Encapsulation and release mechanisms in coordination polymer nanoparticles

The interplay of guest encapsulation and release mechanisms in nanoscale metal-organic vehicles and its effect on the drug-delivery kinetics of these materials were investigated through a new multidisciplinary approach. Two rationally-designed molecular guests were synthesized, which consist of a red-fluorescent benzophenoxazine dye covalently tethered to a coordinating catechol group and a protected, non-coordinating catechol moiety. This allowed loading of the guests into compositionally and structurally equivalent coordination polymer particles through distinct encapsulation mechanisms: coordination and mechanical entrapment. The two types of particles delivered their fluorescent cargo with remarkably different kinetic profiles, which could be satisfactorily modeled considering degradation- and diffusion-controlled release processes. This demonstrates that careful selection of the method of guest incorporation into coordination polymer nanoparticles allows selective tuning of the rate of drug delivery from these materials and, therefore, of the time window of action of the encapsulated therapeutic agents. Drug-release mechanisms uncovered! Coordination polymer nanoparticles loaded with coordinated and mechanically entrapped fluorescent guests were prepared as benchmark systems to investigate diffusion- and degradation-controlled drug delivery from these materials (see figure)

Enhanced photocatalytic activity of gold nanoparticles driven by supramolecular host-guest chemistry

Functionalization of gold nanoparticles with supramolecular hosts allows their plasmon-based photocatalytic activity to be enhanced. This is mainly ascribed to the formation of labile host-guest complexes with the reagent molecules on the metal surface, thus promoting nanoparticle-substrate approximation without interfering with the light-induced catalytic process

Encapsulation and release mechanisms in coordination polymer nanoparticles

The interplay of guest encapsulation and release mechanisms in nanoscale metal-organic vehicles and its effect on the drug-delivery kinetics of these materials were investigated through a new multidisciplinary approach. Two rationally-designed molecular guests were synthesized, which consist of a red-fluorescent benzophenoxazine dye covalently tethered to a coordinating catechol group and a protected, non-coordinating catechol moiety. This allowed loading of the guests into compositionally and structurally equivalent coordination polymer particles through distinct encapsulation mechanisms: coordination and mechanical entrapment. The two types of particles delivered their fluorescent cargo with remarkably different kinetic profiles, which could be satisfactorily modeled considering degradation- and diffusion-controlled release processes. This demonstrates that careful selection of the method of guest incorporation into coordination polymer nanoparticles allows selective tuning of the rate of drug delivery from these materials and, therefore, of the time window of action of the encapsulated therapeutic agents. Drug-release mechanisms uncovered! Coordination polymer nanoparticles loaded with coordinated and mechanically entrapped fluorescent guests were prepared as benchmark systems to investigate diffusion- and degradation-controlled drug delivery from these materials (see figure)

Formation of cyclobutane thymine dimers by tiaprofenic acid and its photoproducts : approach to the photosensitizer triplet state energy limit value

Cyclobutane thymine dimers, the major photoproducts produced in UV-irradiated DNA, are the main causative agents for mutagenesis and skin cancer. This lesion can also be initiated under UVA radiation, involving triplet-triplet energy transfer mechanism from a photosensitizer to the thymine nucleobase. According to previous reports, only photosensitizers with a triplet state energy >270 kJ mol-1 should be able to induce cyclobutane thymine dimers photosensitization. However, tiaprofenic acid, a non-steroidal anti-inflammatory drug widely prescribed in the treatment of inflammation and pain, has shown cyclobutane thymine dimers photosensitization, although its triplet energy state value and those of its photoproducts are lower than the one previously reported for thymine in DNA. In this context, the in vitro photosensitizing properties of tiaprofenic acid and its photoproducts were studied by agarose gel electrophoresis and phosphorescence experiments and demonstrated clearly the formation of cyclobutane thymine dimers by tiaprofenic acid and its photoproducts. This study allows us to approach the lower limit threshold of the triplet state energy of a photosensitizer for cyclobutane thymine dimers formation and thereby to improve the prediction of the photogenotoxic potential of current and future drugs

Enhanced photocatalytic activity of gold nanoparticles driven by supramolecular host-guest chemistry

Functionalization of gold nanoparticles with supramolecular hosts allows their plasmon-based photocatalytic activity to be enhanced. This is mainly ascribed to the formation of labile host-guest complexes with the reagent molecules on the metal surface, thus promoting nanoparticle-substrate approximation without interfering with the light-induced catalytic process

Probing a polar cluster in the retinal binding pocket of bacteriorhodopsin by a chemical design approach

Bacteriorhodopsin has a polar cluster of amino acids surrounding the retinal molecule, which is responsible for light harvesting to fuel proton pumping. From our previous studies, we have shown that threonine 90 is the pivotal amino acid in this polar cluster, both functionally and structurally. In an attempt to perform a phenotype rescue, we have chemically designed a retinal analogue molecule to compensate the drastic effects of the T90A mutation in bacteriorhodopsin. This analogue substitutes the methyl group at position C13 of the retinal hydrocarbon chain by and ethyl group (20-methyl retinal). We have analyzed the effect of reconstituting the wild-type and the T90A mutant apoproteins with all-trans-retinal and its 20-methyl derivative (hereafter, 13-ethyl retinal). Biophysical characterization indicates that recovering the steric interaction between the residue 90 and retinal, eases the accommodation of the chromophore, however it is not enough for a complete phenotype rescue. The characterization of these chemically engineered chromoproteins provides further insight into the role of the hydrogen bond network and the steric interactions involving the retinal binding pocket in bacteriorhodopsin and other microbial sensory rhodopsins

Singlet Oxygen Generation on Porous Superhydrophobic Surfaces: Effect of Gas Flow and Sensitizer Wetting on Trapping Efficiency

We describe physical-organic studies of singlet oxygen generation and transport into an aqueous solution supported on superhydrophobic surfaces on which silicon–phthalocyanine (Pc) particles are immobilized. Singlet oxygen (¹O₂) was trapped by a water-soluble anthracene compound and monitored <i>in situ</i> using a UV–vis spectrometer. When oxygen flows through the porous superhydrophobic surface, singlet oxygen generated in the plastron (i.e., the gas layer beneath the liquid) is transported into the solution within gas bubbles, thereby increasing the liquid–gas surface area over which singlet oxygen can be trapped. Higher photooxidation rates were achieved in flowing oxygen, as compared to when the gas in the plastron was static. Superhydrophobic surfaces were also synthesized so that the Pc particles were located in contact with, or isolated from, the aqueous solution to evaluate the relative effectiveness of singlet oxygen generated in solution and the gas phase, respectively; singlet oxygen generated on particles wetted by the solution was trapped more efficiently than singlet oxygen generated in the plastron, even in the presence of flowing oxygen gas. A mechanism is proposed that explains how Pc particle wetting, plastron gas composition and flow rate as well as gas saturation of the aqueous solution affect singlet oxygen trapping efficiency. These stable superhydrophobic surfaces, which can physically isolate the photosensitizer particles from the solution may be of practical importance for delivering singlet oxygen for water purification and medical devices