Elsa Galbis

Solving the hydration structure of the heaviest actinide aqua ion known: the californium(III) case.

The solution chemistry of actinide ions has been a fundamental question since the beginning of the nuclear technologies, given that the solvent stabilizes the high oxidation states of actinides. The development of procedures to avoid the migration of actinides from the already accumulated nuclear waste into natural water systems is a field of great activity. One of the primary properties of actinide ions in solution is their solvation, as it is intimately joined to complexation, precipitation, and resolution processes. The rareness and hazardousness of the heavier actinide elements, which steeply increase with the atomic number, has prevented a complete examination of the trends along the series, beyond the middle of the series. The curium cation Cm has often been considered as the heaviest actinide species characterized, and it has attracted much attention from both experimental and theoretical views in recent years. Systematic studies of the aqueous trivalent lanthanides have revealed a contraction of the metal–oxygen distance and a decrease of the total first coordination number along the series. Recent investigations using extended X-ray absorption fine structure (EXAFS) techniques have examined if this contraction takes place in a monotone or an irregular way along the series. The data available for the actinide series up to Cm indicates a similar contraction, 5, 7] although a conclusive answer cannot be given owing to the uncertainty of the structural data, particularly concerning the hydration number, and the scarce information on the second half of the series. Beyond the middle of the series, there is only one study reported for berkelium (Bk) and a preliminary EXAFS study for californium(III) carried out by one of us. Owing to the position of Cf in the actinide series, an accurate enough determination of the coordination number and Cf O distance could certainly shed light on the question of the actinide contraction. This objective gives the study a more fundamental than applied character, owing to the extreme rareness of this element. The most similar available crystallographic data of Cf with Cf O bonds is that of single crystals of Cf(IO3)3, which present a significantly distorted tricapped trigonal prism with a wide range of Cf O distances (2.353–2.921 ). This limited information does not meet the required level of accuracy for answering the question on the basis of a conventional EXAFS data analysis. Herein we present an alternative way to study this extreme case, by coupling new highly refined EXAFS data obtained in an actinide-dedicated beamline in the European Synchrotron Radiation Facility (ESRF, Grenoble), with the first Monte Carlo (MC) simulations of Cf in water. Specifically developed Cf OH2 intermolecular potentials based on ab initio quantum mechanical (QM) potential energy surfaces and the polarizable and flexible MCDHO water model have been used. Figure 1 shows the experimental and fitted k-weighted EXAFS spectra of a Cf aqueous solution using two model structures, the square antiprism configuration (SA; see Figure 2a), which represents an octacoordination of water

Collecting high-order interactions in an effective pairwise intermolecular potential using the hydrated ion concept: The hydration of Cf3+

This work proposes a new methodology to build interaction potentials between a highly charged metal cation and water molecules. These potentials, which can be used in classical computer simulations, have been fitted to reproduce quantum mechanical interaction energies (MP2 and BP86) for a wide range of [M(H2O)n](m+)(H2O)ℓ clusters (n going from 6 to 10 and ℓ from 0 to 18). A flexible and polarizable water shell model (Mobile Charge Density of Harmonic Oscillator) has been coupled to the cation-water potential. The simultaneous consideration of poly-hydrated clusters and the polarizability of the interacting particles allows the inclusion of the most important many-body effects in the new polarizable potential. Applications have been centered on the californium, Cf(III) the heaviest actinoid experimentally studied in solution. Two different strategies to select a set of about 2000 structures which are used for the potential building were checked. Monte Carlo simulations of Cf(III)+500 H2O for three of the intermolecular potentials predict an aquaion structure with coordination number close to 8 and average R(Cf-O) in the range 2.43-2.48 Å, whereas the fourth one is closer to 9 with R(Cf-O) = 2.54 Å. Simulated EXAFS spectra derived from the structural Monte Carlo distribution compares fairly well with the available experimental spectrum for the simulations bearing 8 water molecules. An angular distribution similar to that of a square antiprism is found for the octa-coordination.

Tandem ATRP/Diels–Alder synthesis of polyHEMA-based hydrogels

The efficient, controlled polymerization of a batch of new poly(hydroxyethyl methacrylate-co-furfuryl methacrylate)s, [poly(HEMA-co-FMA)], of various compositions was achieved using atom transfer radical polymerization (ATRP) in methanol. When the FMA composition did not exceed the 10 mol% ratio, the evolution of molecular weight with conversion was linear, and polydispersities were around 1.1 for polymerization reactions at 15 °C and around 1.3–1.4 at 25 °C, indicating good control over the polymerization process. HEMA-based hydrogels were obtained by means of the Diels–Alder reaction between poly(HEMA-co-FMA) and an hydrophilic bisdienophile. Gelification was monitored by diffusion-filtered 1H NMR and solution 1H NMR spectroscopy. Modulated temperature differential scanning calorimetry (MTDSC) suggests the thermo-reversibility of the Diels–Alder coupling reaction of HEMA polymeric networks. Rheological studies showed that the linear viscoelasticity functions of hydrogels were influenced by the chemical composition.

A diabatic parameterization of the twofold ground state potential energy surface of the H2O-OH molecular complex.

We present a matrix functional form to fit the nearly degenerated potential energy surface of the H2O-OH molecular complex. The functional form is based on second order perturbation theory, which allows us to define two diabatic states coupled together in the field of the surrounding water molecules. The fit reproduces faithfully the fine details of the potential energy surface (PES) like the crossings and the shallow barrier between the main and secondary minima. The explicit dependence of the model on polarization ensures its transferability to systems made of several water molecules. The potential is used to investigate the structural properties of the OH radical in solution by Monte Carlo simulation. The twin surface fit shows that the second PES is shifted above the ground state by typically 1600 cm(-1) for the configurations explored at a temperature of 300 K and a density of 1.0 g/cm(3). The second PES has thus little influence on the structuring of water around the OH radical at such a temperature and density. Our study confirms that under these thermodynamic conditions, OH is a weak hydrogen acceptor.

Opposite effects of successive hydration shells on the aqua ion structure of metal cations

The conformation adopted by water molecules around a metal ion in aqueous solution can be approached from a discrete representation of the solvent by studying the structure and stability of microsolvation clusters including a different number of water molecules. In this contribution, we present a quantum mechanics and ab initio molecular dynamics study on how the arrangement of water molecules around and shows preferentially a T h or S 6 symmetry depending on the number of hydration shells explicitly included in the calculation. The behaviour observed for both cases is the following: (1) for a cluster composed of the metal ion plus a first hydration shell, the preferred geometry shows a T h symmetry; (2) when a second hydration shell is added, a minimum can be found with an S 6 disposition of water molecules around the metal centre; (3) however, if a third hydration shell is considered a T h arrangement of water molecules around the central ion is strongly favoured. The structures of the different solvation complexes studied in this work are characterised. The preference for a T h or S 6 distribution of water ligands is rationalised in terms of total energies, interaction energies and the hydrogen bond network.

Validation of Smart Nanoparticles as Controlled Drug Delivery Systems: Loading and pH-Dependent Release of Pilocarpine

Micelles are good devices for use as controlled drug delivery systems because they exhibit the ability to protect the encapsulated substance from the routes of degradation until they reach the site of action. The present work assesses loading kinetics of a hydrophobic drug, pilocarpine, in polymeric micellar nanoparticles (NPs) and its pH-dependent release in hydrophilic environments. The trigger pH stimulus, pH 5.5, was the value encountered in damaged tissues in solid tumors. The new nanoparticles were prepared from an amphiphilic block copolymer, [(HEMA19%-DMA31%)-(FMA5%-DEA45%)]. For the present research, three systems were validated, two of them with cross-linked cores and the other without chemical stabilization. A comparison of their loading kinetics and release profiles is discussed, with the support of additional data obtained by scanning electron microscopy and dynamic light scattering. The drug was loaded into the NPs within the first minutes; the load was dependent on the degree of cross-linking. All of the systems experienced a boost in drug release at acidic pH, ranging from 50 to 80% within the first 48 h. NPs with the highest degree (20%) of core cross-linking delivered the highest percentage of drug at fixed times. The studied systems exhibited fine-tuned sustained release features, which may provide a continuous delivery of the drug at specific acidic locations, thereby diminishing side effects and increasing therapeutic rates. Hence, the studied NPs proved to behave as smart controlled drug delivery systems capable of responding to changes in pH.

Potential energy curves and spin-orbit coupling of light alkali-heavy rare gas molecules

The potential energy curves of the X, A, and B states of alkali-rare gas diatomic molecules, MKr and MXe, are investigated for M = Li, Na, K. The molecular spin-orbit coefficients a(R)=<(2)Π(½)|Ĥ(SO)|(2)Π(½)> and b(R)=<(2)Π(-½)|Ĥ(SO)|(2)Σ(½)> are calculated as a function the interatomic distance R. We show that a(R) increases and b(R) decreases as R decreases. This effect becomes less and less important as the mass of the alkali increases. A comparison of the rovibrational properties deduced from our calculations with experimental measurements recorded for NaKr and NaXe shows the quality of the calculations.

Reversible pH-sensitive chitosan-based hydrogels. Influence of dispersion composition on rheological properties and sustained drug delivery

The present work deals with the synthesis of micro-structured biomaterials based on chitosan (CTS) for their applications as biocompatible carriers of drugs and bioactive compounds. Twelve dispersions were prepared by means of functional cross-linking with tricarballylic acid (TCA); they were characterized by Fourier transform infrared spectroscopy (FT-IR), modulated temperature differential scanning calorimetry (MTDSC) and scanning electron microscopy (SEM), and their rheological properties were studied. To the best of the authors’ knowledge, no study has been carried out on the influence of CTS concentration, degree of cross-linking and drug loading on chitosan hydrogels for drug delivery systems (DDS) and is investigated herein for the first time. The influence of dispersion composition (polymer concentration and degree of cross-linking) revealed to exert a marked impact on its rheological properties, going from liquid-like to viscoelastic gels. The release profiles of a model drug, diclofenac sodium (DCNa), as well as their relationships with polymer concentration, drug loading and degree of cross-linking were evaluated. Similar to the findings on rheological properties, a wide range of release profiles was encountered. These formulations were found to display a well-controlled drug release strongly dependent on the formulation composition. Cumulative drug release under physiological conditions for 96 h ranged from 8% to 67%. For comparative purpose, Voltaren emulgel® from Novartis Pharmaceuticals was also investigated and the latter was the formulation with the highest cumulative drug release (85%). Some formulations showed similar spreadability values to the commercial hydrogel. The comparative study of three batches confirmed the reproducibility of the method, leading to systems particularly suitable for their use as drug carriers.

Loading studies of the anticancer drug camptothecin into dual stimuli-sensitive nanoparticles. Stability scrutiny

Graphical abstract Figure. No Caption available. Abstract In recent years, the preparation of valuable drug delivery systems (DDS) from self‐assembled amphiphilic copolymers has attracted much attention since these nanomaterials provide new opportunities to solve problems such as the lack of solubility in water of lipophilic drugs, improve their bioavailability, prolong their circulation time and decrease the side effects associated with their administration. In the current study two types of biocompatible pH‐responsive nanoparticles derived from poly(2‐hydroxyethyl methacrylate) (pHEMA) have been used as drug nano‐carriers, being one of them core cross‐linked to circumvent their instability upon dilution in human fluids. The present paper deals with the optimization of the loading process of the labile, hydrophobic and highly active anticancer drug, Camptothecin (CPT) into the nanoparticles with regard to four independent variables: CPT/polymer ratio, sonication, temperature and loading time. Forty experiments were carried out and a Box–Behnken experimental design was used to evaluate the significance of the independent variables related to encapsulation efficiency and drug retention capacity. The enhanced drug loading and encapsulation efficiency values (58% and >92%, respectively) of CPT were achieved by the core cross‐linked NPs in 2 h at 32 °C at CPT/polymer ratio 1.5:1 w/w and 14 min of sonication. The optimized CPT‐loaded NPs were studied by dynamic light scattering and scanning electron microscopy, and an increase in size of the loaded‐NP compared to the unloaded counterparts was found. Other twenty experiments were conducted to study the enability to retain CPT into the conjugates at different ionic strength values and times. The stability studies demonstrated that the core cross‐linked nanocarriers displayed an excellent drug retention capacity (>90%) at 25 °C for 15 days in every ionic‐strength environments whereas the non‐cross‐linked ones were more stable at physiological ionic strength. The optimized systems proved to be a major step forward to encapsulate and retain CPT in the NP nuclei, what makes them ideal devices to control the delivery of CPT upon the triggered acidic conditions of solid tumors.

Glucose-nucleobase pairs within DNA: impact of hydrophobicity, alternative linking unit and DNA polymerase nucleotide insertion studies

Glucose-nucleobase pairs were designed, synthesized and incorporated into duplex DNA. Their stability, structure and polymerase replication was investigated.