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Multi-target-directed ligands (MTDLs) represent a promising frontier in tackling the complexity of multifactorial pathologies like Alzheimer's disease (AD). The synergistic inhibition of MAO-B, MAO-A, and AChE is believed to enhance treatment efficacy. A novel coumarin-based molecule substituted with O-phenylpiperazine via three- and four-carbon linkers at the 5- and 7-positions, has been identified as an effective MTDL against AD. Employing a medicinal chemistry approach, combined with molecular docking, molecular dynamic simulation, and ΔGbind estimation, two series of derivatives emerged as potent MTDLs: 8-acetyl-7-hydroxy-4-methylcoumarin (IC50: 1.52–4.95 μM for hAChE, 6.97–7.65 μM for hMAO-A) and 4,7-dimethyl-5-hydroxycoumarin (IC50: 1.88–4.76 μM for hMAO-B). They displayed binding free energy (ΔGbind) of −76.32 kcal/mol (11) and −70.12 kcal/mol (12) against AChE and −66.27 kcal/mol (11) and −62.89 kcal/mol (12) against MAO-A. It is noteworthy that compounds 11 and 12 demonstrated efficient binding to both AChE and MAO-A, while compounds 3 and 10 significantly reduced MAO-B and AChE aggregation in vitro. These findings provide structural templates for the development of dual MAO and AChE inhibitors for the treatment of neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

In photodynamic therapy (PDT), photosensitizer (PS) molecules are irradiated by light to generate reactive oxygen species (ROS), the presence of which subsequently leads to cell death. At present, the modality is limited to the treatment of skin diseases because of the low tissue penetration of visible or ultraviolet light required for producing ROS. To increase tissue penetration and extend the therapeutic possibilities of PDT to the treatment of deep-seated cancer, rare-earth doped nanoparticles capable of up-converting infrared to visible light are investigated. These up-converting nanoparticles (UCNPs) are conjugated with PS molecules to efficiently generate ROS. In this work, we employ hexagonal β-NaYF4:Yb3 + ,Er3 + as UCNPs and Rose Bengal (RB) as PS molecules and demonstrate efficient in vitro PDT using this nanoformulation. Covalent bonding of the RB molecules is accomplished without their functionalization—an approach which is expected to increase the efficiency of ROS generation by 30%. Spectroscopic studies reveal that our approach results in UCNP surface fully covered with RB molecules. The energy transfer from UCNPs to RB is predominantly non-radiative as evidenced by luminescence lifetime measurements. As a result, ROS are generated as efficiently as under visible light illumination. The in vitro PDT is tested on murine breast 4T1 cancer cells incubated with 250 µg ml−1 of the nanoparticles and irradiated with NIR light under power density of 2 W cm−2 for 10 minutes. After 24 hours, the cell viability decreased to 33% demonstrating a very good treatment efficiency. These results are expected to simplify the protocols for preparation of the PDT agents and lead to improved therapeutic effects. [ABSTRACT FROM AUTHOR]

The incorporation of a large ion which violates the Goldschmidt geometric tolerance factor, such as hydroxyethyl ammonium (HEA+), into lead halide perovskites leads to the formation of a lead and halide deficient crystal. The resulting material has a long-range order typical of a three dimensional crystal, which is locally disrupted by octahedron-free channels. Here, we report on low-temperature magneto-optical spectroscopy of lead- and iodine-deficient MAPbI3 (d-MAPbI3) with varying concentrations of Pb–I vacancies in high magnetic fields of up to 68 T. The hybrid nature of the structure of this material is reflected by the surprising coexistence of 3D-like optical transitions at low energy (1.54 eV) and lower dimensional (LD) transitions at high energy (1.9–2.4 eV). The intensity variation between the LD and 3D-like transitions when the concentration of Pb-I vacancies is varied indicates a strong correlation between the structural modifications introduced by the oversized cations and the optical properties. The reduced dimensionality associated with the high energy transitions is supported by the observed smaller diamagnetic shift and shorter carrier lifetimes. [ABSTRACT FROM AUTHOR]

Fluorescent nanothermometers are positioned to revolutionize research into cell functions and provide strategies for early diagnostics. Fluorescent nanostructures hold particular promise to fulfill this potential if nontoxic, stable varieties allowing for precise temperature measurement with high thermal sensitivities can be fabricated. In this work, we investigate the performance of micelle-encapsulated CuInS 2 /ZnS core/shell colloidal quantum dots (QDs) as fluorescent nanothermometers. We demonstrate four temperature readout modes, which are based on variations in the photoluminescence intensity, energy, and lifetime and on a specific ratio of excitation efficiencies. We further leverage this multimodal readout to construct a fifth, multiparametric thermometer calibration based on the multiple linear regression (MLR) model. We show that the MLR approach boosts the thermometer sensitivity by up to 7-fold while reducing the readout error by about a factor of 3. As a result, our QDs offer the highest sensitivities among semiconducting QDs emitting in the first biological window. The obtained results indicate that CuInS 2 /ZnS QDs are excellent candidates for intracellular in vivo thermometry and provide guidelines for further optimization of their performance.

van der Waals heterostructures are currently the focus of intense investigation; this is essentially due to the unprecedented flexibility offered by the total relaxation of lattice matching requirements and their new and exotic properties compared to the individual layers. Here, we investigate the hybrid transition-metal dichalcogenide/2D perovskite heterostructure WS 2 /(PEA) 2 PbI 4 (where PEA stands for phenylethylammonium). We present the first density functional theory (DFT) calculations of a heterostructure ensemble, which reveal a novel band alignment, where direct electron transfer is blocked by the organic spacer of the 2D perovskite. In contrast, the valence band forms a cascade from WS 2 through the PEA to the PbI 4 layer allowing hole transfer. These predictions are supported by optical spectroscopy studies, which provide compelling evidence for both charge transfer and nonradiative transfer of the excitation (energy transfer) between the layers. Our results show that TMD/2D perovskite (where TMD stands for transition-metal dichalcogenides) heterostructures provide a flexible and convenient way to engineer the band alignment.

Lanthanide-doped nanoparticles enable conversion of near-infrared photons to visible ones. This property is envisioned as a basis of a broad range of applications: from optoelectronics, via energy conversion, to bio-sensing and phototherapy. The spectrum of applications can be extended if magnetooptical properties of lanthanide dopants are well understood. However, at present, there are many conflicting reports on the influence of the magnetic field on the upconverted luminescence. In this work, we resolve this discrepancy by performing a comprehensive study of β-NaYF4:Er3+,Yb3+ nanoparticles. Crucially, we show that the magnetic field impacts the luminescence only via a Zeeman-driven detuning between the excitation laser and the absorption transition. On the other hand, the energy transfer and multiphonon relaxation rates are unaffected. We propose a phenomenological model, which qualitatively reproduces the experimental results. The presented results are expected to lead to design of novel, dual-mode opto-magnetic upconverting nanomaterials.