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The controllable packing of functional nanoparticles (NPs) into crystalline lattices is of interest in the development of NP-based materials. Here we demonstrate that the size, morphology and symmetry of such supercrystals can be tailored by adjusting the surface dynamics of their constituent NPs. In the presence of excess tetraethylammonium cations, atomically precise [Au

DNA-stabilized silver nanoclusters (AgN-DNAs) are known to have one or two DNA oligomer ligands per nanocluster. Here, we present the first evidence that AgN-DNA species can possess additional chloride ligands that lead to increased stability in biologically relevant concentrations of chloride. Mass spectrometry of five chromatographically isolated near-infrared (NIR)-emissive AgN-DNA species with previously reported X-ray crystal structures determines their molecular formulas to be (DNA)2[Ag16Cl2]8+. Chloride ligands can be exchanged for bromides, which red-shift the optical spectra of these emitters. Density functional theory (DFT) calculations of the 6-electron nanocluster show that the two newly identified chloride ligands were previously assigned as low-occupancy silvers by X-ray crystallography. DFT also confirms the stability of chloride in the crystallographic structure, yields qualitative agreement between computed and measured UV-vis absorption spectra, and provides interpretation of the 35Cl-nuclear magnetic resonance spectrum of (DNA)2[Ag16Cl2]8+. A reanalysis of the X-ray crystal structure confirms that the two previously assigned low-occupancy silvers are, in fact, chlorides, yielding (DNA)2[Ag16Cl2]8+. Using the unusual stability of (DNA)2[Ag16Cl2]8+ in biologically relevant saline solutions as a possible indicator of other chloride-containing AgN-DNAs, we identified an additional AgN-DNA with a chloride ligand by high-throughput screening. Inclusion of chlorides on AgN-DNAs presents a promising new route to expand the diversity of AgN-DNA structure-property relationships and to imbue these emitters with favorable stability for biophotonics applications.

Most inorganic nanoparticles are directly surface-terminated (and -stabilized) by protecting ligands, which could greatly affect the atomic packing and physical/chemical properties of their inorganic cores. Here, we show that the intermolecular interactions between the adsorbed molecules and surface ligands can also affect the core structure of inorganic nanoparticles. Through the coupling/decoupling of cationic surfactants (cetyltrimethylammonium cations, CTA+) and anionic surface ligands (para-mercaptobenzoic acid, p-MBA) in the aqueous phase, we have achieved a reversible transformation between two isomers of [Au25(p-MBA)18]− nanoclusters. The interconversion process between the two isomers shows the characteristics of a reversible nanocluster isomerization process, with a measured forward and backward activation barrier of 1.16 and 1.17 eV, respectively. One of the isomers has the structure similar to the single-crystal data of [Au25(SR)18]− known since 2008. The other isomer features a distinctly different optical absorption spectrum and color change (i.e., reddish brown to dark green) in the solution phase, and its structure is identified to be the one recently predicted and observed in gas phase through density functional theory (DFT) calculations. The two isomers are topologically connected via a simple rotation of the gold core without breaking any Au-S bonds at the metal-ligand interface. Molecular dynamics simulations suggest that the adsorbed CTA+ cations would interact with the p-MBA layer through the CH∙∙∙π interaction and stabilize the more open ligand shell of the new isomer in the forward isomerization process. Interestingly, this principle can also be extended to organic phases by using organo-soluble cations to stimulate the surface interactions. Our research proposes a new approach to control the structure of inorganic nanoparticles, which helps to customize their electronic and optical properties in the solution phase without changing their surface ligands.

We present a novel strategy for tailoring the fluorescent azadioxatriangulenium (KU) dye-based pH sensor to the target pH range by regulating the p

High-resolution electrospray ionization ion mobility mass spectrometry has revealed a gas-phase isomer of the ubiquitous, extremely well-studied Au25(SR)18 cluster both in anionic and cationic form. The relative abundance of the isomeric structures can be controlled by in-source activation. The measured collision cross section of the new isomer agrees extremely well with a recent theoretical prediction (Matus, M. F.; et al. Chem. Commun. 2020, 56, 8087) corresponding to a Au25(SR)18– isomer that is energetically close and topologically connected to the known ground-state structure via a simple rotation of the gold core without breaking any Au–S bonds. The results imply that the structural dynamics leading to isomerization of thiolate-protected gold clusters may play an important role in their gas-phase reactions and that isomerization could be controlled by external stimuli. peerReviewed

Denervation of skeletal muscles induces severe muscle atrophy, which is preceded by cellular alterations such as increased plasma membrane permeability, reduced resting membrane potential and accelerated protein catabolism. The factors that induce these changes remain unknown. Conversely, functional recovery following denervation depends on successful reinnervation. Here, we show that activation of nicotinic acetylcholine receptors (nAChRs) by quantal release of acetylcholine (ACh) from motoneurons is sufficient to prevent changes induced by denervation. Using in vitro assays, ACh and non-hydrolysable ACh analogs repressed the expression of connexin43 and connexin45 hemichannels, which promote muscle atrophy. In co-culture studies, connexin43/45 hemichannel knockout or knockdown increased innervation of muscle fibers by dorsal root ganglion neurons. Our results show that ACh released by motoneurons exerts a hitherto unknown function independent of myofiber contraction. nAChRs and connexin hemichannels are potential molecular targets for therapeutic intervention in a variety of pathological conditions with reduced synaptic neuromuscular transmission., Denervation of muscle fibres induces muscle atrophy, via mechanisms that remain unclear. Here, the authors show that binding of acetylcoline to its receptor at the neuromuscular junction represses the expression of connexins 43 and 45, which promote atrophy, and is sufficient to prevent denervation-induced loss of myofibre mass.

Energetically low-lying structural isomers of the much-studied thiolate-protected gold cluster Au25(SR)18− are discovered from extensive (80 ns) molecular dynamics (MD) simulations using the reactive molecular force field ReaxFF and confirmed by density functional theory (DFT). A particularly interesting isomer is found, which is topologically connected to the known crystal structure by a low-barrier collective rotation of the icosahedral Au13 core. The isomerization takes place without breaking of any Au–S bonds. The predicted isomer is essentially iso-energetic with the known Au25(SR)18− structure, but has a distinctly different optical spectrum. It has a significantly larger collision cross-section as compared to that of the known structure, which suggests it could be detectable in gas phase ion-mobility mass spectrometry.

In recent years, the studies of RNA and its use for the development of RNA based vaccines have increased drastically. Although cyanine dyes are commonly used probes for studying nucleic acids, in a wide range of applications, there is still a growing need for better and brighter dyes. To meet this demand, we have systematically studied the structure of SYBR green-related cyanine dyes to gain a deeper understanding of their interactions with biomolecules especially how they interact with nucleic acids and the structural components which makes them strongly fluorescent. Herein, five new dyes were synthesized, and their photophysical properties were evaluated. Observations of photophysical characteristics were compared to calculations by using density functional theory in its ground state and time-dependent form to model the optical absorption spectra and excited state properties of the selected molecules. Single crystal X-ray crystal structures of five cyanine dyes were determined and the interactions of the cyanine dye-DNA complex were studied by using molecular docking and molecular dynamics calculations. Three molecular structural features were discovered: a) removing the benzene ring from the thiazolium moiety of the dye lowers the fluorescence drastically, and that the quantum yield can be enhanced, therefore increasing the fluorescence, by b) incorporating methanethiol substituent at the quinoline moiety instead of dimethylamine or c) changing the thiazolium moiety to an oxazolium moiety. peerReviewed

Potential biomedical applications of gold nanoparticles have increasingly been reported with great promise for diagnosis and therapy of several diseases. However, for such a versatile nanomaterial, the advantages and potential health risks need to be addressed carefully, as the available information about their toxicity is limited and inconsistent. Atomically precise gold nanoclusters (AuNCs) have emerged to overcome this challenge due to their unique features, such as superior stability, excellent biocompatibility, and efficient renal clearance. Remarkably, the elucidation of their structural and physicochemical properties provided by theory-experiment investigations offers exciting opportunities for site-specific biofunctionalization of the nanoparticle surface, which remains a significant concern for most of the materials in the biomedical field. This concept highlights the advantages conferred by atomically precise AuNCs for biomedical applications and the powerful strategy combining computational and experimental studies towards finding an optimal biocompatible AuNCs-based nanosystem.

Energetically low-lying structural isomers of the much-studied thiolate-protected gold cluster Au25(SR)18- are discovered from extensive (80 ns) molecular dynamics (MD) simulations using the reactive molecular force field ReaxFF and confirmed by density functional theory (DFT). A particularly interesting isomer is found, which is topologically connected to the known crystal structure by a low-barrier collective rotation of the icosahedral Au13 core. The isomerization takes place without breaking of any Au-S bonds. The predicted isomer is essentially iso-energetic with the known Au25(SR)18- structure, but has a distinctly different optical spectrum. It has a significantly larger collision cross-section as compared to that of the known structure, which suggests it could be detectable in gas phase ion-mobility mass spectrometry.

Prostate cancer is one of the neoplastic diseases with the highest morbidity and mortality in the world. The diversity of available treatments and side effects related to therapeutic treatments are severe and affect a patient's quality of life. Thus, to creating new therapeutic alternatives to reduce morbidity and creating safe and effective therapies is a constant challenge. Recently, the use of traditional medicine and chemoprevention has gained importance. Several clinical and epidemiological studies suggest that a high-terpenoid compound-based diet is associated with a reduced risk of prostate cancer. This review is focused on the anti-proliferative effects of different terpenoids isolated from natural sources on human prostate cancer cells, with the aim of setting the basis to use these compounds as phytotherapeutic, nutraceutical and functional ingredients.

Despite the numerous advantages offered by diverse platforms based on nanomedicine, several nanomaterials have shown significant cell toxicity that could induce chronic adverse effects on human health. Blood compatibility is one of the leading factors to consider for the design and development of nanosystems as therapeutics. Aforementioned is because systemic circulation is the gateway for most nano-drug therapeutic systems and its interactions with the blood components such as platelets could influence the maintenance of hemostasis and thrombus formation. Unfortunately, the thrombotoxicity of some nanomaterials regarding the activation/inhibition of platelets limits their biomedical applications. Additionally, the critical factors that drive those effects on platelet function are still not entirely elucidated. In this work, we describe the effect of different nanomaterials on the platelet function, its action mechanisms, and future potential as nanotherapeutics.

Nanotherapeutics is a promising field for numerous diseases and represents the forefront of modern medicine. In the present work, full atomistic computer simulations were applied to study poly(lactic acid) (PLA) nanoparticles conjugated with polyethylene glycol (PEG). The formation of this complex system was simulated using the reactive polarizable force field (ReaxFF). A full picture of the morphology, charge and functional group distribution is given. We found that all terminal groups (carboxylic acid, methoxy and amino) are randomly distributed at the surface of the nanoparticles. The surface design of NPs requires that the charged groups must surround the surface region for an optimal functionalization/charge distribution, which is a key factor in determining physicochemical interactions with different biological molecules inside the organism. Another important point that was investigated was the encapsulation of drugs in these nanocarriers and the prediction of the polymer-drug interactions, which provided a better insight into structural features that could affect the effectiveness of drug loading. We employed blind docking to predict NP-drug affinity testing on an antiaggregant compound, cilostazol. The results suggest that the combination of molecular dynam ics ReaxFF simulations and blind docking techniques can be used as an explorative tool prior to experiments, which is useful for rational design of new drug delivery systems. Fil: Matus, María Francisca. Universidad de Talca; Chile Fil: Ludueña, Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentina Fil: Vilos, Cristian. Universidad Andrés Bello; Chile Fil: Palomo, Iván. Universidad de Talca; Chile Fil: Mariscal, Marcelo. Universidad Nacional de Córdoba. Facultad de Cs.químicas. Departamento de Química Teórica y Computacional; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentina

Objectives Inhibition of acetylcholinesterase (AChE) is a common treatment for early stages of Alzheimer's disease. In this study, nine isoxazoles derivatives were tested for their in-vitro AChE activity. The molecular docking showed the interaction of the compounds with the active site. Methods The isoxazoles were synthesized using 1,3-dipolar cycloaddition in the presence of sodium hypochlorite. They were also isolated and characterized by spectroscopic methods. The in-vitro activity was measured by an adapted version of Ellman's assay. Key findings The isoxazoles are described as inhibitors of AChE. The most potent compound in the series exhibited a moderate inhibitory activity (50% inhibitory concentration = 134.87 μm). The design of new compounds was created by using the RACHEL module of the SYBYL software. Conclusions Our research provided enough evidence of the efficacy of isoxazoles as AChE inhibitors. The isoxazoles were synthesized and evaluated as inhibitors of AChE. The docking study based on a novel series of complexes isoxazole with AChE from Electroporus electricus has demonstrated that the ligand bind is similar to the compounds used as reference. To find new candidates with the isoxazole core that act as inhibitors of AChE, part of the structure of the compound 9 was used for de-novo design. Molecular docking models of the ligand-AChE complexes suggest that the compound 10 is located on the periphery of the AChE active site.