Marta Airoldi

Interaction of Doxorubicin with Polynucleotides. A Spectroscopic Study

The interaction of doxorubicin (DX) with model polynucleotides poly(dG-dC)·poly(dG-dC) (polyGC), poly(dA-dT)·poly(dA-dT) (polyAT), and calf thymus DNA has been studied by several spectroscopic techniques in phosphate buffer aqueous solutions. UV-vis, circular dichroism, and fluorescence spectroscopic data confirm that intercalation is the prevailing mode of interaction, and also reveal that the interaction with AT-rich regions leads to the transfer of excitation energy to DX not previously documented in the literature. Moreover, the DX affinity for AT sites has been found to be on the same order of magnitude as that reported for GC sites.

A spectroscopic study of poly(dA–dT)·poly(dA–dT) in microemulsions

The behaviour of high molecular weight [poly(dA–dT)·poly(dA–dT)] (polyAT) [(0.9–1.9)×106 Da] in the quaternary water-in-oil microemulsion CTAB–n-pentanol–n-hexane–water has been studied as a function of temperature and NaCl concentration by means of UV and circular dichroism (CD) spectroscopy. Solubilization in the microemulsion stabilises the polymer double helix and no helix-to-coil thermal transition has been observed. At increasing NaCl concentration, the CD spectrum of polyAT exhibits dramatic changes and for salt concentrations 7.5×10−1 M the spectral pattern suggests the formation of aggregates of the ψ(−) type. Condensation is induced by the peculiar characteristics of the aqueous core of the microemulsion. The condensates seem to destabilise the microemulsive system and, with time, separate from it.

Selective homogeneous hydrogenation of cycloocta-1,5, and cycloocta-1,3-diene to cyclooctene in the presence of (η4-cycloocta-1,5-diene)(η6-cycloocta-1,3,5-triene)ruthenium(0)

Cyclooctadiene isomers (1,3- and 1,5-COD) are selectively, homogenously hydrogenated to cyclooctene (C8H14) in tetrahydrofuran (THF) solution, under mild conditions of temperature (20 °C) and hydrogen pressure (1 atm), in the presence of catalytic amounts of (cycloocta-1,5-diene)(cycloocta-1,3,5,-triene)ruthenium(0), [Ru(η4-COD)(η6-C8H10)] (1). The rate of hydrogenation is higher when 1,3-COD is the substrate. Evidence for the isomerization 1,5-COD → 1,3-COD is reported. Similar studies carried out in several alcoholic solutions, although showing a decreased selectivity in the hydrogenation, confirm the isomerization 1,5-COD → 1,3-COD, and allow a discrimination between the isomerization and the hydrogenation. The nature of the alcohol strongly influences the isomerization process, to a lesser extent the hydrogenation process. Isomerization appears to be a necessary step for the catalytic hydrogenation of 1,5-COD, in the presence of 1. Indeed, a non-isomerizable diene (bicyclo[2,2,1] hepta-2,5-diene, norbornadiene (NBD)) is not hydrogenated in the above experimental conditions. These results elucidate the mechanism of previously reported catalytic hydrogenation of conjugated trienes in the presence of 1.

Reactivity of cycloheptatrienyl tricarbonyl ferrate(−1: synthesis and sterepchemistry of ditropylium metal carbonyl complexes

Abstract Exo -deprotonation of [Fe(CO) 3 (η 4 -C 7 H 8 )] (1) (C 7 H 8 = cyclohepta-1,35-triene) gives the anionic compound [Fe(CO) 3 (]gh 3 -C 7 H 7 )] − (2). The reactivity of 2 towards several electrophiles has been studied. Mixed ditropylium complexes of the type [FeM(CO) 6 (C 14 H 14 )] (3) are obtained on treating 2 with [M(CO) 3 (η 7 -C 7 H 7 )] + (M = Cr, Mo, W). A minor product of these reactions is a ditropylium hexacarbonyldiiron derivative which becomes the major product in the reaction of 2 with several alkl and allyl halides. The exo-stereochemisty of the ditropylium complexes is discussed on the basis of spectroscopic data and reactivity.

Selective, homogeneous hydrogenation of cycloheptatriene to cycloheptene catalyzed by (η4-cycloocta-1,5-diene)(η6-cyclohepta-1,3,5-triene)ruthenium(0)

Abstract In the presence of small amounts of [Ru(η 4 -COD)](η 6 -C 8 H 10 )] (1), cycloheptatriene is hydrogenated to cycloheptene, under one atmosphere of hydrogen at room temperature in homogeneous phase. The formation of a small amount of cyclooctene and the existence of an induction period, which do not occur when [Ru(η 4 -COD)(η 6 -C 7 H 8 )] (2) is used as the catalyst, suggest that 2 is the real catalyst. The selectivity of this hydrogenation is 100% in n-hexane as solvent, 99.5% in THF, and low in ethanol. Conversion is quantitative in THF and ethanol, but not more than 65% in n-hexane. In the presence of 1 or 2, cycloheptene is rapidly hydrogenated to cycloheptane in THF and ethanol, but not in n-hexane. A mechanism for these catalytic hydrogenations is proposed, and discussed on the basis of the dominant role of the solvents. Increase of temperature and/or pressure of hydrogen increases the rate of hydrogenation.

Complexes of organometallic compounds : XLIII. Synthesis and infrared spectra of fluoro-, chloro- and bromo-phenylantimonates(V)

Abstract The synthesis of halogenophenylantimonates(V) M I PhSbX 5 (M I = Me 4 N, Ph 4 As; X = F, Cl, Br) is described, and their IR spectra (1100-100 cm −1 ) interpreted.

Different factors affecting polyAT conformation in microemulsions: effects of variable P0 and KCl concentration

The behaviour of the synthetic polynucleotide polyAT entrapped in the inner core of a quaternary cationic microemulsion has been investigated by means of CD and UV spectroscopies in the presence of KCl (variable temperature at constant W0 = [H2O]/[CTAB] and P0 = [cosurfactant]/[CTAB]) and NaCl (variable P0 at constant W0 and temperature). While the presence of KCl gives rise to effects which are not substantially different from those already reported for NaCl (absence of thermal melting and formation of compact ψ(−) structures), the peculiar results obtained as a consequence of the progressive addition of cosurfactant (denaturation of the polymer at low [NaCl] and W0; transition from B- to A-form at intermediate [NaCl], formation of ψ(−) aggregates at high [NaCl]) can be attributed to the characteristics of the microemulsive system (restricted volume), of the micellar water (low dielectric constant and reduced activity) and of the interface (progressively higher cosurfactant concentration).

Acid Titrations of poly(dG-dC).poly(dG-dC) in Aqueous Solution and in a w/o Microemulsion

Abstract The model polynucleotide poly(dG-dC).poly(dG-dC) (polyGC) was titrated with a strong acid (HCl) in aqueous unbuffered solutions and in the quaternary w/o microemulsion CTAB/n-pentanol/n-hexane/water. The titrations, performed at several concentrations of NaCl in the range 0.005 to 0.600 M, were followed by recording the modifications of the electronic absorption and of the CD spectra (210≤ λ ≤350 nm) upon addition of the acid. In solution, the polynucleotide undergoes two acid-induced transitions, neither of which corresponds to denaturation of the duplex to single coil. The first transition leads to the Hoogsteen type synG.C+ duplex, while the second leads to the C+.C duplex. The initial B- form of polyGC was recovered by back-titration with NaOH. The apparent pKa values were obtained for both steps of the titration, at all salt concentrations. A reasonably linear dependence of pKa(1) and pKa(2) from p[NaCl] was obtained, with both pKa values decreasing with increasing ionic strength. In microemulsion, at salt concentrations ≤ 0.300 M, an acid-induced transition was observed, matching the first conformational transition recorded also in solution. However, further addition of acid led to denaturation of the protonated duplex. Renaturation of polyGC was obtained by back-titration with NaOH. At salt concentrations > 0.300 M, polyGC is present as a mixture of B-form and ψ(-) aggregates, that slowly separate from the microemulsion. The acid titration induces at first a conformational transition similar to the one observed at low salt or in solution, then denaturation occurs, which is however preceded by the appearance of a transient conformation, that has been tentatively classified as a left-handed Z double helix.

Cycloheptatrinyl bridged heterobimetallic complexes: synthesis, fluxional behaviour and X-ray crystal structure of syn-[(μ-η3;η2-C7H7)Fe(CO)3Pt(η2, σ1-C8H12C5H5)]☆

Abstract The reaction of [(η3C7H7)Fe(CO)3]− with [(η4-C8H12)(η5-C5H5)Pt]+ leads to the formation of syn-[(μ-η3;η2-C7H7)-Fe(CO)3Pt)η2,σ1-C8H12-C5H5)] (1), a bridged cycloheptatrienyl complex with an FePt bond. In solution two structural isomers of 1 are present ini roughly the same concentration, whereas in the solid only one isomer is detected. Both isomers are fluxional and undergo ring whizzing of the C7H7 ring. The slow-exchange limiting NMR spectrum of the cycloheptatrienyl unit cannot be reached even at low temperature (∼173 K). The C7H7 ring has an uncoordinated double bond and the cyclopentadienyl unit is linked to the C8H12 ring through an sp2 carbon; the resulting cyclooctenyl unit is coordinated η2,σ1 to platinum. The C5H5 transfer, mediated by platinum, can be of interest in the synthesis of the skeleton of natural occurring products. Crystal data for syn-[(μ-η3;ν2-C7h7)Fe(CO)3Pt(ν2,σ1-C8H12-C5H5)]: monoclinic, space grou[ C2/C (No. 15), a = 45.197(6), b=13.306(1), c=7.509(1) A , β=92.96(1)°, V=4509.8(9) A 3 , Z=8, R=0.033, R w =0.080 .

Interaction of the Alternating Double Stranded Copolymer poly(dA-dT)·poly(dA-dT) with NiCl2 and CdCl2: Solution Behavior

Abstract The thermal denaturation of the synthetic high molecular weight double stranded polynucleotide poly(dA-dT)·poly(dA-dT) has been studied in aqueous buffered solution (Tris 1.0mM; pH 7.8±0.2) in the presence of increasing concentrations of either Ni2+ (borderline cation) or Cd2+ (soft cation) at four different constant ionic strength values (NaCl), making use of UV and circular dichroism (CD) spectroscopies. The experimental results show that the B-type double helix of the polymer is stabilized against thermal denaturation in the presence of both cations at low concentrations, relative to the systems where only NaC1 is present, in the same conditions of ionic strength and pH. The effect is more pronounced for Ni2+ than for Cd2+. At higher concentrations, both cations start to destabilize the double helix, with Cd cations inducing larger variations of Tm. In many cases, when denaturation starts, interstrand cross- linking occurs with formation of aggregates that precipitate.