RESUMEN

In the past several decades, noble metal nanoclusters (NMNCs) have been developed as an emerging class of luminescent materials due to their superior photo-stability and biocompatibility, but their luminous quantum yield is relatively low and the physical origin of the bright photoluminescence (PL) of NMNCs remain elusive, which limited their practical application. As the well-defined structure and composition of NMNCs have been determined, in this mini-review, the effect of each component (metal core, ligand shell and interfacial water) on their PL properties and corresponded working mechanism were comprehensively introduced, and a model that structural water molecules dominated p band intermediate state was proposed to give a unified understanding on the PL mechanism of NMNCs and a further perspective to the future developments of NMNCs by revisiting the development of our studies on the PL mechanism of NMNCs in the past decade.

RESUMEN

This mini-review summarizes the seminal exploration of aqueous supramolecular chemistry of crown ether macrocycles. In history, most research of crown ethers were focusing on their supramolecular chemistry in organic phase or in gas phase. In sharp contrast, the recent research evidently reveal that crown ethers are very suitable for studying abroad range of the properties and applications of water interactions, from: high water-solubility, control of Hofmeister series, "structural water", and supramolecular adhesives. Key studies revealing more details about the properties of water and aqueous solutions are highlighted.

RESUMEN

Protein-protein interactions are at the basis of many protein functions, and the knowledge of 3D structures of protein-protein complexes provides structural, mechanical and dynamical pieces of information essential to understand these functions. Protein-protein interfaces can be seen as stable, organized regions where residues from different partners form non-covalent interactions that are responsible for interaction specificity and strength. They are commonly described as a peripheral region, whose role is to protect the core region that concentrates the most contributing interactions, from the solvent. To get insights into the dynamics of protein-protein complexes, we carried out all-atom molecular dynamics simulations in explicit solvent on eight different protein-protein complexes of different functional class and interface size by taking into account the bound and unbound forms. On the one hand, we characterized structural changes upon binding of the proteins, and on the other hand we extensively analyzed the interfaces and the structural waters involved in the binding. Based on our analysis, in 6 cases out of 8, the interfaces rearranged during the simulation time, in stable and long-lived substates with alternative residue-residue contacts. These rearrangements are not restricted to side-chain fluctuations in the periphery but also affect the core interface. Finally, the analysis of the waters at the interface and involved in the binding pointed out the importance to take into account their role in the estimation of the interaction strength.

RESUMEN

Novel agents to treat invasive fungal infections are urgently needed because the small number of established targets in pathogenic fungi makes the existing drug repertoire particularly vulnerable to the emergence of resistant strains. Recently, we reported that Candida albicans Bdf1, a bromodomain and extra-terminal domain (BET) bromodomain with paired acetyl-lysine (AcK) binding sites (BD1 and BD2) is essential for fungal cell growth and that an imidazopyridine (1) binds to BD2 with selectivity versus both BD1 and human BET bromodomains. Bromodomain binding pockets contain a conserved array of structural waters. Molecular dynamics simulations now reveal that one water molecule is less tightly bound to BD2 than to BD1, explaining the site selectivity of 1. This insight is useful in the performance of ligand docking studies to guide design of more effective Bdf1 inhibitors, as illustrated by the design of 10 new imidazopyridine BD2 ligands 1a-j, for which experimental binding and site selectivity data are presented.

Asunto(s)

Candida albicans , Factores de Transcripción , Humanos , Candida albicans/metabolismo , Ligandos , Factores de Transcripción/metabolismo , Sitios de Unión

RESUMEN

To promote the application of entropy concepts in uncertainty analysis of water resources complex system, a quantitative evaluation and obstacle factor diagnosis model of agricultural drought disaster risk was proposed using connection number and information entropy. The results applied to Suzhou City showed that the agricultural drought disaster risks in Suzhou during 2007-2017 were all in middle-risk status, while it presented a decreasing trend from 2010. The information entropy values of the difference degree item bI were markedly lower than those of the difference degree b, indicating that bI provided more information in the evaluation process. Furthermore, the status of drought damage sensitivity and drought hazard were improved significantly. Nevertheless, high exposure to drought and weak drought resistance capacity seriously impeded the reduction of risk. Thus, the key to decreasing risk was to maintain the level of damage sensitivity, while the difficulties were to reduce exposure and enhance resistance. In addition, the percentage of the agricultural population, population density, and percentage of effective irrigation area were the main obstacle factors of risk and also the key points of risk control in Suzhou. In short, the results suggest that the evaluation and diagnosis method is effective and conducive to regional drought disaster risk management.

RESUMEN

The development of Mg-ion batteries is hindered by the lack of cathode materials that allow facile and reversible Mg2+ intercalation at high potential. Herein, the authors present a polyanion cathode material of K2 (VO)2 (HPO4 )2 (C2 O4 )⋅4.5H2 O (KVPCH) for Mg-ion batteries. The inductive effect of polyanions ensures the high redox potential of the vanadium centers. In addition, the material contains structural water located between the layers. It helps with Mg2+ desolvation at the electrode-electrolyte interface and facilitates its diffusion in the structure, as confirmed by experimental analysis and theoretical calculations. Thanks to those factors, the KVPCH electrode presents excellent Mg storage capability at room temperature. It delivers 121 mAh g-1 capacity at 1C with a high average discharge potential of 0.16 V versus Ag/Ag+ (3.2 V vs Mg/Mg2+ ). A capacity retention of 87% is realized after 1500 cycles at 5C. A rocking-chair Mg-ion full cell is also demonstrated with the KVPCH cathode and a MoOx anode, which achieves 46 mAh g-1 capacity (based on the total active material mass of two electrodes). This work would bring effective paths for the design of cathode materials for Mg-ion batteries.

RESUMEN

The Rhodopsin family of G-protein­coupled receptors (GPCRs) comprises the targets of nearly a third of all pharmaceuticals. Despite structural water present in GPCR X-ray structures, the physiological relevance of these solvent molecules to rhodopsin signaling remains unknown. Here, we show experimental results consistent with the idea that rhodopsin activation in lipid membranes is coupled to bulk water movements into the protein. To quantify hydration changes, we measured reversible shifting of the metarhodopsin equilibrium due to osmotic stress using an extensive series of polyethylene glycol (PEG) osmolytes. We discovered clear evidence that light activation entails a large influx of bulk water (∼80­100 molecules) into the protein, giving insight into GPCR activation mechanisms. Various size polymer osmolytes directly control rhodopsin activation, in which large solutes are excluded from rhodopsin and dehydrate the protein, favoring the inactive state. In contrast, small osmolytes initially forward shift the activation equilibrium until a quantifiable saturation point is reached, similar to gain-of-function protein mutations. For the limit of increasing osmolyte size, a universal response of rhodopsin to osmotic stress is observed, suggesting it adopts a dynamic, hydrated sponge-like state upon photoactivation. Our results demand a rethinking of the role of water dynamics in modulating various intermediates in the GPCR energy landscape. We propose that besides bound water, an influx of bulk water plays a necessary role in establishing the active GPCR conformation that mediates signaling.

Asunto(s)

Receptores Acoplados a Proteínas G , Rodopsina , Conformación Proteica , Receptores Acoplados a Proteínas G/metabolismo , Rodopsina/metabolismo , Solventes/química , Agua/química

RESUMEN

Water constitutes roughly a quarter of the cortical bone by volume yet can greatly influence mechanical properties and tissue quality. There is a growing appreciation for how water can dynamically change due to age, disease, and treatment. A key emerging area related to bone mechanical and tissue properties lies in differentiating the role of water in its four different compartments, including free/pore water, water loosely bound at the collagen/mineral interfaces, water tightly bound within collagen triple helices, and structural water within the mineral. This review summarizes our current knowledge of bone water across the four functional compartments and discusses how alterations in each compartment relate to mechanical changes. It provides an overview on the advent of- and improvements to- imaging and spectroscopic techniques able to probe nano-and molecular scales of bone water. These technical advances have led to an emerging understanding of how bone water changes in various conditions, of which aging, chronic kidney disease, diabetes, osteoporosis, and osteogenesis imperfecta are reviewed. Finally, it summarizes work focused on therapeutically targeting water to improve mechanical properties.

RESUMEN

On the origin of photoluminescence of noble metal NCs, there are always hot debates: metal-centered quantum-size confinement effect VS ligand-centered surface state mechanism. Herein, we provided solid evidence that structural water molecules (SWs) confined in the nanocavity formed by surface-protective-ligand packing on the metal NCs are the real luminescent emitters of Au-Ag bimetal NCs. The Ag cation mediated Au-Ag bimetal NCs exhibit the unique pH-dependent dual-emission characteristic with larger Stokes shift up to 200 nm, which could be used as potential ratiometric nanosensors for pH detection. Our results provide a completely new insight on the understanding of the origin of photoluminescence of metal NCs, which elucidates the abnormal PL emission phenomena, including solvent effect, pH-dependent behavior, surface ligand effect, multiple emitter centers, and large-Stoke's shift.

RESUMEN

Aqueous zinc-ion batteries are considered promising next-generation systems for large-scale energy storage due to low cost, environmental friendliness, and high reversibility of the Zn anode. However, the interfacial charge-transfer resistance for the insertion of divalent Zn2+ into cathode materials is normally high, which limits the kinetics of Zn2+ transfer at the cathode/electrolyte interface. This study reveals the presence of rich structural water in spinel ZnMn2O4 (ZnMn2O4·0.94H2O, denoted as ZMO), synthesized by a scalable and low-temperature process, significantly overcoming the great interfacial charge-transfer resistance. ZMO exhibits excellent electrochemical performance toward Zn storage, that is, high capacity (230 and 101 mA h g-1 at 0.5 and 8 A g-1), high specific energy/specific power (329 W h kg-1/706 W kg-1 and 134 W h kg-1/11,160 W kg-1), and stable cycle retention (75% after 2000 cycles at 4 A g-1) can be achieved. On the contrary, the controlled sample ZMO-450 with deficient structural water, prepared by post-heat treatment of ZMO at 450 °C, demonstrates limited discharge capacity (45 and 15 mA h g-1 at 0.5 and 8 A g-1). As examined by electrochemical impedance spectroscopy, rich structural water in ZMO effectively reduces the activation energy barrier upon Zn2+ insertion, rendering fast interfacial kinetics for Zn storage. Benefiting from rich structural water in ZMO, the involvement of Zn2+ during the charge/discharge process exhibits good reversibility, as characterized by X-ray diffraction and X-ray photoelectron spectroscopy.

RESUMEN

The utilization of structural water in chemical self-assembly has not only effectively eliminated the negative influences of solvents from solutions or gels but has also provided new insight into the fabrication of new materials in bulk. However, up to now, supramolecular polymerization triggered by structural water has been dominated more by serendipity than rational design. After carefully analyzing the chemical structures of artificial monomers and gaining a deep understanding of the water-triggered assembly process, we report herein the bulk formation of polymeric materials from water and low-molecular weight monomers by rational design instead of serendipity.

RESUMEN

Stabilizing unique receptor conformations, allosteric modulators of G-protein coupled receptors (GPCRs) might open novel treatment options due to their new pharmacological action, their enhanced specificity and selectivity in both binding and signaling. Ligand binding occurs at intrahelical allosteric sites and involves significant induced fit effects that include conformational changes in the local protein environment and water networks. Based on the analysis of available crystal structures of metabotropic glutamate receptor 5 (mGlu5) we investigated these effects in the binding of mGlu5 receptor negative allosteric modulators. A large set of retrospective virtual screens revealed that the use of multiple protein structures and the inclusion of selected water molecules improves virtual screening performance compared to conventional docking strategies. The role of water molecules and protein flexibility in ligand binding can be taken into account efficiently by the proposed docking protocol that provided reasonable enrichment of true positives. This protocol is expected to be useful also for identifying intrahelical allosteric modulators for other GPCR targets.

Asunto(s)

Conformación Proteica , Receptor del Glutamato Metabotropico 5/química , Receptores Acoplados a Proteínas G/química , Agua/química , Regulación Alostérica/genética , Sitio Alostérico/genética , Cristalografía por Rayos X , Diseño de Fármacos , Humanos , Indoles/química , Ligandos , Simulación del Acoplamiento Molecular , Unión Proteica/genética , Receptor del Glutamato Metabotropico 5/ultraestructura , Receptores Acoplados a Proteínas G/ultraestructura , Interfaz Usuario-Computador

RESUMEN

Voltage-dependent potassium channels (Kvs) gate in response to changes in electrical membrane potential by coupling a voltage-sensing module with a K+-selective pore. Animal toxins targeting Kvs are classified as pore blockers, which physically plug the ion conduction pathway, or as gating modifiers, which disrupt voltage sensor movements. A third group of toxins blocks K+ conduction by an unknown mechanism via binding to the channel turrets. Here, we show that Conkunitzin-S1 (Cs1), a peptide toxin isolated from cone snail venom, binds at the turrets of Kv1.2 and targets a network of hydrogen bonds that govern water access to the peripheral cavities that surround the central pore. The resulting ectopic water flow triggers an asymmetric collapse of the pore by a process resembling that of inherent slow inactivation. Pore modulation by animal toxins exposes the peripheral cavity of K+ channels as a novel pharmacological target and provides a rational framework for drug design.

Asunto(s)

Membrana Celular/efectos de los fármacos , Proteínas de Drosophila/antagonistas & inhibidores , Activación del Canal Iónico/efectos de los fármacos , Canal de Potasio Kv.1.2/antagonistas & inhibidores , Venenos de Moluscos/toxicidad , Canales de Potasio de la Superfamilia Shaker/antagonistas & inhibidores , Animales , Membrana Celular/metabolismo , Cristalografía por Rayos X , Proteínas de Drosophila/genética , Proteínas de Drosophila/aislamiento & purificación , Proteínas de Drosophila/metabolismo , Diseño de Fármacos , Femenino , Enlace de Hidrógeno/efectos de los fármacos , Canal de Potasio Kv.1.2/genética , Canal de Potasio Kv.1.2/aislamiento & purificación , Canal de Potasio Kv.1.2/metabolismo , Dosificación Letal Mediana , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Venenos de Moluscos/química , Mutación , Oocitos , Proteínas Recombinantes/genética , Proteínas Recombinantes/aislamiento & purificación , Proteínas Recombinantes/metabolismo , Canales de Potasio de la Superfamilia Shaker/genética , Canales de Potasio de la Superfamilia Shaker/aislamiento & purificación , Canales de Potasio de la Superfamilia Shaker/metabolismo , Agua/química , Agua/metabolismo , Xenopus laevis

RESUMEN

HYPOTHESIS: In a saturated cement paste, there are three different types of water: the structural water chemically reacted with cement, the constrained water absorbed to the surface of the pores, and the free water in the center of the pores. Each type has different physicochemical state and unique relation to cement porosity. The different water types have different dynamics which can be detected using quasi-elastic neutron scattering (QENS). Since the porosity of a hardened cement paste is impacted strongly by the water to cement ratio (w/c), it should be possible to extract the hydration dependence of the pores by exploiting the dynamical parameters of the confined water. EXPERIMENTS: Three C-S-H samples with different water levels, 8%, 17% and 30% were measured using QENS. The measurements were carried out in the scattering vector, Q, range from 0.5 Å-1 to 1.3 Å-1, and in the temperature interval from 230 K to 280 K. The data were analyzed using a novel global model developed for cement QENS spectra. FINDINGS: The results show that while increasing the water content, the structural water index (SWI) decreases and the confining radius, a, increases. Both SWI and a have a linear relationship with the water content. The Arrhenius plot of the translational relaxation time shows that the constrained water dominates the non-structural water at water contents lower than 17%. The rotational activation energy is smaller for lower water content. The analysis demonstrated that our newly proposed global model is practical and useful for analyzing cement QENS data.

Asunto(s)

Compuestos de Calcio/química , Modelos Químicos , Difracción de Neutrones/métodos , Silicatos/química , Agua/química , Algoritmos , Elasticidad , Porosidad , Temperatura , Termodinámica

RESUMEN

Structures of many metal-binding proteins are often obtained without structural cations in their apoprotein forms. Missing cation coordinates are usually updated from structural templates constructed from many holoprotein structures. Such templates usually do not include structural water, the important contributor to the ion binding energy. Structural templates are also inconvenient for taking into account structural modifications around the binding site at apo-/holo- transitions. An approach based upon statistical potentials readily takes into account structural modifications associated with binding as well as contribution of structural water molecules. Here, we construct a set of statistical potentials for Mg2+, Ca2+, and Zn2+ contacting with protein atoms of a different type or structural water oxygens. Each type of the cations tends to form tight contacts with protein atoms of specific types. Structural water contributes relatively more into the binding pseudo-energy of Mg2+ and Ca2+ than of Zn2+. We have developed PIONCA (Protein-Ion Calculator), a fast CUDA GPGPU-based algorithm that predicts ion-binding sites in apoproteins. Comparative tests demonstrate that PIONCA outperforms most of the tools based on structural templates or docking. Our software can be also used for locating bound cations in holoprotein structures with missing cation heteroatoms. PIONCA is equipped with an interactive web interface based upon JSmol.

Asunto(s)

Apoproteínas/química , Cationes/química , Metales/química , Agua/química , Algoritmos , Apoproteínas/metabolismo , Sitios de Unión , Cationes/metabolismo , Biología Computacional/métodos , Metales/metabolismo , Unión Proteica , Programas Informáticos , Termodinámica

RESUMEN

Low-cost, environment-friendly aqueous Zn batteries have great potential for large-scale energy storage, but the intercalation of zinc ions in the cathode materials is challenging and complex. Herein, the critical role of structural H2 O on Zn2+ intercalation into bilayer V2 O5 ·nH2 O is demonstrated. The results suggest that the H2 O-solvated Zn2+ possesses largely reduced effective charge and thus reduced electrostatic interactions with the V2 O5 framework, effectively promoting its diffusion. Benefited from the "lubricating" effect, the aqueous Zn battery shows a specific energy of ≈144 Wh kg-1 at 0.3 A g-1 . Meanwhile, it can maintain an energy density of 90 Wh kg-1 at a high power density of 6.4 kW kg-1 (based on the cathode and 200% Zn anode), making it a promising candidate for high-performance, low-cost, safe, and environment-friendly energy-storage devices.

RESUMEN

Bitter taste receptors (T2Rs) belong to the super family of G protein-coupled receptors (GPCRs). There are 25 T2Rs expressed in humans, and these interact with a large and diverse group of bitter ligands. T2Rs are expressed in many extra-oral tissues and can perform diverse physiological roles. Structure-function studies led to the identification of similarities and dissimilarities between T2Rs and Class A GPCRs including amino acid conservation and novel motifs. However, the efficacy of most of the T2R ligands is not yet elucidated and the biochemical pharmacology of T2Rs is poorly understood. Recent studies on T2Rs characterized novel ligands including blockers for these receptors that include inverse agonist and antagonists. In this review we discuss the techniques used for elucidating bitter blockers, concept of ligand bias, generic amino acid numbering, the role of cholesterol, and conserved water molecules in the biochemistry and pharmacology of T2Rs.

Asunto(s)

Receptores Acoplados a Proteínas G/química , Receptores Acoplados a Proteínas G/metabolismo , Percepción del Gusto/efectos de los fármacos , Secuencia de Aminoácidos , Animales , Humanos , Ligandos , Receptores Acoplados a Proteínas G/genética

RESUMEN

We have developed a novel method for calculation of the water bridges that can be formed in the active sites of proteins in the absence or in the presence of small-molecule ligands. We tested its efficiency on a representative set of human ATP-binding proteins, and show that the docking accuracy of ligands can be substantially improved when water bridges are included in the modeling of protein-ligand interactions. Our analysis of binding pocket hydration can be a useful addition to the in silico approaches of Drug Design.

Asunto(s)

Proteínas Portadoras/metabolismo , Dominio Catalítico/fisiología , Simulación por Computador , Proteínas/química , Agua/química , Proteínas Portadoras/genética , Humanos , Unión Proteica

RESUMEN

A series of nanocrystalline calcium hydroxyapatites was prepared by dry milling and characterized using proton and 31P MAS NMR, TEM, and TGA methods. The samples contained stubby rod-shaped crystals, which length and width varied in the 130-30 and 95-20 nm ranges, respectively. It was confirmed that concentration of structural hydroxyl groups in nanocrystalline apatites decreases with the decreasing crystal size. In the series of the studied apatites, the decrease was from 86 to ca. 50 % in reference to stoichiometric apatite. Water was found in the surface hydrated layer and in the c-axis channels, in which compartments existed as adsorbed and structural, respectively. Molecules of the adsorbed water were capable of moving from the crystal surface into the lattice c-axis channels of apatite. This process introduced considerable structural disorder within and around those channels and reduced the content of the structural hydroxyl groups, particularly in the region underneath the apatite crystal surface.