Gerardo A. Argüello

New advances in the study on the interaction of [Cr(phen)2(dppz)]3+ complex with biological models; association to transporting proteins.

The present study reports a detailed investigation with the interaction of [Cr(phen)(2)(dppz)](3+) with serum albumins, the key protein for the transport of drugs in the blood plasma, which allows us to understand further the role of [Cr(phen)(2)(dppz)](3+) as sensitizer in Photodynamic Therapy (PDT). Chromium(III) complex [Cr(phen)(2)(dppz)](3+), (dppz = dipyridophenazine and phen=1,10-phenanthroline), where dppz is a planar bidentate ligand with an extended π system, has been found to bind strongly with bovine and human serum albumins (BSA and HSA) with an intrinsic binding constants, K(b), of (1.7±0.3)×10(5) M(-1) and (2.2±0.3)×10(5) M(-1) at 295K, respectively. The interactions of serum albumins with [Cr(phen)(2)(dppz)](3+) were assessed employing fluorescence spectroscopy, circular dichroism and UV-vis absorption spectroscopy. The serum albumins-[Cr(phen)(2)(dppz)](3+) interactions caused conformational changes with the loss of helical stability of the protein and local perturbation in the domain IIA binding pocket. The relative fluorescence intensity of the albumin (BSA or HSA) bound to the Cr(III) complex decreased, suggesting that perturbation around the Trp 214 residue took place. The analysis of the thermodynamic parameters ΔG, ΔH, ΔS indicated that the hydrophobic interactions played a major role in both BSA-Cr(III) and HSA-Cr(III) association processes. The binding distances and transfer efficiencies for BSA-Cr(III) and HSA-Cr(III) binding reactions were calculated according to the Föster theory of non-radiation energy transfer. All these experimental results suggests that [Cr(phen)(2)(dppz)](3+) binds to serum albumins, by which these proteins could act as carriers of this complex for further applications in PDT.

Aspartame-stabilized gold-silver bimetallic biocompatible nanostructures with plasmonic photothermal properties, antibacterial activity and long-term stability

Gold-silver core-shell nanoparticles stabilized with a common sweetener, aspartame (AuNP@Ag@Asm), combine the antimicrobial properties of silver with the photoinduced plasmon-mediated photothermal effects of gold. The particles were tested with several bacterial strains, while biocompatibility was verified with human dermal fibroblasts.

New insights in the DNA-[Cr(phen)2(dppz)]3+ binding and photocleavage properties by the complex with an intercalating ligand

Due to the key role of DNA in cell life and pathological processes, the design of specific chemical nucleases, DNA probes and alkylating agents is an important research area for the development of new therapeutic agents and tools in Biochemistry. Hence, the interaction of small molecules with DNA has attracted in particular a great deal of attention. The aim of this study was to investigate the ability of [Cr(phen)(2)(dppz)](3+) to associate with DNA and to characterize it as photocleavage reagent for Photodynamic Therapy (PDT). Chromium(III) complex [Cr(phen)(2)(dppz)](3+), (dppz = dipyridophenazine, phen = 1,10-phenanthroline), where dppz is a planar bidentate ligand with an extended pi system, has been found to bind strongly to double strand oligonucleotides (ds-oligo) and plasmid DNA with intrinsic DNA binding constants, K(b,) of (3.9+/-0.3)x10(5) M(-1) and (1.1+/-0.1)x10(5) M(-1), respectively. The binding properties to DNA were investigated by UV-visible (UV-Vis) absorption spectroscopy and electrophoretic studies. UV-Vis absorption data provide clearly that the chromium(III) complex interacts with DNA intercalatively. Competitive binding experiments show that the enhancement in the emission intensity of ethidium bromide (EthBr) in the presence of DNA was quenched by [Cr(phen)(2)(dppz)](3+), indicating that the Cr(III) complex displaces EthBr from its binding site in plasmid DNA. Moreover, [Cr(phen)(2)(dppz)](3+), non-covalently bound to DNA, promotes the photocleavage of plasmid DNA under 457 nm irradiation. We also found that the irradiated Cr(III)-plasmid DNA association is able to impair the transforming capacity of bacteria. These results provide evidence confirming the responsible and essential role of the excited state of [Cr(phen)(2)(dppz)](3+) for damaging the DNA structure. The combination of DNA, [Cr(phen)(2)(dppz)](3+) and light, is necessary to induce damage. In addition, assays of the photosensitization of transformed bacterial suspensions suggest that Escherichia coli may be photoinactivated by irradiation in the presence of [Cr(phen)(2)(dppz)](3+). In sum, our results allow us to postulate the [Cr(phen)(2)(dppz)](3+) complex as a very attractive candidate for DNA photocleavage with potential applications in Photodynamic Therapy (PDT).

The effect of pH on the luminescence quenching of tris(2,2′-bipyridine) ruthenium (II) by phenolic compounds

Abstract The effect of pH on the luminescence quenching of the excited state ( 3 CT) of tris(2,2′-bipyridine) ruthenium (II) by a series of phenols was studied in aerated aqueous solutions at constant temperature and ionic strength. The experimental rate constants ( k q ) were obtained separately from static (luminescence intensity) and dynamic (lifetime measurements) methods and they were coincident. In all the systems studied the pH was carefully controlled and the obtained Stern—Volmer constants ( K sv ) showed a marked increase when the pH increases. The lifetime in the absence of any quencher (τ 0 ) was found to be constant in the pH range tested. An electron transfer mechanism was assumed for the quenching process. Since the reactivity of the phenolic compound in this quenching process is affected by the position of its acid—base equilibrium, it is possible to estimate k q s from the K sv data at different pHs for the ionized ( k q (PhO − )) and non-ionized ( k q (PhOH)) forms of the quencher. A computer program developed for this purpose allowed us to get a good fit of the experimental data and to obtain the values of k q (PhO − ), k q (PhOH) and the acid dissociation constant for each studied phenolic compound. The proposed method may be used to extrapolate the quenching rate constant value in media that is either too acid or too basic when direct experimental measurement is difficult to obtain. Moreover, the effect of substitution in the phenolic compounds upon the quenching process has also been examined.

Oxidative Stress and Antimicrobial Activity of Chromium(III) and Ruthenium(II) Complexes on Staphylococcus aureus and Escherichia coli

The prevalence of antibiotic resistance has resulted in the need for new approaches to be developed to combat previously easily treatable infections. The main aim of this work was to establish the potential of the synthetic α-diimine chromium(III) and ruthenium(II) complexes (where the α-diimine ligands are bpy = 2,2-bipyridine, phen = 1,10-phenanthroline, and dppz = dipyrido[3,2-a:2′,3′-c]-phenazine) like [Cr(phen)3]3+, [Cr(phen)2(dppz)]3+, [Ru(phen)3]2+, and [Ru(bpy)3]2+ as antibacterial agents by generating oxidative stress. The [Cr(phen)3]3+ and [Cr(phen)2(dppz)]3+ complexes showed activity against Gram positive and Gram negative bacteria with minimum inhibitory concentrations (MICs) ranging from 0.125 μg/mL to 1 μg/mL, while [Ru(phen)3]2+ and [Ru(bpy)3]2+ do not exhibit antimicrobial activity against the two bacterial genera studied at the concentration range used. When ciprofloxacin was combined with [Cr(phen)3]3+ for the inhibition of Staphylococcus aureus and Escherichia coli, an important synergistic effect was observed, FIC 0.066 for S. aureus and FIC 0.064 for E. coli. The work described here shows that chromium(III) complexes are bactericidal for S. aureus and E. coli. Our results indicate that α-diimine chromium(III) complexes may be interesting to open new paths for metallodrug chemotherapy against different bacterial genera since some of these complexes have been found to exhibit remarkable antibacterial activities.

Advances on the interaction of polypyridyl Cr(III) complexes with transporting proteins and its potential relevance in photodynamic therapy

The present study reports a detailed investigation into the interaction of [Cr(phen)(2)(dppz)](3+) and [Cr(phen)(3)](3+) with transferrin, the key protein for the transport of Fe(3+) in blood plasma; its cycle holds promise as an attractive system for strategies of drug targeting to tumor tissues. This can allow us to understand further the role of both complexes as sensitizers in photodynamic therapy (PDT). Chromium(III) complexes, [Cr(phen)(2)(dppz)](3+) and [Cr(phen)(3)](3+), (phen=1,10-phenanthroline and dppz=dipyridophenazine), where dppz is a planar bidentate ligand with an extended π system, have been found to bind strongly with apotransferrin (apoTf) with an intrinsic binding constant, K(b), of (1.8±0.3)×10(5)M(-1) and (1.1±0.1)×10(5)M(-1) at 299K, for apoTf-[Cr(phen)(2)(dppz)](3+) and apoTf-[Cr(phen)(3)](3+), respectively. The interactions of apoTf with the different Cr(III) complexes were assessed employing UV-visible absorption, fluorescence and circular dichroism spectroscopy. The relative fluorescence intensity of the protein decreased when the increasing concentration of Cr(III) complex was added, suggesting that perturbation around the Trp and Tyr residues took place. The analysis of the thermodynamic parameters ΔG, ΔH, ΔS indicated that the presence of the Cr(III) complex stabilizes the protein with a strong entropic contribution. The binding distances and transfer efficiencies for apoTf-[Cr(phen)(2)(dppz)](3+) and apoTf-[Cr(phen)(3)](3+) binding reactions were calculated according to Föster theory of non-radiation energy transfer. All these experimental results suggest that [Cr(phen)(2)(dppz)](3+) and [Cr(phen)(3)](3+) bind strongly to apoTf indicating that this protein could act as a carrier of these complexes for further applications in PDT.

Quenching of tris(2,2'-bipyridine) chromium(III) and tris(1,10-phenanthroline) chromium(III) excited states by phenols : temperature and pH effect

Abstract The quenching rate constant kq of the excited states *Cr(bpy)33+ and *Cr(phen)33+ by several substituted phenols was investigated as a function of temperature using the time resolved luminescence quenching technique. The activation parameters showed a pH dependence. The most important contribution to the total activation entropy in basic media was found to be the electrostatic factor. The data obtained from log kq vs. ΔG0 plot were analyzed on the basis of the current theories for electron transfer processes. The best fitting analysis in the ΔG# vs. ΔG0 plot yielded reorganization energies of 59 and 55 kcal/mol for the bipyridine and phenanthroline chromium complexes, respectively. The high values of reorganization energies found (λ) were interpreted as a hydrogen bond term contribution (λH) to the outer-sphere reorganization energy, λo′, where λo′ = λo+ λH. The effect of the ionic strength and [Cl−] on the quenching rate constant for the reaction of *Cr(phen)33+ with 2,6-dimethylphenol was investigated. It was found that neither the ionic pair formation nor the [Cl−] concentration seem to affect the quenching mechanism.

Quantum yield in the gas phase photolysis of perfluoroacetyl chloride: a comparison with related compounds

Abstract The photolysis of perfluoroacetyl chloride vapour was studied in the pressure range 4.6–59.9 Torr and with addition of inert gas up to 535.2 Torr using light of 254 and 280 nm. The quantum yield for the decomposition of CF 3 COCl taken as Φ [CF 3 Cl+2C 2 F 6 ] = 0.98±0.13 was not affected by the total pressure, the intensity and the wavelength of the light within the studied range of conditions. In the presence of c-C 6 H 12 a clear hydrogen abstraction reaction took place indicating the presence of CF 3 radicals. An upper limit for the rate of hydrogen abstraction of log k H (cm 3 mol −1 s −1 ) = 7.9 at 298 K was obtained. Light emission was not observed over the range 330–600 nm. Mechanisms for the decomposition of perfluoroacyl halides are discussed.

Quantum yield and total pressure effect in perfluoroglutaric anhydride photolysis in the gas phase

Abstract The quantum yield of the photolysis of perfluoroglutaric anhydride (PFGA) in the gas phase (φ CO = 0.34 ± 0.07) was determined in runs using light of wavelength 254 nm. This value is intermediate between the quantum yields of open-chain perfluorinated anhydrides and of strained cyclic perfluorinated anhydrides. The PFGA quantum yield is independent of time and total pressure. The photolysis of PFGA vapour produces CO, CO 2 , C 2 F 4 and c -C 3 F 6 . The ratio [C 2 F 4 ]/[ c -C 3 F 6 ] is significantly dependent on the total pressure as shown by runs with the addition of inert gases such as helium, argon, oxygen, nitrogen, CCl 2 F 2 and C 2 Cl 3 F 3 . Each of these gases produces a specific effect as can be seen from their collisional deactivation coefficients.

Photolysis of perfluoroglutaric anhydride vapor at low pressures: effect of wavelength on the product ratio

Abstract The photolysis of perfluoroglutaric anhydride vapor has been investigated in the pressure range 0.03 – 2 Torr using light of wavelength 270, 265, 254, 240 and 232 nm. The products were CO, CO2, C2F4 and cC3F6. The [C2F4]/[c-C3F6] ratio is directly proportional to the energy supplied but is inversely proportional to the pressure.