DNA Oxidation Photoinduced by Norharmane Rhenium(I) Polypyridyl Complexes: Effect of the Bidentate N,N'-Ligands on the Damage Profile.

ReI -polypyridyl complexes have interesting and distinctive photochemical and photosensitizing properties. This work describes the capability to induce (or photoinduce) DNA damage of three ReI -complexes with a naturally occurring alkaloid called norharmane (nHo) as ligand: [Re(CO)3 (nHo)(L)]CF3 SO3 where L=2,2'-bipyridine (ReBpy), phenanthroline (RePhen) or dipyrido[3,2-a:2',3'-c]phenazine (ReDppz). The interaction of the complexes with DNA was investigated by steady-state and time-resolved spectroscopy. Data show that the mode and strength of interaction depend on the chemical structure of the bidentate ligand. The complexes show a major static contribution to the overall interaction, giving rise to the formation of noncovalent adducts with DNA, and the particular trend observed was RePhen>ReDppz>ReBpy. Photo-oxidation at the purine bases represents the major DNA damaging mechanism. RePhen also induces single-strand breaks in a yield similar to that of base damage, suggesting an additional photosensitizing pathway. We also performed the Ames test to evaluate the cytotoxic and mutagenic properties of both non-irradiated and photoexcited complexes. RePhen, but not the other complexes, turned out to be both toxic and phototoxic for the bacteria.

Association studies to transporting proteins of fac-ReI(CO)3(pterin)(H2O) complex.

A new synthetic route to acquire the water soluble complex fac-ReI(CO)3(pterin)(H2O) was carried out in aqueous solution. The complex has been obtained with success via the fac-[ReI(CO)3(H2O)3]Cl precursor complex. ReI(CO)3(pterin)(H2O) has been found to bind strongly with bovine and human serum albumins (BSA and HSA) with intrinsic-binding constants, Kb, of 6.5 × 105 M-1 and 5.6 × 105 M-1 at 310 K, respectively. The interactions of serum albumins with ReI(CO)3(pterin)(H2O) were evaluated employing UV-vis fluorescence and absorption spectroscopy and circular dichroism. The results suggest that the serum albumins-ReI(CO)3(pterin)(H2O) interactions occurred in the domain IIA-binding pocket without loss of helical stability of the proteins. The comparison of the fluorescence quenching of BSA and HSA due to the binding to the Re(I) complex suggested that local interaction around the Trp 214 residue had taken place. The analysis of the thermodynamic parameters ΔG0, ΔH0, and ΔS0 indicated that the hydrophobic interactions played a major role in both HSA-Re(I) and BSA-Re(I) association processes. All these experimental results suggest that these proteins can be considered as good carriers for transportation of ReI(CO)3(pterin)(H2O) complex. This is of significant importance in relation to the use of this Re(I) complex in several biomedical fields, such as photodynamic therapy and radiopharmacy.

Norharmane rhenium(I) polypyridyl complexes: synthesis, structural and spectroscopic characterization.

Two novel Re(i) complexes with the general formula fac-[Re(CO)3(L)(nHo)]CF3SO3, where L = 2,2'-bipyridine (bpy) or 1,10 phenanthroline (phen) and nHo (9H-pyrido[3,4-b]indole; norharmane) have been synthesized. The Re(i)-nHo complexes were characterized by structural X-ray diffraction, (1)H and (13)C NMR, UV-vis absorption and FT-IR spectroscopy, and by a combination of two mass spectrometry techniques, namely ESI-MS and UV-MALDI-MS. All characterizations showed that nHo is coordinated to the metal atom by the pyridine nitrogen of the molecule. X-ray structural analysis revealed that the crystal lattices for both complexes are further stabilized by a strong >N-HO bond between the pyrrole NH group of the pyridoindole ligand and one oxygen atom of the trifluoromethanesulfonate counter-ion. Ground state geometry optimization by DFT calculations showed that in fluid solution the nHo ligand may rotate freely. The nature of the electronic transitions of Re(CO)3(bpy)(nHo)(+) were established by TD-DFT calculations. The set of the most important electronic transitions present in this complex are comprised of π→π* electronic transitions centered on bpy and nHo moieties, LLCTnHo→COs, MLLCTRe(CO)3→bpy and LLCTnHo→bpy transitions. Additionally, TD-DFT calculations predict the existence of another two intense MLLCTRe(CO)3→nHo electronic transitions. Calculated UV-vis absorption spectra are in good agreement with the corresponding experimental data for the bpy-containing complex.

Solvent dependent switching of 3MLLCT and 1IL luminescent states in [ClRe(CO)3(bathocuproinedisulfonate)]2-: spectroscopic and computational study.

Steady state and time-resolved luminescence experiments and calorimetric studies, as well as time-dependent density functional theory calculations performed on [ClRe(CO)(3)(Bathocuproinedisulfonate)](2-), show that the photophysical properties of the Re(I) anionic complex are determined by the balance between intraligand ((1)IL) and metal-ligand-to-ligand charge transfer ((3)MLLCT) excited states. In organic solvents, (3)MLLCT states prevail and the usual expected behavior is observed: bathochromic shift of the emission maximum, a reduced luminescence quantum yield and the shortening of the excited-state lifetime upon increasing the polarity of the solvent. In addition, singlet oxygen ((1)O2) is generated with high quantum yields (Φ(Δ) ≈ 0.5 in CH(3)CN) due to the quenching of the (3)MLLCT luminescence by (3)O2. The total quenching rate constant of triplet state by oxygen, k(q), reach values between 2.2 and 2.4 × 10(9) M(-1) s(-1) for the organic solvents studied. In CH(3)CN, the fraction of triplet states quenched by O2 which yield (1)O2, f(O2)T, is nearly unity. In aqueous solution, where no singlet oxygen is generated, the luminescence of the Re(I) complex is of (1)IL character with a emission quantum yield (Φ(em)) strongly pH dependent: Φ(em,(pH=2))/Φ(em,(pH=10)) ≈ 5.6. The variation of the pH of the solution tunes the photophysical properties of the Re(I) complex by changing the relative amount of the different species existing in aqueous solutions: [ClRe(CO)3(BCS)](2-), [(OH)Re(CO)3(BCS)](2-) and [(H2O)Re(CO)3(BCS)](−). TD-DFT calculations show that the percentage of charge transfer character of the electronic transitions is substantially higher in the organic solvents than in aqueous solutions, in agreement with the increase of (1)IL character of HOMO in [(H2O)Re(CO)3(BCS)](−) relative to [ClRe(CO)3(BCS)](2-).

Photosensitized generation of singlet oxygen from Re(I) complexes: a photophysical study using LIOAS and luminescence techniques.

Quantum yields and efficiencies of (1)O2 ((1)Δg) production along with photophysical properties for a number of Re(I) complexes in acetonitrile solutions are reported. Two different classes of Re(I) complexes, L(S)-CO2-Re(CO)3(bpy) (L(S) = 2-pyrazine, 2-naphthalene, 9-anthracene, 1-pyrene, 2-anthraquinone) and XRe(CO)3L (X = CF3SO3, py; L = bpy, phen), were probed as photosensitizers for (1)O2 ((1)Δg) production in air-saturated acetonitrile solutions. Depending on the nature of the Re(I) complex, the excited state responsible for the generation of (1)O2 ((1)Δg) is either a metal-to-ligand charge transfer ((3)MLCT) or a ligand centered ((3)LC) state. With L(S)-CO2-Re(CO)3(bpy) complexes, (1)O2 ((1)Δg) is produced by oxygen quenching of (3)LC states of anthracene and pyrene with high quantum yields (ΦΔ between 0.8 and 1.0), while the complexes bearing the ligands L(S) = 2-anthraquinone, 2-pyrazine, and 2-naphthalene did not yield (1)O2. XRe(CO)3L complexes generate (1)O2 ((1)Δg) mainly by oxygen quenching of their (3)MLCT luminescence with an efficiency of (1)O2 ((1)Δg) formation close to unity. Bimolecular rate constants for the quenching of the XRe(CO)3L complexes' emission by molecular oxygen range between 1 × 10(9) and 2 × 10(9) M(-1) s(-1), and they are all ≤ (1/9)kd, in good agreement with the predominance of the singlet channel in the mechanism of (1)O2 ((1)Δg) generation using these Re(I) complexes as photosensitizers. All the experimental singlet oxygen efficiencies are consistent with calorimetric and luminescence data for the studied complexes. With L(S)-CO2-Re(CO)3(bpy) complexes, calorimetric experiments were utilized in the calculation of the quantum yields of triplet formation; namely φT = 0.76 and 0.83 for the triplet states of anthracene and pyrene, respectively.

Mass spectrometry of rhenium complexes: a comparative study by using LDI-MS, MALDI-MS, PESI-MS and ESI-MS.

A group of rhenium (I) complexes including in their structure ligands such as CF(3)SO(3)-, CH(3)CO(2)-, CO, 2,2'-bipyridine, dipyridil[3,2-a:2'3'-c]phenazine, naphthalene-2-carboxylate, anthracene-9-carboxylate, pyrene-1-carboxylate and 1,10-phenanthroline have been studied for the first time by mass spectrometry. The probe electrospray ionization (PESI) is a technique based on electrospray ionization (ESI) that generates electrospray from the tip of a solid metal needle. In this work, mass spectra for organometallic complexes obtained by PESI were compared with those obtained by classical ESI and high flow rate electrospray ionization assisted by corona discharge (HF-ESI-CD), an ideal method to avoid decomposition of the complexes and to induce their oxidation to yield intact molecular cation radicals in gas state [M](+·) and to produce their reduction yielding the gas species [M](-·). It was found that both techniques showed in general the intact molecular ions of the organometallics studied and provided additional structure characteristic diagnostic fragments. As the rhenium complexes studied in the present work showed strong absorption in the UV-visible region, particularly at 355 nm, laser desorption ionization (LDI) mass spectrometry experiments could be conducted. Although intact molecular ions could be detected in a few cases, LDI mass spectra showed diagnostic fragments for characterization of the complexes structure. Furthermore, matrix-assisted laser desorption ionization (MALDI) mass spectra were obtained. Nor-harmane, a compound with basic character, was used as matrix, and the intact molecular ions were detected in two examples, in negative ion mode as the [M](-·) species. Results obtained with 2-[(2E)-3-(4-tert-buthylphenyl)-2-methylprop-2-enylidene] malononitrile (DCTB) as matrix are also described. LDI experiments provided more information about the rhenium complex structures than did the MALDI ones.

Photolytic and radiolytic oxidation of humic acid.

The reactions of Br(2)(˙-), Br˙, HO˙ and N(3)˙ with Aldrich humic acid (AHA) were investigated. The Br/Br(2)(˙-) radicals were obtained in flash-photolysis experiments (λ(exc) = 266 nm) performed with NaS(2)O(8) solutions in the presence of bromide ions. HO˙ and N(3)˙ radicals were generated by pulse radiolysis of N(2)O-saturated solutions. From the combination of a bilinear analysis and computer simulations of the absorbance traces, it was possible to obtain information on the rate constants for the reactions of Br(2)(˙-), Br˙, HO˙ and N(3)˙ with AHA and on the intermediate species involved in the mechanism. Evidence for the participation of phenoxyl radicals (λ(max) = 410 nm) is given.

On the mechanism of Re(I)-carboxylate bond cleavage by perchloric acid: a kinetic and spectroscopic study.

We have studied the reaction between pz-CO(2)-Re(CO)(3)(bpy) and perchloric acid in acetonitrile by following the UV-vis and IR spectral changes in the reaction mixture. A fast equilibrium was found to be established between solvated protons, pz-CO(2)-Re(CO)(3)(bpy), and the protonated intermediate [pz-C(OH)O-Re(CO)(3)(bpy)](+) which finally yields pz-COOH and Re(CO)(3)(bpy)(CH(3)CN)(+) as reaction products. This intermediate has been characterized by UV-vis and IR spectroscopies and by DFT calculations. The fully optimized DFT/CPCM structures for pz-CO(2)-Re(CO)(3)(bpy) and [pz-C(OH)O-Re(CO)(3)(bpy)](+) were compared with the X-ray structure of pz-CO(2)-Re(CO)(3)(bpy). The structural parameters associated with the carboxyl group in the protonated intermediate are between those of pz-CO(2)-Re(CO)(3)(bpy) and pz-COOH. Multivariate curve resolution methods were employed to obtain the spectrum of the protonated intermediate and the concentration profiles from the full matrix of time-resolved UV-vis spectra. The proposed mechanism was numerically simulated by using Runge-Kutta methods. Model parameters were estimated by nonlinear regression fitting of the concentration profiles, yielding values of log(K) = 4.9 ± 0.3 and k = 0.16 ± 0.03 min(-1) for the formation equilibrium constant and the decay rate constant of the protonated intermediate, respectively.