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Crystallization of organic steric molecules often leads to multiple polyhedral crystal morphologies. However, the relationships among the molecular structure, supramolecular interaction, aggregation mode and crystal morphology are still unclear. In this work, we elaborate two model crystals formed by spiro[fluorene‐9,9′‐xanthene] (SFX) and spiro[cyclopenta[1,2‐b : 5,4‐b′]dipyridine‐5,9′‐xanthene] (SDAFX) to demonstrate the feasibility of morphology prediction by periodic bond chain (PBC) theory based on interaction energy (IE) values in terms of single point energy. With non‐directional van der Waals forces, only one PBC direction is found in SFX crystal, leading to the irregular 1D rod‐like structure. Compared with SFX, the extra N heteroatoms in SDAFX can bring additional hydrogen bonds and some other interactions into the bulky molecular skeletons, inducing 3‐dimensionally oriented PBCs to form the explicit F‐face network in SDAFX which leads to the final octahedral structure. A simple and accurate method has been provided to quantify PBC vector on the supramolecular level in the organic molecular system, and the PBC theory has also been further demonstrated and developed in the morphology prediction of organic spiro‐molecules. [ABSTRACT FROM AUTHOR]

Abstract A series of resveratrol dimer derivatives against Alzheimer's disease (AD) was obtained by structural modification and transformation using resveratrol as substrate. Biological analysis revealed that these derivatives had moderate inhibitory activity against human monoamine oxidase B (h MAO-B). In particular, 3 and 7 showed the better inhibitory activity for h MAO-B (IC 50 = 3.91 ± 0.23 μ M, 0.90 ± 0.01 μ M) respectively. Compound 3 (IC 50 = 46.95 ± 0.21 μ M for DPPH, 1.43 and 1.74 trolox equivalent by ABTS and FRAP method respectively), and 7 (IC 50 = 35.33 ± 0.15 μ M for DPPH, 1.70 and 1.97 trolox equivalent by ABTS method and FRAP method respectively) have excellent antioxidant effects. Cellular assay shown that 3 and 7 had lower toxicity and were resistant to neurotoxicity induced by oxidative toxins (H 2 O 2 , rotenone and oligomycin-A). More importantly, the selected compounds have neuroprotective effects against ROS generation, H 2 O 2 -induced apoptosis and a significant in vitro anti-inflammatory activity. The results of the parallel artificial membrane permeability assay for blood-brain barrier indicated that 3 and 7 would be predominant to cross the blood-brain barrier. In this study, mouse microglia BV2 cells were used to establish cell oxidative stress injury model with H 2 O 2 and to explore the protective effect and mechanism of 3 and 7. In general, 3 and 7 can be considered candidates for potential treatment of AD. Graphical abstract Image 1 Highlights • A series of resveratrol dimer derivatives against Alzheimer's disease (AD) was obtained by structural modification and transformation using resveratrol as substrate. • Most of the compounds showed moderate to good inhibitory activities against MAO-B as well as remarkable antioxidant activities. • Compounds 3 and 7 displayed a balanced multifunctional profile having MAO-B inhibition, excellent antioxidant activity. • Compounds 3 and 7 possessed significant neuroprotection against H2O2-induced oxidative damage on PC12 cells and BV2 microglial cells and Lipopolysaccharides (LPS)-stimulated inflammation on BV2 microglial cells. • Compounds 3 and 7 have lower toxicity and could cross the blood-brain barrier. [ABSTRACT FROM AUTHOR]

The formation of amyloid- β (A β) plaques in the brain is one of the main pathological features of Alzheimer's disease (AD). The imaging probes, capable of detecting A β deposition, are important tools for early diagnosis of AD. In this article, we designed, synthesized and evaluated a cyanine-based near-infrared fluorescence (NIRF) probe ZT-1 for the detection of A β deposits in the brain. The probe had excellent fluorescent properties with an emission maximum above 720 nm upon binding to A β aggregates with affinity of 445.0 nM (K d). Furthermore, ZT-1 exhibited good biostability, photostability, and binding selectivity toward A β 1-42 aggregates by in vitro fluorescence staining experiments. In vivo NIRF imaging result also revealed that our probe could efficiently differentiate transgenic and wild-type mice. All these studies indicated that ZT-1 is a promising fluorescent probe for A β plaques in the AD brains. Image 1 • A probe ZT-1 for the detection of A β deposits in the brain was synthesized and evaluated. • ZT-1 exhibited good biostability, photostability, and binding selectivity toward A β 1-42 aggregates. • ZT-1 could efficiently differentiate transgenic and wild-type mice by in vivo NIRF imaging. [ABSTRACT FROM AUTHOR]

A series of salicyladimine derivatives were designed, synthesized and evaluated as multi-target-directed ligands for the treatment of Alzheimer’s disease (AD). Biological activity results demonstrated that some derivatives possessed significant inhibitory activities against amyloid- β (A β ) aggregation and human monoamine oxidase B ( h MAO-B) as well as remarkable antioxidant effects and low cell toxicity. The optimal compound, 5 , exhibited excellent potency for inhibition of self-induced A β 1–42 aggregation (91.3 ± 2.1%, 25 μM), inhibition of h MAO-B (IC 50 , 1.73 ± 0.39 μM), antioxidant effects (43.4 ± 2.6 μM of IC 50 by DPPH method, 0.67 ± 0.06 trolox equivalent by ABTS method), metal chelation and BBB penetration. Furthermore, compound 5 had neuroprotective effects against ROS generation, H 2 O 2 -induced apoptosis, 6-OHDA-induced cell injury, and a significant in vitro anti-inflammatory activity. Collectively, these findings highlighted that compound 5 was a potential balanced multifunctional neuroprotective agent for the development of anti-AD drugs. [ABSTRACT FROM AUTHOR]