Carolina Jullian

Generation of superoxide radicals by copper–glutathione complexes: Redox-consequences associated with their interaction with reduced glutathione

The interaction between Cu(2+) ions and GSH molecules leads to the swift formation of the physiologically occurring Cu(I)-[GSH](2) complex. Recently, we reported that this complex is able to reduce molecular oxygen into superoxide in a reversible reaction. In the present study, by means of fluorescence, luminescence, EPR and NMR techniques, we investigated the superoxide-generating capacity of the Cu(I)-[GSH](2) complex, demonstrated the occurrence and characterized the chemical nature of the oxidized complex which is formed upon removing of superoxide radicals from the former reaction, and addressed some of the redox consequences associated with the interaction between the Cu(I)-[GSH](2) complex, its oxidized complex form, and an in-excess of GSH molecules. The interaction between Cu(I)-[GSH](2) and added GSH molecules led to an substantial exacerbation of the ability of the former to generate superoxide anions. Removal of superoxide from a solution containing the Cu(I)-[GSH](2) complex, by addition of Tempol, led to the formation and accumulation of Cu(II)-GSSG. Interaction between the latter complex and GSH molecules permitted the re-generation of the Cu(I)-[GSH](2) complex and led to a concomitant recovery of its superoxide-generating capacity. Some of the potential redox and biological implications arising from these interactions are discussed.

Complexation of morin with three kinds of cyclodextrin: A thermodynamic and reactivity study

Properties of inclusion complexes between morin (M) and beta-cyclodextrin (betaCD), 2-hydroxypropyl-beta-cyclodextrin (HPbetaCD) and Heptakis (2,6-O-di methyl) beta-cyclodextrin (DMbetaCD) such as aqueous solubility and the association constants of this complex have been determined. The water solubility of morin was increased by inclusion with cyclodextrins. The phase-solubility diagrams drawn from UV spectral measurements are of the A(L)-type. Also ORAC(FL) studies were done. An increase in the antioxidant reactivity is observed when morin form inclusion complex with the three cyclodextrin studied. Finally, thermodynamics studies of cyclodextrin complexes indicated that for DMbetaCD the inclusion is primarily enthalpy-driven process meanwhile betaCD and HPbetaCD are entropy-driven processes. This is corroborated by the different inclusion geometries obtained by 2D-NMR.

Spectroscopic characterization of the inclusion complexes of luteolin with native and derivatized β-cyclodextrin

The inclusion complexes of Luteolin (LU) with cyclodextrins (CDs) including beta-cyclodextrin (betaCD), hydroxypropyl-beta-cyclodextrin (HPbetaCD) and dimethyl-beta-cyclodextrin (DMbetaCD), Scheme 1, have been investigated using the method of steady-state fluorescence. The stoichiometric ratio of the three complexes was found to be 1:1 and the stability constants (K) were estimated from spectrofluorometric titrations, as well as the thermodynamic parameters. Maximum inclusion ability was obtained in the case of HPbetaCD followed by DMbetaCD and betaCD. Moreover, 1H NMR and 2D NMR were carried out, revealing that LU has different form of inclusion which is in agreement with molecular modeling studies. These models confirm that when LU-betaCD and LU-DMbetaCD complexes are formed, the B-ring is oriented toward the primary rim; however, for LU-HPbetaCD complex this ring is oriented toward the secondary rim. The ESR results showed that the antioxidant activity of luteolin was the order LU-HPbetaCD>LU-DMbetaCD>LU-betaCD>LU, hence the LU-complexes behave are better antioxidants than luteolin free.

Characterization, phase-solubility, and molecular modeling of inclusion complex of 5-nitroindazole derivative with cyclodextrins

The slightly water-soluble 5-nitroindazole derivative (5-NI) and its inclusion with either beta-cyclodextrin (betaCD) or Heptakis (2,6-di-O-methyl)-beta-cyclodextrin (DMbetaCD) were investigated. The stoichiometric ratios and stability constants describing the extent of formation of the complexes were determined by phase-solubility measurements obtaining type-A(L) diagrams in both cases. According to the continuous variation method (Jobs plot) a 1:1 stoichiometry has been proposed for the complexes. Also electrochemical studies were carried out on both CDs complexes, where the observed change in the E(PC) value for DMbetaCD indicated a lower feasibility of the nitro group reduction. The detailed spatial configuration is proposed based on two-dimensional NMR methods. These results are further interpreted using molecular modeling studies. The latter results are in good agreement with the experimental data.

Molecular encapsulation of 5-nitroindazole derivatives in 2,6-dimethyl-β-cyclodextrin: Electrochemical and spectroscopic studies

Four different 5-nitroindazole derivatives (1-4) and its inclusion with Heptakis(2,6-di-O-methyl)-beta-cyclodextrin (DMbetaCD) were investigated. The stoichiometric ratios and stability constants describing the extent of formation of the complexes were determined by phase-solubility measurements obtaining in all cases a type-A(L) diagram. Also electrochemical studies were carried out, where the observed change in the E(PC) value indicated a lower feasibility of the nitro group reduction. The same behavior was observed in the ESR studies. The detailed spatial configuration is proposed based on 2D NMR methods. These results are further interpreted using molecular modeling studies. The latter results are in good agreement with the experimental data.

NMR and molecular fluorescence spectroscopic study of the structure and thermodynamic parameters of EGCG/β-cyclodextrin inclusion complexes with potential antioxidant activity

The present study is focused on the characterization of the interaction between (−)-epigallocatechingallate (EGCG) and cyclodextrins like β-cyclodextrin (βCD), heptakis(2,6 di-O-methyl)-β-cyclodextrin (DMβCD), and hydroxypropyl-β-cyclodextrin (HPβCD) in aqueous solution. These inclusion complexes previously demonstrated improvements in the antioxidant activity respect to free EGCG. The structural evidence obtained by 2D-ROESY and selective 1D-ROESY experiments was rationalized by autodock studies and indicates that all the complexes have similar inclusion geometries, but the difference resides on the exposition degree of the antioxidant rings of EGCG, such as pyrogallol and galloyl groups. The thermodynamic study allowed estimating that the inclusion process is entalpically driven for the derivatized cyclodextrins complexes and entropically driven for βCD complexes due to the predominance of hydrophobic interactions with EGCG.

New synthesis of naphtho- and benzoxazoles: Decomposition of naphtho- and benzoxazinones with KOH

A method that allows the synthesis of 4 different heterocyclic systems of fused aryl oxazoles, i.e., naphtho[1,2-d], naphtho[2,1-d], naphtho[2,3-d], and benzo[d]oxazoles in reasonable yield is described. This method consists of the decomposition of naphtho- and benzoxazinones with KOH.

IMPROVEMENT OF GALANGIN SOLUBILITY USING NATIVE AND DERIVATIVE CYCLODEXTRINS: AN UV-Vis AND NMR STUDY

The slightly water-soluble flavonoid galangin (G) and its inclusion with either β-cyclodextrin (βCD), hydro xypropyl-β-cyclodextrin (HPβCD) or Heptakis-2,6-O-di methyl-β-cyclodextrin (DMβCD) were investigated. The stoichiometric ratios and stability constants describing the extent of the formation of the complexes have been determined by phase-solubility measurements; in all cases type-AL diagrams have been obtained (soluble 1:1 complexes). The results showed that the complex efficiency of βCD and its derivatives was the order: DMβCD > HPβCD > βCD. The NMR study indicate that the inclusion of galangin in the cyclodextrin nano-cavity is different depending on the type of cyclodextrin used.

Photoreduction of oxoisoaporphines by amines: laser flash and steady-state photolysis, pulse radiolysis, and TD-DFT studies.

Photoreduction of oxoisoaporphine (OIA) (1-aza-benzo-[de]anthracen-7-one) and its 5-methoxy (5-MeO-OIA) derivative by selected amines (two non-alpha-hydrogen-donating amines (1,4-diaza[2.2.2]-bicyclooctane (DABCO) and 2,2,6,6-tetramethylpiperidine (TMP)) and three alpha-hydrogen-donating amines (triethylamine (TEA), diethylmethylamine (DEMA), and dimethylethylamine (DMEA))) has been studied in deaerated neat acetonitrile solutions using laser flash and steady-state photolysis. The triplet excited states of OIA and 5-MeO-OIA are characterized by intense absorption maxima located at lambda(max) = 450 nm and lifetimes of 34.7 +/- 0.5 and 44.6 +/- 0.4 micros, respectively. In the presence of tertiary amines, both triplets are quenched with a rate constant that varies from the near diffusion limit (>10(9) M(-1) s(-1)) to a rather low value (approximately 10(7) M(-1) s(-1)) and shows the expected dependence on the reduction potential for one-electron-transfer reactions. The transient absorption spectra observed after quenching of the respective triplet states are characterized by distinct absorption maxima located at lambda(max) = 480 and 490 nm (for OIA and 5-MeO-OIA, respectively) and accompanied by broad shoulders in the range of 510-560 nm. They were assigned to either solvent-separated radical ion pairs and/or isolated radical anions. In the presence of alpha-hydrogen-donating amines these species undergo protonation that leads to the formation of neutral hydrogenated radicals A1H(*)/A2H(*) with two possible sites of protonation, N and O atoms. Pulse radiolysis and molecular modeling together with TD-DFT calculations were used to support the conclusions about the origin of transients.

Photoreduction of oxoisoaporphines. Another example of a formal hydride-transfer mechanism

Photoreduction of 5,6-dimethoxy-, 5-methoxy- and 2,3-dihydro-7H-dibenzo[de,h]quinolin-7-one (A) by tertiary amines in oxygen-free solutions generates long-lived semi-reduced metastable photoproducts, A-NH(-), via a stepwise electron-proton-electron transfer mechanism with a limit quantum yield of about 0.1 at high TEA concentrations. These metastable photoproducts revert thermally to the initial oxoisoaporphine nearly quantitatively in the presence or absence of oxygen. We present spectrophotometric, NMR and UV-vis data for the metastable photoproducts. The spectrophotometric results and PM3 and ZINDO/S calculations support the proposed mechanism for the photoreduction of the oxoisoaporphines.