Determination of the optimal pH for doxorubicin encapsulation in polymeric micelles.

Hypothesis: The anticancer drug doxorubicin hydrochloride (DX) shows a high solubility in aqueous media thanks to the positive charge in the ammonium group. This feature, however, affects the drug encapsulation in the hydrophobic domains of polymeric micelles (PMs) used for the targeted delivery of the drug. At basic pH, DX deprotonates but also acquires a negative charge in the phenolic groups of the anthracycline structure.

Unveiling the Excited State Dynamics of Indole in Solution.

In this paper, we reconstruct in detail the dynamics of the emitting electronic excited state of aqueous indole, investigating its relaxation mechanism and kinetics to be related to the time-dependent fluorescence signal. Taking advantage of the results shown in a very recent paper, we were able to model the relaxation process in solution in terms of the transitions between two gas-phase singlet electronic states (L and L), subsequently irreversibly relaxing to the gas-phase singlet dark state (πσ*). A comparison of the results with the available experimental data shows that the relaxation mechanism we obtain by our theoretical-computational model is reliable, reproducing rather accurately all the experimental observables.

Complexation and organization of doxorubicin on polystyrene sulfonate chains: impacts on doxorubicin dimerization and quenching.

Anthracycline doxorubicin hydrochloride (DX) is a positively charged fluorescent drug, which in water self-associates into non-fluorescent antiparallel dimers upon increasing concentration and/or ionic strength. The positive charge of DX allows for complexation with negatively charged polymers and drug carriers. The fluorescence of DX following complexation with polyanion polystyrene sulfonate (PSS) is studied here.

On the Role of Water in the Formation of a Deep Eutectic Solvent Based on NiCl·6HO and Urea.

The metal-based deep eutectic solvent (MDES) formed by NiCl·6HO and urea in 1:3.5 molar ratio has been prepared for the first time and characterized from a structural point of view. Particular accent has been put on the role of water in the MDES formation, since the eutectic could not be obtained with the anhydrous form of the metal salt.

Absorption behavior of doxorubicin hydrochloride in visible region in different environments: a combined experimental and computational study.

The experimental absorption measurements in the interval 350-600 nm (Vis), molecular dynamics simulations, quantum-mechanics calculations and an advanced molecular treatment of simulation data are here combined to provide a complete picture of the absorption behavior in the visible portion of the electromagnetic spectrum of the doxorubicin hydrochloride (DX) molecule in different environments. By such an approach, we have shown that it is possible to characterize the effect of the environment on the DX absorption behavior - including the vibronic contributions - as well as to interpret such differences in terms of molecular electronic excited states, which are found to be strongly influenced by the environment.

Polarity studies of single polyelectrolyte layers in polyelectrolyte multilayers probed by steady state and life time doxorubicin fluorescence.

Hypothesis: Polarity in polyelectrolyte multilayers (PEMs) may vary from the inner to the top layers of the film as the charge compensation of the layers is more effective inside the PEMs than in outer layers. Doxorubicin hydrochloride (DX) is used here to sense polarity at the single polyelectrolyte level inside PEMS.

Experimental: DX is complexed electrostatically to a polyanion, either polystyrene sulfonate (PSS) or polyacrylic acid (PAA) and assembled at selected positions in a multilayer of the polyanion and polyallylamine hydrochloride (PAH) as polycation.

Poloxamer/sodium cholate co-formulation for micellar encapsulation of doxorubicin with high efficiency for intracellular delivery: An in-vitro bioavailability study.

Hypothesis: Doxorubicin hydrochloride (DX) is widely used as a chemotherapeutic agent, though its severe side-effects limit its clinical use. A way to overcome these limitations is to increase DX latency through encapsulation in suitable carriers. However, DX has a high solubility in water, hindering encapsulation.

Deoxycholic acid and l-Phenylalanine enrich their hydrogel properties when combined in a zwitterionic derivative.

Hypothesis: Sodium Deoxycholate (NaDC) and Phenylalanine (Phe) are important biological hydrogelators. NaDC hydrogels form by lowering the pH or by increasing the ionic strength. Phe gels form from saturated solution by thermal induction and slow kinetics.

A fluorescence study of the loading and time stability of doxorubicin in sodium cholate/PEO-PPO-PEO triblock copolymer mixed micelles.

Hypothesis: Doxorubicin hydrochloride (DX) is one of the most powerful anticancer agents though its clinical use is impaired by severe undesired side effects. DX encapsulation in nanocarrier systems has been introduced as a mean to reduce its toxicity. Micelles of the nonionic triblock copolymers of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO) (PEO-PPO-PEO), are very promising carrier systems.

A Stereochemically Driven Supramolecular Polymerisation.

Anthracyclines self-assemble in water into dimers. In the presence of sufficiently high salt (NaCl) concentrations, solutions of the antibiotic doxorubicin, but not those of the closely related molecules daunomycin and epirubicin, turn into gels barely compatible with the presence of small oligomers. The use of spectroscopic, scattering, imaging and computational techniques, allowed light to be shed on the self-assembly process that triggered doxorubicin gelification.

Effect of ionic strength on intra-protein electron transfer reactions: The case study of charge recombination within the bacterial reaction center.

It is a common believe that intra-protein electron transfer (ET) involving reactants and products that are overall electroneutral are not influenced by the ions of the surrounding solution. The results presented here show an electrostatic coupling between the ionic atmosphere surrounding a membrane protein (the reaction center (RC) from the photosynthetic bacterium Rhodobacter sphaeroides) and two very different intra-protein ET processes taking place within it. Specifically we have studied the effect of salt concentration on: i) the kinetics of the charge recombination between the reduced primary quinone acceptor QA(-) and the primary photoxidized donor P(+); ii) the thermodynamic equilibrium (QA(-)↔QB(-)) for the ET between QA(-) and the secondary quinone acceptor QB.

On the self-assembly of a tryptophan labeled deoxycholic acid.

Self-assembly of peptides and bile acids has been widely investigated because of their biological role and their potential as a tool for the preparation of nanostructured biomaterials. We herein report both the synthesis and the self-association behavior of a compound that combines the aggregation properties of bile acid- and amino acid-based molecules. The derivative has been prepared by introducing a L-tryptophan residue into the C-3 position of the deoxycholic acid skeleton and resulted in an amphoteric fluorescent labeled bile acid that shows a pH-dependent self-assembly.

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.

Tetrakis(thiadiazole)porphyrazines. 8. Singlet oxygen production, fluorescence response and liposomal incorporation of tetrakis(thiadiazole)porphyrazine macrocycles [TTDPzM] (M = Mg(II)(H2O), Zn(II), Al(III)Cl, Ga(III)Cl, Cd(II), Cu(II), 2H(I)).

The photoactivity for the generation of singlet oxygen, (1)O(2), the key cytotoxic agent in the anticancer treatment known as photodynamic therapy (PDT), and the fluorescence response of the highly electron-deficient tetrakis(thiadiazole)porphyrazines of formula [TTDPzM] (M = Mg(II)(H(2)O), Zn(II), Al(III)Cl, Ga(III)Cl, Cd(II), Cu(II), 2H(I)) were examined (c ≅ 10(-5) M) in dimethylformamide (DMF) and/or in DMF preacidified with HCl (DMF/HCl; [HCl] = 1-4 × 10(-4) M). The singlet oxygen quantum yield (Φ(Δ)) of all the compounds was determined by using a widely employed procedure based on the selective oxidation of the 1,3-diphenylisobenzofuran (DPBF), modified in part as reported. The list of the Φ(Δ) values indicates excellent photosensitizing properties for the series of compounds carrying "closed shell" metal ions, with values measured in DMF/HCl respectful of the "heavy atom effect" for the first four lighter centers, increasing in the order Mg(II) < Al(III) < Zn(II) < Ga(III).

Effect of the alkaline cations on the stability of the model polynucleotide poly(dG-dC)·poly(dG-dC).

When the model polynucleotide poly(dG-dC)∙poly(dG-dC) [polyGC] is titrated with a strong acid (HCl) in unbuffered aqueous solutions containing the chlorides of the alkali metals in the concentration range 0.010 M-0.600 M, two transitions in the absorbance vs.

Effects of the measuring light on the photochemistry of the bacterial photosynthetic reaction center from Rhodobacter sphaeroides.

The bacterial reaction center (RC) has become a reference model in the study of the diverse interactions of quinones with electron transfer complexes. In these studies, the RC functionality was probed through flash-induced absorption changes where the state of the primary donor is probed by means of a continuous measuring beam and the electron transfer is triggered by a short intense light pulse. The single-beam set-up implies the use as reference of the transmittance measured before the light pulse.

The CdCl2 effects on synthetic DNAs encaged in the nanodomains of a cationic water-in-oil microemulsion.

The present work is dedicated to the study of the interactions of CdCl(2) with the synthetic polynucleotides polyAT and polyGC confined in the nanoscopic aqueous compartment of the water-in-oil microemulsion CTAB/pentanol/hexane/water, with the goal to mimic in vitro the situation met by the nucleic acids in vivo. In biological structures, in fact, very long strings of nucleic acids are segregated into very small compartments having a radius exceedingly smaller than the length of the encapsulated macromolecule. For comparison, the behaviour of polyGC was also studied in aqueous solutions of matched composition.

Tetra-2,3-pyrazinoporphyrazines with externally appended pyridine rings. 6. Chemical and redox properties and highly effective photosensitizing activity for singlet oxygen production of penta- and monopalladated complexes in dimethylformamide solution.

Tetrakis-2,3-[5,6-di-(2-pyridyl)pyrazino]porphyrazinatopalladium(II) [Py 8TPyzPzPd] ( 1) and the corresponding pentapalladated species [(PdCl 2) 4Py 8TPyzPzPd] ( 2), dissolved (c approximately 10 (-5)-10 (-6) M) in preacidified dimethylformamide ([HCl] approximately 10 (-4) M), behave as potent photosensitizing agents for the production of singlet oxygen, (1)O 2, with Phi Delta values of 0.89 +/- 0.04 and 0.

Water Activity Regulates the Q(A)(-) to Q(B) electron transfer in photosynthetic reaction centers from Rhodobacter sphaeroides.

We report on the effects of water activity and surrounding viscosity on electron transfer reactions taking place within a membrane protein: the reaction center (RC) from the photosynthetic bacterium Rhodobacter sphaeroides. We measured the kinetics of charge recombination between the primary photoxidized donor (P(+)) and the reduced quinone acceptors. Water activity (aW) and viscosity (eta) have been tuned by changing the concentration of cosolutes (trehalose, sucrose, glucose, and glycerol) and the temperature.

Circular dichroism of polynucleotides: Interactions of NiCl2 with poly(dA-dT).poly(dA-dT) and poly(dG-dC).poly(dG-dC) in a water-in-oil microemulsion.

The thermal behavior of the synthetic, high molecular weight, double stranded polynucleotides poly(dA-dT).poly(dA-dT) [polyAT] and poly(dG-dC).poly(dG-dC) [polyGC] solubilized in the aqueous core of the quaternary water-in-oil cationic microemulsion CTAB|n-pentanol|n-hexane|water in the presence of increasing amounts of NiCl(2) at several constant ionic strength values (NaCl) has been studied by means of circular dichroism and electronic absorption spectroscopies.

Small angle scattering and zeta potential of liposomes loaded with octa(carboranyl)porphyrazine.

In this work, the physicochemical characterization of liposomes loaded with a newly synthesized carboranyl porphyrazine (H2HECASPz) is described. This molecule represents a potential drug for different anticancer therapies, such as boron neutron capture therapy and for photodynamic therapy or photothermal therapy. Different loading methods and different lipid mixtures were tested.

Interaction of the alternating double stranded copolymer poly(dA-dT) x poly(dA-dT) with NiCl(2) and CdCl(2): solution behavior.

The thermal denaturation of the synthetic high molecular weight double stranded polynucleotide poly(dA-dT) x poly(dA-dT) has been studied in aqueous buffered solution (Tris 1.0 mM; pH 7.8+/-0.

Alkaline titrations of poly(dG-dC).poly(dG-dC): microemulsion versus solution behavior.

PolyGC was titrated with a strong base in the presence of increasing concentrations of NaCl (from 0.00 to 0.60M) either in water solution or with the polynucleotide solubilized in the aqueous core of reverse micelles, i.

Functionality of photosynthetic reaction centers in polyelectrolyte multilayers: toward an herbicide biosensor.

The bacterial reaction center (RC), a membrane photosynthetic protein, has been adsorbed onto a glass surface by alternating deposition with the cationic polymer poly(dimethyldiallylammonium chloride) (PDDA) obtaining as an end result an ordinate polyelectrolyte multilayer (PEM) where the protein retains its integrity and photoactivity over a period of several months. Such a system has been characterized from the functional point of view by checking the protein photoactivity at different hydration conditions, from extensive drought to full hydration. The kinetic analysis of charge recombination indicates that incorporation of RCs into dehydrated PEM hinders the conformational dynamics gating QA- to QB electron-transfer leaving unchanged the protein relaxation that stabilizes the primary charge separated state P+QA-.