Fast transport of HCl across a hydrophobic layer over macroscopic distances by using a Pt(II) compound as the transporter: micro- and nanometric aggregates as effective transporters.

Bis-(diethyl-dithioxamidate)platinum(ii) is able to transport HCl from the donor aqueous phase to the receiving one over a mean distance of 12 cm in about 3 minutes across an organic membrane in the bulk, without stirring of the organic phase, i.e. at a rate far exceeding the unidirectional macroscopic diffusion coefficient. The way in which this surprising phenomenon can happen is linked to the behaviour of HCl which, because of dynamic interactions with [Pt(HEt2C2N2S2)2] (in which HCl is hosted as a tight ion pair [Pt(H2Et2C2N2S2)2][Cl]2) and chloroform molecules, gives rise to observable nanometric and micrometric domains, more dense than the surrounding bulk, whose formation and disaggregation processes accelerate the unidirectional macroscopic diffusion of HCl. Thermodynamic parameters obtained from the study of acid-base behaviour of the system Pt(ii) species/HCl/CHCl3 also agree with the proposed mechanism of HCl transport.

Designing expanded bipyridinium as redox and optical probes for DNA.

We report on the light-switch behaviour of two head-to-tail expanded bipyridinium species as a function of their interaction with calf thymus DNA and polynucleotides. In particular, both DNA and polynucleotides containing exclusively adenine or guanine moieties quench the luminescence of the fused expanded bipyridinium species. This behaviour has been rationalized demonstrating that a reductive photoinduced electron transfer process takes place involving both adenine or guanine moieties. The charge separated state so produced recombines in the tens of picoseconds. These results could help in designing new organic substrates for application in DNA probing technology and lab on chip-based sensing systems.

Carbohydrates and Charges on Oligo(phenylenethynylenes): Towards the Design of Cancer Bullets.

Two new tetralkylammonium-OPEs, bearing one or two positively charged groups directly linked to the aromatic residues and two ß-d-glucopyranose terminations, were synthesized. Their peculiar structural features, joining the biologically relevant sugar moieties, flat aromatic cores and positive charges, make these luminescent dyes soluble in aqueous media and able to strongly interact with DNA. As a result of UV/Vis spectral variations, DNA melting temperature measures, viscometric titrations and induced CD, we propose a partial insertion of the OPEs aromatic core into the helix, stabilized by glucose H-bonding with the groups accessible from the grooves. This interaction leads to the quenching of the OPE luminescence due to guanine reduction. The biocompatibility of the monocationic OPE with healthy and cancer cells, and the reduction of proliferation in HEp-2 cancer cells induced by the dicationic one, make this class of compounds promising for future biological applications.

Metal Complexes as Self-Indicating Titrants for Acid-Base Reactions in Chloroform.

The paper reports an unprecedented spectrophotometric determination of amines in chloroform, in which amines are not transformed into colored derivatives. This result has been achieved by exploiting the acid-base properties of the tight-ion-paired metal complexes [(HR2DTO)Pt(H2R2DTO)][Cl], which are able to donate a HCl molecule to an amine, giving rise to an ammonium salt and to the neutral complexes [(HR2DTO)2Pt]. The circumstance that [(HR2DTO)Pt(H2R2DTO)][Cl] and [(HR2DTO)2Pt] species show different absorptions in the visible region of the electromagnetic spectrum enables the aforementioned platinum complexes to behave as self-indicating titrants in the spectrophotometric determination of aliphatic amines, which are known to be UV-vis transparent. The new method has been tested by determining a series of fatty amines in the bulk and gave excellent results. The limits of applicability of this method (pKa > 4) were found by testing a series of benzodiazepines.

SO4= uptake and catalase role in preconditioning after H2O2-induced oxidative stress in human erythrocytes.

Preconditioning (PC) is an adaptive response to a mild and transient oxidative stress, shown for the first time in myocardial cells and not described in erythrocytes so far. The possible adaptation of human erythrocytes to hydrogen peroxide (H2O2)-induced oxidative stress has been here verified by monitoring one of band 3 protein functions, i.e., Cl-/HCO3- exchange, through rate constant for SO4= uptake measurement. With this aim, erythrocytes were exposed to a mild and transient oxidative stress (30 min to either 10 or 100 µM H2O2), followed by a stronger oxidant condition (300- or, alternatively, 600-µM H2O2 treatment). SO4= uptake was measured by a turbidimetric method, and the possible role of catalase (CAT, significantly contributing to the anti-oxidant system in erythrocytes) in PC response has been verified by measuring the rate of H2O2 degradation. The preventive exposure of erythrocytes to 10 µM H2O2, and then to 300 µM H2O2, significantly ameliorated the rate constant for SO4= uptake with respect to 300 µM H2O2 alone, showing thus an adaptive response to oxidative stress. Our results show that (i) SO4= uptake measurement is a suitable model to monitor the effects of a mild and transient oxidative stress in human erythrocytes, (ii) band 3 protein anion exchange capability is retained after 10 µM H2O2 treatment, (iii) PC response induced by the 10 µM H2O2 pretreatment is clearly detected, and (iv) PC response, elicited by low-concentrated H2O2, is mediated by CAT enzyme and does not involve band 3 protein tyrosine phosphorylation pathways. Erythrocyte adaptation to a short-term oxidative stress may serve as a basis for future studies about the impact of more prolonged oxidative events, often associated to aging, drug consumption, chronic alcoholism, hyperglycemia, or neurodegenerative diseases.

Crystal structure of (µ-N,N'-di-benzyl-dithio-oxamidato-κN,S:N',S')bis-[(η(3)-crotyl)palladium(II)].

In the centrosymmetric dinuclear title compound, [Pd2(C4H7)2(C16H14N2S2)], the metal atom is η(3)-coordinated by three C atoms of a crotyl ligand [Pd-C = 2.147 (4), 2.079 (5) and 2.098 (5) Å], the longest distance influenced by the steric inter-action with the benzyl substituents of the di-benzyl-dithio-oximidate (DTO) ligand. The Pd-N and Pd-S bonds to this ligand are 2.080 (3) and 2.3148 (9) Å, respectively, completing a square-planar coordination environment for Pd(II). The benzyl groups are oriented so as to maximize the inter-action between a benzylic H atom and an S atom, resulting in a dihedral angle of 77.1 (2)° between the benzene rings and the metal complex plane. In the crystal, no inter-complex hydrogen-bonding inter-actions are present.

Crystal structure of N,N'-bis-(4-methyl-phen-yl)di-thio-oxamide.

Two half mol-ecules of the title compound, C16H16N2S2, are present in the asymmetric unit and both mol-ecules are completed by crystallographic inversion centers at the mid-points of the central C-C bonds: the lengths of these bonds [1.538 (5) and 1.533 (5) Å] indicate negligible electronic delocalization. The trans-di-thio-oxamide fragment in each mol-ecule is characterized by a pair of intra-molecular N-H⋯S hydrogen bonds. In the crystal, mol-ecules are linked by weak C-H..π inter-actions, generating a three-dimensional network.

Fast transport of HCl across a hydrophobic layer over macroscopic distances by using a Pt(II) compound as the transporter.

[Pt(H-(ethyl)2-dithiooxamidate)2] plays the role of a HCl symporter, allowing fast HCl transport over macroscopic distances (cm scale) across a hydrophobic layer made of a chloroform solution, without any stirring. The process is limited by interfacial transfer, whereas HCl is transported within the hydrophobic phase at extremely high rates.

Luminescent Ir(III) complex exclusively made of polypyridine ligands capable of intercalating into calf-thymus DNA.

Efficient intercalation of a luminescent Ir(III) complex exclusively made of polypyridine ligands in natural and synthetic biopolymers is reported for the first time. The emission of the complex is largely enhanced in the presence of [poly(dA-dT)(2)] and strongly quenched in the presence of [poly(dG-dC)(2)]. By comparing the emission decays in DNA and in synthetic polynucleotides, it is proposed that the emission quenching of the title compound by guanine residues in DNA is no longer effective over a distance of four dA-dT base pairs.

Tight-contact ion pairs involving Pt(II) dithiooxamide complexes: the acid-base reactions between hydrohalogenated ion-paired complexes and pyridine.

The equilibrium constants relative to HCl exchange between Pt(II)-containing tight contact ion pairs (TCIP) and pyridine have been investigated in chloroform solution at 298 K. The general formulas of the metal species are: {[Pt(H(2)-R(2)-dithiooxamide)(2)](2+), 2Cl(-)} (a-type compounds; R = methyl (1a), ethyl (2a), n-propyl (3a), iso-propyl (4a), n-butyl (5a), cyclohexyl (6a), benzyl (7a), beta-phenyl-ethyl (8a), allyl (9a)) and {[(H-R(2)-dithiooxamidate)Pt(H(2)-R(2)-dithiooxamide)](+), Cl(-)} (b-type compounds; R has the same meanings as before, given rise to 1b-9b species; moreover, the mixed R compound 10b, containing R = benzyl on a DTO (dthiooxamidate/dithiooxamide) ligand and R = ethyl on the other DTO ligand, has also been investigated). Moreover, the parent species [Pt(H-R(2)-dithiooxamidate)(2)] (c-type compounds; 1c-10c) have also been prepared. Out of 29 compounds reported in the paper, 19 compounds are here reported for the first time, and their synthesis and characterization data are also given. Compounds of a-type exhibit two successive equilibrium constants, which are related to successive HCl transfer from the TCIP to pyridine. By comparing the equilibrium constants Kc of the various b-type species, we have been able to (i) obtain information on the relative stability of the TCIP and, by taking advantage of the two equilibrium constants Kc1 and Kc2 found for each a-type species, (ii) gain knowledge on the electronic interaction between the two basic sites of the Pt(II) bis-dithiooxamide complexes, mediated by the metal center. Linear relationships are found between the pKc of the compounds and the sigma-Taft value (Sigma sigma*) of the amine substituents of the DTO ligands. Interestingly, the slope of such linear correlations is much steeper for pKc2 than for pKc1, indicating that the electronic interaction between the basic sites increases with the electron donating ability of the R substituent. A parallel is proposed between the splitting of HCl transfer equilibrium constants in a-type TCIP and oxidation potential splitting in dinuclear, bridge-linked metal complexes.

Luminescence properties of Pt(II) complexes containing polypyridine ligands with extended aromatic moieties.

The luminescence properties of eleven Pt(II) complexes containing polypyridine ligands with extended aromatic moieties have been studied, both in acetonitrile fluid solution at 298 K and in butyronitrile rigid matrix at 77 K. For comparison purposes, also the phosphorescence properties of three free ligands at 77 K in butyronitrile have been investigated. The absorption spectra of all the compounds exhibit intense bands (epsilon in the range 10(4)-10(5) M(-1) cm(-1)) in the UV region, which are attributed to spin-allowed ligand-centered (LC) transitions, and moderately intense bands (epsilon in the range 10(3)-10(4) M(-1) cm(-1)) in the visible region, which receive contribution from both spin-allowed LC transitions and spin-allowed metal-to-ligand charge-transfer (MLCT) transitions. At low energy, less intense spin-forbidden MLCT bands are also present. At 77 K in rigid matrix, all the studied compounds exhibit structured and long-lived (lifetimes from 840 micros on the millisecond timescale) luminescence, which is attributed to triplet LC states in all cases. At room temperature in fluid solution the luminescence lifetime of all the compounds is largely shortened (nanosecond timescale), and most of the emission spectra are unstructured and red-shifted. For species exhibiting structured emission spectra even at room temperature, low luminescence quantum yields are always obtained (Phi < 10(4)), and their emission is assigned to triplet LC states, which mainly deactivate to the ground state by thermal-activated surface crossing to a closely-lying metal-centered (MC) triplet state. Compounds exhibiting unstructured emission show relatively high emission quantum yields (about 0.1) and their emission is assigned to a mixed LC/MLCT state.

DNA and RNA noncovalent interaction of platinum(II) polypyridine complexes.

A comparative investigation of the noncovalent interaction of the platinum(II) polypyridine complexes [Pt(dipy)(n-Rpy)2]2+ and [Pt(4,4'-Me2dipy)(2-Rpy)2]2+ (dipy = 2,2'-dipyridine; Me = CH3; n = 2-4; R = H or CH3) with double-helical DNA (calf thymus) and RNA [poly(A).poly(U)] has been conducted. With the exception of [Pt(dipy)(2-Mepy)2]2+, all of the complexes interact strongly, by intercalation, with both nucleic acids giving rise to large changes in the electronic spectra and induced circular dichroism signals; in addition, viscosity experiments on rodlike DNA and RNA show that both biopolymers elongate upon interaction with the complexes. The binding constant values, KB, determined at 25 degrees C, indicate that, at 0.101 M ionic strength, the affinity for poly(A).poly(U) is strongly dependent on the complexes nature, while for DNA it is leveled off. [Pt(dipy)(2-Mepy)2]2+ binds to DNA but does not interact appreciably with poly(A).poly(U).

Luminescence of a Pt(II) complex in the presence of DNA. Dependence of luminescence changes on the interaction binding mode.

Luminescence intensity changes of a Pt(II) complex which is known to bind externally to DNA at low [DNA]/[complex] ratio and to intercalate at high [DNA]/[complex] ratio are studied in the presence of calf thymus DNA. External binding is demonstrated to induce luminescence enhancement whereas intercalation leads to luminescence quenching. The reasons for this behaviour are discussed.

Role of the coulombic interaction in ligand-induced biopolymer aggregation.

The interaction mechanisms responsible for the binding between metal complexes and biopolymers in aqueous solution, as well as the consequent aggregation process of biopolymers themselves, involve many factors, from geometrical aspects and hydrophobic contributions, as examples, to the electrostatic potential. In this paper aqueous solutions of a polynucleotide, polyadenylic acid (PolyA), which mimics the helix arrangement of RNA or single-stranded DNA but has a simpler structure, are used as a model system. The role of the electrostatic interactions in the binding process between some platinum(II) complexes and PolyA and in the aggregation among PolyA molecules is investigated, by means of elastic and quasielastic light scattering and electrophoretic mobility. The results show that the presence of large, planar aromatic moiety in the dicationic platinum(II) complexes is essential for the binding with PolyA and suggest that the consequent lowering of the local electrostatic barrier between PolyA molecules can be involved in triggering the aggregation process.

DNA interaction of platinum(II) complexes with 1,10-phenanthroline and extended phenanthrolines.

The interaction with DNA of the platinum(II) square planar complexes [Pt(N-N)(py)(2)](2+) (N-N = 1,10-phenanthroline (phen), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq), dipyrido[3,2-a:2',3'-c]phenazine (dppz), benzodipyrido[b:3,2-h:2'3'-f]phenazine (bdppz)) has been investigated by means of absorption, circular and linear dichroism spectroscopy, DNA melting, and viscosity. In the presence of excess [DNA] all the complexes intercalate to the double helix. For those with the most extended phenanthrolines the binding mode depends on the [DNA]/[complex] ratio (q); at low q values the substances bind externally to DNA probably self-aggregating along the double helix. When the DNA concentration is large enough, the aggregate breaks up and the complex intercalates within the nucleobases. The complexes self-aggregate, without added DNA, in the presence of a large salt concentration.

The intercalation to DNA of bipyridyl complexes of platinum(II) with thioureas.

The non-covalent interaction of the complexes [Pt(bpy)(R,R'NCSNR'',R''')(2)]Cl(2) (bpy=2,2'-bipyridine; R=R'=R''=R'''=H; R=Me, R'=R''=R'''=H; R=n-Bu, R'=R''=R'''=H; R=p-tolyl, R'=R''=R'''=H; R=Et, R'=H, R''=Et, R'''=H) with calf thymus DNA has been studied at pH 7 and 25 degrees C. The processes give rise to: (i) reversible bathochromic shifts and strong hypochromicity of the absorption bands of the complexes, (ii) induced circular dichroism and (iii) an increase both in the melting temperature and viscosity of the DNA comparable to that observed for other well known metallointercalators. The binding constants, K(B), have been determined spectrophotometrically using the McGhee von Hippel equation. Plot of logK(B) vs -log[Na(+)] for the complex with unsubstituted thiourea gives a straight line with a slope value close to that expected for a dicationic intercalator. The binding affinity of the various complexes for DNA is independent of the thiourea nature; this suggests that the intercalation occurs through stacking of the bpy moiety while the ancillary ligands lie outside the nucleobases far away from the sugar phosphate backbone. The data show also that the electronic effects of the ligand substituents are not transmitted to the intercalating unit.

Ambivalent intercalators for DNA: L-shaped platinum(II) complexes.

Novel platinum(II) square planar coordination complexes, in which two heteroaromatic ligands are held by the metal in an unusual L-shaped geometry orthogonal to each other, have been synthesized, and their interaction with DNA was investigated with absorption and linear dichroism spectroscopy. As a rule, the ligand that is coplanar with the coordination square of Pt is found to be oriented perpendicular relative to the DNA helix axis when bound, suggestive of its intercalation between the base pairs of DNA. However, when this coplanar ligand is replaced by two pyridines, the opposite ligand, orthogonal to the coordination square, is instead preferentially intercalated. This behavior shows that these new complexes do indeed show some properties of true ambintercalators, i.e., compounds that can bind by intercalation of either of two distinct aromatic moieties.

Differential scanning calorimetry differences in micronized and unmicronized nimesulide uptake processes in biomembrane models.

Nimesulide release from micronized and unmicronized drug particles was tested at pH 7.4 by measuring the transfer to dimyristoylphosphatidylcholine liposomes (multilamellar and unilamellar vesicles), chosen as a biomembrane model. The perturbing effect of increasing molar fractions of pure nimesulide on the thermotropic behaviour of dimyristoylphosphatidylcholine liposomes was investigated by differential scanning calorimetry. In order to study the drug dissolution process by its uptake into void liposomes, measurements were carried out on suspensions of blank liposomes added to weighed amounts of free powdered nimesulide (micronized and unmicronized). The amount of drug transferred was quantified by comparing the effect caused by the dissolved and released drug to that caused by the free drug that had been previously molecularly dissolved in the liposomes. The calorimetric results show that the dissolution rate depends on the nimesulide form (micronized or unmicronized), and that the transfer to the void liposomes is quicker when the drug is in a micronized form. The uptake was faster when unilamellar vesicles were used instead of multilamellar vesicles because of the greater lipid surface. The calorimetric technique could represent an alternative 'in vitro' method that can be applied to the study of the dissolution kinetics directly at the site of drug uptake, mimicking a biological system.

Interface properties of simplified tear-like fluids in relation to lipid and aqueous layers composition.

The Langmuir trough approach to the study of the physical properties of an in vitro system representing the natural tear lipid-aqueous interface gives useful information on the effect produced by changes of composition of both phases. We found that variations of the composition of the lipid mixture affect more strongly the characteristics of the film rather than changes in the aqueous phase composition. Therefore, future investigations should consider the possibility of searching for and optimising additions of lipid mixtures to the natural tear film. These novel mixtures should stabilise the lipid layer, and thus treat the evaporative Dry Eye Syndrome. More critical and worthy of further investigation is the effect of surface-active water-soluble components that can reduce and ultimately destroy the lipid film integrity and effectiveness. The beneficial effect of water-soluble components, either naturally occurring or artificially added, may be more precisely compared with possible side effects on the stability of the lipid tear layer. In any case, these side effects may be largely compensated by the presence of stability enhanced lipid composition. The present work may be considered as an introductory investigation that takes the physical-chemical approach into the realm of debated data about the tear film structure and properties. Refining the model we have adopted in the present work is certainly necessary. For instance, introducing into the model tear composition other components such as ceramides and cerebrosides will provide insight to their contribution to the packing structure. We may also couple different techniques such as measuring elastic and rheological properties of the films that may be relevant to its physiological behaviour.

Stacking Surface Effect in the DNA Intercalation of Some Polypyridine Platinum(II) Complexes.

The interaction of the platinum(II) polypyridine complexes [Pt(bipy)(2)](2+), [Pt(quaterpy)](2+), [Pt(terpy)(n-Rpy)](2+) and [Pt(bipy)(py)(2)](2+) (bipy = 2,2'-bipyridine; terpy = 2,2':6',2' '-terpyridine; quaterpy = 2,2':6',2' ':6' ',2' "-quaterpyridine; n-R = H, 2-CH(3), or 4-CH(3) ) with double-helix DNA has been studied with a variety of experimental techniques. Induced circular dichroism, strong hypochromism and red shifts of the absorption maxima of the complexes, increase in melting temperature and viscosity of DNA, and inhibition of the reaction of the complexes with thiourea in the presence of DNA, characterize the processes. Intercalation, implying the whole molecule or part of it, is the suggested binding mode. The binding constants, K(B), determined spectrophotometrically at 25 degrees C, pH 7, and I = 0.15 M, using the McGhee-von Hippel approach, increase in the order [Pt(bipy)(py)(2)](2+)< [Pt(terpy)(py)](2+)< [Pt(quaterpy)](2+), on increasing aromatic planar surface extension. The steric interference with double helix of the methyl group in [Pt(terpy)(2-Mepy)](2+) destabilizes the interaction by reducing the stacking surface.