scholarly journals Theoretical Study of 2-(Trifluoromethyl)phenothiazine Derivatives with Two Hydroxyl Groups in the Side Chain-DFT and QTAIM Computations

Molecules ◽  
2021 ◽  
Vol 26 (17) ◽  
pp. 5242
Author(s):  
Andrzej Poła ◽  
Anna Palko-Łabuz ◽  
Kamila Środa-Pomianek
Keyword(s):  
Quantum Chemical ◽  
Biological Effects ◽  
Chemical Properties ◽  
Hydroxyl Group ◽  
Side Chain ◽  
Hydroxyl Groups ◽  
Dissociation Enthalpy ◽  
Wide Range ◽  
Thermochemical Parameters ◽  
Intramolecular Hydrogen

Phenothiazines are known as synthetic antipsychotic drugs that exhibit a wide range of biological effects. Their properties result from the structure and variability of substituents in the heterocyclic system. It is known that different quantum chemical properties have a significant impact on drug behavior in the biological systems. Thus, due to the diversity in the chemical structure of phenothiazines as well as other drugs containing heterocyclic systems, quantum chemical calculations provide valuable methods in predicting their activity. In our study, DFT computations were applied to show some thermochemical parameters (bond dissociation enthalpy—BDE, ionization potential—IP, proton dissociation enthalpy—PDE, proton affinity—PA, and electrontransfer enthalpy—ETE) describing the process of releasing the hydrogen/proton from the hydroxyl group in the side chain of four 2-(trifluoromethyl)phenothiazine (TFMP) derivatives and fluphenazine (FLU). Additional theoretical analysis was carried out based on QTAIM theory. The results allowed theoretical determination of the ability of compounds to scavenge free radicals. In addition, the intramolecular hydrogen bond (H-bond) between the H-atom of the hydroxyl group and the N-atom located in the side chain of the investigated compounds has been identified and characterized.

scholarly journals Complexation of Cu(BF4)2 with 3-hydroxyflavone in acetonitrile: quantum chemical calculation

2018 ◽  
Keyword(s):  
Hydrogen Bond ◽  
Hydrogen Atom ◽  
Intramolecular Hydrogen Bond ◽  
Quantum Chemical ◽  
Phenyl Ring ◽  
Fluorine Atom ◽  
Quantum Chemical Study ◽  
Hydroxyl Group ◽  
Chemical Calculation ◽  
Intramolecular Hydrogen

In the article the results of the quantum chemical study of copper (II) solvato-complexes with acetonitrile (AN), tetrafluoroborate anion (BF4–) and 3-hydroxyflavone (flv) of the composition [Cu(AN)6]2+, [Cu(BF4)(AN)5]+, [Cu(flv)(AN)5]2+, [Cu(flv)(BF4)(AN)4]+ are presented. Calculations were done using density function theory (DFT) on the M06-2X/6-311++G(d,p) level of theory. Obtained results were interpreted in terms of complexes geometry and topology of electron density distribution using non-covalent interactions (NCI) approach. It was shown that flv molecule is a monodentate ligand in copper (II) complexes and coordinates central atom via carbonyl oxygen. Intramolecular hydrogen bond that exists in an isolated flv molecule was found to be broken upon [Cu(flv)(AN)5]2+ complex formation. In [Cu(flv)(AN)5]2+ complex, a significant rotation of phenyl ring over the planar chromone fragment was spotted as a consequence of intramolecular hydrogen bond breaking. Upon inclusion of BF4– anion to the first solvation shell of Cu2+, an intracomplex hydrogen bond was formed between hydrogen atom of hydroxyl group of flv molecule and the closest fluorine atom of BF4– anion. NCI analysis had shown that a hydrogen bond between hydrogen atom of hydroxyl group of flv molecule and the closest fluorine atom of BF4– anion is significantly stronger than intramolecular hydrogen bond in an isolated flv molecule. In addition, flexible phenyl ring of flv molecule in [Cu(flv)(BF4)(AN)4]+ complex was found to be internally stabilized by the weak van der Waals attraction between oxygen atoms of chromone ring and phenyl hydrogens. These evidences led to a conclusion that [Cu(flv)(BF4)(AN)4]+ complex is more stable, comparing to the in [Cu(flv)(AN)5]2+ complex.

scholarly journals Study of the Reactivity of Lignin Model Compounds to Fluorobenzylation Using 13C and 19F NMR: Application to Lignin Phenolic Hydroxyl Group Quantification by 19F NMR

Molecules ◽  
2020 ◽  
Vol 25 (14) ◽  
pp. 3211
Author(s):  
Esakkiammal Sudha Esakkimuthu ◽  
Nathalie Marlin ◽  
Marie-Christine Brochier-Salon ◽  
Gérard Mortha
Keyword(s):  
Reaction Medium ◽  
19F Nmr ◽  
Hydroxyl Group ◽  
Hydroxyl Groups ◽  
Nmr Analysis ◽  
Model Compounds ◽  
Lignin Model Compounds ◽  
Wide Range ◽  
Lignin Model ◽  
13C And 19F Nmr

Lignin is an aromatic biopolymer derived from lignocellulosic biomass. Providing a comprehensive structural analysis of lignin is the primary motivation for the quantification of various functional groups, with a view to valorizing lignin in a wide range of applications. This study investigated the lignin fluorobenzylation reaction and performed a subsequent 19F-NMR analysis to quantify hydroxyl groups, based on a work developed two decades ago by Barrelle et al. The objectives were to check the assignments proposed in this previous study and to examine the reactivity of various types of lignin hydroxyls with the derivatization agent. Selected lignin model compounds containing phenolic and aliphatic hydroxyls were subjected to the fluorobenzylation reaction, and the obtained reaction medium was analyzed by 13C and 19F NMR spectroscopy. The model compound results showed that phenolic hydroxyls were totally derivatized, whereas aliphatic hydroxyls underwent minimal conversion. They also confirmed that 19F NMR chemical shifts from −115 ppm to −117.3 ppm corresponded to phenolic groups. Then, a 19F NMR analysis was successfully applied to Organosolv commercial lignin after fluorobenzylation in order to quantify its phenolic group content; the values were found to be in the range of the reported values using other analytical techniques after lignin acetylation.

scholarly journals Structural Alerts for Predicting Clastogenic Activity of Pro-oxidant Flavonoid Compounds

2011 ◽  
Vol 17 (2) ◽  
pp. 216-224 ◽  
Author(s):  
Estela Guardado Yordi ◽  
Enrique Molina Pérez ◽  
Maria Joao Matos ◽  
Eugenio Uriarte Villares
Keyword(s):  
Molecular Design ◽  
Biological Effects ◽  
Screening Method ◽  
Automatic Generation ◽  
Quantitative Structure Activity Relationship ◽  
Hydroxyl Group ◽  
Hydroxyl Groups ◽  
Qsar Study ◽  
Molecular Features ◽  
Structural Alerts

Flavonoids have been reported to exert multiple biological effects that include acting as pro-oxidants at very high doses. The authors determined a structural alert to identify the clastogenic activity of a series of flavonoids with pro-oxidant activity. The methodology was based on a quantitative structure–activity relationship (QSAR) study. Specifically, the authors developed a virtual screening method for a clastogenic model using the topological substructural molecular design (TOPS-MODE) approach. It represents a useful platform for the automatic generation of structural alerts, based on the calculation of spectral moments of molecular bond matrices appropriately weighted, taking into account the hydrophobic, electronic, and steric molecular features. Therefore, it was possible to establish the structural criteria for maximal clastogenicity of pro-oxidant flavonoids: the presence of a 3-hydroxyl group and a 4-carbonyl group in ring C, the maximal number of hydroxyl groups in ring B, the presence of methoxyl and phenyl groups, the absence of a 2,3-double bond in ring C, and the presence of 5,7 hydroxyl groups in ring A. The presented clastogenic model may be useful for screening new pro-oxidant compounds. This alert could help in the design of new and efficient flavonoids, which could be used as bioactive compounds in nutraceuticals and functional food.

scholarly journals Synthesis of Analogues of (+)-Gomphoside, a Potent HIF-1 Inhibitor and Cardenolide

2018 ◽  
Vol 13 (3) ◽  
pp. 1934578X1801300
Author(s):  
Eckehard Cuny
Keyword(s):  
Hypoxia Inducible Factor ◽  
Chemical Properties ◽  
Structural Features ◽  
Hydroxyl Group ◽  
Breast Cancer Cell Lines ◽  
Hydroxyl Groups ◽  
Human Breast ◽  
Carbon 14 ◽  
Sugar Ring ◽  
Carbonyl Function

The milkweed bush Gomphocarpus fruticosus R.Br. found in Australia contains the steroidal glycoside (+)-gomphoside, its derivatives (-)-3'-dehydrogomphoside and (+)-3'- epi-gomphoside, as well as other glycoside compounds. The key structural features of these unique herbal agents are bislinked steroid to sugar linkages. (+)-Gomphoside is an extremely potent cardenolide and highly effective Hypoxia-Inducible Factor (HIF)-1 inhibitor. In addition, (+)-gomphoside exhibits strong cytotoxicity on human breast cancer cell lines. The syntheses of (+)-gomphoside analogues with modified steroidal D rings are described here. The syntheses started with glycosylation of (+)-(2α,3β,5α)-2,3-cholestanediol with benzoylated 2-keto sugar bromides, promoted by silver carbonate. Two regioisomeric glycosides with bent up and bent down ring anellation geometry were obtained, because of the two hydroxyl groups in the diol. Modification of the sugar ring of these glycosides by base-induced elimination of benzoic acid yielded (-)-3'-dehydrogomphoside analogues. The analogues of (+)-gomphoside and (+)-3'- epi-gomphoside were then obtained by stereoselective reduction of the 3'-carbonyl function. Compared to natural (+)-gomphoside, these analogues have the following unique structural features: a steroidal D ring with C8H17-alkyl chain instead of an exocyclic butenolide moiety, a different configuration at bridgehead carbon-14, and lack of a hydroxyl group at this position. The resulting altered chemical properties make them interesting structures for pharmacological evaluation and they are potentially suitable candidates for the development of new inhibitors in cancer therapy.

Simple, Efficient, and Selective Synthesis of Phthaloylserine and Phthaloylthreonine

2015 ◽  
Vol 1088 ◽  
pp. 363-366
Author(s):  
Yu Ting Liu ◽  
Si Meng Song ◽  
Da Wei Yin ◽  
Dan Chen
Keyword(s):  
Amino Acids ◽  
Phthalic Anhydride ◽  
Side Reaction ◽  
Hydroxyl Group ◽  
Side Chain ◽  
Hydroxyl Groups ◽  
Synthetic Method ◽  
Selective Synthesis ◽  
Protection Method ◽  
Amino Protection

An amino protection method was developed in which phthalic anhydride was used as the amino protection group, N,N-dimethylformamide (DMF) as solvent, L-threonine and L-serine with hydroxyl groups in side chain as the protected amino acids.The structures of products were confirmed by IR、1H NMR and 13C NMR. It is an efficient and simple protection method of amino acids with a hydroxyl group in the side chain.In addition, the synthetic method avoids the side reaction and significantly improves reaction yields(over 90%).

Formation of borate complexes of inosamines (aminodeoxyinositols) and their separation by paper electrophoresis

1974 ◽  
Vol 27 (4) ◽  
pp. 853 ◽  
Author(s):  
JL Frahn ◽  
JA Mills
Keyword(s):  
Carbon Dioxide ◽  
Paper Electrophoresis ◽  
Hydroxyl Group ◽  
Hydroxyl Groups ◽  
Amino Group ◽  
Ph Values ◽  
Borate Complex ◽  
Wide Range ◽  
Borate Complexes ◽  
Probable Site

The electrophoretic mobility of an inosamine in borate buffer is very dependent on configuration, and a set of 10 inosamines showed a wide range of mobilities. The order of mobilities within the set changed as the pH of the buffer was changed in the range 7.7-9.5. Paper electrophoresis in borate buffers can effectively separate mixtures of inosamines. The probable site of reaction between an inosamine and borate ions has been identified for some isomers. In aminodeoxy-scyllo-inositol and 3-amino-3-deoxy-epi-inositol the amino group is involved in the formation of a tridentate borate complex of adamantane-type structure, which is electrically neutral over the above range of pH values. Aminodeoxy-scyllo-inositol simultaneously combines with a second molecule of borate, forming a bis-tridentate complex with one anionic centre. There is evidence that in other isomers protonation of the amino group and formation of anionic borate complexes at hydroxyl groups are not independent reactions. Paper electrophoresis in non-complexing buffers provides evidence for the relative basicities of inosamines. DL-2-Amino-2-deoxy-epi-inositol, which has an interaction between axial amino and hydroxyl group in the preferred conformation, was the strongest base in the set, whereas the bases with an axial amino group free of such an interaction were the weakest. Inosamines form N-carboxyl derivatives in the normal way on exposure to carbon dioxide in the presence of strong alkali.

Cyclization Effect on pKa of the Side Chain of Aspartic Acid in Dipeptides: A DFT Study

2020 ◽  
Vol 17 (5) ◽  
pp. 381-387
Author(s):  
Mohsen Sargolzaei ◽  
Majid Namayandeh Jorabchi
Keyword(s):  
Aspartic Acid ◽  
Life Sciences ◽  
Pharmaceutical Chemistry ◽  
Side Chain ◽  
Cyclic Dipeptide ◽  
Cyclic Dipeptides ◽  
Pka Values ◽  
Wide Range ◽  
Strong Acidity ◽  
Intramolecular Hydrogen

Cyclic dipeptides are very important compounds that have a wide range of applications in pharmaceutical chemistry and life sciences. In the current work, the acidity of the side chain of aspartic acid was calculated for various linear and a cyclic dipeptide. pKa values were derived using the thermodynamics cycle and DFT/B3LYP approach. The obtained pKa values show strong acidity for cyclic with respect to linear dipeptides. We found an intramolecular hydrogen bond in cyclic dipeptide structure, which can be used to justify the increasing acidity of the side chain of Asp as compared to linear structures.

Studies on biliary excretion in the rabbit II. The relationship between the chemical structure of certain natural or synthetic pentacyclic triterpenes and their icterogenic activity. Part 1: The substituents on carbon atoms 3, 17, 22 and 24

1963 ◽  
Vol 157 (969) ◽  
pp. 473-491 ◽  
Keyword(s):  
Bile Flow ◽  
Chemical Structure ◽  
Hydroxyl Group ◽  
Side Chain ◽  
Hydroxyl Groups ◽  
Pentacyclic Triterpene ◽  
Triterpene Acid ◽  
Pentacyclic Triterpenes ◽  
Bilirubin Excretion ◽  
The Relationship

Considerable interest has been aroused by the use of the pentacyclic triterpene acid, icterogenin, in studies associated with bilirubin excretion and the genesis of icterus of the intrahepatic cholestasis type. This compound, which produces within a few hours after administration to sheep and rabbits a very marked decline in bile flow and the amount of bilirubin excreted hourly without any histological damage to the liver parenchyma visible in the ordinary light microscope, has proved to be very useful in the study of the South African ovine photosensitization disease known as 'geeldikkop’ (‘yellow thick head’). In connexion with research on this disease, a study of the relationship between the chemical structure of the pentacyclic triterpenes and their icterogenic activity is in progress. The first part of this work dealing with certain structural variations in triterpenes of the oleanane and 24-noroleanane (hedragane) series is reported in this paper. Assays are recorded of sixteen of these compounds and some of their derivatives for such activity, using a modification of the rabbit test described in the first paper of this series (Heikel, Knight, Rimington, Ritchie & Williams 1960). Four new icterogenic agents are discussed, namely: 22 β -angeloyloxyoleanolic acid, 22 β -angeloyloxyhedragolic acid, 22 β -angeloyloxy-24-hydroxyoleanolic acid and 22 β -angeloyloxy-24-oxo-oleanonic acid. The first two mentioned compounds are extremely active, their potency far surpassing that of icterogenin. Icterogenic activity of these acids appears, so far, to be based upon the presence of a β -equatorially orientated hydroxyl group at C(3) or a hydroxyl at C(24) and a 22 β -angeloyl side-chain on the triterpene molecule. Stereoisomer specificity is shown in respect of icterogenicity by these compounds since the epimers of two of these substances carrying α -axially orientated hydroxyls at C(3) have been shown to have no such effect on bile flow or bilirubin excretion. Removal of the angelic acid side-chain, substitution of the hydroxyl groups or replacement of these with a ketone function, is followed by loss of activity.

Synthesis and Biological Activity of Embelin and its Derivatives: An Overview

2020 ◽  
Vol 20 (5) ◽  
pp. 396-407 ◽  
Author(s):  
Zhaojun Sheng ◽  
Siyuan Ge ◽  
Min Gao ◽  
Rongchao Jian ◽  
Xiaole Chen ◽  
...  
Keyword(s):  
Biological Activity ◽  
Biological Effects ◽  
New Drugs ◽  
Hydroxyl Groups ◽  
Carbonyl Groups ◽  
Cellular Mechanisms ◽  
Embelia Ribes ◽  
Naturally Occurring ◽  
Ic50 Value ◽  
Apoptosis Protein

Embelin is a naturally occurring para-benzoquinone isolated from Embelia ribes (Burm. f.) of the Myrsinaceae family, and contains two carbonyl groups, a methine group and two hydroxyl groups. With embelin as the lead compound, more than one hundred derivatives have been reported. Embelin is well known for its ability to antagonize the X-linked inhibitor of apoptosis protein (XIAP) with an IC50 value of 4.1 μM. The potential of embelin and its derivatives in the treatment of various cancers has been extensively studied. In addition, these compounds display a variety of other biological effects: antimicrobial, antioxidant, analgesic, anti-inflammatory, anxiolytic and antifertility activity. This paper reviews the recent progress in the synthesis and biological activity of embelin and its derivatives. Their cellular mechanisms of action and prospects in the research and development of new drugs are also discussed.

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