Synthesis and physicochemical haracterization of N-aromatic monosubstituted carbohydrazones аnd thiocarbohydrazones

U ovoj doktorskoj disertaciji je radi fizičko-hemijske karakterizacije i ispitivanja potencijalne biološke aktivnosti sintetisano  40  derivata mono(tio)karbohidrazona. Strukture dobijenih jedinjenja su potvrđene  NMR  i  FT–IR  spektroskopijom,  elementalnom  i  rendgenskom  strukturnom  analizom. Uticaj  rastvarača  i  prisutnog  supstituenta  na  položaje apsorpcionih  maksimuma  ispitani  su  po principima LSER i LFER metoda. Teorijski proračuni za sintetisana jedinjenja izvedeni su  primenom TD–DFT  metode.  Jonizacione  konstante  derivata  mono(tio)karbohidrazona  su  određene potenciometrijskim  titracijama.  Antioksidativna  aktivnost  je  određena  primenom  tri  testa:  DPPH, ABTS  i  FRAP  testa.  Antimikrobna  aktivnost  je  ispitana  mikrodilucionom  metodom  na  dva  soja bakterija:  Staphylococcus  aureus  i  Escherichia  coli.  Za  jedinjenja  koja  su  pokazali  antimikrobnu aktivnost je  ispitan procenat citotoksičnosti.  Sveukupan  zaključak o sličnosti i razlikama sintetisanih derivata izveden je na osnovu multivarijatnih metoda klaster analize i analize glavnih komponenti.In this doctoral dissertation, 40 mono(thio)carbohydrazone derivatives were synthesized for the purpose of physico-chemical characterization and examination of potential biological activity. The structures of the obtained compounds were confirmed by NMR and FT –IR spectroscopy, elemental analysis  and  X-ray  structural  analysis.  The  influence  of  solvent  and  substituent  present  on  the positions  of  absorption maxima  was  examined  according  to  the  principles  of  LSER  and  LFER methods.  Theoretical  calculations  for  the  synthesized  compounds  were  performed  by  the  TD–DFT method.  The  acid  constants  of  mono(thio)carbohydrazone  derivatives  were  determined  by potentiometric  titrations.  Antioxidant  activity  was  determined  using  three  tests:  DPPH,  ABTS  and FRAP test. Antimicrobial activity was examined by microdilution method on two strains of bacteria: Staphylococcus  aureus  and  Escherichia  coli.  The  percentage  of  cytotoxicity  was  examined  for compounds  that  showed  antimicrobial  activity.  Overall  conclusion  about  the  similarities  and differences of the synthesized  derivatives was studied by multivariate  methods of cluster analysis and analysis of principal components

Synthesis and physicochemical haracterization of N-aromatic monosubstituted carbohydrazones аnd thiocarbohydrazones

U ovoj doktorskoj disertaciji je radi fizičko-hemijske karakterizacije i ispitivanja potencijalne biološke aktivnosti sintetisano  40  derivata mono(tio)karbohidrazona. Strukture dobijenih jedinjenja su potvrđene  NMR  i  FT–IR  spektroskopijom,  elementalnom  i  rendgenskom  strukturnom  analizom. Uticaj  rastvarača  i  prisutnog  supstituenta  na  položaje apsorpcionih  maksimuma  ispitani  su  po principima LSER i LFER metoda. Teorijski proračuni za sintetisana jedinjenja izvedeni su  primenom TD–DFT  metode.  Jonizacione  konstante  derivata  mono(tio)karbohidrazona  su  određene potenciometrijskim  titracijama.  Antioksidativna  aktivnost  je  određena  primenom  tri  testa:  DPPH, ABTS  i  FRAP  testa.  Antimikrobna  aktivnost  je  ispitana  mikrodilucionom  metodom  na  dva  soja bakterija:  Staphylococcus  aureus  i  Escherichia  coli.  Za  jedinjenja  koja  su  pokazali  antimikrobnu aktivnost je  ispitan procenat citotoksičnosti.  Sveukupan  zaključak o sličnosti i razlikama sintetisanih derivata izveden je na osnovu multivarijatnih metoda klaster analize i analize glavnih komponenti.In this doctoral dissertation, 40 mono(thio)carbohydrazone derivatives were synthesized for the purpose of physico-chemical characterization and examination of potential biological activity. The structures of the obtained compounds were confirmed by NMR and FT –IR spectroscopy, elemental analysis  and  X-ray  structural  analysis.  The  influence  of  solvent  and  substituent  present  on  the positions  of  absorption maxima  was  examined  according  to  the  principles  of  LSER  and  LFER methods.  Theoretical  calculations  for  the  synthesized  compounds  were  performed  by  the  TD–DFT method.  The  acid  constants  of  mono(thio)carbohydrazone  derivatives  were  determined  by potentiometric  titrations.  Antioxidant  activity  was  determined  using  three  tests:  DPPH,  ABTS  and FRAP test. Antimicrobial activity was examined by microdilution method on two strains of bacteria: Staphylococcus  aureus  and  Escherichia  coli.  The  percentage  of  cytotoxicity  was  examined  for compounds  that  showed  antimicrobial  activity.  Overall  conclusion  about  the  similarities  and differences of the synthesized  derivatives was studied by multivariate  methods of cluster analysis and analysis of principal components

Determination of ionization constants of selected monocarbohydrazone derivatites

Poster presented at: 13th International Scientific Conference Contemporary Materials 2020, Banja Luka, 11th September, 2020Abstract: [https://cer.ihtm.bg.ac.rs/handle/123456789/3688]The paper: [https://cer.ihtm.bg.ac.rs/handle/123456789/4361

Одређивање јонизационих константи одабраних деривата монокарбохидразона

Carbohydrazone derivatives represent a very significant class of compounds due to their wide biological activity. Ionization states of functional groups present in the molecule are of vital importance for understanding of the pharmacokinetic and pharmacodynamic properties of the newly synthesized compounds. One of the physicochemical parameters, the ionization constant (pKa), can be used as a molecular descriptor in order to relate structure and activity of a compound, which may indicate further potential application of newly synthesized derivatives. In this work, ionization constants of thirteen monocarbohydrazone derivatives were determined using potentiometric method, in order to obtain information about their ionization states under certain conditions.Деривати карбохидразона представљају веома значај- на једињења за проучавање с обзиром да многа од њих показују веома изражену биолошку активност. Познавање јонизационог стања функци- оналних група присутних у молекулу је од виталног значаја за разумева- ње фармакокинетичких и фармакодинамичких особина новосинтетиса- них једињења. Један од важнијих физичко-хемијских параметара, кисе- линска константа (pKa), може да послужи као молекулски дескриптор за повезивање односа стуктуре и активности једињења, што може укази- вати на даљу потенцијалну примену новосинтетисаних деривата. У овом раду, применом потенциометријске методе, одређене су киселин- ске константе за тринаест синтетисаних једињења из серије монокарбо- хидразона у циљу добијања информација о њиховим јонизационим ста- њима при одређеним условима.Abstract: [https://cer.ihtm.bg.ac.rs/handle/123456789/3688]Poster: [https://cer.ihtm.bg.ac.rs/handle/123456789/3689

Determination of ionization constants of selected monocarbohydrazone derivatites

Carbohydrazone derivatives represent a very significant class of compounds due to their wide biological activity. Ionization states of functional groups present in the molecule are of vital importance for understanding of the pharmacokinetic and pharmacodynamic properties of the newly synthesized compounds. One of the physicochemical parameters, the ionization constant (pKa), can be used as a molecular descriptor in order to relate structure and activity of a compound, which may indicate further potential application of newly synthesized derivatives. In this work, ionization constants of twenty monocarbohydrazone derivatives were determined using potentiometric method, in order to obtain information about their ionization states under certain conditions.Poster: [https://cer.ihtm.bg.ac.rs/handle/123456789/3689]The paper: [https://cer.ihtm.bg.ac.rs/handle/123456789/4361

Испитивање физичко-хемијских својстава и потенцијалне биолошке активности деривата 2-пиридин-(тио) карбохидразона

Карбохидразони и њихови тио-аналози представљају једињења добијена кондензацијом карбохидразида, односно тиокарбохи- дразида са карбонилним једињењима. Захваљујући њиховој структури, релативно једноставној синтези и великој реактивности, поменути дери- вати имају широк спектар примене у свим сферама. У оквиру овог рада, за четири новосинтетисана моно(тио)карбохидразона, одређене су кисе- линске константе применом потенциметријске методе. Такође, методом линеарне корелације енергија солватације и применом Catalan-овог моде- ла испитан је утицај специфичних и неспецифичних међумолекулских интеракција на померања у UV-Vis апсорпционим спектрима. У циљу испитивавања потенцијалне биолошке активности 2 - пиридин-(тио) кар- бохидразона, применом DPPH теста, одређен је њихов антиоксидативни потенцијал и закључено је да су деривати тиокарбохидразона значајно активнији у односу на карбохидразоне.Carbohydrazones and their thio analogs represent compounds obtained by condensation of carbohydrazide and thiocarbohydrazide with carbonyl compounds. Due to their structure, relatively simple synthesis, and high reactivity, mentioned derivatives have a wide range of applications in all fields. In this study, ionization constants of four newly synthesized mono(thio)carbohydrazones were determined by applying the potentiometric method. Also, the influence of specific and nonspecific intermolecular interactions on maxima shifting in UV-Vis absorption spectra was investigated and quantified using the linear solvation energy relationships method and Catalan’s model. Finally, by applying the DPPH assay, the antioxidant potential of the newly synthesized compounds was determined, and thiocarbohydrazone derivatives proved to be significantly more active when compared to carbo-hydrazones

Investigation of physicochemical properties and potential biological activity of 2-pyridine-(thio)carbohydrazone derivatives

Carbohydrazones and their thio analogs represent compounds obtained by condensation of carbohydrazide and thiocarbohydrazide with carbonyl compounds. Due to their structure, relatively simple synthesis, and high reactivity, mentioned derivatives have a wide range of applications in all fields. In this study, ionization constants of four newly synthesized mono(thio)carbohydrazones were determined by applying the potentiometric method. Also, the influence of specific and nonspecific intermolecular interactions on maxima shifting in UV-Vis absorption spectra was investigated and quantified using the linear solvation energy relationships method and Catalan’s model. Finally, by applying the DPPH assay, the antioxidant potential of the newly synthesized compounds was determined, and thiocarbohydrazone derivatives proved to be significantly more active when compared to carbohydrazones.XIV international scientific conference contemporary materials 2021 / XIV Међународни научни скуп савремени материјали 2021, Banja Luka, 9-10.9.202

Supplementary data for the article: Mrđan, G. S.; Vastag, G. G.; Škorić, D. Đ.; Radanović, M. M.; Verbić, T. Ž.; Milčić, M. K.; Stojiljković, I. N.; Marković, O. S.; Matijević, B. M. Synthesis, Physicochemical Characterization, and TD–DFT Calculations of Monothiocarbohydrazone Derivatives. Structural Chemistry 2021, 32 (3), 1231–1245. https://doi.org/10.1007/s11224-020-01700-y.

Supplementary material for: [https://doi.org/10.1007/s11224-020-01700-y]Related to published version: [https://cherry.chem.bg.ac.rs/handle/123456789/4453

STUDY OF SOLVATOCHROMIC PROPERTIES OF SELECTED ARYL AZO PYRIDONE DYES

Azo boje predstavljaju veoma značajnu grupu jedinjenja budući da više od 50% sintetičkih boja pripada upravo ovim strukturama. Zahvaljujući jednostavnoj i ekonomičnoj sintezi, kao i velikoj otpornosti prema svetlosti i pranju lako su pronašle primenu u raznim granama industrije. Pored uobičajene upotrebe u tekstilnoj, kozmetičkoj i prehrambenoj industriji, azo boje se koriste i za izradu solarnih ćelija, LCD ekrana, fotografskih, itd. Neka jedinjenja iz ove grupe su pokazala i dobru biološku aktivnost, a po najnovijim istraživanjima mogu se primeniti u lečenju tumora. U ovom radu je ispitan uticaj rastvarača na apsorpcione spektre odabranih arilazo piridonskih boja radi dobijanja informacija o solvatohromnim osobinama koje mogu imati veliki uticaj na potencijalnu biološku aktivnost. Spektri sedam derivata 5-(disupstituisanih fenilazo)-3-cijano-6-hidroksi-4-metil-2-piridona snimljeni su u deset rastvarača različitih svojstava u opsegu talasnih dužina 300-600 nm. Kvantitativna analiza interakcija između odabranih azo boja i okolnog medijuma je urađena primenom odgovarajućeg solvatohromnog modela metodom višestruke linerane korelacije solvatohromnih energija (LSER metoda).Azo dyes represent a very important group of compounds since more than 50% of synthetic dyes belong to these structures. Because of their economic synthesis, as well as great light and washing resistance, they have easily found applications in industry. In addition to the use in textile, cosmetic, and food industries, azo dyes are also used for making solar cells, LCD screens, photographic systems, etc. Some derivatives have shown good biological activity, and they can be used in the treatment of tumors. In this paper, the influence of solvents on the absorption spectra of selected aryl azo pyridone dyes was investigated to obtain information on solvatochromic properties that can have a great influence on potential biological activity. Spectra of seven 5-(disubstituted phenyl azo)-3-cyano-6-hydroxy-4-methyl-2-pyridones were recorded in ten solvents of different properties in the wavelength range 300- 600 nm. Quantitative analysis of interactions between selected azo dyes and the surrounding medium was performed using the corresponding solvatochromic model by the method of multiple linear correlations of solvatochromic energies.Naučni skupovi ; knj. 58. Odjeljenje prirodno-matematičkih i tehničkih nauka ; knj. 5

SOLVATOCHROMIC PROPERTIES OF NEWLY SYNTHESIZED ARYL AZO PYRIDONE DYES

Pyridone aryl azo dyes belong to a class of compounds that have wide application, not only as agents for coloring various materials in many branches of the industry but also in medicine as biologically active compounds. It has been proven that they have anti-tumor, anti-inflammatory, and anti-tuberculosis activity and are widely used for therapeutic purposes. Their application can highly depend on the inter- or intra- molecular interactions that occur between the dissolved compound and the surrounding medium. Therefore, the study of these interactions is of great importance for newly synthesized compounds. The spectrophotometric method can be used to examine intermolecular interactions thoroughly by studying the solvatochromic properties of newly synthesized compounds in different molecular environments. To this end, absorption spectra of seven newly synthesized aryl azo pyridone dyes based on 5-((disubstituted phenyl)diazenyl)-6- hydroxy-4-methyl-2-oxo-1,2-dihydropyridine-3-carbonitrile were recorded in ten solvents of different properties. The spectra were recorded in the range from 300 to 600 nm and showed one absorption maximum. By applying different models based on the principle of multiple linear correlations of solvatochromic energies (LSER method), information about the effects of certain interactions that take place between the tested compounds and the surrounding medium were obtained