Multifunctional derivatives of zwitterionic 2-pyridones and their potential application

Предмет истраживања ове дисертације представљају синтеза и потенцијална примјена серије одабраних 2-пиридона и двије серије арилазо пиридонских боја. Супституисани 2- пиридони синтетисани су Гуареши-Торпеовом циклизацијом. За добијање арилазо пиридонских боја примењен је поступак диазотовања моно- и дисупституисаних анилина и накнадног купловања диазонијум-јона са 6-хидрокси-4-метил-3-(пиридинијум-1-ил)-2- пиридоном. Сва једињења су детаљно окарактерисана одређивањем тачке топљења, 1H и 13C NMR, АТR-FTIR, UV-Vis спектрофотометријом, MS спектроскопијом и елементалном анализом. Одређена је кристална структура синтетисаних 2-пиридона. Кристално паковање је анализирано помоћу PIXEL модула тако што је енергија кристалне решетке подијељена на кулоновске, поларизационе, дисперзионе и репулзионе доприносе. Доприноси појединачних типова интеракција дискутовани су на основу Хиршфелдове анализе површине и јединствeних псеудосиметричних 2Д графикона интеракција између атома у кристалу. Могућност примјене деривата 2-пиридона испитивана је одређивањем њихове антиоксидативне и антимикробне активности, као и цитотоксичног дејства. У наставку је проучавана таутомерија арилазо пиридонских боја. Показано је да су молекули боја у свом протонованом облику позитивно наелектрисани, а њиховим депротоновањем настају дипол-јони. Могућност примјене ових боја испитана је одређивањем њихове биолошке активности и бојењем текстилног материјала различитог сировинског састава, и то: диацетата целулозе, бијељеног памука, полиамида, полиестра, полиакрилонитрила и вуне. Показано је да се дипол-јонски облик брже везује, док се са хидразонским обликом успостављају јаче интеракције. Боје се најбоље везују за ацетат целулозе и вуну, па је испитиван и механизам везивања њихових молекуа за ова два влакна.The aim of this doctoral dissertation is to synthesize a series of selected 2-pyridone derivatives and two series of arylazo pyridone dyes and to investigate their application potential. 2- Pyridone derivatives were prepared using the Guareschi-Thorpe cyclisation. Arylazo pyridone dyes were obtained by diazotization of mono- and disubstituted anilines and subsequent coupling of the diazonium ions with 6-hydroxy-4-methyl-3-(pyridinium-1-yl)-2-piridone. The compounds were characterized by melting points, ATR-FTIR, 1H and 13C NMR, UV-Vis and MS spectroscopy and elemental analysis. The crystal structure of 2-pyridone derivatives was determined and the crystal packing was described using PIXEL lattice energy calculations and X-ray analysis. The Hirshfeld surfaces analysis and 2D fingerprint plots of the crystals were used to underline differences between the crystal packing and highlight the distinctions in the crystal environment. The application potential of 2-pyridone derivatives was examined by determination of their antioxidant, antimicrobial and anticancer activities. In the continuation, tautomeric features of the dyes were discussed. It was observed that the dyes protonated form is in fact cationic, while their deprotonated form is zwitterionic. The application potential of arylazo pyridone dyes was examined by determination of their biological activities as well as by dying fabrics of different chemical composition: diacetate, bleached cotton, naylon, polyester, polyacriloniterile, wool. Considering the preformed characterization, it was shown that the dye-fabric adhesion depends on the dye form wherein the zwitterionic form interacts with fabric faster, while the hydrazone form establishes firmer interactions. The dye-fabric interactions were elucidated depending on the molecular structure of the dyes, with regard to the electronic effects of the substituents

Supplementary material for the article: Lazić, A. M.; Mašulović, A. D.; Lađarević, J. M.; Valentić, N. V. Assessing the pharmacological potential of selected xanthene derivatives. Journal of the Serbian Chemical Society 2023, 88(9), 811-824. https://doi.org/10.2298/JSC230131035L

A convenient and efficient approach toward the synthesis of seven aromatically substituted xanthendiones 1‒7 and one structurally-related xanthenone 8 through condensation of dimedone and the appropriate aromatic aldehyde is reported. Further, their chemical structure was confirmed by melting points, elemental analysis, FT-IR, 1H-, 13C-NMR and UV–Vis spectroscopic methods. The relationship between the chemical structure and pharmacological activity was determined empirically using appropriate software packages and in vitro using the 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) method. The results of in silico prediction suggested that all investigated compounds possess good oral bioavailability. The results of the ABTS assay indicate that five compounds possess the ability to scavenge the ABTS•+ radical cation. Based on the comparison of the IC50 values, the activity of the compounds was found to be as follows: 6 > 1 > 7 > 2 > 8. The effects of solvent dipolarity/polarizability and solute solvent–hydrogen-bonding interactions on the shifts of the absorption maxima were rationalized by means of the linear solvation energy relationship concepts proposed by Kamlet–Taft and Catalán.Related to: [https://technorep.tmf.bg.ac.rs/handle/123456789/6809]Supplementary material for: [https://doi.org/10.2298/JSC230131035L

Multifunctional derivatives of zwitterionic 2-pyridones and their potential application

Предмет истраживања ове дисертације представљају синтеза и потенцијална примјенасерије одабраних 2-пиридона и двије серије арилазо пиридонских боја. Супституисани 2-пиридони синтетисани су Гуареши-Торпеовом циклизацијом. За добијање арилазопиридонских боја примењен је поступак диазотовања моно- и дисупституисаних анилина инакнадног купловања диазонијум-јона са 6-хидрокси-4-метил-3-(пиридинијум-1-ил)-2-пиридоном. Сва једињења су детаљно окарактерисана одређивањем тачке топљења, 1H и 13CNMR, АТR-FTIR, UV-Vis спектрофотометријом, MS спектроскопијом и елементалноманализом.Одређена је кристална структура синтетисаних 2-пиридона. Кристално паковање јеанализирано помоћу PIXEL модула тако што је енергија кристалне решетке подијељена накулоновске, поларизационе, дисперзионе и репулзионе доприносе. Доприноси појединачнихтипова интеракција дискутовани су на основу Хиршфелдове анализе површине ијединствeних псеудосиметричних 2Д графикона интеракција између атома у кристалу.Могућност примјене деривата 2-пиридона испитивана је одређивањем њиховеантиоксидативне и антимикробне активности, као и цитотоксичног дејства.У наставку је проучавана таутомерија арилазо пиридонских боја. Показано је да сумолекули боја у свом протонованом облику позитивно наелектрисани, а њиховимдепротоновањем настају дипол-јони. Могућност примјене ових боја испитана јеодређивањем њихове биолошке активности и бојењем текстилног материјала различитогсировинског састава, и то: диацетата целулозе, бијељеног памука, полиамида, полиестра,полиакрилонитрила и вуне. Показано је да се дипол-јонски облик брже везује, док се сахидразонским обликом успостављају јаче интеракције. Боје се најбоље везују за ацетатцелулозе и вуну, па је испитиван и механизам везивања њихових молекуа за ова два влакна.The aim of this doctoral dissertation is to synthesize a series of selected 2-pyridonederivatives and two series of arylazo pyridone dyes and to investigate their application potential. 2-Pyridone derivatives were prepared using the Guareschi-Thorpe cyclisation. Arylazo pyridone dyeswere obtained by diazotization of mono- and disubstituted anilines and subsequent coupling of thediazonium ions with 6-hydroxy-4-methyl-3-(pyridinium-1-yl)-2-piridone. The compounds werecharacterized by melting points, ATR-FTIR, 1H and 13C NMR, UV-Vis and MS spectroscopy andelemental analysis.The crystal structure of 2-pyridone derivatives was determined and the crystal packing wasdescribed using PIXEL lattice energy calculations and X-ray analysis. The Hirshfeld surfacesanalysis and 2D fingerprint plots of the crystals were used to underline differences between thecrystal packing and highlight the distinctions in the crystal environment. The application potentialof 2-pyridone derivatives was examined by determination of their antioxidant, antimicrobial andanticancer activities.In the continuation, tautomeric features of the dyes were discussed. It was observed that thedyes protonated form is in fact cationic, while their deprotonated form is zwitterionic. Theapplication potential of arylazo pyridone dyes was examined by determination of their biologicalactivities as well as by dying fabrics of different chemical composition: diacetate, bleached cotton,naylon, polyester, polyacriloniterile, wool. Considering the preformed characterization, it wasshown that the dye-fabric adhesion depends on the dye form wherein the zwitterionic form interactswith fabric faster, while the hydrazone form establishes firmer interactions. The dye-fabricinteractions were elucidated depending on the molecular structure of the dyes, with regard to theelectronic effects of the substituents

Multifunctional derivatives of zwitterionic 2-pyridones and their potential application

Предмет истраживања ове дисертације представљају синтеза и потенцијална примјена серије одабраних 2-пиридона и двије серије арилазо пиридонских боја. Супституисани 2- пиридони синтетисани су Гуареши-Торпеовом циклизацијом. За добијање арилазо пиридонских боја примењен је поступак диазотовања моно- и дисупституисаних анилина и накнадног купловања диазонијум-јона са 6-хидрокси-4-метил-3-(пиридинијум-1-ил)-2- пиридоном. Сва једињења су детаљно окарактерисана одређивањем тачке топљења, 1H и 13C NMR, АТR-FTIR, UV-Vis спектрофотометријом, MS спектроскопијом и елементалном анализом. Одређена је кристална структура синтетисаних 2-пиридона. Кристално паковање је анализирано помоћу PIXEL модула тако што је енергија кристалне решетке подијељена на кулоновске, поларизационе, дисперзионе и репулзионе доприносе. Доприноси појединачних типова интеракција дискутовани су на основу Хиршфелдове анализе површине и јединствeних псеудосиметричних 2Д графикона интеракција између атома у кристалу. Могућност примјене деривата 2-пиридона испитивана је одређивањем њихове антиоксидативне и антимикробне активности, као и цитотоксичног дејства. У наставку је проучавана таутомерија арилазо пиридонских боја. Показано је да су молекули боја у свом протонованом облику позитивно наелектрисани, а њиховим депротоновањем настају дипол-јони. Могућност примјене ових боја испитана је одређивањем њихове биолошке активности и бојењем текстилног материјала различитог сировинског састава, и то: диацетата целулозе, бијељеног памука, полиамида, полиестра, полиакрилонитрила и вуне. Показано је да се дипол-јонски облик брже везује, док се са хидразонским обликом успостављају јаче интеракције. Боје се најбоље везују за ацетат целулозе и вуну, па је испитиван и механизам везивања њихових молекуа за ова два влакна.The aim of this doctoral dissertation is to synthesize a series of selected 2-pyridone derivatives and two series of arylazo pyridone dyes and to investigate their application potential. 2- Pyridone derivatives were prepared using the Guareschi-Thorpe cyclisation. Arylazo pyridone dyes were obtained by diazotization of mono- and disubstituted anilines and subsequent coupling of the diazonium ions with 6-hydroxy-4-methyl-3-(pyridinium-1-yl)-2-piridone. The compounds were characterized by melting points, ATR-FTIR, 1H and 13C NMR, UV-Vis and MS spectroscopy and elemental analysis. The crystal structure of 2-pyridone derivatives was determined and the crystal packing was described using PIXEL lattice energy calculations and X-ray analysis. The Hirshfeld surfaces analysis and 2D fingerprint plots of the crystals were used to underline differences between the crystal packing and highlight the distinctions in the crystal environment. The application potential of 2-pyridone derivatives was examined by determination of their antioxidant, antimicrobial and anticancer activities. In the continuation, tautomeric features of the dyes were discussed. It was observed that the dyes protonated form is in fact cationic, while their deprotonated form is zwitterionic. The application potential of arylazo pyridone dyes was examined by determination of their biological activities as well as by dying fabrics of different chemical composition: diacetate, bleached cotton, naylon, polyester, polyacriloniterile, wool. Considering the preformed characterization, it was shown that the dye-fabric adhesion depends on the dye form wherein the zwitterionic form interacts with fabric faster, while the hydrazone form establishes firmer interactions. The dye-fabric interactions were elucidated depending on the molecular structure of the dyes, with regard to the electronic effects of the substituents

In vitro antioxidant activity evaluation of selected xanthene derivatives

Xanthendiones (1,8-dioxooctahydroxanthenes) are a special class of oxygenincorporating tricyclic compounds bearing as a basic feature a pyran nucleus fused on either side with cyclohex-2-enone rings. They are often found as a structural motif in natural products with a wide range of biological activities, such as: antioxidant, antimicrobial, trypanocidal, antiinflammatory, antiproliferative and anticancer. A convenient and efficient approach toward the synthesis of seven aromatically substituted xanthendiones 1‒7 and one structurally-related xanthenone 8 through condensation of dimedone and the appropriate aromatic aldehyde is reported. The relationship between the chemical structure and pharmacological activity was determined empirically using appropriate software packages and in vitro using the 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) method. The results of the ABTS assay indicate that five compounds possess the ability to scavenge the ABTS•+ radical cation. Based on the comparison of the IC50 values, the activity of the compounds was found to be as follows: 6 > 1 > 7 > 2 > 8

Charge assisted assembly of zwitterionic pyridone hydrates

Two pyridone derivatives, bearing the pyridinium moiety (1), or dimethylpyridinium moiety (2), have been synthesized and their crystal structures have been determined. The compounds crystalize in hydrated zwitterionic forms with either two (1.2H(2)O) or four (2.4H(2)O) water molecules. The zwitteri-onic networks contain different types of water clusters, generated into channels, incorporating them into the network by sandwiching. The type of channel depends on the crystal lattice and the nature of non-covalent interactions established between zwitterions as well as the number of water molecules incorporated into the architecture. 1 affords tubes filled in with water channels formed by water tetramers, contrary to 2, which affords a layered network altering the zwitterionic layer and the layer formed by water tetramers and hexamers. A detailed study of intermolecular interactions of both crystal structures and a quantification of interaction energies has been performed using PIXEL lattice energy calculations, giving an insight to a quantitative evaluation of interactions through Coulombic, disperse, repulsion and polarization energies. The strongest pairwise, in both structures, is found to be a dipole-dipole interaction between oppositely charged heterocyclic rings. The differences in the crystal packings of these hydrates have been elucidated by the fingerplot analysis. The comparative studies between experimental and calculated (DFT) data of molecules 1.H2O and 2.4H(2)O for systems of different complexity are performed. Furthermore, correlations of experimental and calculated bond lengths and the simulation of compound solvation with the CPCM model are done

Structure-Dependent Electrochemical Behavior of 2-Pyridone Derivatives: A Combined Experimental and Theoretical Study

In this work, the electrooxidation ability of nine pyridones was evaluated using cyclic(CV) and square-wave voltammetry (SWV) in Britton–Robinson (BR) aqueous buffer solutions on aglassy carbon electrode (GC). The dependence of electrochemical activity on pyridone structure waselucidated by means of experimentally obtained spectra and quantum chemical calculations. Firstly, itwas shown that electrochemical activity is determined by the –OH group as a substituent in position6 of the pyridone ring. By coupling the experimentally obtained UV-Vis spectra and DFT calculations,the most stable forms, both protonated and deprotonated, were defined. The calculated values areconsistent with the electrochemical behavior observed, indicating that the deprotonated anionic formwas the most electrochemically active. Moreover, the impact of the substituent in position 3 of thepyridone scaffold was discusse

Synthesis, UV-Vis spectrophotometric titration and theoretical calculations of 6-hydroxy-4-methyl-3-(pyridinium-1-yl)-2-pyridone

U ovom radu prikazana je sinteza i karakterizacija 6-hidroksi-4-metil-3-(piridinijum-1-il)-2-piridona. Sintetisano jedinjenje dobijeno je u obliku dipol-jona. Spektrofotometrijskom titracijom u rastvoru etanola ispitan je uticaj pH vrijednosti na strukturu jedinjenja. Kako bi se detaljno opisala struktura derivata 2-piridona, eksperimentalno dobijene vrijednosti dobijenih apsorpcionih maksimuma upoređeni su sa kvantno-hemijskim proračunima optimizovanih geometrija i teorijskih UV-Vis spektara pri različitim pH vrijednostima.In this research, synthesis and characterization of 6-hydroxy-4-methyl-3-(pyridinium-1-yl)-2-pyridone was shown. Synthesized compound was achieved in the zwitterionic form. UV-Vis spectrophotometric titration was performed in order to examine the influence of pH values on the structure of the compound. For the purpose of detail characterization of 2-pyridone derivative, experimentally obtained results were compared to quantum-chemical calculations of optimized geometries and theoretical UV-Vis spectra of solution for different pH values

Novel eco-friendly initiation system based on vitamin C for energy efficient synthesis of PMAA hydrogel used for delivery of phenolic compounds

This study reports successful free radical synthesis of pH-sensitive hydrogels based on poly(methacrylic acid) (PMAA) by using new green initiation system based on vitamin C and hydrogen peroxide (VC/H2O2). The application of proposed initiation system provides many advantages, above all cost effective and eco-friendly synthesis which can be carried out under ambient conditions. The obtained PMAA hydrogels are analyzed by various technics: Differential Scanning Calorimetry, Fourier Transform Infrared spectroscopy, Scanning Electron Microscopy and by using single compression tests. In line with the intended application, PMAA hydrogels are further investigated in terms of their potential to be used for encapsulation and controlled release of active substances such as antioxidant phenolic compounds. To keep it green, the total phenolic compounds (TPC) were obtained from orange peels waste by applying ultrasonic-assisted extraction and deep eutectic solvent (DES) based on glycerol:urea:water. The TPC were successfully encapsulated into the PMAA hydrogels which were previously estimated to have the optimal mechanical and swelling properties with respect to the final application. The swelling behavior of the PMAA hydrogels and controlled release of the TPC were tested as a function of the various synthesis parameters in several media with different pH values. It was shown that TPC can be released in control manner in medium which simulates the environment in human intestines, finally resulting in enhanced bioavailability of TPC, reduced side effects and improved therapeutic effects