Structural and Antioxidative Features of Chlorogenic Acid

This work contributes to the structure clarification of chlorogenic acid (5-O-caffeoylquinic acid, 5CQA) by comparing the experimental and simulated IR, Raman, 1H-NMR, 13C-NMR, and UV-vis spectra. The lowest-energy conformers in the gas-phase and solution were used for all calculations. Very good agreement between all experimental and simulated spectra indicates correct arrangement of the atoms in the 5CQA molecule. In addition, the bond dissociation enthalpies, proton affinities, electron transfer enthalpies, ionization potentials, and proton dissociation enthalpies for 5CQA were used for thermodynamic consideration of the major antioxidative mechanisms: HAT (Hydrogen Atom Transfer), SPLET (Sequential Proton-Loss Electron-Transfer), and SET-PT (Single Electron Transfer – Proton Transfer). It was found that HAT may be the predominant mechanism in nonpolar solvents, while HAT and SPLET are competitive pathways in polar media. All quantum-chemical calculations were carried out by means of the MN12-SX method. Its performance is similar to those of the B3LYP-D2, B3LYP-D3, and M06-2X functionals. This work is licensed under a Creative Commons Attribution 4.0 International License

Testing the quality of molecular structure descriptors. Vertex-degree-based topological indices

The correlation abilities of 20 vertex-degree-based topological indices occurring in the chemical literature were tested for the case of standard heats of formation and normal boiling points of octane isomers. It is found that the correlation ability of many of these indices is either rather weak or nil. The augmented Zagreb index and the atom-bond connectivity index yield the best results

Actual contamination of the Danube and Sava Rivers at Belgrade (2013)

This study was focussed on a comprehensive investigation on the state of pollution of the Danube and Sava Rivers in the region of Belgrade. Different complementary analytical approaches were employed covering both i) organic contaminants in the river water by target analyses of hormones and neonicotinoids as well as non-target screening analyses and ii) heavy metals in the sediments. Finally, some common water quality parameters were analysed. The overall state of pollution is on a moderate level. Bulk parameters did not reveal any unusual observations. Moreover, quantification of preselected organic contaminants did not indicate to elevated pollution. More significant contaminations were registered for chromium, nickel, zinc and partially copper in sediments with values above the target values according to Serbian regulations. Lastly, non-target screening analysis revealed a wider spectrum of organic contaminants comprising pharmaceuticals, technical additives, personal care products and pesticides. The study presented a comprehensive view on the state of pollution of the Sava and Danube Rivers and is the base for setting up further monitoring programs. As a superior outcome, it was illustrated how different chemical analyses can result in different assessments of the river quality. A comparison of target and non-target analyses pointed to potential misinterpretation of the real state of pollution

Strukturne i antioksidativne osobine hlorogenske kiseline

Priložen rukopis jednim delom obuhvata ispitivanje strukturnih osobina, a drugim delom ispitivanje antioksidativnog potencijala hlorogenske kiseline. Posebna pažnja je usmerena ka termodinamičkom i kinetičkom ispitivanju mehanizama antioksidativnog delovanja ovog jedinjenja. Prvi deo istraživanja se odnosi na utvrđivanje najstabilnije konformacije hlorogenske kiseline u gasovitoj fazi i u rastvoru upoređivanjem eksperimentalnih IR, Raman, 1H-NMR, 13C-NMR i UV spektara sa spektrima simuliranim pomoću teorije funkcionala gustine. Detaljnom konformacionom analizom je ustanovljeno da hlorogenska kiselina postoji u obliku smeše različitih konformera. Zajednička osobina svih ovih konformera je da se na hinskom delu molekula nalaze usmerene vodonične veze, pri čemu je karboksilni kiseonik usmeren ka vodoniku iz susedne hidroksilne grupe, a ne ka karboksilnom kiseoniku. Najstabilnija konformacija u gasovitoj fazi poseduje O4–H4···O9’ vodoničnu vezu, dok najstabilniji konformer u rastvoru poseduje O4–H4···O10’ vodoničnu vezu. U okviru ove doktorske disertacije po prvi put su ispitani svi vibracioni oblici u IR spektru hlorogenske kiseline. Eksperimentalno dobijeni Raman-ski i NMR spektri hlorogenske kiseline su u saglasnosti sa postojećim rezultatima iz literature. Veoma dobro slaganje između simuliranih i eksperimentalnih spektara ukazuje na to da su atomi u hlorogenskoj kiselini pravilno raspoređeni. Sledeći korak se odnosio na upoređivanje antioksidativne aktivnosti hlorogenske kiseline sa antioksidativnom aktivnošću njena dva strukturna izomera (neohlorogenska i kriptohlorogenska kiselina) i kafeinskom kiselinom. Iz tog razloga su ispitivani termodinamički parametari: entalpija disocijacije veze (Bond Dissociation Enthalpy, BDE), afinitet prema protonu (Proton Affinity, PA), entalpija prenosa elektorna (Electron Transfer Enthalpy, ETE), jonizacioni potencijal (Ionisation Potential, IP) i entalpija disocijacije protona (Proton Dissociation Enthalpy, PDE), u rastvaračima različite polarnosti. Za potrebe izračunavanja termodinamičkih parametara određene su entalpije solvatisanog protona i elektrona u različitim rastvaračima pomoću različitih teorijskih metoda. Detaljno su ispitani i radikali, anjoni i radikal katjoni koji nastaju iz kafeinske i kafeoilhinskih kiselina. Osobine hidroksicimetnog dela u odgovarajućim radikalima, anjonima i radikal katjonima su veoma slične i praktično ne zavise od položaja esterifikacije. Hinski deo ostaje nepromenjen u svim novonastalim reaktivnim vrstama. Posledica toga je da sve četiri fenolne kiseline imaju slične vrednosti termodinamičkih parametara: BDE, PA, ETE, IP i PDE. Iz svega navedenog je zaključeno da kafeinska i kafeoilhinske kiseline ispoljavaju veoma sličnu antioksidativnu aktivnost. Isti ovi zaključci izvedeni su i iz eksperimenata, ali do sada nisu imali uporište u hemijskoj teoriji. Zatim je usledilo ispitivanje ponašanja hlorogenske kiseline u reakciji sa slobodno radikalskim vrstama (DPPH•, HO• i O2 −•) pomoću ESR spektroskopije. Izvedeni eksperimenti su pokazali da je hlorogenska kiselina selektivna prema DPPH•, HO• i HOO•/O2−• radikalima. Usledilo je i termodinamičko ispitivanje mogućih antioksidativnih mehanizama (prenos vodonikovog atoma (Hydrogen Atom Transfer, HAT), obrazovanje radikalskog adukta (Radical Adduct Formation, RAF), gubitak protona praćen prenosom elektrona (Sequential Proton Loss Electron Transfer, SPLET) i prenos elektrona praćen prenosom protona (Single Electron Transfer – Proton Transfer, SET-PT)) ove kiseline u prisustvu ispitivanih radikala. Otkriveno je da u vodenom rastvoru ni jedan mehanizam nije pogodan za reakciju između hlorogenske kiseline i O2−• što vodi ka zaključku da je u kiseloj sredini HOO• odgovoran za ponašanje HOO•/O2−• smeše. HAT i RAF su povoljni antioksidativni mehanizmi u slučaju reakcija hlorogenske kiseline sa HOO• i HO•, dok je u slučaju DPPH• radikala jedini očekivani mehanizam HAT. U narednom koraku je pomoću računarske metodologije koja je poznata pod nazivom: test za procenjivanje ukupne antioksidativne aktivnosti zasnovan na kvantno mehaničkim proračunima (Quantum Mechanics-based test for Overall free Radical Scavenging Activity (QM-ORSA) ispitivana antioksidativna aktivnost hlorogenske kiseline u odnosu na troloks koji je predstavljao referentni sistem. Primenjena metodologija podrazumeva termodinamičko i kinetičko ispitivanje svih mogućih mehanizama i uključuje različite aspekte koji mogu da utiču na antioksidativni kapacitet jedinjenja. Najpre je vršeno ispitivanje u nepolarnim rastvaračima. Dobijeno je da hlorogenka kiselina i troloks sa HO• radikalom reaguju preko HAT i RAF mehanizama, dok je u slučaju CH3OO• radikala HAT jedini mogući reakcioni put. Hlorogenska kiselina je reaktivnija prema HO•, dok je prema CH3OO• manje reaktivna od troloksa. Zatim je vršeno istraživanje antioksidativne aktivnosti hlorogenske kiseline u odnosu na troloks u vodenom rastvoru pri fiziološkim uslovima. Na pH = 7.4 hlorogenska kiselina postoji u obliku monoanjona (87 %) i dianjona (13 %), dok se troloks dominantno nalazi u obliku monoanjona (> 99 %). Ispitivane su reakcije monoanjona i dianjona hlorogenske kiseline i monoanjona troloksa sa HO• i CH3OO• radikalima. Oba anjonska oblika hlorogenske kiseline u prisustvu CH3OO• podležu isključivo HAT mehanizmu. U prisustvu HO• operativni su HAT, RAF, SPLET i SETPT mehanizmi. Kako su sve antioksidativne reakcije dianjona kontrolisane difuzijom, njegov doprinos u „hvatanju“ HO• je gotovo isti kao i doprinos monoanjonskog oblika koji se pri datim uslovima nalazi u mnogo većoj koncentraciji. Izračunata vrednost konstante brzine za reakciju između hlorogenske kiseline i HO• radikala je u savršenoj saglasnosti sa odgovarajućom eksperimentalnom vrednošću. Redosled reaktivnosti hlorogenske kiseline prema izabranim radikalima je isti u polarnoj i nepolarnoj sredini.One part of the enclosed manuscript is devoted to investigation of structural features of chlorogenic acid, whereas the other is associated with examination of the antioxidative potential of chlorogenic acid. Particular attention is dedicated to thermodynamic and kinetic investigation of antioxidative mechanisms of chlorogenic acid. The first part of the investigation was devoted to determination of the most stable conformation of chlorogenic acid in gaseous phase and in solution by comparison of experimental IR, Raman, 1H-NMR, 13C-NMR, and UV spectra with the spectra simulated using density functional theory methods. Detailed conformational analysis has established that chlorogenic acid exists as a mixture of several conformations. A common feature of all conformations is that quinic moeity is characterized with directed hydrogen bonds, with carboxyl hydrogen oriented toward aproximate hydroxyl group, but not toward carboxyl oxygen. The most stable structure in gaseous phase is characterized with O4–H4···O9’, whereas the most stable conformation in solution is characterized with O4–H4···O10’. Within this dissertation, all vibrational modes of the IR spectrum of chlorogenic acid were examined for the first time. Experimentally obtained Raman and NMR spectra of chlorogenic acid are in perfect accord with the literature results. Very good agreement between simulated and experimental spectra indicate correct arrangement of atoms in this compound. The next step was related to the comparison of the antioxidative activity of chlorogenic acid with the antioxidative potentials of its two structural isomers (neochlorogenic and cryptochlorogenic acids) and caffeic acid. For this reason, thermodynamic parameters: Bond Dissociation Enthalpy (BDE), Proton Affinity (PA), Electron Transfer Enthalpy (ETE), Ionisation Potential (IP), and Proton Dissociation Enthalpy (PDE) in solutions of different polarity were examined. To obtain thermodynamic parameters, the enthalpies of the solvated proton and electron in various solutions with different theoretical methods were determined. Detailed examination of radicals, anions, and radical cations derived from caffeic and caffeoylquinic acids was conducted. The properties of the hydroxycinnamic moiety in the corresponding radicals, anions and radical cations are very similar and practically do not depend on the esterification position. Quinic moiety remains the same in the derived reactive species. As a result, all four phenolic acids have similar values of thermodynamic parameters BDE, PA, ETE, IP, and PDE. Taking all these facts into account, it was concluded that caffeic and caffeoylquinic acids exhibit very similar antioxidant activity. The same results have been derived from experiments, however, they have not been supported by chemical theory so far. Subsequently, the behavior of chlorogenic acid in the reactions with free radicals (DPPH•, HO•, and О2 −•) was investigated using ESR spectroscopy. The obtained results showed that chlorogenic acid is selective toward DPPH•, HO•, and HOO•/O2−• radicals. Thermodynamic investigation of all possible antioxidative mechanisms (Hydrogen Atom Transfer (HAT), Radical Adduct Formation (RAF), Sequential Proton Loss Electron Transfer (SPLET), and Single Electron Transfer – Proton Transfer (SET-PT)) of chlorogenic acid in the presence of investigated free radicals was also conducted. The results revealed that no mechanism is suitable for scavenging O2−•, which leads to conclusion that HOO• is responsible for the behavior of HOO•/O2−• mixture. HAT and RAF are plausible antioxidative mechanisms in the case of the reaction of chlorogenic acid with HOO• and HO•, whereas the only possible mechanism in the case of DPPH• radical is HAT. Following the computational methodology, also known as Quantum Mechanics-based test for Overall free Radical Scavenging Activity (QM-ORSA), the antioxidative activity of chlorogenic acid relative to trolox as reference compound was examined. The applied methodology implies thermodynamic and kinetic investigation of all possible mechanisms. This approach also considers various effects that can influence antioxidative activity of a compound. Firstly, investigation in nonpolar solvents was performed. The results showed that both chlorogenic acid and trolox react with HO• via HAT and RAF mechanisms, whereas in the case of CH3OO• HAT is the only favourable reaction pathway. Chlorogenic acid is more reactive toward HO•, but less reactive toward CH3OO• than trolox. The following step was investigation of antioxidative activity of chlorogenic acid relative to trolox in aquous solution at physiological conditions. At pH = 7.4 chlorogenic acid exists in monoanionic (87 %) and dianionic (13 %) forms, whereas dominant form of trolox is monoanionic (> 99 %). The reactions of chlorogenic acid monoanion and dianion, as well as of trolox monoanion, with HO• and CH3OO• were examined. Both anionic forms of chlorogenic acid undergo only HAT raction with CH3OO• radical. Operative mechanistic pathways in the case of HO• are HAT, RAF, SPLET, and SET-PT. Considering that all the reactions with dianion are diffusion-controlled, its contribution to scavenging HO• is almost equivalent to that of more abundant monoanion. The calculated rate constant value for the reaction of chlorogenic acid with HO• is in perfect agreement with corresponding experimentaly obtained value. The order of reactivity toward selected free radicals is the same in polar and nonpolar solution

Strukturne i antioksidativne osobine hlorogenske kiseline

Priložen rukopis jednim delom obuhvata ispitivanje strukturnih osobina, a drugim delom ispitivanje antioksidativnog potencijala hlorogenske kiseline. Posebna pažnja je usmerena ka termodinamičkom i kinetičkom ispitivanju mehanizama antioksidativnog delovanja ovog jedinjenja. Prvi deo istraživanja se odnosi na utvrđivanje najstabilnije konformacije hlorogenske kiseline u gasovitoj fazi i u rastvoru upoređivanjem eksperimentalnih IR, Raman, 1H-NMR, 13C-NMR i UV spektara sa spektrima simuliranim pomoću teorije funkcionala gustine. Detaljnom konformacionom analizom je ustanovljeno da hlorogenska kiselina postoji u obliku smeše različitih konformera. Zajednička osobina svih ovih konformera je da se na hinskom delu molekula nalaze usmerene vodonične veze, pri čemu je karboksilni kiseonik usmeren ka vodoniku iz susedne hidroksilne grupe, a ne ka karboksilnom kiseoniku. Najstabilnija konformacija u gasovitoj fazi poseduje O4–H4···O9’ vodoničnu vezu, dok najstabilniji konformer u rastvoru poseduje O4–H4···O10’ vodoničnu vezu. U okviru ove doktorske disertacije po prvi put su ispitani svi vibracioni oblici u IR spektru hlorogenske kiseline. Eksperimentalno dobijeni Raman-ski i NMR spektri hlorogenske kiseline su u saglasnosti sa postojećim rezultatima iz literature. Veoma dobro slaganje između simuliranih i eksperimentalnih spektara ukazuje na to da su atomi u hlorogenskoj kiselini pravilno raspoređeni. Sledeći korak se odnosio na upoređivanje antioksidativne aktivnosti hlorogenske kiseline sa antioksidativnom aktivnošću njena dva strukturna izomera (neohlorogenska i kriptohlorogenska kiselina) i kafeinskom kiselinom. Iz tog razloga su ispitivani termodinamički parametari: entalpija disocijacije veze (Bond Dissociation Enthalpy, BDE), afinitet prema protonu (Proton Affinity, PA), entalpija prenosa elektorna (Electron Transfer Enthalpy, ETE), jonizacioni potencijal (Ionisation Potential, IP) i entalpija disocijacije protona (Proton Dissociation Enthalpy, PDE), u rastvaračima različite polarnosti. Za potrebe izračunavanja termodinamičkih parametara određene su entalpije solvatisanog protona i elektrona u različitim rastvaračima pomoću različitih teorijskih metoda. Detaljno su ispitani i radikali, anjoni i radikal katjoni koji nastaju iz kafeinske i kafeoilhinskih kiselina. Osobine hidroksicimetnog dela u odgovarajućim radikalima, anjonima i radikal katjonima su veoma slične i praktično ne zavise od položaja esterifikacije. Hinski deo ostaje nepromenjen u svim novonastalim reaktivnim vrstama. Posledica toga je da sve četiri fenolne kiseline imaju slične vrednosti termodinamičkih parametara: BDE, PA, ETE, IP i PDE. Iz svega navedenog je zaključeno da kafeinska i kafeoilhinske kiseline ispoljavaju veoma sličnu antioksidativnu aktivnost. Isti ovi zaključci izvedeni su i iz eksperimenata, ali do sada nisu imali uporište u hemijskoj teoriji. Zatim je usledilo ispitivanje ponašanja hlorogenske kiseline u reakciji sa slobodno radikalskim vrstama (DPPH•, HO• i O2 −•) pomoću ESR spektroskopije. Izvedeni eksperimenti su pokazali da je hlorogenska kiselina selektivna prema DPPH•, HO• i HOO•/O2−• radikalima. Usledilo je i termodinamičko ispitivanje mogućih antioksidativnih mehanizama (prenos vodonikovog atoma (Hydrogen Atom Transfer, HAT), obrazovanje radikalskog adukta (Radical Adduct Formation, RAF), gubitak protona praćen prenosom elektrona (Sequential Proton Loss Electron Transfer, SPLET) i prenos elektrona praćen prenosom protona (Single Electron Transfer – Proton Transfer, SET-PT)) ove kiseline u prisustvu ispitivanih radikala. Otkriveno je da u vodenom rastvoru ni jedan mehanizam nije pogodan za reakciju između hlorogenske kiseline i O2−• što vodi ka zaključku da je u kiseloj sredini HOO• odgovoran za ponašanje HOO•/O2−• smeše. HAT i RAF su povoljni antioksidativni mehanizmi u slučaju reakcija hlorogenske kiseline sa HOO• i HO•, dok je u slučaju DPPH• radikala jedini očekivani mehanizam HAT. U narednom koraku je pomoću računarske metodologije koja je poznata pod nazivom: test za procenjivanje ukupne antioksidativne aktivnosti zasnovan na kvantno mehaničkim proračunima (Quantum Mechanics-based test for Overall free Radical Scavenging Activity (QM-ORSA) ispitivana antioksidativna aktivnost hlorogenske kiseline u odnosu na troloks koji je predstavljao referentni sistem. Primenjena metodologija podrazumeva termodinamičko i kinetičko ispitivanje svih mogućih mehanizama i uključuje različite aspekte koji mogu da utiču na antioksidativni kapacitet jedinjenja. Najpre je vršeno ispitivanje u nepolarnim rastvaračima. Dobijeno je da hlorogenka kiselina i troloks sa HO• radikalom reaguju preko HAT i RAF mehanizama, dok je u slučaju CH3OO• radikala HAT jedini mogući reakcioni put. Hlorogenska kiselina je reaktivnija prema HO•, dok je prema CH3OO• manje reaktivna od troloksa. Zatim je vršeno istraživanje antioksidativne aktivnosti hlorogenske kiseline u odnosu na troloks u vodenom rastvoru pri fiziološkim uslovima. Na pH = 7.4 hlorogenska kiselina postoji u obliku monoanjona (87 %) i dianjona (13 %), dok se troloks dominantno nalazi u obliku monoanjona (> 99 %). Ispitivane su reakcije monoanjona i dianjona hlorogenske kiseline i monoanjona troloksa sa HO• i CH3OO• radikalima. Oba anjonska oblika hlorogenske kiseline u prisustvu CH3OO• podležu isključivo HAT mehanizmu. U prisustvu HO• operativni su HAT, RAF, SPLET i SETPT mehanizmi. Kako su sve antioksidativne reakcije dianjona kontrolisane difuzijom, njegov doprinos u „hvatanju“ HO• je gotovo isti kao i doprinos monoanjonskog oblika koji se pri datim uslovima nalazi u mnogo većoj koncentraciji. Izračunata vrednost konstante brzine za reakciju između hlorogenske kiseline i HO• radikala je u savršenoj saglasnosti sa odgovarajućom eksperimentalnom vrednošću. Redosled reaktivnosti hlorogenske kiseline prema izabranim radikalima je isti u polarnoj i nepolarnoj sredini.One part of the enclosed manuscript is devoted to investigation of structural features of chlorogenic acid, whereas the other is associated with examination of the antioxidative potential of chlorogenic acid. Particular attention is dedicated to thermodynamic and kinetic investigation of antioxidative mechanisms of chlorogenic acid. The first part of the investigation was devoted to determination of the most stable conformation of chlorogenic acid in gaseous phase and in solution by comparison of experimental IR, Raman, 1H-NMR, 13C-NMR, and UV spectra with the spectra simulated using density functional theory methods. Detailed conformational analysis has established that chlorogenic acid exists as a mixture of several conformations. A common feature of all conformations is that quinic moeity is characterized with directed hydrogen bonds, with carboxyl hydrogen oriented toward aproximate hydroxyl group, but not toward carboxyl oxygen. The most stable structure in gaseous phase is characterized with O4–H4···O9’, whereas the most stable conformation in solution is characterized with O4–H4···O10’. Within this dissertation, all vibrational modes of the IR spectrum of chlorogenic acid were examined for the first time. Experimentally obtained Raman and NMR spectra of chlorogenic acid are in perfect accord with the literature results. Very good agreement between simulated and experimental spectra indicate correct arrangement of atoms in this compound. The next step was related to the comparison of the antioxidative activity of chlorogenic acid with the antioxidative potentials of its two structural isomers (neochlorogenic and cryptochlorogenic acids) and caffeic acid. For this reason, thermodynamic parameters: Bond Dissociation Enthalpy (BDE), Proton Affinity (PA), Electron Transfer Enthalpy (ETE), Ionisation Potential (IP), and Proton Dissociation Enthalpy (PDE) in solutions of different polarity were examined. To obtain thermodynamic parameters, the enthalpies of the solvated proton and electron in various solutions with different theoretical methods were determined. Detailed examination of radicals, anions, and radical cations derived from caffeic and caffeoylquinic acids was conducted. The properties of the hydroxycinnamic moiety in the corresponding radicals, anions and radical cations are very similar and practically do not depend on the esterification position. Quinic moiety remains the same in the derived reactive species. As a result, all four phenolic acids have similar values of thermodynamic parameters BDE, PA, ETE, IP, and PDE. Taking all these facts into account, it was concluded that caffeic and caffeoylquinic acids exhibit very similar antioxidant activity. The same results have been derived from experiments, however, they have not been supported by chemical theory so far. Subsequently, the behavior of chlorogenic acid in the reactions with free radicals (DPPH•, HO•, and О2 −•) was investigated using ESR spectroscopy. The obtained results showed that chlorogenic acid is selective toward DPPH•, HO•, and HOO•/O2−• radicals. Thermodynamic investigation of all possible antioxidative mechanisms (Hydrogen Atom Transfer (HAT), Radical Adduct Formation (RAF), Sequential Proton Loss Electron Transfer (SPLET), and Single Electron Transfer – Proton Transfer (SET-PT)) of chlorogenic acid in the presence of investigated free radicals was also conducted. The results revealed that no mechanism is suitable for scavenging O2−•, which leads to conclusion that HOO• is responsible for the behavior of HOO•/O2−• mixture. HAT and RAF are plausible antioxidative mechanisms in the case of the reaction of chlorogenic acid with HOO• and HO•, whereas the only possible mechanism in the case of DPPH• radical is HAT. Following the computational methodology, also known as Quantum Mechanics-based test for Overall free Radical Scavenging Activity (QM-ORSA), the antioxidative activity of chlorogenic acid relative to trolox as reference compound was examined. The applied methodology implies thermodynamic and kinetic investigation of all possible mechanisms. This approach also considers various effects that can influence antioxidative activity of a compound. Firstly, investigation in nonpolar solvents was performed. The results showed that both chlorogenic acid and trolox react with HO• via HAT and RAF mechanisms, whereas in the case of CH3OO• HAT is the only favourable reaction pathway. Chlorogenic acid is more reactive toward HO•, but less reactive toward CH3OO• than trolox. The following step was investigation of antioxidative activity of chlorogenic acid relative to trolox in aquous solution at physiological conditions. At pH = 7.4 chlorogenic acid exists in monoanionic (87 %) and dianionic (13 %) forms, whereas dominant form of trolox is monoanionic (> 99 %). The reactions of chlorogenic acid monoanion and dianion, as well as of trolox monoanion, with HO• and CH3OO• were examined. Both anionic forms of chlorogenic acid undergo only HAT raction with CH3OO• radical. Operative mechanistic pathways in the case of HO• are HAT, RAF, SPLET, and SET-PT. Considering that all the reactions with dianion are diffusion-controlled, its contribution to scavenging HO• is almost equivalent to that of more abundant monoanion. The calculated rate constant value for the reaction of chlorogenic acid with HO• is in perfect agreement with corresponding experimentaly obtained value. The order of reactivity toward selected free radicals is the same in polar and nonpolar solution

Spectroscopic features of caffeic acid: Theoretical study

In order to investigate spectroscopic features of caffeic acid (CA), the IR, Raman, 13C-NMR, 1H-NMR, and UV spectra of this compound were simulated. For this purpose the B3LYP-D3/6-311+G(d,p) theoretical model was used in combination with CPCM solvation model. Very good agreement between all experimental and simulated spectra was achieved. This result indicates that B3LYP-D3 can be a method of choice in studies that refer to spectroscopic investigations. Spectroscopic features of CA are very similar to those of chlorogenic acid (5-O-caffeoylquinic acid) (MARKOVIĆ, TOŠOVIĆ and DIMITRIĆ MARKOVIĆ, 2016), pointing out the significance of caffeic moiety

Antioxidative action of ellagic acid—A kinetic DFT study

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. Although one can find numerous studies devoted to the investigation of antioxidative activity of ellagic acid (EA) in the scientific literature, the mechanisms of its action have not yet been fully clarified. Therefore, further kinetic studies are needed to understand its antioxidative capacity completely. This work aims to reveal the underlying molecular mechanisms responsible for the antioxidative action of EA. For this purpose, its reactions with HO· and CCl3OO· radicals were simulated at physiological conditions using the quantum mechanics-based test for overall free-radical scavenging activity. The density functional theory in combination with the conductor-like polarizable continuum solvation model was utilized. With HO· radical EA conforms to the hydrogen atom transfer and radical adduct formation mechanisms, whereas sequential proton loss electron transfer mechanism is responsible for scavenging of CCl3OO· radical. In addition, compared to trolox, EA was found more reactive toward HO·, but less reactive toward CCl3OO·. The calculated rate constants for the reactions of EA with both free radicals are in a very good agreement with the corresponding experimental values

Conserved water networks identification for drug design using density clustering approaches on positional and orientational data

[Image: see text] This work describes the development and testing of a method for the identification and classification of conserved water molecules and their networks from molecular dynamics (MD) simulations. The conserved waters in the active sites of proteins influence protein–ligand binding. Recently, several groups have argued that a water network formed from conserved waters can be used to interpret the thermodynamic signature of the binding site. We implemented a novel methodology in which we apply the complex approach to categorize water molecules extracted from the MD simulation trajectories using clustering approaches. The main advantage of our methodology as compared to current state of the art approaches is the inclusion of the information on the orientation of hydrogen atoms to further inform the clustering algorithm and to classify the conserved waters into different subtypes depending on how strongly certain orientations are preferred. This information is vital for assessing the stability of water networks. The newly developed approach is described in detail as well as validated against known results from the scientific literature including comparisons with the experimental data on thermolysin, thrombin, and Haemophilus influenzae virulence protein SiaP as well as with the previous computational results on thermolysin. We observed excellent agreement with the literature and were also able to provide additional insights into the orientations of the conserved water molecules, highlighting the key interactions which stabilize them. The source code of our approach, as well as the utility tools used for visualization, are freely available on GitHub

Antioxidative activity of caffeic acid: Mechanistic DFT study

This paper reports the results of comprehensive mechanistic investigations of the hydrogen atom transfer (HAT), radical adduct formation (RAF), single electron transfer – proton transfer (SET-PT), and sequential proton loss electron transfer (SPLET) mechanisms of caffeic acid (CA). The goals of the work were achieved by simulating the reactions of CA with hydroxyl radical in benzene and water solutions. It was found that SET-PT is not a favourable antioxidative mechanism of CA. On the other hand, HAT and RAF are competitive, because HAT pathways yield thermodynamically more stable radical products, and RAF pathways require smaller activation barriers. In polar basic environment SPLET is a probable antioxidative mechanism of CA, with exceptionally large rate

Insight into the origin of pyrocatechol inhibition on oscillating bray-liebhafsky reaction: Combined experimental and theoretical study

© 2020 The Chemical Society of Japan. The pyrocatechol inhibitory effect on the oscillatory Bray- Liebhafsky (BL) reaction is reported. Obtained results are compared with those available in the literature (R. Cervellati et al, Helvetica Chimica Acta 2001) for Briggs-Rauscher (BR) reaction with pyrocatechol addition. The two orders of magnitude larger calibration curve slope obtained in BR in comparison to BL reaction, suggests that different reactions are responsible for inhibitory effects in these systems. The potential explanation of pyrocatechol behavior is given by employing the ultravioletvisible (UV/VIS) spectroscopy, density functional theory, and coupled cluster computational methods. The last two were employed for the first time to discover potential candidates among unstable chemical species HIO, HIO2, I2O, HOO·, HO·, IO·, IO2·, and I· of the BL (and BR) system for reaction with pyrocatechol. The calculated reaction rate constants for the hydrogen atom transfer reactions between pyrocatechol and free radical intermediates indicate the following order of reactivity: HO· > IO· > HOO· > IO2·. The same order of reactivity is also observed in the case of a thermodynamic investigation. In addition, kinetic insight indicates that the inhibitory behavior of pyrocatechol could not be explained with one particular chemical reaction in the BL (or in the BR) oscillatory system