Asparagine and Glutamine Deprivation Alters Ionizing Radiation Response, Migration and Adhesion of a p53null Colorectal Cancer Cell Line.

Colorectal cancer (CRC) is the most prominent form of colon cancer for both incidence (38.7 per 100,000 people) and mortality (13.9 per 100,000 people). CRC's poor response to standard therapies is linked to its high heterogeneity and complex genetic background. Dysregulation or depletion of the tumor suppressor p53 is involved in CRC transformation and its capability to escape therapy, with p53null cancer subtypes known, in fact, to have a poor prognosis. In such a context, new therapeutic approaches aimed at reducing CRC proliferation must be investigated. In clinical practice, CRC chemotherapy is often combined with radiation therapy with the aim of blocking the expansion of the tumor mass or removing residual cancer cells, though contemporary targeting of amino acid metabolism has not yet been explored. In the present study, we used the p53null Caco-2 model cell line to evaluate the effect of a possible combination of radiation and L-Asparaginase (L-ASNase), a protein drug that blocks cancer proliferation by impairing asparagine and glutamine extracellular supply. When L-ASNase was administered immediately after IR, we observed a reduced proliferative capability, a delay in DNA-damage response and a reduced capability to adhere and migrate. Our data suggest that a correctly timed combination of X-rays and L-ASNase treatment could represent an advantage in CRC therapy.

Tunable Linear and Nonlinear Optical Properties from Room Temperature Phosphorescent Cyclic Triimidazole-Pyrene Bio-Probe.

Organic materials with multiple emissions tunable by external stimuli represent a great challenge. TTPyr, crystallizing in different polymorphs, shows a very rich photophyisics comprising excitation-dependent fluorescence and phosphorescence at ambient conditions, and mechanochromic and thermochromic behavior. Transformation among the different species has been followed by thermal and X-ray diffraction analyses and the emissive features interpreted through structural results and DFT/TDDFT calculations. Particularly intriguing is the polymorph TTPyr(HT), serendipitously obtained at high temperature but stable also at room temperature, whose non-centrosymmetric structure guarantees an SHG efficiency 10 times higher than that of standard urea. Its crystal packing, where only the TT units are strongly rigidified by π-π stacking interactions while the Pyr moieties possess partial conformational freedom, is responsible for the observed dual fluorescence. The potentialities of TTPyr for bioimaging have been successfully established.

Intrinsic and Extrinsic Heavy-Atom Effects on the Multifaceted Emissive Behavior of Cyclic Triimidazole.

Considering that heavy halogen atoms can be used to tune the emissive properties of organic luminogens, the understanding of their role in photophysics is fundamental for materials engineering. Here, the extrinsic and intrinsic heavy-atom effects on the photophysics of organic crystals were separately evaluated by comparing cyclic triimidazole (TT) with its monoiodo derivative (TTI) and its co-crystal with diiodotetrafluorobenzene (TTCo). Crystals of TT showed room-temperature ultralong phosphorescence (RTUP) originated from H-aggregation. TTI and TTCo displayed two additional long-lived components, the origin of which is elucidated through single-crystal X-ray and DFT/TDDFT studies. The results highlight the different effects of the I atom on the three phosphorescent emissions. Intrinsic heavy-atom effects play a major role on molecular phosphorescence, which is displayed at room temperature only for TTI. The H-aggregate RTUP and the I⋅⋅⋅N XB-induced (XB=halogen bond) phosphorescence on the other side depend only on packing features.

Solid State Room Temperature Dual Phosphorescence from 3-(2-Fluoropyridin-4-yl)triimidazo[1,2-a:1',2'-c:1″,2″-e][1,3,5]triazine.

Organic room temperature persistent luminescence is a fascinating but still largely unexplored phenomenon. Cyclic-triimidazole and its halogenated (Br, I) derivatives have recently revealed as intriguing phosphors characterized by multifaceted emissive behavior including room temperature ultralong phosphorescence (RTUP) associated with the presence of H-aggregates in their crystal structure. Here, we move towards a multicomponent system by incorporating a fluoropyridinic fragment on the cyclic-triimidazole scaffold. Such chromophore enhances the molecular properties resulting in a high photoluminescence quantum yield (PL QY) in solution but preserves the solid-state RTUP. By means of X-ray diffraction (XRD) analysis, theoretical calculations, steady-state and time-resolved spectroscopy on solutions, polymethylmethacrylate (PMMA) blends and crystals, the nature of the different radiative deactivation channels of the compound has been disclosed. In particular, the molecular fluorescence and phosphorescence, this latter observed in frozen solution and in PMMA blends, are associated to deactivation from S1 and T1 respectively, while the low energy RTUP, observed only for crystals, is interpreted as originated from H aggregates.

Chemical shift assignment of mono- and di-bromo triimidazo[1,2-a:1',2'-c:1″,2″-e][1,3,5]triazine derivatives by DFT/NMR integrated approach.

Mono- and di-bromo derivatives of triimidazo[1,2-a:1',2'-c:1″,2″-e][1,3,5]triazine have been proposed as new organic molecules presenting a very rich and complex photophysical behavior. Thus, we afforded the correct chemical shift assignment by integrating the experimental data with DFT calculation of NMR parameters. Our findings lay foundation for a structural reference in the organic synthesis and characterization of new congeners of this intriguing class of molecules.

Cyclic Triimidazole Derivatives: Intriguing Examples of Multiple Emissions and Ultralong Phosphorescence at Room Temperature.

The performance of solid luminogens depends on both their inherent electronic properties and their packing status. Intermolecular interactions have been exploited to achieve persistent room-temperature phosphorescence (RTP) from organic molecules. However, the design of organic materials with bright RTP and the rationalization of the role of interchromophoric electronic coupling remain challenging tasks. Cyclic triimidazole has been shown to be a promising scaffold for such purposes owing to its crystallization-induced room-temperature ultralong phosphorescence (RTUP), which has been associated with H-aggregation. Herein, we report three triimidazole derivatives as significant examples of multifaceted emission. In particular, dual fluorescence, RTUP, and phosphorescence from the molecular and supramolecular units were observed. H-aggregation is responsible for the red RTUP, and Br substituents favor yellow molecular phosphorescence while halogen-bonded Br⋅⋅⋅Br tetrameric units are involved in the blue-green phosphorescence.

Molting success of Ixodes scapularis varies among individual blood meal hosts and species.

The blacklegged tick (Ixodes scapularis) is an important vector of emerging human pathogens. It has three blood-feeding stages, as follows: larva, nymph, and adult. Owing to inefficient transovarial transmission, at least for the Lyme disease agent (Borrelia burgdorferi), larval ticks rarely hatch infected, but they can acquire infection during their larval blood meal. Nymphal ticks are primarily responsible for transmitting pathogens to hosts, including humans. The transition from uninfected host-seeking larva to infectious host-seeking nymph is therefore a key aspect of human risk of infection. It can be divided into a series of steps, as follows: finding a host, taking a blood meal, becoming infected, molting, and overwintering. The chance of succeeding in each of these steps may depend on the species identity of the blood meal host. We used a Bayesian method to estimate the molting success of larval I. scapularis collected from four commonly parasitized species of birds and eight commonly parasitized small and mid-sized mammals found in the forests of Dutchess County, New York. We show that molting success varies substantially among host species; white-footed mice, veeries, and gray catbirds support particularly high molting success, whereas ticks feeding on short-tailed shrews, robins, and wood thrushes were less successful. We also show that larval molting success varies substantially between individual blood meal hosts, and that this intraspecific variability is much higher in some species than in others. The causes of both inter- and intraspecific variation in molting success remain to be determined.

Unravelling the intricate photophysical behavior of 3-(pyridin-2-yl)triimidazotriazine AIE and RTP polymorphs.

The development of purely organic materials showing multicolor fluorescent and phosphorescent behaviour represents a formidable challenge in view of practical applications. Herein the rich photophysical behaviour of 3-(pyridin-2-yl)triimidazotriazine (TT-Py) organic molecule, comprising excitation-dependent fluorescence and phosphorescence under ambient conditions in both blended films and the crystalline phase, is investigated by means of steady state, time resolved and ultrafast spectroscopies and interpreted on the basis of X-ray diffraction studies and DFT/TDDFT calculations. In particular, by proper excitation wavelength, dual fluorescence and dual phosphorescence of molecular origin can be observed together with low energy phosphorescences resulting from aggregate species. It is demonstrated that the multiple emission properties originate from the copresence, in the investigated system, of an extended polycyclic nitrogen-rich moiety (TT), strongly rigidified by π-π stacking interactions and short C-H···N hydrogen bonds, and a fragment (Py) having partial conformational freedom.

Contact heterogeneity in deer mice: implications for Sin Nombre virus transmission.

Heterogeneities within disease hosts suggest that not all individuals have the same probability of transmitting disease or becoming infected. This heterogeneity is thought to be due to dissimilarity in susceptibility and exposure among hosts. As such, it has been proposed that many host-pathogen systems follow the general pattern whereby a small fraction of the population accounts for a large fraction of the pathogen transmission. This disparity in transmission dynamics is often referred to as '20/80 Rule', i.e. approximately 20 per cent of the hosts are responsible for 80 per cent of pathogen transmission. We investigated the role of heterogeneity in contact rates among potential hosts of a directly transmitted pathogen by examining Sin Nombre virus (SNV) in deer mice (Peromyscus maniculatus). Using foraging arenas and powder marking, we documented contacts between wild deer mice in Great Basin Desert, central Utah. Our findings demonstrated heterogeneity among deer mice, both in frequency and in duration of contacts with other deer mice. Contact dynamics appear to follow the general pattern that a minority of the population accounts for a majority of the contacts. We found that 20 per cent of individuals in the population were responsible for roughly 80 per cent of the contacts observed. Larger-bodied individuals appear to be the functional group with the greatest SNV transmission potential. Contrary to our predictions, transmission potential was not influenced by breeding condition or sex.

Extrinsic Heavy Metal Atom Effect on the Solid-State Room Temperature Phosphorescence of Cyclic Triimidazole.

Four coordination compounds [Zn3 (CH3 COO)6 (H2 O)2 ](TT)2 [Cd(H2 O)6 ](ClO4 )2 (TT)2 , [Cd(H2 O)6 ](BF4 )2 (TT)2 , [Zn(H2 O)6 ](BF4 )2 (TT)2 (1-4) accommodating the crystallization induced emissive triimidazo[1,2-a:1',2'-c:1'',2''-e][1,3,5]triazine (TT) as a guest in their crystal lattice are isolated and fully photophysically and structurally characterized. Their emission properties are compared with those of afterglow TT and interpreted taking into account the heavy atom effect and crystal packing similarities and differences. In the case of 1, due to the closeness of the TT H-aggregates arrangement with that of the phosphor's pure phase, the observed intensification of the phosphorescent emission at the expense of the prompt one is attributed to the extrinsic heavy atom effect of Zn. In 2 and 3, the heavier Cd atom is responsible for a decrease in the lifetimes of the afterglow emission, despite the presence of tightly overlapped H-dimers in the crystal structure. Finally, for 4, isostructural with 3, the Zn atom reveals in RTUP lifetime comparable with that of 1.

H-Aggregates Granting Crystallization-Induced Emissive Behavior and Ultralong Phosphorescence from a Pure Organic Molecule.

Solid-state luminescent materials with long lifetimes are the subject of ever-growing interest from both a scientific and a technological point of view. However, when dealing with organic compounds, the achievement of highly efficient materials is limited by aggregation-caused quenching (ACQ) phenomena on one side and by ultrafast deactivation of the excited states on the other. Here, we report on a simple organic molecule, namely, cyclic triimidazole (C9H6N6), 1, showing crystallization-induced emissive (CIE) behavior and, in particular, ultralong phosphorescence due to strong coupling in H-aggregated molecules. Our experimental data reveal that luminescence lifetimes up to 1 s, which are several orders of magnitude longer than those of conventional organic fluorophores, can be realized under ambient conditions, thus expanding the class of organic materials for phosphorescence applications.