Search

The Ru PR 3 bonds of 1 – 2 ( a - b )- PC , Ru CHPh bonds of 1a - b , 2 - Inact / Act and 1a - b , 2 - RCB were analyzed by charge decomposition (CDA) and natural bond orbital (NBO). We have found that the dissociation step of the Ru PR 3 bond is driven by charge transfer, while the RCB by polarization effects. Furthermore, the π(C ipso )–π*(Ru C) interaction was associated with delocalization effects in the benzylidene ring. Likewise, the nature of the rotameric changes in the carbene was studied through the resonance stabilization energy ( E NLW ). 2 presented a lower Δ E NLW (Inactive → Active) than 1a - b , which confirms that the delocalization effects are related to a low carbene rotameric energy. [ABSTRACT FROM AUTHOR]

Abstract: Nucleophilicity and elecrophilicity of mono and disubstituted silylenes are analyzed using the molecular electrostatic potential and the dual descriptor , defined within the so called conceptual DFT. A set of 32 compounds has been chosen which can be classified into 4 groups or families based on a linear relationship between the molecular electrostatic potential measured in the electrophilic (empty 3 orbital) and nucleophilic (lone pair) regions around of the silicon atom. The electrophilic and nucleophilic character of silylenes given by is connected to the orbital-resolved dual descriptor through the -electron donating property of the substituent. [Copyright &y& Elsevier]

Abstract: We have explored the relationships between the reaction force F(ξ), the reaction force constant κ(ξ) and the projected force constants of the intramolecular proton transfer HO−Nsp="0.25" />→OSH along the intrinsic reaction coordinate ξ. The structural changes and energetics associated with the reaction are analyzed in terms of the three regions defined by F(ξ): reactant, transition and product. The significance of the similarity between κ(ξ) and the variation of the force constant associated to the reaction coordinate mode, kξ (ξ), is discussed in detail. [Copyright &y& Elsevier]

Abstract: The average local ionization energy and the Fukui function f(r) are conceptually-independent measures of molecular reactive behavior. In this Letter, we use Janak’s theorem to establish a plausible link between and f(r). In particular, both can generally be expected to identify the same sites as most reactive toward electrophiles. [Copyright &y& Elsevier]

Highlights: [•] We analyzed the PES of Si10Li8 including planar and three-dimensional structures. [•] The most stable isomer over Si10Li8 PES is a three-dimensional structure. [•] The structure is stabilized by electrostatic interactions between its fragments. [•] The polarizability values correlate in good order with the relative stability. [Copyright &y& Elsevier]

Four new neutral N,N imidoyl-indazole ligands ( L1 , L3, L6, L7 ) and six new Pt(II)-based complexes ( C1 – 5 and C7 ) were synthesized and characterized by spectroscopic and spectrometric techniques. Additionally, compounds L6 , L7 , C3 , C5 and C7 were analyzed using X-ray diffraction. An evaluation of cytotoxicity and cell death in vitro for both ligands and complexes was performed by colorimetric assay and flow cytometry, in four cancer cell lines and VERO cells as the control, respectively. Cytotoxicity and selectivity demonstrated by each compound were dependent on the cancer cell line assayed. IC 50 values of complexes C1 – 5 and C7 were lower than those exhibited for the reference drug cisplatin, and selectivity of these complexes was in general terms greater than cisplatin on three cancer cell lines studied. In HL60 cells, complexes C1 and C5 exhibited the lowest values of IC 50 and were almost five times more selective than cisplatin. Flow cytometry results suggest that each complex predominantly induced necrosis, and its variant necroptosis, instead of apoptosis in all cancer cell lines studied. DNA binding assays, using agarose gel electrophoresis and UV–visible spectrophotometry studies, displayed a strong interaction only between C4 and DNA. In fact, theoretical calculations showed that C4 -DNA binding complex was the most thermodynamic favorable interaction among the complexes in study. Overall, induction of cell death by dependent and independent-DNA-metal compound interactions were possible using imidoyl-indazole Pt(II) complexes as anticancer agents. [ABSTRACT FROM AUTHOR]

During the last decade, the one drug-one target strategy has resulted to be inefficient in facing diseases with complex ethiology like Alzheimer's disease and many others. In this context, the multitarget paradigm has emerged as a promising strategy. Based on this consideration, we aim to develop novel molecules as promiscuous ligands acting in two or more targets at the same time. For such purpose, a new series of indolylpropyl-piperazinyl oxoethyl-benzamido piperazines were synthesized and evaluated as multitarget-directed drugs for the serotonin transporter (SERT) and acetylcholinesterase (AChE). The ability to decrease β-amyloid levels as well as cell toxicity of all compounds were also measured. In vitro results showed that at least four compounds displayed promising activity against SERT and AChE. Compounds 18 and 19 (IC 50 = 3.4 and 3.6 μM respectively) exhibited AChE inhibition profile in the same order of magnitude as donepezil (DPZ, IC 50 = 2.17 μM), also displaying nanomolar affinity in SERT. Moreover, compounds 17 and 24 displayed high SERT affinities (IC 50 = 9.2 and 1.9 nM respectively) similar to the antidepressant citalopram, and significant micromolar AChE activity at the same time. All the bioactive compounds showed a low toxicity profile in the range of concentrations studied. Molecular docking allowed us to rationalize the binding mode of the synthesized compounds in both targets. In addition, we also show that compounds 11 and 25 exhibit significant β-amyloid lowering activity in a cell-based assay, 11 (50% inhibition, 10 μM) and 25 (35% inhibition, 10 μM). These results suggest that indolylpropyl benzamidopiperazines based compounds constitute promising leads for a multitargeted approach for Alzheimer's disease. Image 1 • A series of indolylpropyl benzamidopiperazines have been synthesized as dual target compounds for Alzheimer's Disease. • A variety of substitution patterns of indole and benzamide ring has been studied. • Potent AChE inhibitors and SERT ligands were achieved. • Two compounds exhibited promising Aβ inhibition profiles. • The most active compounds displayed low toxicity in biological assays. [ABSTRACT FROM AUTHOR]