroperoxides) is nearly independent on the adopted yield of HPALD and di-HPCARP-RO<sub>2</sub> as both degrade relatively fast (< 1 h), forming OH radical and CO among other products. Taking into consideration this and earlier isoprene studies, considerable uncertainties remain on the oxygenated products distribution, which affect radical levels and organic aerosol downwind of unpolluted isoprene dominated regions.</p>

scholarly journals Taccalonolides: A Novel Class of Microtubule-Stabilizing Anticancer Agents

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 920
Author(s):  
Xiaoyan Chen ◽  
Angela Winstead ◽  
Hongtao Yu ◽  
Jiangnan Peng
Keyword(s):  
Drug Resistance ◽  
Mechanism Of Action ◽  
Covalent Binding ◽  
Chemotherapeutic Agents ◽  
Stabilizing Agents ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Wide Range ◽  
Unique Mechanism

Microtubule stabilizing agents, such as paclitaxel, docetaxel, and cabazitaxel have been among the most used chemotherapeutic agents in the last decades for the treatment of a wide range of cancers in the clinic. One of the concerns that limit their use in clinical practice is their intrinsic and acquired drug resistance, which is common to most anti-cancer chemotherapeutics. Taccalonolides are a new class of microtubule stabilizers isolated from the roots of a few species in the genus of Tacca. In early studies, taccalonolides demonstrated different effects on interphase and mitotic microtubules from those of paclitaxel and laulimalide suggesting a unique mechanism of action. This prompts the exploration of new taccalonolides with various functionalities through the identification of minor constituents of natural origin and semi-synthesis. The experiments on the new highly potent taccalonolides indicated that taccalonolides possessed a unique mechanism of covalently binding to the microtubule. An X-ray diffraction analysis of a crystal of taccalonolides AJ binding to tubulin indicated that the covalent binding site is at β-tubulin D226. Taccalonolides circumvent all three mechanisms of taxane drug resistance both in vitro and in vivo. To improve the activity, the structure modification through semi-synthesis was conducted and the structure-activity relationships (SARs) was analyzed based on natural and semi-synthetical taccalonolides. The C22–C23 epoxide can significantly increase the antiproliferation potency of taccalonolides due to the covalent link of C22 and the carboxylic group of D226. Great progress has been seen in the last few years in the understanding of the mechanism of this class of microtube-stabilizing agents. This review summarizes the structure diversity, structure-activity relationships (SARs), mechanism of action, and in vivo activities of taccalonolides.

scholarly journals 3D-QSAR, Molecular Docking, and MD Simulations of Anthraquinone Derivatives as PGAM1 Inhibitors

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuwei Wang ◽  
Yifan Guo ◽  
Shaojia Qiang ◽  
Ruyi Jin ◽  
Zhi Li ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Rational Design ◽  
Binding Free Energy ◽  
3D Qsar ◽  
Md Simulations ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Wide Range ◽  
Anthraquinone Derivatives

PGAM1 is overexpressed in a wide range of cancers, thereby promoting cancer cell proliferation and tumor growth, so it is gradually becoming an attractive target. Recently, a series of inhibitors with various structures targeting PGAM1 have been reported, particularly anthraquinone derivatives. In present study, the structure–activity relationships and binding mode of a series of anthraquinone derivatives were probed using three-dimensional quantitative structure–activity relationships (3D-QSAR), molecular docking, and molecular dynamics (MD) simulations. Comparative molecular field analysis (CoMFA, r2 = 0.97, q2 = 0.81) and comparative molecular similarity indices analysis (CoMSIA, r2 = 0.96, q2 = 0.82) techniques were performed to produce 3D-QSAR models, which demonstrated satisfactory results, especially for the good predictive abilities. In addition, molecular dynamics (MD) simulations technology was employed to understand the key residues and the dominated interaction between PGAM1 and inhibitors. The decomposition of binding free energy indicated that the residues of F22, K100, V112, W115, and R116 play a vital role during the ligand binding process. The hydrogen bond analysis showed that R90, W115, and R116 form stable hydrogen bonds with PGAM1 inhibitors. Based on the above results, 7 anthraquinone compounds were designed and exhibited the expected predictive activity. The study explored the structure–activity relationships of anthraquinone compounds through 3D-QSAR and molecular dynamics simulations and provided theoretical guidance for the rational design of new anthraquinone derivatives as PGAM1 inhibitors.

scholarly journals Importance of isomerization reactions for OH radical regeneration from the photo-oxidation of isoprene investigated in the atmospheric simulation chamber SAPHIR

2020 ◽  
Vol 20 (6) ◽  
pp. 3333-3355 ◽  
Author(s):  
Anna Novelli ◽  
Luc Vereecken ◽  
Birger Bohn ◽  
Hans-Peter Dorn ◽  
Georgios I. Gkatzelis ◽  
...  
Keyword(s):  
Relative Yield ◽  
Oh Radicals ◽  
Oh Radical ◽  
Peroxy Radicals ◽  
Unimolecular Reactions ◽  
Model Calculations ◽  
Hydrogen Shift ◽  
Wide Range ◽  
Regeneration Efficiency ◽  
Simulation Chamber

Abstract. Theoretical, laboratory, and chamber studies have shown fast regeneration of the hydroxyl radical (OH) in the photochemistry of isoprene, largely due to unimolecular reactions which were previously thought not to be important under atmospheric conditions. Based on early field measurements, nearly complete regeneration was hypothesized for a wide range of tropospheric conditions, including areas such as the rainforest where slow regeneration of OH radicals is expected due to low concentrations of nitric oxide (NO). In this work the OH regeneration in isoprene oxidation is directly quantified for the first time through experiments covering a wide range of atmospherically relevant NO levels (between 0.15 and 2 ppbv – parts per billion by volume) in the atmospheric simulation chamber SAPHIR. These conditions cover remote areas partially influenced by anthropogenic NO emissions, giving a regeneration efficiency of OH close to 1, and areas like the Amazonian rainforest with very low NO, resulting in a surprisingly high regeneration efficiency of 0.5, i.e. a factor of 2 to 3 higher than explainable in the absence of unimolecular reactions. The measured radical concentrations were compared to model calculations, and the best agreement was observed when at least 50 % of the total loss of isoprene peroxy radicals conformers (weighted by their abundance) occurs via isomerization reactions for NO lower than 0.2 ppbv. For these levels of NO, up to 50 % of the OH radicals are regenerated from the products of the 1,6 α-hydroxy-hydrogen shift (1,6-H shift) of Z-δ-RO2 radicals through the photolysis of an unsaturated hydroperoxy aldehyde (HPALD) and/or through the fast aldehydic hydrogen shift (rate constant ∼10 s−1 at 300 K) in di-hydroperoxy carbonyl peroxy radicals (di-HPCARP-RO2), depending on their relative yield. The agreement between all measured and modelled trace gases (hydroxyl, hydroperoxy, and organic peroxy radicals, carbon monoxide, and the sum of methyl vinyl ketone, methacrolein, and hydroxyl hydroperoxides) is nearly independent of the adopted yield of HPALD and di-HPCARP-RO2 as both degrade relatively fast (<1 h), forming the OH radical and CO among other products. Taking into consideration this and earlier isoprene studies, considerable uncertainties remain on the distribution of oxygenated products, which affect radical levels and organic aerosol downwind of unpolluted isoprene-dominated regions.

Medicinal applications of coumarins bearing azetidinone and thiazolidinone moieties

2021 ◽  
Author(s):  
Siddappa A Patil ◽  
Shivaputra A Patil ◽  
Temilade Fariyike ◽  
Kostiantyn O Marichev ◽  
Hector Mario Heras Martinez ◽  
...  
Keyword(s):  
Physicochemical Properties ◽  
Biological Activities ◽  
Heterocyclic Ring ◽  
Pharmacological Properties ◽  
Structure Activity Relationships ◽  
Naturally Occurring ◽  
Structure Activity ◽  
Wide Range ◽  
Synthetic Routes ◽  
Synthetic Methodologies

Coumarins (2 H-chromen-2-ones), also known as benzopyran-2-ones, are a family of naturally occurring heterocyclic ring systems that contain a lactone moiety. Coumarins exhibit a wide range of well-studied pharmacological properties. Over the last few decades, as a result of advances in diverse oriented synthetic routes, physicochemical properties and numerous biological activities, coumarins have become globally studied molecules from various synthetic and medicinal chemists. Recently, several bioactive coumarins bearing azetidinone and thiazolidinone moieties have been found to display a range of therapeutic characteristics, including antimicrobial, anticancer, antidiabetic and anti-inflammatory properties. This review offers a brief description of the synthetic methodologies, known bioactivity and structure–activity relationships of coumarins bearing azetidinones and thiazolidinones.

Indole derivatives (2010–2020) as versatile tubulin inhibitors: synthesis and structure–activity relationships

2021 ◽  
Vol 13 (20) ◽  
pp. 1795-1828
Author(s):  
Fatima Naaz ◽  
Kumari Neha ◽  
Md Rafi Haider ◽  
Syed Shafi
Keyword(s):  
Cancer Therapy ◽  
Present Article ◽  
Dynamic Equilibrium ◽  
Biological Activities ◽  
Indole Derivatives ◽  
Tubulin Inhibitors ◽  
Structure Activity Relationships ◽  
Drug Candidates ◽  
Structure Activity ◽  
Wide Range

Tubulin inhibitors are conjugates that interfere with the dynamic equilibrium of the polymerization and depolymerization of microtubules. Among all the reported conjugates, indole moiety is one of the most significant classes for the development of new drug candidates for cancer therapy. Due to their presence in a wide range of natural as well as synthetic antitubulin agents, indole has become a versatile scaffold in research, and various synthetic and semisynthetic indole-based antitubulin agents have been identified and reported. The present article focuses on the reported indole-based tubulin inhibitors of synthetic origin from last the decade. Synthesis, structure–activity relationships and biological activities of synthetic indole derivatives along with brief updates on their antitubulin activity are presented.

scholarly journals Importance of isomerization reactions for the OH radical regeneration from the photo-oxidation of isoprene investigated in the atmospheric simulation chamber SAPHIR

2019 ◽  
Author(s):  
Anna Novelli ◽  
Luc Vereecken ◽  
Hans-Peter Dorn ◽  
Andreas Hofzumahaus ◽  
Frank Holland ◽  
...  
Keyword(s):  
Relative Yield ◽  
Oh Radicals ◽  
Peroxy Radicals ◽  
Atmospheric Conditions ◽  
Unimolecular Reactions ◽  
Model Calculations ◽  
Hydrogen Shift ◽  
Wide Range ◽  
Regeneration Efficiency ◽  
Simulation Chamber

Abstract. Theoretical, laboratory and chamber studies have shown fast regeneration of hydroxyl radical (OH) in the photochemistry of isoprene largely due to previously disregarded unimolecular reactions. Based on early field measurements, nearly complete regeneration was hypothesized for a wide range of tropospheric conditions, including areas such as the rainforest where slow regeneration of OH radicals is expected due to low concentrations of nitric oxide (NO). In this work the OH regeneration in the isoprene oxidation is directly quantified for the first time through experiments covering a wide range of atmospheric conditions (i.e. NO between 0.15 and 2 ppbv and temperature between 25 and 41 °C) in the atmospheric simulation chamber SAPHIR. These conditions cover remote areas partially influenced by anthropogenic NO emissions, giving a regeneration efficiency of OH close to one, and areas like the Amazonian rainforest with very low NO, resulting in a surprisingly high regeneration efficiency of 0.5, i.e. a factor of 2 to 3 higher than explainable in the absence of unimolecular reactions. The measured radical concentrations were compared to model calculations and the best agreement was observed when at least 50 % of the total loss of isoprene peroxy radicals conformers (weighted by their abundance) occurs via isomerization reactions for NO lower than 0.2 parts per billion (ppbv). For these levels of NO, up to 50 % of the OH radicals are regenerated from the products of the 1,6 α-hydroxy-hydrogen shift (1,6-H shift) of Z-δ-RO2 radicals through photolysis of an unsaturated hydroperoxy aldehyde (HPALD) and/or through the fast aldehyde hydrogen shift (rate constant ∼ 10 s−1 at 300 K) in di-hydroperoxy carbonyl peroxy radicals (di-HPCARP-RO2), depending on their relative yield. The agreement between all measured and modelled trace gases (hydroxyl, hydroperoxy and organic peroxy radicals, carbon monoxide and the sum of methyl vinyl ketone, methacrolein and hydroxyl hydroperoxides) is nearly independent on the adopted yield of HPALD and di-HPCARP-RO2 as both degrade relatively fast (

scholarly journals A structure activity relationship for ring closure reactions in unsaturated alkylperoxy radicals

2021 ◽  
Author(s):  
Luc Vereecken ◽  
Giang Vu ◽  
Andreas Wahner ◽  
Astrid Kiendler-Scharr ◽  
Hue Thi Minh Nguyen
Keyword(s):  
Volatile Organic Compounds ◽  
Organic Compounds ◽  
Structure Activity Relationship ◽  
Ring Closure ◽  
Activity Relationship ◽  
Peroxy Radicals ◽  
Important Class ◽  
Structure Activity ◽  
Volatile Organic ◽  
Alkylperoxy Radicals

Terpenoids are an important class of multi-unsaturated volatile organic compounds emitted to the atmosphere. During their oxidation in the troposphere, unsaturated peroxy radicals are formed, which may undergo ring closure...

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