STUDY OF THE INTERACTION BETWEEN OXICAM DERIVATIVES AND COX1 USING FINGERPRINT DESCRIPTORS AND MOLECULAR DOCKING

Oxicam derivatives play an important role in the treatment of pain and inflammation. The mechanism of action of these compounds consists in the inhibition of cyclooxygenase (COX) and the blockade of isoform 1 of this enzyme (COX-1) is considered to generate adverse effects. The aim of this paper is to establish which of the atoms in the oxicams molecules are responsible for their inhibitory activities, using electronegativity as fingerprint descriptor. Using this descriptor and molecular docking programs, the atoms in the molecule that have a greater contribution to COX-1 inhibition have been identified. In the case of the studied molecules, the oxygen atoms and the nitrogen atoms are highlighted. The oxygen atoms participate in the interaction as electron acceptors through U-MO molecular levels (74.1%) and the nitrogen atoms participate in the interaction both as a nucleophilic center through the molecular state of HOMO (13.7%) and as an electrophilic center through the molecular state of LUMO (13.2%). In the case of three out of four of the studied compounds, the 4-hydroxyl group of the thiazine ring participates in the interaction with COX-1. The results are also supported by the 2D and 3Ddiagrams of the applied docking method.

Unprecedented Coumarin-Pyronin Hybrid Dyes: Synthesis, Fluorescence Properties and Theoretical Calculations

A novel class of rosamine dyes bearing a 7-substituted 4-hydroxycoumarin unit as <i>meso</i>-heteroaryl ring is presented. The latent <i>C</i>-nucleophilic character of 4-hydroxycoumarin derivatives (<i>i.e.</i>, their C-3 position as nucleophilic center) has been drawn on in the designing of two unprecedented synthetic routes towards these atypical xanthene dyes. They are based on an effective formal Knoevenagel condensation with either pyronin derivatives or a mixed bis-aryl ether bearing both an aldehyde and a masked phenylogous amine, possibly applicable to a wide range of latent cyclic <i>C</i>-nucleophiles. We also report experimental and theoretical photophysical investigations of these unique coumarin-pyronin hybrid structures and particularly their form low-lying quenching states, some of dark twisted intramolecular charge transfer (TICT) nature, depending on the medium (CHCl₃ and water). Furthermore, two fluorophore compounds <b>9</b> and <b>11</b> have been applied for imaging in paraformaldehyde-fixed A549 cells to gain insights into their permeation and localization.

Unprecedented Coumarin-Pyronin Hybrid Dyes: Synthesis, Fluorescence Properties and Theoretical Calculations

A novel class of rosamine dyes bearing a 7-substituted 4-hydroxycoumarin unit as <i>meso</i>-heteroaryl ring is presented. The latent <i>C</i>-nucleophilic character of 4-hydroxycoumarin derivatives (<i>i.e.</i>, their C-3 position as nucleophilic center) has been drawn on in the designing of two unprecedented synthetic routes towards these atypical xanthene dyes. They are based on an effective formal Knoevenagel condensation with either pyronin derivatives or a mixed bis-aryl ether bearing both an aldehyde and a masked phenylogous amine, possibly applicable to a wide range of latent cyclic <i>C</i>-nucleophiles. We also report experimental and theoretical photophysical investigations of these unique coumarin-pyronin hybrid structures and particularly their form low-lying quenching states, some of dark twisted intramolecular charge transfer (TICT) nature, depending on the medium (CHCl₃ and water). Furthermore, two fluorophore compounds <b>9</b> and <b>11</b> have been applied for imaging in paraformaldehyde-fixed A549 cells to gain insights into their permeation and localization.

INFLUENCE OF SUBSTITUTES ON THE RATE OF THE REACTION OF META- АND PARASUBSTITUTED BENZOIC ACIDS WTH ANILINE, CATALYZED BY POLYBUTOXYTITANATES

The polybutoxytitanates catalysis of acylation of anilines by meta- and parasubstituted benzoic acid results in substituted benzanilides. The rate constants of this second-order reaction (the first in terms of aniline and substituted benzoic acid; boiling ortho-xylene, 145 °С) correlates well according to the Hammett equation with two straight lines for individual groups of substituents with ρ = 1.76 (electron donors) and 0.12 (electron acceptors). Oxybenzoic and phthalic acids, that do not react with aniline and inhibit the interaction of the latter with benzoic acid, fall out of this dependence. Based on these data, as well as the results of a previous studies of the interaction of substituted anilines with a benzoic acid made under comparable conditions, a mechanism of bifunctional catalysis due to the formation of titanium polybutoxybenzoates in the first minutes of the reaction in situ — the true catalysts of the process, is proposed. The nucleophilic center of the catalyst can be represented by the carbonyl group of a substituted benzoate bound to a titanium atom, forming an H-bond with hydrogen atoms of the amino group of aniline, thus activated to react with a substituted benzoic acid. The titanium atoms of polytitanate (coordination catalysis) and their complexes with the resulting substituted benzanilides (acid catalysis) can act as the electrophilic center of a catalyst that activates the carbonyl group of a substituted benzoic acid to nucleophilic attack by aniline. A titanium atom bound to a substituted benzoate exhibits, depending on the nature of the substituent, various catalytic activity.

Organic synthesis of fixed CO2 using nitrogen as a nucleophilic center

With nitrogen as the nucleophilic center, CO2 is fixed by using metal catalysis, non-metal catalysis, photocatalysis and electrocatalysis.

The reaction of anthracyl-α-hydroxyphosphonate with anthracene: Facile Access to diverse (bis)-anthracylphosphonates as a suitable source for useful extensive π-conjugates

Molecular anthracene has been used as arene in the Friedel-Crafts (FC) type arylation reaction of anthracyl-α-hydroxyphosphonate in the presence of acid. A diverse product formation is observed, in which anthracene unit is found to be linked through its C1 position with α-C of phosphonate. Interestingly, the molecular conformation (X-ray structure) of this phosphonate reveals one of the bond angles of a tetrahedral carbon as 118o which is close to the C of sp 2 character. The attacks from C1, C2 or C9 nucleophilic center of molecular anthracene to C10 atom of 9-anthrylphosphonate are also recognized. The diverse molecular structures are established spectroscopically. The bis-anthracyl compounds with a P-CH2 unit have been successfully utilized in Horner-Wadsworth-Emmons (HWE) reactions to afford extensive bis-anthracyl-linked π-conjugates. Thus, the electronically different substituent is attached to the system by varying the aldehydes. Among all these π-conjugates, the compound with three anthracyl core is noticed as a weak AIEgen (Aggregation-Induced emission active fluorogen).

Palladium-catalyzed domino Heck/intermolecular cross-coupling: efficient synthesis of 4-alkylated isoquinoline derivatives

The first example of a σ-alkylpalladium(ii) intermediate promoting cyclization of alkynes containing a proximate nucleophilic center is presented.

Flocculation of Quaternary Chitosan on Acid Dyeing Waste Water

In order to increase the positively charge, solubility in water and grafted degree of chitosan, quaternary chitosan was synthesized with chitosan and glycidyl-trimethyl-ammonium chloride by the heterogeneous reaction. FT-IR was used to characterize the structure of the synthesized. The quaternary chitosan was then used to treat simulated acid dyeing wastewater, the effect of quaternary chitosan concentration, agitation mode and pH values on flocculation were discussed. The results indicated that the H+in nucleophilic center-NH2was displaced by-CH2CH(OH)CH2N+(CH3)3and the 2-hydroxypropyltrimethyl ammonium chloride chitosan (quaternary chitosan) was synthesized. When applied to treatment of acid dye waste water, the decolorization rate was 95.5%, and the COD removal was 86.4%.

Ring constructions by the use of fluorine substituent as activator and controller

By using the properties of fluorine such as electronic effects and leaving-group ability, two types of ring-forming reactions have been achieved starting from fluoroolefins: (i) fluorinated vinyl ketones with a vinyl and/or an aryl group, which undergo fluorine-directed and/or -activated Nazarov, Friedel-Crafts, and tandem cyclizations in their combination to construct highly functionalized and fused ring systems and (ii) gem-difluoroolefins bearing a nucleophilic center on the carbon δ to the flourines undergo intramolecular substitution for the fluorine via "anti-Baldwin" 5-endo-trig closures leading to ring-fluorinated heterocycles. Throughout these reactions, fluorines function as an activator of the substrates and a controller over the reaction pathways.