Ícaro S. Moreira

Electrochemical and spectroscopic studies on RuCl2(PPh3)2(N)2 and RuCl2(PPh3)2(N–N) complexes (N=pyridine derivatives and N–N=phenanthroline or bipyridine derivatives). X-ray structure of RuCl2(PPh3)2(phen)

Abstract A series of RuCl2(PPh3)2(N)2 and RuCl2(PPh3)2(N–N) complexes were synthesized from RuCl2(PPh3)3, (N)2=pyridine (py), 4-(N,N-dimethylamino)pyridine (4-dmNpy), 4-tert-butylpyridine (4-tBu-py), 4-methylpyridine (4-Mepy), 4-vinylpyridine (4-Vpy), 4-phenylpyridine (4-Phpy), isonicotinamide (4-CONH2py), 4-cyanopyridine (4-CNpy) N–N=1,10-phenanthroline (phen), 2,2′-bipyridine (bipy), 2,2′-bipyridine-4,4′-dimethoxy (MeO-bipy), 2,2′-bipyridine-4,4′-dimethyl (Me-bipy), 2,2′-bipyridine-4,4′-dithiomethyl (MeS-bipy), 2,2′-bipyridine-4,4′-dichloro (Cl-bipy) and 2,2′-bipyridine-4,4′-dinitro (NO2-bipy). The complexes were characterized by elemental analysis, cyclic voltammetry and UV–Vis, NMR and IR spectroscopies. The structure of the RuCl2(PPh3)2(phen) was established by single crystal X-ray crystallography.

An inorganic iron complex that inhibits wild-type and an isoniazid-resistant mutant 2-trans-enoyl-ACP (CoA) reductase from Mycobacterium tuberculosis

The in vitro kinetics of inactivation of both wild-type and I21V InhA enzymes by [FeII(CN)5(INH)]3- indicate that this process requires no activation by KatG, and no need for the presence of NADH. This inorganic complex may represent a new class of lead compounds to the development of anti-tubercular agents aiming at inhibition of a validated target.

Synthesis, characterization and cytotoxic activities of the [RuCl2(NO)(dppp)(L)]PF6 complexes

The synthesis and characterization of ruthenium compounds of the type [RuCl(2)(NO)(dppp)(L)]PF(6) [dppp=1,3-bis(diphenylphosphino)propane; L=pyridine, 4-methylpyridine, 4-phenylpyridine and dimethyl sulfoxide] are described. The complexes were characterized by elemental analysis, UV/Vis and infrared spectroscopy, cyclic voltammetry, and X-ray crystallography for the complexes with the pyridine and 4-methylpyridine ligands. In vitro evaluation of these nitrosyl complexes revealed cytotoxic activity from 7.1 to 19.0 microM against the MDA-MB-231 breast tumor cells and showed that, in this case, they are more active than the reference metallodrug cisplatin. The 1,3-bis(diphenylphosphino)propane and the N-heterocyclic ligands alone failed to show cytotoxic activities at the concentrations tested (maximum concentration utilized=200 microM).

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

Structure and properties of iron–cyclam complex of 2-aminophenol

The cis-[Fe(cyclam)Cl2]Cl and trans-[Fe(cyclam)Cl2]BF4 complexes were prepared by a new synthetic procedure. These isomers were characterized by elemental analysis, electronic spectroscopy (lmax 238, 334 and lmax 238, 302 and 355 nm for cis- and trans-[Fe(cyclam)Cl2], respectively) and electrochemistry (E1:2 212 and 83 mV; vs. Ag AgCl, KCl 3.5 M, 25°C m0.1 M NaTFA, pH 3.0 for cis -a ndtrans-[Fe(cyclam)Cl2], respectively). The reaction of cis-[Fe(cyclam)Cl2] isomer with 2-aminophenol (catH3) ligand yields the cis-[Fe(cyclam)(qH)] 2 complex, where (qH) is the quinonoid oxidized form of the (catH3) ligand that is originated by an intramolecular electron transfer reaction. The cis-[Fe(cyclam)(qH)](PF6)2 complex crystallizes in the space group P21:n, with two different values for Fe‐N bond length, due to the s and p distinct contributions. The electrochemical analysis of this species shows three one-electron sequential processes: E1:2 (I) 316 mV, E1:2 (II) 361 mV and E1:2 (III)1.013 mV assigned to (sqH:catH3), (qH:sqH) and (Fe(III):Fe(II)) redox process, respectively.

Manifestation of sulfur-to-sulfur interaction in complexes of iron, ruthenium and osmium

Abstract The electron conducting ability of the SS bridge was investigated using iron, ruthenium and osmium as metal centers and the bridging ligands 4,4′-dithiodipyridine and bis(4-pyridine)sulfide. The observed back-bonding manifestations in mononuclear complexes, (evaluated through pKa, MLCT and E°′1/2 data), the calculated comproportionation constant (Kc) for the homobinuclear species and the near-infrared (NIR) band characteristics of the homobinuclear and heterobinuclear mixed valence complexes consistently indicate a strong electron delocalization through the disulfide bridge. The available data strongly suggest a correlation between the conducting efficiency of the SS bridge and the existence of a multiply bonded L ⋯ S ⋯ S ⋯ L core.

Spectroscopic and substitution kinetic studies of pentacyanoferrate(II) complexes with sulphur heterocyclic ligands

Abstract The pentacyanoferrate(II) complexes of 1,4-thioxane, 1,4-dithiane and 1,3-dithiane have been prepared in ethanol-water solution and their sodium salts isolated. Microanalysis, UV-visible, infrared and Mo¨ssbauer spectroscopies, were used to characterize the complexes. Each complex has an absorption band in the visible region which is assigned to ad-d transition. Infrared measurements indicate that 1,4-thioxane, 1,4-dithiane and 1,3-dithiane ligand are coordinated through the sulphur atom with the pentacyanoferrate(II) ion. The Mo¨ssbauer parameters, isomer shift and quadrupole splitting allowed the analysis of the σ donor and π acceptor ability of the ligands in these complexes. The kinetics of ligand exchange were studied by the standard spectrophotometric technique for slow reactions, using pyridine as entering ligand. The existence of a rate saturation is interpreted as being consistent with a dissociative (D) mechanism. The rate constants of dissociation were found to be 5.7 × 10−4 s−1, 5.6 × 10−4 s−1 and 3.4 × 10−4 s−1 for 1,4-thioxane, 1,4-dithiane and 1,3-dithiane, respectively. The approximately constant values of ΔG‡ and the linear correlation between ΔH‡ and ΔS‡ suggest the existence of a sole mechanism for the studied reactions.

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.

Characterization of the [Ru(CN)5(pyS)]4− ion complex adsorbed on gold, silver and copper substrates by surface-enhanced Raman spectroscopy

Abstract The adsorption of the [Ru(CN) 5 (pyS)] 4− (pyS=4-mercaptopyridine) ion complex on gold, silver and copper surfaces has been studied by surface-enhanced Raman spectroscopy (SERS). The influence of the nature of the metallic substrates in the adsorption geometry of the complex is reflected in a strong variation of the SERS spectra, particularly, the relative intensities of characteristic vibrational modes of pyS and CN ligands, which is likely to result from changes in specific chemical interactions involving both ligands and the surface. The effect of the surface modification procedure on the properties of the adsorbed monolayers has also been investigated for the gold surface. Surface modification has been performed by self-assembly or under an electrochemical potential. The spectroscopic results have shown that, according to the modification procedure, the modifier can be bound to the surface via sulfur atom or via CN nitrogen atoms. The ability to control the orientation of the adsorbed monolayer permits control over the properties of the interface, as demonstrated by the study of the electrochemistry of cytochrome- c (cyt- c ) on the differently prepared surfaces. A reversible electrochemical response of the metalloprotein is only observed on the self-assembly prepared surface, where CN moieties of the surface modifier are available to interact with the protein molecule.