A. Kirsch-De Mesmaeker

Layered double hydroxides exchanged with tungstate as biomimetic catalysts for mild oxidative bromination

The manufacture of a range of bulk and fine chemicals, including flame retardants, disinfectants and antibacterial and antiviral drugs, involves bromination. Conventional bromination methods typically use elemental bromine, a pollutant and a safety and health hazard. Attempts to develop alternative and more benign strategies have been inspired by haloperoxidase enzymes, which achieve selective halogenation at room temperature and nearly neutral pH by oxidizing inorganic halides with hydrogen peroxide,. The enzyme vanadium bromoperoxidase has attracted particular interest, in this regard, and several homogeneous inorganic catalysts mimicking its activity are available, although they are limited by the requirement for strongly acidic reaction media. A heterogenous mimic operating at neutral pH has also been reported, but shows only modest catalytic activity. Here we describe a tungstate-exchanged layered double hydroxide that catalyses oxidative bromination and bromide-assisted epoxidation reactions in a selective manner. We find that the catalyst is over 100 times more active than its homogeneous analogue. The low cost and heterogeneous character of this system, together with its ability to operate efficiently under mild conditions using bromides rather than elemental bromine, raise the prospect of being able to develop a clean and efficient industrial route to brominated chemicals and drugs and epoxide intermediates.

Sonoelectrochemistry in aqueous electrolyte: A new type of sonoelectroreactor

Abstract A new type of sonoelectroreactor is presented. Its most interesting characteristic is the nature of the working electrode which is made up of the immersed titanium horn itself (anode or cathode). The frequency of the home-made reactor is around 20 kHz. The performances of this sonoelectroreactor are tested during the copper electrodeposition.

Synthesis and characterisation of a new DNA-binding bifunctional ruthenium(II) complex

A new DNA-binding molecule, Ru(tap)2POQ2+, in which a polypyridylruthenium(II) complex is linked to an aminochloroquinoline by a flexible chain, has been prepared and characterised (tap = 1,4,5,8-tetraazaphenanthrene and POQ corresponds to a 1,10-phenanthroline linked to an aminochloroquinoline by an aliphatic chain). This complex is regarded as bifunctional because it contains two moieties of different binding modes and photoreactivities vs. DNA. The 1H NMR data of this compound indicate the presence of an equilibrium between two molecular species. The spectroscopic properties of Ru(tap)2POQ2+ in absorption and luminescence are examined and compared with those of the corresponding ruthenium(II) complex which does not contain the aminochloroquinoline moiety: Ru(tap)2phen2+. Luminescence relative quantum yields and lifetimes show that the MLCT excited-state behaviour is influenced by the presence of the linked quinoline. An intramolecular photoinduced electron transfer in one of the two species in equilibrium, is considered to be responsible for a quenching of the ruthenium(II) complex iuminescence. Preliminary results on the binding characteristics of Ru(tap)2POQ2+ to DNA and [poly(d[A-T])]2 from luminescence and thermal denaturation studies are reported. The intramolecular quenching of luminescence in Ru(tap)2POQ2+ is inhibited when it interacts with nucleic acids. Consequently, the resulting emission is more substantially enhanced in the presence of the polynucleotide relative to the luminescence increase observed with the reference complex, Ru(tap)2phen2+.

Spectroscopic studies of structurally similar DNA-binding Ruthenium (II) complexes containing the dipyridophenazine ligand

Abstract Nanosecond transient resonance Raman and picosecond transient absorption spectroscopic investigations of the two structurally analogous Ru-polypyridyl complexes, [Ru(phen) 2 dppz] 2+ ( 1 ) and [Ru(tap) 2 dppz] 2+ ( 2 ), are presented (phen=1,10-phenanthroline, dppz=dipyrido [3,2- a :2′,3′- c ] phenazine; tap=1,4,5,8 tetraazaphenanthrene). The findings offer insight into the differing nature of the lowest excited states of the two complexes, and describe the role of these states within the very distinct photophysical behaviour of each, both in relation to solvent response and their interaction with DNA (facilitated in each case through the intercalating dppz ligand). The active, solvent-sensitive, dppz-based 3 MLCT states involved in the ‘light-switch’ behaviour of ( 1 ) are probed, alongside evidence of a progression through a precursor transient state when the complex is in non-aqueous environment. Evidence has been provided of a photophysical pathway for ( 2 ), involving formation of a tap-based lowest 3 MLCT state. When ( 2 ) is bound to DNA through the dppz ligand, a photo-driven electron transfer process ensues between the guanine base of DNA and the lowest 3 MLCT state.

Photocrosslinking in ruthenium-labelled duplex oligonucleotides.

The formation of a photoadduct between a [Ru(1,4,5,8‐tetraazaphenanthrene)24,7‐diphenylphenanthroline]2+ complex chemically attached to a synthetic oligonucleotide, and a guanine moiety in a complementary targeted single‐stranded DNA molecule was studied for ten 17‐mer duplexes by denaturing gel electrophoresis. This photoadduct formation leads to photocrosslinking of the two strands. The percentage quenching of luminescence of the complex by electron transfer was compared to the resulting yield of photocrosslinked product. This yield does not only depend on the ionisation potential of the guanine bases, which are electron donors, but also on other factors, such as the position of the guanine bases as compared to the site of attachment of the complex. The photocrosslinking yield is higher when the guanine moieties are towards the 3′ end on the complementary strand as compared to the tethering site. Computer modelling results are in agreement with this preference for the 3′ side for the photoreaction. Interestingly, the photocrosslink is not alkali labile. Moreover, a type III exonuclease enzyme is blocked at the position of photocrosslinking.

Quenching of excited polyazaaromatic Ru(II) complexes by oxygen: evidence for an electron transfer process by photoelectrochemical study

Abstract The possible contribution of an electron transfer process to the quenching of excited Ru(II) polypyridyl complexes by oxygen has been the subject of controversy for many years; the existence of this process is re-examined in this work with new polyazaaromatic complexes and by a photoelectrochemical (PEC) method. The luminescence quenching rate constants kQ by oxygen in acetonitrile for a series of polyazaaromatic complexes with 1,4,5,8-tetraazaphenanthrene (tap), 1,4,5,8,9,12-hexaazatriphenylene (hat) and 2,2′-bipyridine (bpy) as ancillary ligand, can clearly be correlated with the oxidation potentials in the excited state. A PEC study of the quenching of Ru(bpy)32+* by oxygen in acidic medium allows determination of the quenching rate constant via the measurements of cathodic photocurrents induced at a transparent SnO2 electrode. These two investigations show that the electron transfer mechanism is certainly involved in the luminescence quenching of these Ru(II) complexes by oxygen and that the energy transfer contribution becomes rather weak for the more reducing excited complexes.

Photoelectrochemistry of a new ruthenium complex, the Ru(II)-tris-(1,4,5,8-tetraazaphenanthrene) dication

Abstract It is shown that the excited states of Ru(TAP) 2+ 3 (TAP ≡ 1,4,5,8-tetraazaphenanthrene) and Ru(TAPMe 2 ) 2+ 3 (TAPMe 2 ≡ 2,7-dimethyl-1,4,5,8-tetraazaphenanthrene) are too weak reductants to be oxidized at SnO 2 electrodes. On the other hand, in the presence of a reducing agent such as hydroquinone, the photo-generated reduced complexes are able to inject electrons into the SnO 2 conduction band. The good agreement between the Stern-Volmer constants obtained by luminescence quenching and by photoelectrochemistry confirms this electron transfer process.

Ruthenium oligonucleotides, targeting HPV16 E6 oncogene, inhibit the growth of cervical cancer cells under illumination by a mechanism involving p53

High-risk Human Papillomaviruses (HPV) has been found to be associated with carcinomas of the cervix, penis, vulva/vagina, anus, mouth and oro-pharynx. As the main tumorigenic effects of the HPV have been attributed to the expression of E6 and E7 genes, different gene therapy approaches have been directed to block their expression such as antisense oligonucleotides (ASO), ribozymes and small interfering RNAs. In order to develop a gene-specific therapy for HPV-related cancers, we investigated a potential therapeutic strategy of gene silencing activated under illumination. Our aim according to this antisense therapy consisted in regulating the HPV16 E6 oncogene by using an E6-ASO derivatized with a polyazaaromatic ruthenium (RuII) complex (E6-Ru-ASO) able, under visible illumination, to crosslink irreversibly the targeted sequence. We examined the effects of E6-Ru-ASO on the expression of E6 and on the cell growth of cervical cancer cells. We demonstrated using HPV16+ SiHa cervical cancer cells that E6-Ru-ASO induces after illumination, a reactivation of p53, the most important target of E6, as well as the inhibition of cell proliferation with a selective repression of E6 at the protein level. These results suggest that E6-Ru ASOs, activated under illumination and specifically targeting E6, are capable of inhibiting HPV16+ cervical cancer cell proliferation.

The photo-electrochemistry of the Rhodamine B-hydroquinone system at optically transparent bubbling gas electrodes

Abstract Use of the technique called ‘bubbling gas electrode’ yields very reproducible polarograms on solid electrodes. It is applied here to study the photoelectrochemistry of the Rhodamine B-hydroquinone system on optically transparent n -type SnO 2 and gold electrodes, in order to understand the operation of a photovoltaic cell based on due-supersensitizer couples. Rhodamine alone gives no photo-currents on gold, and weak ones on SnO 2 ; added hydroquinone gives rise to very intense photo-currents on both electrodes. Increasing supersensitizer concentrations lead to a plateau, allowing an estimate of the lifetime of an electro-active transient. Two mechanisms for supersensitization are envisioned: hydroquinone can donate an electron to the photo-electrogenerated oxidized rhodamine, reducing thus the cathodic tunnel-current; or the diphenol might transfer an electron to the photo-excited dye, producing thus a new oxidizable species. Taken alone, the second mechanism is unable to explain all findings. Action spectra, recorded for a large number of experimental conditions suggest a major contribution from adsorbed dye molecules; in the presence of hydroquinone, some contributions from the solution may be operative.

Binding of Ru(II) polyazaaromatic complexes to DNA: A 23Na NMR spin-lattice relaxation study

The possibility of using sodium-23 spin-lattice relaxation rate measurements to probe the interaction modes of Ru11 polyazaaaromatic complexes with DNA is investigated. The following complexes are considered: Ru(phen)3(2+) (phen = 1.10-phenanthroline), Ru(phen)2HAT2+ (HAT = 1,4,5,8,9,12-hexaazatriphenylene), and Ru(diMeTAP)3(2+) (diMeTAP = 2,7-dimethyl-1,4,5,8-tetraazaphenanthrene). The addition of Ru(diMeTAP)3(2+) to a solution of NaDNA leads to a decrease in the sodium-23 spin-lattice relaxation rate (R1) similar to the effect observed upon addition of Mg2+. This indicates that Ru(diMeTAP)3(2+) interacts like Mg2+ with DNA and consequently that the electrostatic interaction dominates the association with DNA, Ru(phen)3(2+) and Ru(phen)2HAT2+ diminish R1 more efficiently than Mg2+, in a manner similar to ethidium bromide, which is known for its intercalation properties. Thus interactions other than electrostatic occur between these two complexes and DNA. These results are in agreement with data obtained from other techniques, according to which Ru(phen)3(2+) and Ru(phen)2HAT2+ are located partially inside the DNA double helix, in contrast to Ru(diMeTAP)3(2+) which remains in the ionic atmosphere around the phosphate backbone.