Self-Assembly-Directed Exciton Diffusion in Solution-Processable Metalloporphyrin Thin Films

The study of excited-state energy diffusion has had an important impact in the development and optimization of organic electronics. For instance, optimizing excited-state energy migration in the photoactive layer in an organic solar cell device has been shown to yield efficient solar energy conversion. Despite the crucial role that energy migration plays in molecular electronic device physics, there is still a great deal to be explored to establish how molecular orientation impacts energy diffusion mechanisms. In this work, we have synthesized a new library of solution-processable, Zn (alkoxycarbonyl)phenylporphyrins containing butyl (ZnTCB₄PP), hexyl (ZnTCH₄PP), 2-ethylhexyl (ZnTCEH₄PP), and octyl (ZnTCO₄PP) alkoxycarbonyl groups. We establish that, by varying the length of the peripheral alkyl chains on the metalloporphyrin macrocycle, preferential orientation and molecular self-assembly is observed in solution-processed thin films. The resultant arrangement of molecules consequently affects the electronic and photophysical characteristics of the metalloporphyrin thin films. The various molecular arrangements in the porphyrin thin films and their resultant impact were determined using UV-Vis absorption spectroscopy, steady-state and time-resolved fluorescence emission lifetimes, and X-ray diffraction in thin films. The films were doped with C₆₀ quencher molecules and the change in fluorescence was measured to derive a relative quenching efficiency. Using emission decay, relative quenching efficiency, and dopant volume fraction as input, insights on exciton diffusion coefficient and exciton diffusion lengths were obtained from a Monte Carlo simulation. The octyl derivative (ZnTCO₄PP) showed the strongest relative fluorescence quenching and, therefore, the highest exciton diffusion coefficient (5.29 × 10⁻³ cm² s⁻¹) and longest exciton diffusion length (~81 nm). The octyl derivative also showed the strongest out-of-plane stacking among the metalloporphyrins studied. This work demonstrates how molecular self-assembly can be used to modulate and direct exciton diffusion in solution-processable metalloporphyrin thin films engineered for optoelectronic and photonic applications.     

A New Oxadiazole-Based Topsentin Derivative Modulates Cyclin-Dependent Kinase 1 Expression and Exerts Cytotoxic Effects on Pancreatic Cancer Cells

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal form of cancer characterized by drug resistance, urging new therapeutic strategies. In recent years, protein kinases have emerged as promising pharmacological targets for the treatment of several solid and hematological tumors. Interestingly, cyclin-dependent kinase 1 (CDK1) is overexpressed in PDAC tissues and has been correlated to the aggressive nature of these tumors because of its key role in cell cycle progression and resistance to the induction of apoptosis. For these reasons, CDK1 is one of the main causes of chemoresistance, representing a promising pharmacological target. In this study, we report the synthesis of new 1,2,4-oxadiazole compounds and evaluate their ability to inhibit the cell growth of PATU-T, Hs766T, and HPAF-II cell lines and a primary PDAC cell culture (PDAC3). Compound 6b was the most active compound, with IC₅₀ values ranging from 5.7 to 10.7 µM. Molecular docking of 6b into the active site of CDK1 showed the ability of the compound to interact effectively with the adenosine triphosphate binding pocket. Therefore, we assessed its ability to induce apoptosis (which increased 1.5- and 2-fold in PATU-T and PDAC3 cells, respectively) and to inhibit CDK1 expression, which was reduced to 45% in Hs766T. Lastly, compound 6b passed the ADME prediction, showing good pharmacokinetic parameters. These data demonstrate that 6b displays cytotoxic activity, induces apoptosis, and targets CDK1, supporting further studies for the development of similar compounds against PDAC.     

Enriching the Arsenal of Pharmacological Tools against MICAL2

Molecule interacting with CasL 2 (MICAL2), a cytoskeleton dynamics regulator, are strongly expressed in several human cancer types, especially at the invasive front, in metastasizing cancer cells and in the neo-angiogenic vasculature. Although a plethora of data exist and stress a growing relevance of MICAL2 to human cancer, it is worth noting that only one small-molecule inhibitor, named CCG-1423 (1), is known to date. Herein, with the aim to develop novel MICAL2 inhibitors, starting from CCG-1423 (1), a small library of new compounds was synthetized and biologically evaluated on human dermal microvascular endothelial cells (HMEC-1) and on renal cell adenocarcinoma (786-O) cells. Among the novel compounds, 10 and 7 gave interesting results in terms of reduction in cell proliferation and/or motility, whereas no effects were observed in MICAL2-knocked down cells. Aside from the interesting biological activities, this work provides the first structure–activity relationships (SARs) of CCG-1423 (1), thus providing precious information for the discovery of new MICAL2 inhibitors.     

Detergent-Induced Removal of β-Lactoglobulin from Stainless Steel Surfaces as Influenced by Surface Pretreatment

The adsorption of β-lactoglobulin to stainless steel and its subsequent removal were followed using in situ null ellipsometry. The influence of the surface pretreatment on the protein removal by the surfactant SDS and by sodium hydroxide was studied. All surfaces were precleaned in strongly alkaline solution. Some surfaces received no further pretreatment, while others were either passivated in nitric acid or plasma-cleaned prior to experiments. Stainless steel surfaces subjected to different surface pretreatments showed considerable differences in cleaning behavior. Cleaning, using NaOH, of surfaces which had been precleaned with alkali only or with plasma resulted in practically complete β-lactoglobulin removal. In contrast, appreciable amounts of protein remained on passivated stainless steel. Protein removal by SDS was limited and comparable for all three surface pretreatments investigated. Only minor effects on the protein adsorption tendency were observed. The amounts of β-lactoglobulin adsorbed tended to be somewhat lower on the passivated surfaces.     

Simultaneous Quantification of 25 Fentanyl Derivatives and Metabolites in Oral Fluid by Means of Microextraction on Packed Sorbent and LC–HRMS/MS Analysis

Fentanyl and fentalogs’ intake as drugs of abuse is experiencing a great increase in recent years. For this reason, there are more and more cases in which it is important to recognize and quantify these molecules and related metabolites in biological matrices. Oral fluid (OF) is often used to find out if a subject has recently used a psychoactive substance and if, therefore, the person is still under the effect of psychotropics. Given its difficulty in handling, good sample preparation and the development of instrumental methods for analysis are essential. In this work, an analytical method is proposed for the simultaneous determination of 25 analytes, including fentanyl, several derivatives and metabolites. OF was collected by means of passive drool; sample pretreatment was developed in order to be fast, simple and possibly semi-automated by exploiting microextraction on packed sorbent (MEPS). The analysis was performed by means of LC–HRMS/MS obtaining good identification and quantification of all the analytes in less than 10 min. The proposed method was fully validated according to the Scientific Working Group for Forensic Toxicology (SWGTOX) international guidelines. Good results were obtained in terms of recoveries, matrix effect and sensitivity, showing that this method could represent a useful tool in forensic toxicology. The presented method was successfully applied to the analysis of proficiency test samples.     

A torsion-based solution to the hyperbolic regime of the $$J_2$$ -problem

A popular intermediary in the theory of artificial satellites is obtained after the elimination of parallactic terms from the \(J_2\)-problem Hamiltonian. The resulting quasi-Keplerian system is in turn converted into the Kepler problem by a torsion. When this reduction process is applied to unbounded orbits, the solution is made of Keplerian hyperbolae. For this last case, we show that the torsion-based solution provides an effective alternative to the Keplerian approximation customarily used in flyby computations. Also, we check that the extension of the torsion-based solution to higher orders of the oblateness coefficient yields the expected convergence of asymptotic solutions to the true orbit.

     

Negishi Cross-Coupling in the Preparation of Benzyl Substituted Pyrrolo[2,3-d]pyrimidine Based CSF1R Inhibitors

The colony-stimulating factor 1 receptor (CSF1R) is a protein kinase emerging as an attractive target with clinical relevance in cancer, CNS and inflammatory diseases. Molecular docking experiments followed by synthesis and structure–activity relationship have been used to identify low molecular weight structures as promising hits for lead optimization. These molecules are synthesized from a 4-chloro-6-iodo-pyrrolo[2,3-d]pyrimidine building block using Negishi and Suzuki–Miyaura cross-coupling reactions in high yields. Several inhibitors possessed excellent enzymatic potency, and the parent compound preferably binds to the autoinhibited form of CSF1R. Cellular and in vivo profiling indicate that further tuning of drug structure is needed prior to efficacy studies.     

eHydrogenation: Hydrogen-free Electrochemical Hydrogenation

Hydrogenation reactions are staple transformations commonly used across scientific fields to synthesise pharmaceuticals, natural products, and various functional materials. However, the vast majority of these reactions require the use of a toxic and costly catalyst leading to unpractical, hazardous and often functionally limited conditions. Herein, we report a new, general, practical, efficient, mild and high-yielding hydrogen-free electrochemical method for the reduction of alkene, alkyne, nitro and azido groups. Finally, this method has been applied to deuterium labelling.     

A simple and fast method for evaluating the athermal limit of semirigid liquid polymers

A simple method is reported allowing the fast evaluation of the athermal limit that is implicitly present within the set of equations recently proposed by Jonah, Brostow and Hess, dealing with the anisotropic‐isotropic equilibria of single monodisperse or nearly monodisperse semirigid liquid polymers, including polymer liquid crystals. We have found an athermal limit dependent on the degree of rigidity θ of the given semirigid liquid polymer (θ being the fraction of its monomeric units belonging to rigid rodlike sequences within each semiflexible polymeric chain) and marked off by critical lengths η_al of the rigid sequences, giving rise to non‐finite asymptotic values of the anisotropic‐isotropic temperatures.     

Influence of processing method and components molecular structure on the phase behaviour of polyethylenes/dye blends

The phase dispersion of terthiophene alkyl derivatives on different polyethylene matrices was investigated. The PE affinity toward dichroic dyes with different structure, the effect of blending process and the influence of a polyolefinic compatibilizer on the homogeneity of host-guest blends were comparatively investigated by calorimetry, DSC and SEM analyses. For these purposes, polyethylenes with different molecular weights and densities and EVAc were used as host matrices. The polymeric compatibilizer was prepared by radical functionalization of a commercial low density polyethylene. The dichroic nature of the guest phase allowed to perform UV-Vis measurements in polarized light on oriented blend film samples. The dyes affinity toward PE is one of the key factor in obtaining oriented polyolefinic films with high optical performances for several applications.