Izaura C.N. Diógenes

Direct Electrochemistry and Electrocatalysis of Myoglobin Immobilized on l-Cysteine Self-Assembled Gold Electrode

Myoglobin (Mb) has been successfully immobilized on a self-assembled monolayer (SAM) of L-cysteine (Cys) on a gold electrode, Au/Cys. The presence of a pair of well-defined and nearly reversible waves centered at ca. 0.086 V vs Ag/AgCl (pH 6.5) suggests that the native character of Mb heme Fe(III/II) redox couple has been obtained. The formal potential of Mb on Cys SAM exhibited pH-dependent variation in the pH range of 5-9 with a slope of 55 mV/pH, indicating that the electron transfer is accompanied by a single proton exchange. Thermodynamic and kinetic aspects of Mb adsorption processes on Au/Cys were studied by using voltammetric and quartz-crystal microbalance methods. The Au/Cys electrode with immobilized Mb exhibited electrocatalytic activity toward ascorbic acid (AA) oxidation with an overpotential decrease of over 400 mV and a linear dependence of current on the AA concentration from 0.5 to 5.0 mmol L(-1).

Cation-Dependent Stabilization of Electrogenerated Naphthalene Diimide Dianions in Porous Polymer Thin Films and Their Application to Electrical Energy Storage

Porous polymer networks (PPNs) are attractive materials for capacitive energy storage because they offer high surface areas for increased double-layer capacitance, open structures for rapid ion transport, and redox-active moieties that enable faradaic (pseudocapacitive) energy storage. Here we demonstrate a new attractive feature of PPNs--the ability of their reduced forms (radical anions and dianions) to interact with small radii cations through synergistic interactions arising from densely packed redox-active groups, only when prepared as thin films. When naphthalene diimides (NDIs) are incorporated into PPN films, the carbonyl groups of adjacent, electrochemically generated, NDI radical anions and dianions bind strongly to K(+), Li(+), and Mg(2+), shifting the formal potentials of NDIs second reduction by 120 and 460 mV for K(+) and Li(+)-based electrolytes, respectively. In the case of Mg(2+), NDIs two redox waves coalesce into a single two-electron process with shifts of 240 and 710 mV, for the first and second reductions, respectively, increasing the energy density by over 20 % without changing the polymer backbone. In contrast, the formal reduction potentials of NDI derivatives in solution are identical for each electrolyte, and this effect has not been reported for NDI previously. This study illustrates the profound influence of the solid-state structure of a polymer on its electrochemical response, which does not simply reflect the solution-phase redox behavior of its monomers.

Thermodynamic, kinetic, surface pKa, and structural aspects of self-assembled monolayers of thio compounds on gold.

The thermodynamic and kinetic aspects of the formation of self-assembled monolayers (SAMs) of thio compounds on gold have been studied via electrochemical and quartz crystal microbalance (QCM) techniques. The data indicate that the adsorption process involves a significant free energy of adsorption (ΔG° = -36.43 kJ/mol) and that there are slight repulsive interactions between adjacent molecules on the surface. A method for the calculation of surface pK(a) values of molecules containing more than one protonation site is proposed and used for the determination of the pK(a) values of SAMs derived from thioisonicotinamide, thionicotinamide, 5-(4-pyridyl)-1,2,4-oxadiazole-2-thiol, and 4-mercaptopyridine (pyS) on gold. Structural aspects of the SAMs were studied by using impedance with [Fe(CN)(6)](4-/3-) as redox probe. Evidence of faster kinetics for an oxidative decomposition of pyS SAM in the presence of [Fe(CN)(6)](3-) is discussed based on electrochemical and impedance data.

Isoniazid metal complex reactivity and insights for a novel anti-tuberculosis drug design

For over a decade, tuberculosis (TB) has been the leading cause of death among infectious diseases. Since the 1950s, isoniazid has been used as a front-line drug in the treatment of TB; however, resistant TB strains have limited its use. The major route of isoniazid resistance relies on KatG enzyme disruption, which does not promote an electron transfer reaction. Here, we investigated the reactivity of isoniazid metal complexes as prototypes for novel self-activating metallodrugs against TB with the aim to overcome resistance. Reactivity studies were conducted with hydrogen peroxide, hexacyanoferrate(III), and aquopentacyanoferrate(III). The latter species showed a preference for the inner-sphere electron transfer reaction pathway. Additionally, electron transfer reaction performed with either free isoniazid or (isoniazid)pentacyanoferrate(II) complex resulted in similar oxidized isoniazid derivatives as observed when the KatG enzyme was used. However, upon metal coordination, a significant enhancement in the formation of isonicotinic acid was observed compared with that of isonicotinamide. These results suggest that the pathway of a carbonyl-centered radical might be favored upon coordination to the Fe(II) owing to the π-back-bonding effect promoted by this metal center; therefore, the isoniazid metal complex could serve as a potential metallodrug. Enzymatic inhibition assays conducted with InhA showed that the cyanoferrate moiety is not the major player involved in this inhibition but the presence of isoniazid is required in this process. Other isoniazid metal complexes, [Ru(CN)5(izd)]3− and [Ru(NH3)5(izd)]2+ (where izd is isoniazid), were also unable to inhibit InhA, supporting our proposed self-activating mechanism of action. We propose that isoniazid reactivity can be rationally modulated by metal coordination chemistry, leading to the development of novel anti-TB metallodrugs.Graphical abstract

[Fe(CN)5(isoniazid)](3-): an iron isoniazid complex with redox behavior implicated in tuberculosis therapy.

Tuberculosis has re-emerged as a worldwide threat, which has motivated the development of new drugs. The antituberculosis complex Na3[Fe(CN)5(isoniazid)] (IQG607) in particular is of interest on account of its ability to overcome resistance. IQG607 has the potential for redox-mediated-activation, in which an acylpyridine (isonicotinoyl) radical could be generated without assistance from the mycobacterial KatG enzyme. Here, we have investigated the reactivity of IQG607 toward hydrogen peroxide and superoxide, well-known intracellular oxidizing agents that could play a key role in the redox-mediated-activation of this compound. HPLC, NMR and electronic spectroscopy studies showed a very fast oxidation rate for bound isoniazid, over 460-fold faster than free isoniazid oxidation. A series of EPR spin traps were used for detection of isonicotinoyl and derived radicals bound to iron. This is the first report for an isonicotinoyl radical bound to a metal complex, supported by (14)N and (1)H hyperfine splittings for the POBN and PBN trapped radicals. POBN and PBN exhibited average hyperfine coupling constants of aN=15.6, aH=2.8 and aN=15.4, aH=4.7, respectively, which are in close agreement to the isonicotinoyl radical. Radical generation is thought to play a major role in the mechanism of action of isoniazid and this work provides strong evidence for its production within IQG607, which, along with biological and chemical oxidation data, support a redox-mediated activation mechanism. More generally the concept of redox activation of metallo prodrugs could be applied more widely for the design of therapeutic agents with novel mechanisms of action.

Characterization of a 1,4-dithiane gold self-assembled monolayer: an electrochemical sensor for the cyt-c redox process

Electrochemical desorption and spectroscopic investigations of the gold electrode surface modified with 1,4-dithiane (1,4-dt) organothiol species were performed. The wave observed at � /0.87 V versus Ag j AgCl in the LSV (linear sweep voltammetry) reductive curve of the 1,4-dt compared to that for a similar 4-mercaptopyridine (pyS) system (� /0.56 V) is indicative of a most effectively chemisorbed monolayer. The evaluation of the capability of the 1,4-dt self-assembled monolayer (SAM) in assessing the direct electron transfer (ET) of cytochrome c (cyt c) metalloprotein was investigated by cyclic voltammetry. The electrochemical response of the cyt c (E1/2 :/0.0 V vs. Ag j AgCl, DEp :/50 mV) showed the characteristics of a reversible redox process. The cyt c voltammetric parameters acquired with the 24-h air exposure modified electrode, and after 100 cycles suggest a considerable improvement of the 1,4-dt electrode performance. The surface enhanced Raman spectroscopy (SERS) spectra revealed that 1,4-dt species is in a mixed gauche and trans orientation on the gold surface. The shift for higher wavenumbers observed for the C � /S stretching modes in the SERS spectra, comparatively to the normal Raman spectrum, is assigned to the 1,4-dt coordination to surface gold atoms via a p interaction with the sulfur p-orbitals. The data collected suggest that this p interaction plays an important role on the stability of the 1,4-dt adlayer, improving the assessment of the cyt c heterogeneous electron transfer reaction. # 2003 Elsevier Science B.V. All rights reserved.

Self-assembled monolayers formed by [M(CN)5(pyS)]4−(M = Fe, Ru) on gold: a comparative study on stability and efficiency to assess the cyt c heterogeneous electron transfer reaction

A comparative study involving SAMs formed by [(CN)5M(pyS)]4− inorganic complexes (M = Fe, Ru; pyS = 4-mercaptopyridine) on gold (MpySAu) has been performed. The characterization data for these complexes suggests that the ruthenium complex exhibit a greater π-back-bonding effect that more strongly stabilizes the MpyC–S bond, thus anticipating its application as a SAM that would better enhance the gold adlayer stability than the iron complex. The MpySAu electrodes were characterized by SERS and electrochemical (LSV) techniques. The ex situ SERS spectra data for both SAMs suggest a σ interaction between the gold and sulfur atom of the complexes, inducing a perpendicular arrangement in relation to the surface. The spectra performed for freshly prepared MpySAu adlayers did not show any significant changes that would reflect the degradation of the adlayer. The LSV desorption curves of the SAMs indicate a better enhancement in the C–S bond strength of the pyS ligand when coordinated to the [Ru(CN)5]3− moiety. Comparatively to the data obtained for the desorption process of the pyS monolayer, the reductive desorption potentials, Erd, present shifts of −170 and −110 mV for the Ru and Fe complexes, respectively. The voltammetric curves of cytochrome c (cyt c) performed with the MpySAu electrodes showed electrochemical parameters consistent with that reported for the native protein. These results taken together reinforce that the π back-bonding effect from the [M(CN)5]3− metal center [Ru (4d) > Fe (3d)] strongly affects the MpySAu adlayer stability, reflecting the adlayer performance on the assessment of the cyt c hET reaction.

A novel and simple synthetic route for a piperazine derivative

Um novo derivado da piperazina, 5-oxopiperazinio-3-sulfonato monohidratado, foi produzido a partir de uma rota sintetica simples como resultado da adicao do ion bisulfito, HSO3-, ao anel e do ataque nucleofilico de moleculas de agua a moleculas de pirazina. O material isolado foi caracterizado por RMN, espectrometria de massa, infravermelho e difracao de raios-X.

5-(4-pyridinyl)-1,3,4-oxadiazole-2-thiol on gold: SAM Formation and electroactivity

5-(4-pyridinyl)-1,3,4-oxadiazole-2-thiol (Hpyt) spontaneously adsorbs on gold forming SAMs (self-assembled monolayers) that, based on STM (Scanning Tunneling Microscopy) and electrochemical data, contain pinholes through which [Fe(CN)6]4- and [Ru(NH3)6]3+ probe molecules access the underlying gold electrode. For the former molecule, the dependence of the faradaic current on the electrolyte solution pH value allowed the evaluation of the surface pKa as 4.2. The thermodynamic parameters DHads and DGads for the Hpyt adsorption process could be described by the Langmuir model and were calculated as -20.01 and -39.39 kJ mol-1, respectively. Electrodic redox reaction of cytochrome c metalloprotein was accessed by using the Hpyt SAM with a heterogeneous electron transfer rate constant of 2.29 × 10-3 cm s-1.

Tetraammine ruthenate complexes: cationic SAMs for cytochrome c recognition

The redox process of the cyt c metalloprotein was assessed by the cationic SAMs formed with [Ru(CNPy)(NH3)4(1,4-dt)]2+ and [Ru(CNPy)(NH3)4(pyS)]2+ complexes on gold, where CNPy = 4-cyanopyridine, pyS = 4-mercaptopyridine and 1,4-dt = dithiane. The observed cyt c redox potentials are indicative of the native protein form. The voltammograms, however, were observed to be affected by the conformation of the modifiers, determined by SERS spectroscopy. The [Ru(CNPy)(NH3)4(pyS)]2+ complex, which exhibits trans conformation on the surface, presented a well-defined voltammogram. On the other hand, the gauche conformation of the [Ru(CNPy)(NH3)4(1,4-dt)]2+ SAM seems to make the assessment of the cyt c hET reaction difficult. The reductive desorption potentials, at -0.52 and -0.64 V vs Ag|AgCl|Cl- for the [Ru(CNPy)(NH3)4(1,4-dt)]2+ and [Ru(CNPy)(NH3)4(pyS)]2+ SAMs, respectively, are indicative of the bonding mode with the surface and the p withdrawing capability of the CNpy ligand.