Petre Ionita

DeerAnalysis2006 - a comprehensive software package for analyzing pulsed ELDOR data

Pulsed electron-electron double resonance techniques such as the four-pulse double electron-electron resonance experiment measure a dipolar evolution function of the sample. For a sample consisting of spin-carrying nanoobjects, this function is the product of a form factor, corresponding to the internal structure of the nanoobject, and a background factor, corresponding to the distribution of nanoobjects in space. The form factor contains information on the spin-to-spin distance distribution within the nanoobject and on the average number of spins per nanoobject, while the background factor depends on constraints, such as a confinement of the nanoobjects to a two-dimensional layer. Separation of the dipolar evolution function into these two contributions and extraction of the spin-to-spin distance distribution require numerically stable mathematical algorithms that can handle data for different classes of samples, e.g., spin-labelled biomacromolecules and synthetic materials. Furthermore, experimental imperfections such as the limited excitation bandwidth of microwave pulses need to be considered. The software package DeerAnalysis2006 provides access to a comprehensive set of tools for such data analysis within a common user interface. This interface allows for several tests of the reliability and precision of the extracted information. User-supplied models for the spin-to-spin distance distribution within a certain class of nanoobjects can be added to an existing library and be fitted with a universal algorithm.

Spin-labelled Au nanoparticles

A series of Au nanoparticles functionalised with nitroxide spin labels has been prepared and studied by EPR spectroscopy. Samples with low coverage of the spin label were used to investigate the dynamics of the surface-attached labels at different distances from the Au surface. The rotational correlation times of spin labels vary from 10(-10) s to more than 3 x 10(-9) s, depending on the chain length of the label and the surrounding ligand. The samples with higher coverage of the spin label show an increasing contribution of the exchange interaction between nitroxides adsorbed in a close proximity to each other on the same nanoparticle. Quantitative analysis of the EPR spectra of these samples suggests the presence of non-equivalent binding sites on the surface of Au nanoparticles. Additionally, EPR signals of isolated radical pairs were observed at intermediate coverage.

Gold nanoparticle-initiated free radical oxidations and halogen abstractions

We report on the use of EPR spectroscopy and spin trapping technique to detect free radical intermediates formed in the presence of gold nanoparticles. Phosphine- and amine-protected gold nanoparticles were found to initiate air oxidation of organic substrates containing active hydrogen atoms, such as amines and phosphine oxides. Nanoparticles protected by stronger bound ligands (e.g., thiols) were inactive in these reactions. We also found that gold nanoparticles are able to abstract a halogen atom from the halogenated compounds, presumably due to the high affinity of gold metal for halogens. Reaction of Au nanoparticles with chloroform showed an unusual inverse isotope effect. The trichloromethyl spin adduct was observed when Au nanoparticles were mixed with CDCl(3) but not with CHCl(3). This unexpected behaviour suggests that C-H bond breaking is not the rate-determining step in Au-initiated hydrogen abstraction.

Generation of Oxygen-, Sulfur, Carbon-, Nitrogen- and Phosphorus- Centred Short-Lived Radicals Via One-Electron Oxidation with Stable Hydrazyl Radical

Using three readily-prepared free-radicals of DPPH type, with different oxidation potential, it is possible to generate, via one electron transfer or hydrogen-atom abstraction, short-lived radicals, characterised by the EPR spin- trapping technique. PBN, DMPO and DEPMPO were employed as spin-traps. The results show that DPPH and its congeners can be successfully employed for generation of short-lived oxygen-, sulfur-, carbon-, nitrogen-, and phosphorus-centered radicals.

Influence of Cyclodextrins on the Kinetics of Oxidation of Amino Acids and BSA by Hydrazyl Radicals

The kinetics of oxidation of amino acids (Arg, His, Lys, Phe, Thr and Tyr), a dipeptide (Gly-His), and BSA (bovine serum albumin) by two persistent water soluble free radicals of the hydrazyl type has been studied.The rate decreases in the order Arg>Lys>Tyr>Thr>His∼BSA∼Phe∼Gly-His with bothfree radicals. Addition to the reaction mixture of α- and β-cyclodextrin decreases the oxidation rate, probably due to amino acidencapsulation in the cyclodextrin cavity. β-Cyclodextrin protects more efficiently against oxidation than α-cyclodextrin.

A mechanistic glimpse into the oxidation of alcohols using TEMPO/NOx catalytic systems: towards a greener bifunctional catalyst

Starting from the commercially available silica supported TEMPO and gaseous nitrogen dioxide, a heterogeneous catalyst was obtained and characterized; this is able to convert under mild and clean conditions alcohols into aldehydes and ketones, using molecular oxygen as the final oxidant. A mechanistic pathway is proposed, in which silica supported TEMPO acts as a scavenger and a generator for nitrogen dioxide.

Synthesis and biological activities of some new isonicotinic acid 2-(2-hydroxy-8-substituted-tricyclo[7.3.1.02.7]tridec-13-ylidene)-hydrazides

A series of several new isoniazid derivatives, isonicotinic acid 2-(2-hydroxy-8-substituted-tricyclo[7.3.1.0(2.7)]tridec-13-ylidene)-hydrazides, were synthesized and fully characterized. These new isoniazid derivatives were studied regarding their antibacterial activity and cytotoxicity, as well as their influences on some metabolizing enzymes. The best anti-mycobacterial activity was observed in the case of compounds containing alkyl side chains in the 8 position of tricyclo[7.3.1.0(2.7)]tridec-13-ylidene group. On contrary, the antimicrobial activity of these new compounds against various non-tuberculosis strains showed the best activity to be with the phenyl side chain of compound 6. It proved also to be the most toxic, inducing apoptosis and blocking the cell cycle in G0/G1 phase. The cell cycle was blocked in G0/G1 phase also by compound 3, but this compound did not show any toxicity. All compounds induced the expression of NAT1 and NAT2 genes in HT-29 cell line, and the expression of CYP1A1 in HT-29 and HCT-8 cell lines. The expression level of CYP3A4 was increased by compounds 1, 6 and 7 in HCT-8 cells. These results indicated that the activation of other metabolizing pathways, apart from those of isoniazid, take place. It might also point out the possibility of an increased isoniazid acetylation ratio by co-administration with new compounds in slow acetylators.

Synthesis of novel TEMPO stable free (poly)radical derivatives and their host–guest interaction with cucurbit[6]uril

A number of ten stable free mono-, di- and tri-radicals of the TEMPO nitroxide type were synthesized and characterized via physico-chemical methods (elemental analysis, MS, UV-Vis, IR, ESR, and X-ray, where appropriate). The design of the compounds was chosen such that supramolecular interaction could be gained via hydrogen-bonding or π–π interactions; therefore the compounds should contain amino- or urea-moieties, (nitro)aromatic rings, or a crown ether residue. The formation of inclusion complexes between these (poly)radicals and cucurbit[6]uril was studied via Electron Spin Resonance (ESR) spectroscopy. The binding constants were evaluated from the analysis of the rotational correlation time dependence on the concentration of cucurbit[6]uril. These constants are an order of magnitude lower than the values reported before for complexes of TEMPO derivatives with β-cyclodextrin. The complexation behaviour of cucurbit[6]uril was revealed in the ESR spectra of the nitroxides in the presence and in the absence of the host molecules, recorded at low temperatures. The experiments revealed that the mobilities of the nitroxides investigated are higher in the absence of the host molecule, a different behaviour compared with complexes with cyclodextrins. This behavior can be understood by taking into account the role played by the presence of salts necessary to ensure the solubility of cucurbit[6]uril in water.

Thermal behavior of several stable hydrazyl free radicals and of their parent hydrazines

A thermal analysis study has been performed for the stable free radical 2,2-diphenyl-1-picrylhydrazyl and other ten free radical congeners, together with their corresponding parent hydrazines. Qualitative studies on the decomposition products showed that nitrogen dioxide plays a key role. A mechanistic decomposition pathway is also proposed.

Chemical and biological evaluation of some new antipyrine derivatives with particular properties.

Starting from 4-amino-antipyrine, six new compounds were synthesized and characterized. The new compounds contain moieties with particular properties, such are ionophore (benzo-15-crown-5), fluorescent (nitrobenzofurazan), stable free radical (nitroxide), or other types of biological active residues, like nitroderivatives, antipyrine or isoniazid residues. They were fully characterized by appropriate means ((1)H and (13)C NMR, IR, UV-Vis, fluorescence, EPR, elemental analysis) and some of their biological properties were evaluated. Hydrophobicity (R(M0), log P), total antioxidant capacity (TAC), and antimicrobial properties are also presented and discussed.