Extraordinary Control of Photosensitized Singlet Oxygen Generation by Acyclic Cucurbituril-like Containers.

Supramolecular control of singlet oxygen generation is incredibly valuable for several fields with broad applications and thus still challenging. However, macrocyclic inclusion complexes inherently restrict the interaction of photosensitizers with surrounding oxygen in the media. To circumvent this issue, we turned our attention in this work to acyclic cucurbituril-like containers and uncover their properties as supramolecular hosts for photosensitizers with extraordinary control of their photophysics, including singlet oxygen generation. Thermodynamic and photophysical studies were carried out showing that these acyclic containers compare very favorably to benchmark macrocycles such as cucurbiturils and cyclodextrins in terms of their binding affinities and supramolecular control of singlet oxygen generation. Acyclic container with terminal naphthalene walls offers a similar cavity to cucurbit[7]uril and the same carbonyl-lined portals for a tight binding of phenothiazinium dye methylene blue and stabilizing its singlet and triplet excited states. Thus, generation of singlet oxygen for this container is higher than for other macrocycles and even higher than the free photosensitizer. While the acyclic container with smaller terminal benzene walls, stacks over the dye through sulfur-π and π-π interactions deactivating the singlet and triplet excited states, thus showing the lowest generation of singlet oxygen out of all of the studied systems. Due to the great water solubility and biocompatibility of these systems, they possess great potential for novel applications in photocatalysis, synthesis, and biomedical fields, among others.

Singlet oxygen partition between the outer-, inner- and membrane-phases of photo/chemotherapeutic liposomes.

Liposomes carrying membrane-embedded porphyrin-phospholipid (PoP) are capable of chemo- and photo-therapeutic modes of action, which make them a potential candidate material for next-generation cancer treatments. This study examines singlet oxygen (1O2) production and release by PoP liposomes carrying either no chemotherapeutic cargo (EMPTY), or those carrying either doxorubicin (DOX) or irinotecan (IRT) chemotherapy drugs. Herein, we developed a strategy to quantify the fraction of 1O2 lifetime spent in the three distinct local liposomal environments by obtaining four key pieces of information for each system: average 1O2 deactivation rate constants (kΔ) for liposome suspensions in H2O and in D2O solvents, as well as the absolute and the apparent 1O2 production quantum yields (ΦΔ). Despite the characteristic differences in their photophysical behavior, namely in ΦΔ values, all three formulations of PoP liposomes were found to carry out 1O2 release in a similar manner. It was found that >80% of all sensitized 1O2 from the ensemble of PoP liposomes deactivates within the nanostructures themselves, with the largest portion (∼50%) deactivating in the lipid membrane specifically. Based on these findings, we conclude that the current design of the PoP liposomes is well suited for light-induced chemotherapeutic drug release. Importantly, the 1O2 partition quantification approach reported herein has potential to be a tool for characterizing nanoparticulate light-activated chemo- and phototherapeutic systems.

In-Operando Mapping of pH Distribution in Electrochemical Processes.

In aqueous electrochemical processes, the pH evolves spatially and temporally, and often dictates the process performance. Herein, a new method for the in-operando monitoring of pH distribution in an electrochemical cell is demonstrated. A combination of pH-sensitive fluorescent dyes, encompassing a wide pH range from ≈1.5 to 8.5, and rapid electrochemically coupled laser scanning confocal microscopy is used to observe pH changes in the cell. Using electrocoagulation as an example process, we show that the method provides new insights into the reaction mechanisms. The pH close to the aluminium electrode surface is influenced by the applied current density, hydrolysis of aluminium cations, and gas evolution. Through quantification of the pH at the anode, along with gas analysis, we find that hydrogen is evolved at the anode due to a non-Faradaic chemical reaction. This leads to increased production of coagulant, which may open new routes to enhance the process performance. This method for in-operando dynamic visualization of pH paves the way for studies of electrochemical processes, including other water treatment, electrosynthesis, and batteries.

Roles of Near and Far Fields in Plasmon-Enhanced Singlet Oxygen Production.

In plasmon-enhanced singlet oxygen (1O2) production, irradiation of a hybrid photosensitizer-metal nanoparticle leads to a significant alteration of the photosensitizer's 1O2 yield. The quest for a more rational design of these nanomaterials calls for a better understanding of the enhancement mechanism that, to this day, remains largely unexplored. Herein, we introduce a new methodology to distinguish the near- and far-field contributions to the plasmon-enhanced 1O2 production using a tunable model nanoplatform, Rose Bengal-decorated silica-coated metal nanoparticles. By correlating 1O2 production to the experimental and simulated optical properties of our nanoparticles, we effectively discriminate how the near- and far-field effects contribute to the plasmonic interactions. We show that these effects work in synergy; i.e., for nanoparticles with a similar local field, the production of 1O2 correlates with maximized scattering yields. Our results expound the critical plasmonic aspects in terms of near and far fields for the design of an efficient hybrid plasmonic nanoparticle photosensitizer.

Assessment of encapsulated dyes' distribution in silica nanoparticles and their ability to release useful singlet oxygen.

Working with silica nanoparticle encapsulated BODIPY and xanthene photosensitizers, we have determined that singlet oxygen spends up to 78% of its lifetime inside the nanocarriers. Our systematic investigation indicates that hydrophobicity rules the photosensitizer distribution in nanoparticles, which in turn dictates the ability of these structures to release singlet oxygen.

Synthesis, biological evaluation and molecular docking studies of 2-piperazin-1-yl-quinazolines as platelet aggregation inhibitors and ligands of integrin αIIbß3.

A series of 2-piperazin-1-yl-quinazolines were synthesized and evaluated for their antiaggregative activity. The synthesized small molecule compounds have potently inhibited platelet aggregation in vitro and blocked FITC-Fg binding to αIIbß3 integrin in a suspension of washed human platelets. The key αIIbß3 protein-ligand interactions were determined in docking experiments and some correlations have been observed between values of the affinity and docking scores.

Design, Virtual Screening, and Synthesis of Antagonists of αIIbß3 as Antiplatelet Agents.

This article describes design, virtual screening, synthesis, and biological tests of novel αIIbß3 antagonists, which inhibit platelet aggregation. Two types of αIIbß3 antagonists were developed: those binding either closed or open form of the protein. At the first step, available experimental data were used to build QSAR models and ligand- and structure-based pharmacophore models and to select the most appropriate tool for ligand-to-protein docking. Virtual screening of publicly available databases (BioinfoDB, ZINC, Enamine data sets) with developed models resulted in no hits. Therefore, small focused libraries for two types of ligands were prepared on the basis of pharmacophore models. Their screening resulted in four potential ligands for open form of αIIbß3 and four ligands for its closed form followed by their synthesis and in vitro tests. Experimental measurements of affinity for αIIbß3 and ability to inhibit ADP-induced platelet aggregation (IC50) showed that two designed ligands for the open form 4c and 4d (IC50 = 6.2 nM and 25 nM, respectively) and one for the closed form 12b (IC50 = 11 nM) were more potent than commercial antithrombotic Tirofiban (IC50 = 32 nM).

Synthesis, biological evaluation, X-ray molecular structure and molecular docking studies of RGD mimetics containing 6-amino-2,3-dihydroisoindolin-1-one fragment as ligands of integrin αIIbß3.

A series of novel RGD mimetics containing phthalimidine fragment was designed and synthesized. Their antiaggregative activity determined by Born's method was shown to be due to inhibition of fibrinogen binding to αIIbß3. Molecular docking of RGD mimetics to αIIbß3 receptor showed the key interactions in this complex, and also some correlations have been observed between values of biological activity and docking scores. The single crystal X-ray data were obtained for five mimetics.

RGD mimetics containing phthalimidine fragment as novel ligands of fibrinogen receptor.

The novel RGD mimetics with phthalimidine central fragment were synthesized with the use of 4-piperidine-4-yl-butyric, 4-piperidine-4-yl-benzoic, 4-piperazine-4-yl-benzoic and 1,2,3,4-tetrahydroisoquinoline-7-carboxylic acids as surrogates of Arg motif. The synthesized compounds potently inhibited platelet aggregation in vitro and blocked FITC-Fg binding to α(IIb)ß(3) integrin in a suspension of washed human platelets. The key α(IIb)ß(3) protein-ligand interactions were determined in docking experiments.

Derivatives of tetrahydroisoquinoline: synthesis and initial evaluation of novel non-peptide antagonists of the alpha(IIb)beta(3)-integrin.

The novel RGDF mimetics were synthesized with the use of 4-(1,2,3,4-tetrahydroisoquinoline-7-yl)amino-4-oxobutyric or 5-(1,2,3,4-tetrahydroisoquinoline-7-yl)amino-5-oxopentanoic acids as a surrogate of Arg-Gly motif. The synthesized compounds have demonstrated a high potency to inhibit platelet aggregation in vitro and to block FITC-Fg binding to alpha(IIb)beta(3) on washed human platelets.

Synthesis and antiaggregatory activity of RGD-peptidomimetics based on 4-oxo-4-(piperazine-1-yl)butyric acid as Arg-mimetic.

A scheme of synthesis of previously obtained RGDF-peptidomimetic-4-oxo-4-(piperazine-1-yl)butyrylglycyl-D,L-beta-phenyl-beta-alanine (I), was simplified. The novel RGDF-peptidomimetic -4-oxo-4-piperazine-1-yl)butyryl-glycyl-L-aspartyl-L-phenylalanine (II) was synthesized with the use of 4-oxo-4-(piperazine-1-yl)butyric acid as arginyl mimetic. The obtained pseudopeptides were able to inhibit both platelet aggregation in human blood and binding of fibrinogen to its receptor.