Deep penetration of a PDT drug into tumors by noncovalent drug-gold nanoparticle conjugates

Efficient drug delivery to tumors is of ever-increasing importance. Single-visit diagnosis and treatment sessions are the goal of future theranostics. In this work, a noncovalent PDT cancer drug-gold nanoparticle (Au NP) conjugate system performed a rapid drug release and deep penetration of the drug into tumors within hours. The drug delivery mechanism of the PDT drug through Au NPs into tumors by passive accumulation was investigated via fluorescence imaging, elemental analysis, and histological staining. The pharmacokinetics of the conjugates over a 7-day test period showed rapid drug excretion, as monitored via the fluorescence of the drug in urine. Moreover, the biodistribution of Au NPs in this study period indicated clearance of the NPs from the mice. This study suggests that noncovalent delivery via Au NPs provides an attractive approach for cancer drugs to penetrate deep into the center of tumors.     

Comparison of hydration reactions for "piano-stool" RAPTA-B and [Ru(η6-arene)(en)Cl]+ complexes: density functional theory computational study

The hydration process for two Ru(II) representative half-sandwich complexes: Ru(arene)(pta)Cl(2) (from the RAPTA family) and [Ru(arene)(en)Cl](+) (further labeled as Ru_en) were compared with analogous reaction of cisplatin. In the study, quantum chemical methods were employed. All the complexes were optimized at the B3LYP/6-31G(d) level using Conductor Polarizable Continuum Model (CPCM) solvent continuum model and single-point (SP) energy calculations and determination of electronic properties were performed at the B3LYP∕6-311++G(2df,2pd)/CPCM level. It was found that the hydration model works fairly well for the replacement of the first chloride by water where an acceptable agreement for both Gibbs free energies and rate constants was obtained. However, in the second hydration step worse agreement of the experimental and calculated values was achieved. In agreement with experimental values, the rate constants for the first step can be ordered as RAPTA-B > Ru_en > cisplatin. The rate constants correlate well with binding energies (BEs) of the Pt∕Ru-Cl bond in the reactant complexes. Substitution reactions on Ru_en and cisplatin complexes proceed only via pseudoassociative (associative interchange) mechanism. On the other hand in the case of RAPTA there is also possible a competitive dissociation mechanism with metastable pentacoordinated intermediate. The first hydration step is slightly endothermic for all three complexes by 3-5 kcal∕mol. Estimated BEs confirm that the benzene ligand is relatively weakly bonded assuming the fact that it occupies three coordination positions of the Ru(II) cation.     

Development of electrochemical oxygen meter for liquid sodium

The development of an electrochemical oxygen meter for liquid sodium is briefly accounted. The current design, based on a solid electrolyte crucible machined out of a sintered pellet is described along with some technological details. Present experience with testing in sodium loops and post-exposure analysis has shown that the chosen assembly is capable of achieving approximately the Nernst voltage. The service period was limited mainly by corrosion and by some incompatibilities in reference electrode compartment materials.     

Theoretical study of interaction of urate with li(+), na(+), k(+), be(2+), mg(2+), and ca(2+) metal cations

The geometries and energetics of complexes of Li(+), Na(+), K(+), Be(2+), Mg(2+), and Ca(2+)metal cations with different possible uric acid anions (urate) were studied. The complexes were optimized at the B3LYP level and the 6-311++G(d,p) basis set. Complexes of urate with Mg(2+), and Ca(2+)metal cations were also optimized at the MP2/6-31+G(d) level. Single point energy calculations were performed at the MP2/6-311++G(d,p) level. The interactions of the metal cations at different nucleophilic sites of various possible urate were considered. It was revealed that metal cations would interact with urate in a bi-coordinate manner. In the gas phase, the most preferred position for the interaction of Li(+), Na(+), and K(+) cations is between the N(3) and O(2) sites, while all divalent cations Be(2+), Mg(2+), and Ca(2+) prefer binding between the N(7) and O(6) sites of the corresponding urate. The influence of aqueous solvent on the relative stability of different complexes has been examined using the Tomasi's polarized continuum model. The basis set superposition error (BSSE) corrected interaction energy was also computed for complexes. The AIM theory has been applied to analyze the properties of the bond critical points (electron densities and their Laplacians) involved in the coordination between urate and the metal cations. It was revealed that aqueous solvation would have significant effect on the relative stability of complexes obtained by the interaction of urate with Mg(2+) and Ca(2+)cations. Consequently, several complexes were found to exist in the water solution. The effect of metal cations on different NH and CO stretching vibrational modes of uric acid has also been discussed.     

Copper cation interactions with biologically essential types of ligands: a computational DFT study

This work presents a systematic theoretical study on Cu(I) and Cu(II) cations in variable hydrogen sulfide-aqua-ammine ligand fields. These ligands model the biologically most common environment for Cu ions. Molecular structures of the complexes were optimized at the density functional theory (DFT) level. Subsequent thorough energy analyses revealed the following trends: (i) The ammine complexes are the most stable, followed by those containing the aqua and hydrogen sulfide ligands, which are characterized by similar stabilization energies. (ii) The most preferred Cu(I) coordination number is 2 in ammine or aqua ligand fields. A qualitatively different binding picture was obtained for complexes with H(2)S ligands where the 4-coordination is favored. (iii) The 4- and 5-coordinated structures belong to the most stable complexes for Cu(II), regardless of the ligand types. Vertical and adiabatic ionization potentials of Cu(I) complexes were calculated. Charge distribution (using the natural population analysis (NPA) method) and molecular orbital analyses were performed to elucidate the nature of bonding in the examined systems. The results provide in-depth insight into the Cu-binding properties and can be, among others, used for the calibration of bioinorganic force fields.     

A Dogma in Doubt: Hydrolysis of Equatorial Ligands of PtIV Complexes under Physiological Conditions

Due to their high kinetic inertness and consequently reduced side reactions with biomolecules, Pt^IV complexes are considered to define the future of anticancer platinum drugs. The aqueous stability of a series of biscarboxylato Pt^IV complexes was studied under physiologically relevant conditions. Unexpectedly and in contrast to the current chemical understanding, especially oxaliplatin and satraplatin complexes underwent fast hydrolysis in equatorial position (even in cell culture medium and serum). Notably, the resulting hydrolysis products strongly differ in their reduction kinetics, a crucial parameter for the activation of Pt^IV drugs, which also changes the anticancer potential of the compounds in cell culture. The discovery that intact Pt^IV complexes can hydrolyze at equatorial position contradicts the dogma on the general kinetic inertness of Pt^IV compounds and needs to be considered in the screening and design for novel platinum‐based anticancer drugs.     

Synthesis, characterization and computational study of nitrogen-doped CeO2 nanoparticles with visible-light activity

Nitrogen-doped CeO2 nanoparticles were synthesized through a wet-chemical route. Nitrogen has been successfully incorporated into CeO2 nanoparticles and the nitrogen-doping level was also successfully controlled. The optical properties due to the different N-doping levels in CeO2 nanoparticles were characterized by UV-Vis diffuse reflectance spectroscopy (DRS), which showed a visible-light absorbance shift. The resulting nanoparticles show enhanced visible-light sensitivity and photocatalytic activity compared to undoped CeO2 nanoparticles. DFT calculations were performed to explore the effect of nitrogen doping versus oxygen vacancies. The calculations show that the change of the electronic structure upon N-doping CeO2 is quite different from that of N-doped TiO2, which has been studied extensively.     

Effect of the functionalization of the axial phthalocyanine ligands on the energy transfer in QD-based donor-acceptor pairs.

This study examines the electronic coupling between quantum dots (QDs) and molecules on their surfaces as a function of the modality of their interaction. As a probe, the energy transfer (ET) between CdSe QDs and phthalocyanines (Pcs) was monitored and evaluated with regard to the functionalization of the axial phthalocyanine ligand, bulkiness of the functional group bridging the QD donor and Pc acceptor, and the number of the functionalized axial ligands. New silicon PCs and their conjugates with CdSe QDs were synthesized. The ET efficiency and kinetics were studied by steady state and femtosecond time-resolved absorption spectroscopy. We observed a decrease in ET efficiency with the increase in functional group bulkiness, which could be explained by increasing steric hindrance between the ET pair. In addition, a higher ET efficiency was observed for amino and thiol functionalized Pcs compared to Pcs without functional group on the axial alkyl chain.