Search

The article discusses the active control for vertical fin buffet load alleviation. Twin-tail fighter aircraft may experience intense buffet loads when flying at high angles of attack. One such aircraft is the F/A-18 where the broadband buffet loads primarily excite the first bending and torsional modes of the vertical fin. The result would provide significant vibration and dynamic stresses on the vertical tail structure.

Investigates control laws for an active tunable vibration absorber designed for rotor blade damping augmentation. Observation that most Individual Blade Control (IBC) approaches have attempted to suppress the rotor vibration by actively altering the aerodynamic loads on the blade using techniques such as trailing-edge servoflaps; Presentation of the theoretical characterization of the Smart Spring system as a class of active Tunable Vibration Absorbers; Development of a real-time adaptive control system for a Smart Spring to suppress vibration; Results of initial aerodynamic wind tunnel using the proof-of-concept model of the device in a fixed blade.

The aim of this paper is to identify the impacts of different taxes and expenditures on economic growth. The research is focused on 20 selected European Union Member States. These countries are equally divided into four groups based on their average tax burden as presented in the World Tax Index. A comparison of fiscal attributes among these groups is important for the analysis. Annual government finance data from the years 1995 to 2012 are used for an empirical study. The indicators observed are real GDP change, the composition and volume of total government expenditures, tax quotas of individual taxes and total budget balance. These indicators are used within an endogenous growth model together with capital stock and an approximation of human capital. A panel regression with fixed effects is used as an analytic tool. The main results are that an increase in social contributions, property, production and personal income tax quotas has an adverse effect on economic growth.

Objective: To describe the knowledge of, and experience with, the Interest Group in Family Medicine (IgFM) at the University of Toronto, among undergraduate medical students; to explore the effects of the IgFM on undergraduate medical students; and to help determine future directions for the IgFM and other family medicine interest groups in Canada.Design: Qualitative descriptive design and focus groups.Setting: The Faculty of Medicine at the University of Toronto in Ontario.Participants: A total of 45 students in the undergraduate medical school program at the University of Toronto participated in this study. Approximately equal numbers of students from each year were represented in the sample.Method: Focus groups were conducted to determine students' knowledge of, experiences with, and perspectives on the IgFM. The focus groups were audiotaped and transcribed verbatim. Transcripts were coded and analyzed for themes using qualitative content analysis. Data were collected until saturation of emerging themes was reached.Main Findings: The students were generally knowledgeable about the IgFM and many had attended IgFM events. The IgFM had different effects on students depending on their level of interest in family medicine (FM). For those already interested in FM, the IgFM helped to maintain and support that interest. For students still undecided about their career choices, the IgFM helped to support continued interest in FM by dispelling negative myths about the discipline, providing positive peer influences, and supplying information about careers in FM. For students not interested in FM, the IgFM provided helpful information about the discipline. Students also had many useful suggestions regarding the future direction of the IgFM.Conclusion: The IgFM has been successful in increasing medical student exposure to FM and in supporting students' interest in this discipline. Information from this study also provides strategies for future direction to the IgFM and other family medicine interest groups in Canada and the United States. [ABSTRACT FROM AUTHOR]

Developing bioinspired materials to convert sunlight into electricity efficiently is paramount for sustainable energy production. Fluorescent proteins are promising candidates as photoactive materials due to their high fluorescence quantum yield and absorption extinction coefficients in aqueous media. However, developing artificial bioinspired photosynthetic systems requires a detailed understanding of molecular interactions and energy transfer mechanisms in the required operating conditions. Here, the supramolecular self-assembly and photophysical properties of fluorescent proteins complexed with organic dyes are investigated in aqueous media. Supercharged mGreenLantern protein, mutated to have a charge of +22, is complexed together with anionic zinc phthalocyanines having 4 or 16 carboxylate groups. The structural characterization reveals a strong electrostatic interaction between the moieties, accompanied by partial conformational distortion of the protein structure, yet without compromising the mGreenLantern chromophore integrity as suggested by the lack of emission features related to the neutral form of the chromophore. The self-assembled biohybrid shows a total quenching of protein fluorescence, in favor of an energy transfer process from the protein to the phthalocyanine, as demonstrated by fluorescence lifetime and ultrafast transient absorption measurements. These results provide insight into the rich photophysics of fluorescent protein-dye complexes, anticipating their applicability as water-based photoactive materials., (© 2024 The Author(s). Advanced Biology published by Wiley‐VCH GmbH.)

Subphthalocyanines (SubPcs) and their aza-analogues (SubTPyzPzs) are fluorophores with strong orange fluorescence emission; however, their sensing ability towards metal cations remains uncharted. To fill this gap, we have developed an efficient method for introducing aza-crown moieties at the axial position of SubPcs and SubTPyzPzs to investigate the structure-activity relationship for sensing alkali (Li + , Na + , K + ) and alkaline earth metal (Ca 2+ , Mg 2+ , Ba 2+ ) cations. SubPcs showed better photostability than SubTPyzPzs and even a commonly utilized dye, 6-carboxyfluorescein. Selectivity toward metal cations was driven by the size of the aza-crown, irrespective of the counter anion. The stoichiometry of binding was found to be 1 : 1 in all cases, and the interaction between SubPcs and cations was characterized by the corresponding apparent binding constants ( K a ). Notably, an unusually strong interaction of all sensoric SubPcs with Ba 2+ compared to other studied cations was demonstrated. The role of the surrounding environment, i.e. the addition of water or methanol, in sensing cations is shown in detail as well. Selectivity towards K + over Na + was demonstrated in aqueous media with SubPcs bearing the 1-aza-6-crown-18 moiety in Tween 80 micelles. In this case, a 5-fold increase of the fluorescence quantum yield was observed upon binding K + ions. The high brightness, photostability, and sensing activity in aqueous media make SubPc macrocycles promising fluorophores for metal cation sensing.

Biothiols (cysteine, homocysteine, and glutathione) are an important class of compounds with a free thiol group. These biothiols plays an important role in several metabolic processes in living bodies when present in optimum concentration. Researchers have developed several probes for the detection and quantification of biothiols that can absorb in UV, visible, and near-infrared (NIR) regions of the electromagnetic spectrum. Among them, NIR organic probes have attracted significant attention due to their application in in vivo and in vitro imaging. In this review, we have summarized probes for these biothiols, which could work in the NIR region, and discussed their sensing mechanism and potential applications. Along with focusing on the pros and cons of the reported probes we have classified them according to the fluorophore used and summarized their photophysical and sensing properties (emission, response time, limit of detection)., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

The short oligodeoxynucleotide (ODN) probes are suitable for good discrimination of point mutations. However, the probes suffer from low melting temperatures. In this work, the strategy of using acridine-4-carboxamide intercalators to improve thermal stabilisation is investigated. The study of large series of acridines revealed that optimal stabilisation is achieved upon decoration of acridine by secondary carboxamide carrying sterically not demanding basic function bound through a two-carbon linker. Two highly active intercalators were attached to short probes (13 or 18 bases; designed as a part of HFE gene) by click chemistry into positions 7 and/or 13 and proved to increase the melting temperate (Tm) of the duplex by almost 8°C for the best combination. The acridines interact with both single- and double-stranded DNAs with substantially preferred interaction for the latter. The study of interaction suggested higher affinity of the acridines toward the GC- than AT-rich sequences. Good discrimination of two point mutations was shown in practical application with HFE gene (wild type, H63D C > G and S65C A > C mutations). Acridine itself can also serve as a fluorophore and also allows discrimination of the fully matched sequences from those with point mutations in probes labelled only with acridine., (© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Effective interaction with biomembranes is essential for activity of photosensitizers; however, majority of them are highly charged symmetrical species. Amphiphilic cationic phthalocyanines differing in bulkiness of substitution on lipophilic part (-H, -SMe, -StBu) were therefore prepared. Compounds had high singlet oxygen production (Φ Δ =0.38-0.46, DMSO), good fluorescence emission (Φ F =0.21-0.26, DMSO), and log P values ranging -0.07-1.1 (1-octanol/PBS). Study of interaction with liposomes revealed that also bulky -StBu derivatives are able to enter biomembranes. Detail in vitro studies (toxicity, subcellular localization, type of cell death, and morphology) were performed. Compounds were characterized by excellent EC 50 values in range of dozens of nM (HeLa, EA.hy926, MCF-7, HCT116), which were dependent on drug-light interval and reached plateau after 4 h on HeLa cells. Well-balanced lipophilicity with ability to interact with biomembranes rank these derivatives among perspective photosensitizers, even for vascular-targeted PDT (VTP) since they kill EA.hy926 without any preincubation time., (© 2022 Wiley-VCH GmbH.)

Magnesium complexes of phthalocyanines (Pcs) and their aza-analogues have a great potential in medical applications or fluorescence detection. They are known to demetallate to metal-free ligands in acidic environments, however, detailed investigation of this process and its possible prevention is lacking. In this work, a conversion of lipophilic and water-soluble magnesium complexes of Pcs and tetrapyrazinoporphyrazines (TPyzPzs) to metal-free ligands was studied in relation to the acidity of the environment (organic solvent, water) including the investigation of the role of delivery systems (microemulsion or liposomes) in improvement in their acido-stability. The mechanism of the demetallation in organic solvents was based on an acidoprotolytic mechanism with the protonation of the azomethine nitrogen as the first step and a subsequent conversion to non-protonated metal-free ligands. In water, the mechanism seemed to be solvoprotolytic without any protonated intermediate. The water-soluble magnesium complexes were stable in a buffer with a physiological pH 7.4 while a time-dependent demetallation was observed in acidic pH. The demetallation was immediate at pH < 2 while the full conversion to metal-free ligand was done within 10 min and 45 min for TPyzPzs at pH 3 and pH 4, respectively. Incorporation of lipophilic magnesium complexes into microemulsion or liposomes substantially decreased the rate of the demetallation with the latter delivery system being much more efficient in the protection from the acidic environment. A comparison of two different macrocyclic cores revealed significantly higher kinetic inertness of magnesium TPyzPz complexes than their Pc analogues.

The photodynamic properties of a series of non-halogenated, dibrominated and diiodinated BODIPYs with a phthalimido or amino end modification on the phenoxypentyl and phenoxyoctyl linker in the meso position were investigated. Halogen substitution substantially increased the singlet oxygen production based on the heavy atom effect. This increase was accompanied by a higher photodynamic activity against skin melanoma cancer cells SK-MEL-28, with the best compound reaching an EC 50 = 0.052 ± 0.01 µM upon light activation. The dark toxicity (toxicity without light activation) of all studied dyes was not detected up to the solubility limit in cell culture medium (10 µM). All studied BODIPY derivatives were predominantly found in adiposomes (lipid droplets) with further lower signals colocalized in either endolysosomal vesicles or the endoplasmic reticulum. A detailed investigation of cell death indicated that the compounds act primarily through the induction of apoptosis. In conclusion, halogenation in the 2,6 position of BODIPY dyes is crucial for the efficient photodynamic activity of these photosensitizers.

Photodynamic therapy is a treatment modality of cancer based on the production of cytotoxic species upon the light activation of photosensitizers. Zinc phthalocyanine photosensitizers bearing four or eight bulky 2,6-di(pyridin-3-yl)phenoxy substituents were synthesized, and pyridyl moieties were methylated. The quaternized derivatives did not aggregate at all in water and retained their good photophysical properties. High photodynamic activity of these phthalocyanines was demonstrated on HeLa, MCF-7, and EA.hy926 cells with a very low EC 50 of 50 nM (for the MCF-7 cell line) upon light activation while maintaining low toxicity in the dark (TC 50 ≈ 600 μM), giving thus good phototherapeutic indexes (TC 50 /EC 50 ) above 1400. The compounds localized primarily in the lysosomes, leading to their rupture after light activation. This induced an apoptotic cell death pathway with secondary necrosis because of extensive and swift damage to the cells. This work demonstrates the importance of a bulky and rigid arrangement of peripheral substituents in the development of photosensitizers., Competing Interests: The authors declare no competing financial interest., (© 2021 American Chemical Society.)

Although subphthalocyanines (SubPcs) possess advantageous fluorescence properties and serve as an amazing tool to attach a recognition sensor moiety to the axial position, a limited number of switchable SubPcs have been described so far. Isosteric aza-replacement is known to improve sensing properties in closely related phthalocyanine families; however, pyrazino[2,3-b,g,l]subporphyrazines (SubPyzPzs) have not yet been investigated for use in sensing applications. Therefore, this project focuses on the synthesis and sensing abilities of pH-sensitive SubPcs and SubPyzPzs on the principle of photoinduced electron transfer (PET). 4-Dimethylaminophenoxy (for acidic pH) or 4-hydroxyphenoxy (for basic pH) groups were employed as pH-sensitive axial ligands. Electrochemical studies revealed improvements in the electron-accepting properties of SubPyzPzs (E red -0.56 V vs. SCE) in comparison to those of SubPcs (E red -1.0 V vs. SCE). Hydroxy groups on the axial phenoxy ligands of SybPyzPzs and SubPcs have been found to act as donors for PET. The sensing properties under basic conditions could not be studied, since all the SubPcs and SubPyzPzs decomposed under basic conditions, SubPyzPzs were more susceptible to this process. On the other hand, compounds with 4-dimethylaminophenoxy groups as axial ligands showed great potential for sensing applications. These compounds were nonfluorescent (Φ F < 0.01) in acetone due to efficient PET, while their fluorescence steeply increased by two orders of magnitude upon the addition of trifluoroacetic acid, reaching a Φ F value of up to 0.17 (λ em range of 563-590 nm). These compounds maintained their sensing properties in aqueous medium after incorporation into microemulsions. The most basic derivative showed pK A = 2.95 with Φ F = 0.10 in the ON state (fluorescence enhancement factor = 46, λ em = 577 nm).

The development of new non-aggregated phthalocyanines bearing multivalent saccharide moieties on their macrocyclic rims is of great interest. Many characteristics, including water-solubility, non-toxicity and others, can be feasibly obtained by these amphiphiles which can be considered as a key solution for demonstrating highly efficient photoactive materials in water. Herein, a family of five newly prepared dually directional Zn(ii) containing phthalocyanines (PcG1-4) and azaphthalocyanine (AzaPcG1) glycoconjugates is described. The unique spatial arrangement of the glucoside units based on peripherally hexadeca-(PcG1) and nonperipherally octa-(PcG4) macrocycles provides a fully monomeric behaviour along with a high fluorescence (Φ F ∼ 0.21) in aqueous solution. These amphiphiles were characterized by low toxicity, and an extremely low cellular uptake was obtained due to the highly polar nature of the glucoside substituents. Accordingly, their potential as suitable photoactive chromophores for red-emitting extracellular fluorescent probes has been confirmed upon the evaluation of paracellular transport using a layer of MDCKII cells with the permeability coefficient fully comparable with an established evaluator of the integrity of the monolayer.

Though tetrapyrazinoporphyrazines (TPyzPzs) are generally presented as universal dark quenchers for oligonucleotide probes, the availability of TPyzPzs bearing different functional groups suitable for attachment to 3', and 5' ends or intrastrand positions remains rather limited. Therefore, a synthetic route to hexa(bis(2-methoxyethyl)amino) or hexa(diethylamino) TPyzPzs functionalized by an azide, hydroxy, or carboxy group or their combinations was developed. Studies of self-assembly into J-dimers in nonpolar solvents and their stability upon titration with pyridine (association constants, K P values, ranging 0.32-12.7×10 2  M -1 ) revealed that smaller peripheral substituents and functionalization of TPyzPzs improves the stability of J-dimers. Φ Δ and Φ F were low for the monomers (Φ F <0.0001, Φ Δ <0.008, DMF) due to quenching by intramolecular charge transfer; however, they increased in nonpolar solvents and after self-assembly into J-dimer (up to Φ F =0.027, Φ Δ =0.28)., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The spatiotemporal sensing of specific cationic and anionic species is crucial for understanding the processes occurring in living systems. Herein, we developed new fluorescence sensors derived from tetrapyrazinoporphyrazines (TPyzPzs) with a recognition moiety that consists of an aza-crown and supporting substituents. Their sensitivity and selectivity were compared by fluorescence titration experiments with the properties of known TPyzPzs (with either one aza-crown moiety or two of these moieties in a tweezer arrangement). Method of standard addition was employed for analyte quantification in saliva. For K + recognition, the new derivatives had comparable or larger association constants with larger fluorescence enhancement factors compared to that with one aza-crown. Their fluorescence quantum yields in the ON state were 18× higher than that of TPyzPzs with a tweezer arrangement. Importantly, the sensitivity toward cations was strongly dependent on counteranions and increased as follows: NO 3 - < Br - < CF 3 SO 3 - < ClO 4 - ≪ SCN - . This trend resembles the chaotropic ability expressed by the Hofmeister series. The high selectivity toward KSCN was explained by synergic association of both K + and SCN - with TPyzPz sensors. The sensing of SCN - was further exploited in a proof of concept study to quantify SCN - levels in the saliva of a smoker and to demonstrate the sensing ability of TPyzPzs under in vitro conditions.

Magnesium(ii) tetrapyrazinoporphyrazines (TPyzPzs) are excellent red fluorophores (λF ∼ 663 nm, ΦF ∼ 0.53 in THF). In this work, a series of magnesium(ii) complexes of unsymmetrical TPyzPzs bearing one or two phenol substituents was prepared. Suitable substitutions on the phenolic moiety tuned its pKa in the range of 5.5 to 13. Deprotonation of the phenolic group at higher pH induced a strong donor (phenolate) in the macrocycle that led to pH-dependent quenching of the red fluorescence of these indicators. pH sensing was proved in water solutions after the incorporation of TPyzPzs into two delivery systems - microemulsions and liposomes. The latter also serves as a simple model of biomembranes. Finally, a wavelength-ratiometric probe was constructed by the incorporation of a TPyzPz indicator and lipophilic pH-nonsensitive BODIPY dye into liposomes. Synthetic precursors for TPyzPzs, substituted pyrazine-2,3-dicarbonitriles, also represent donor-acceptor systems and the pH-dependent changes in absorption spectra may be easily visible to the naked eye.

Herein, we present a series of isomerically pure, peripherally alkyl substituted, soluble and low aggregating azaphthalocyanines as well as their new, smaller hybrid homologues, azasubphthalocyanines. The focus lies on the effect of the systematically increasing number of aza building blocks [-N[double bond, length as m-dash]] replacing the non-peripheral [-CH[double bond, length as m-dash]] units and their influence on the physical and photophysical properties of these chromophores. The absolute and relative HOMO-LUMO energies of azaphthalocyanines were analyzed using UV-Vis and CV and compared to the density functional theory calculations (B3LYP, TD-DFT). The lowering of the HOMO level is revealed as the determining factor for the trend in the adsorption energies by electronic structure analysis. Crystals of substituted subphthalocyanines, N2-Pc*H2 and N4-[Pc*Zn·H2O], were obtained out of DCM. For the synthesis of the valuable tetramethyltetralin phthalocyanine building block a new highly efficient synthesis involving a nearly quantitative CoII catalyzed aerobic autoxidation step is introduced replacing inefficient KMnO4/pyridine as the oxidant.

Unsymmetrical dialkylamino-substituted zinc azaphthalocyanine (AzaPc) exhibits unique spectral and photophysical properties for dark quenchers of fluorescence in DNA hybridization probes. The panchromatic light absorption of AzaPc from 300 nm up to at least 700 nm and its lack of fluorescence make it an ideal candidate for a universal dark quencher. To prove this experimentally, oligodeoxyribonucleotide probes were labeled at the 3'-end by this AzaPc and at the 5'-end by a fluorophore used in the polymerase chain reaction (PCR)-that is, fluorescein, CAL Fluor Red 610, and Cy5. AzaPc showed a significantly higher quenching efficiency compared to the commercially available dark quenchers (BHQ-1, BHQ-2, BBQ-650) in a developed model of TaqMan PCR assay. The AzaPc-labeled probe proved to also be useful in a practical PCR assay for the quantification of the SLCO2B1 transporter gene expression. The constructed calibration curves indicated linearity in the range from 10 2 to 10 7 of target copies., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A unique combination of two independent mechanisms of fluorescence quenching, namely intramolecular charge transfer (ICT) from a peripheral donor and protonation of azomethine nitrogen atoms in zinc tetrapyrazinoporphyrazines (TPyzPz), provides a new possibility for sensing pH in a specific range. The pH selectivity was controlled by the different basicities of the donor for ICT (dimethylaminoaryl), which was connected to the macrocycle by π-extended linkers of different lengths. ICT and protonation have been studied in detail by photophysical, spectral (UV/Vis and MCD spectra), and electrochemical measurements, and further supported by theoretical calculations (DFT, TDDFT). The pH-sensing properties of the TPyzPzs have been investigated in THF and in water after anchoring the TPyzPzs to liposomes. The salient pK a values were around 1.3 (azomethine nitrogen) and 2.29-4.76 (donor for ICT). The lead indicators (sensing over a pH range of 1.0-2.5) with fairly steep sensing profiles exhibited increases in fluorescence between the OFF/ON states of more than 20-fold and strong absorption in the red region (Q-band maximum >650 nm, ϵ≈2×10 6  m -1  cm -1 )., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)