Role of hydrogen-bond coordination defects in the structural relaxation of supercooled water.

In this work, we shall study the role of threefold and fivefold coordination defects in the structure and dynamics of the hydrogen bond network of liquid water, with special emphasis on the glassy regime. A significant defect clusterization propensity will be made evident, with a prevalence of mixed pairs, that is, threefold- and fivefold-coordinated defects being first neighbors of each other. This structural analysis will enable us to determine the existence of defective and nondefective regions compatible with the high local density and low local density molecular states of liquid water, respectively.

Study of Protein Hydration Water with the Structural Index: Focus on Binding Site Description.

, a new structural indicator for water specially designed to be suitable for hydration and nanoconfined contexts, has been recently introduced and preliminarily applied for water in contact with self-assembled monolayers and graphene-like systems. This index enabled an accurate detection of defective high local density water molecules (called HDA-like given their structural resemblance with the high-density amorphous ice, HDA). In the present work, we shall apply this new metric to characterize protein hydration water with particular interest in protein binding sites.

A structural determinant of the behavior of water at hydration and nanoconfinement conditions.

The molecular nature of the phases that conform the two-liquid scenario is elucidated in this work in the light of a molecular principle governing water structuring, which unveils the relevance of the contraction and reorientation of the second molecular shell to allow for the existence of coordination defects in water's hydrogen bond network. In turn, such principle is shown to also determine the behavior of hydration and nanoconfined water while enabling to define conditions for wettability (quantifying hydrophobicity and predicting drying transitions), thus opening the possibility to unravel the active role of water in central fields of research.

Water at the nanoscale: From filling or dewetting hydrophobic pores and carbon nanotubes to "sliding" on graphene.

In this work, we study the effect of nanoconfinement on the hydration properties of model hydrophobic pores and carbon nanotubes, determining their wetting propensity and the conditions for geometrically induced dehydration. By employing a recently introduced water structural index, we aim at two main goals: (1) to accurately quantify the local hydrophobicity and predict the drying transitions in such systems, and (2) to provide a molecular rationalization of the wetting process. In this sense, we will further discuss the number and strength of the interactions required by the water molecules to promote wetting.

A water structure indicator suitable for generic contexts: Two-liquid behavior at hydration and nanoconfinement conditions and a molecular approach to hydrophobicity and wetting.

In a recent work, we have briefly introduced a new structural index for water that, unlike previous indicators, was devised specifically for generic contexts beyond bulk conditions, making it suitable for hydration and nanoconfinement settings. In this work, we shall study this metric in detail, demonstrating its ability to reveal the existence of a fine-tuned interplay between the local structure and energetics in liquid water. This molecular principle enables the establishment of an extended hydrogen bond network, while simultaneously allowing for the existence of network defects by compensating for uncoordinated sites.

Turning an energy-based defect detector into a multi-molecule structural indicator for water.

Recent studies have provided conclusive evidence for the existence of a liquid-liquid critical point in numerical models of water. Such a scenario implies the competition between two local molecular arrangements of different densities: a high-density liquid (HDL) and a low-density liquid (LDL). Within this context, the development of accurate structural indicators to properly characterize the two interconverting local structures is demanded.

Influence of docosahexaenoic acid on the interfacial behavior of cholesterol-containing lipid membranes: Interactions with small amphiphiles and hydration properties.

Cholesterol is known to significantly modify both the structural and the dynamical properties of lipid membranes. On one side, the presence of free cholesterol molecules has been determined to stiffen the membrane bilayer by stretching the hydrophobic tails. Additionally, recent experimental and computational findings have made evident the fact that cholesterol also alters the dynamics and the hydration properties of the polar head groups of DPPC model lipid membranes.

Persistent Local Structural Defectiveness as an Early Time Predictor of Intermittent Glassy Relaxation Events in Supercooled Water.

To become a glass from the metastable supercooled state, a liquid experiences a dramatic dynamical slowing down within a narrow temperature window. However, the attainment of solid rigidity is not the result of breaking translational symmetry as in a crystal: the structure of the resulting amorphous solid strikingly resembles that of the liquid state. Moreover, the supercooled liquid is dynamically heterogeneous; that is, the dynamics varies by orders of magnitude from one region of the sample to another, but the establishment of the existence of strong structural differences between such regions has demanded hard efforts along the years.

Correlations between defect propensity and dynamical heterogeneities in supercooled water.

A salient feature of supercooled liquids consists in the dramatic dynamical slowdown they undergo as temperature decreases while no significant structural change is evident. These systems also present dynamical heterogeneities (DH): certain molecules, spatially arranged in clusters, relax various orders of magnitude faster than the others. However, again, no static quantity (such as structural or energetic measures) shows strong direct correlations with such fast-moving molecules.

Development of new 1, 3-dihydroxyacridone derivatives as Akt pathway inhibitors in skeletal muscle cells.

In the present work, four new compounds based on the privileged structure acridone were efficiently synthesized following simple operational techniques and biologically tested on proliferative skeletal muscle cells (C2C12) and rhabdomyosarcoma cells (RD) showing no significant changes in the number of dead or viable cells at 1 µM during 24 or 48 h of treatment. Of relevance, acridone derivatives 3a-3d at 0.5 µM for 24 h effectively inhibited Akt activation in C2C12, while at 1 µM only compounds 3a and 3b have effect.

Biophysical interactions of phenolic acids from yerba mate tea with lipid membranes.

Yerba mate (Ilex paraguariensis) tea is a well know source of phenolic antioxidants compounds. Caffeoyl derivatives are the primary constituents that account for the antioxidant capacity of this beverage. It was proposed that the interaction of polyphenols with lipid bilayers of various cell types provides the molecular rationale for their hallmark antioxidant and anti-inflammatory activities.

Advances in the study of supercooled water.

In this review, we report recent progress in the field of supercooled water. Due to its uniqueness, water presents numerous anomalies with respect to most simple liquids, showing polyamorphism both in the liquid and in the glassy state. We first describe the thermodynamic scenarios hypothesized for the supercooled region and in particular among them the liquid-liquid critical point scenario that has so far received more experimental evidence.

Structure and dynamics of nanoconfined water and aqueous solutions.

This review is devoted to discussing recent progress on the structure, thermodynamic, reactivity, and dynamics of water and aqueous systems confined within different types of nanopores, synthetic and biological. Currently, this is a branch of water science that has attracted enormous attention of researchers from different fields interested to extend the understanding of the anomalous properties of bulk water to the nanoscopic domain. From a fundamental perspective, the interactions of water and solutes with a confining surface dramatically modify the liquid's structure and, consequently, both its thermodynamical and dynamical behaviors, breaking the validity of the classical thermodynamic and phenomenological description of the transport properties of aqueous systems.

Structural aspects of an energy-based water classification index and the structure-dynamics link in glassy relaxation.

An energy-based structural indicator for water, [Formula: see text], has been recently introduced by our group. In turn, in this work we aim at: (1) demonstrating that [Formula: see text] is indeed able to correctly classify water molecules between locally structured tetrahedral (T) and locally distorted (D) ones, circumventing the usual problem of certain previous indicators of overestimating the distorted state; (2) correlating [Formula: see text] with dynamic propensity, a measure of the molecular mobility tendency, in order to seek for the existence of a connection between structure and dynamics within the supercooled regime. More specifically, in the first part of this work we will show that [Formula: see text] accurately discriminates between merely thermally deformed local molecular arrangements and truly distorted molecules (defects).

A certain proportion of docosahexaenoic acid tends to revert structural and dynamical effects of cholesterol on lipid membranes.

This work investigates how docosahexaenoic acid (DHA) modifies the effect of Cholesterol (Chol) on the structural and dynamical properties of dipalmitoylphosphatidylcholine (DPPC) membrane. We employ low-cost and non-invasive methods: zeta potential (ZP), conductivity, density, and ultrasound velocity, complemented by molecular dynamics simulations. Our studies reveal that 30% of DHA added to the DPPC-Chol system tends to revert Chol action on a model lipid bilayer.

Effect of cholesterol on the hydration properties of ester and ether lipid membrane interphases.

Fluorescence spectroscopy and Molecular Dynamics results show that cholesterol reduces water along the chains in ether lipids by changing the water distribution pattern between tightly and loosely bound water molecules. Water distribution was followed by emission spectra and generalized polarization of 6-dodecanoyl-2-dimethyl aminonaphthalene (Laurdan) inserted in 1,2-dimiristoyl-sn-glycero-3-phosphocholine (DMPC) and 1,2-di-O-tetradecyl-sn-glycero-3-phosphocholine (14: 0 Diether PC) membranes. Molecular Dynamics simulations indicate that the action of cholesterol could be different in ether PC in comparison to ester PC.

Interaction of hydroxy-xanthones with phosphatidylcholines: The effector decreases compressibility and increases the fluidity of membranes.

This work reports the effect of hydroxy-xanthones (XAs) on 1,2-Dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-Dimyristoyl-sn-glycero-3-phosphocholine (DMPC) bilayers as determined by ultrasound velocimetry, densimetry and molecular dynamics simulations. XAs with different number of hydroxyl group were studied. Experimental results, in good agreement with molecular dynamics simulations, revealed that the presence of XAs in the systems studied increases fluidity while simultaneously decreses the compressibility of both membranes.

A structural indicator for water built upon potential energy considerations.

We introduce a parameter-free structural indicator to classify local environments of water molecules in stable and supercooled liquid states, which reveals a clear two-peak distribution of local properties. The majority of molecules are tetrahedrally coordinated (T molecules), via low-energy hydrogen bonds. The minority component, whose relative concentration decreases with a decrease in the temperature at constant pressure, is characterized by prevalently three-coordinated molecules, giving rise to a distorted local network around them (D molecules).

Structural features of high-local-density water molecules: Insights from structure indicators based on the translational order between the first two molecular shells.

The two-liquids scenario for liquid water assumes the existence of two competing preferential local molecular structural states characterized by either low or high local density. While the former is expected to present good local order thus involving privileged structures, the latter is usually regarded as conforming a high-entropy unstructured state. A main difference in the local arrangement of such "classes" of water molecules can be inferred from the degree of translational order between the first and second molecular shells.

Comparing the performance of two structural indicators for different water models while seeking for connections between structure and dynamics in the glassy regime.

In this work, we compare the performance of two structural indicators based on the degree of translational order up to the second coordination shell in three water models: SPC/E, TIP4P/2005, and TIP5P. Beyond directly contrasting their distributions for different temperatures to evidence their usefulness in estimating the fraction of structured and unstructured molecules and, when possible, their classification capability, we also correlate them with an indirect measure of structural constraint: the dynamic propensity. Furthermore, this procedure enables us to show the existence of evident correlations between structural and dynamical information.

Size dependence of dynamic fluctuations in liquid and supercooled water.

We study the evolution of dynamic fluctuations averaged over different space lengths and time scales to characterize spatially and temporally heterogeneous behavior of TIP4P/2005 water in liquid and supercooled states. Analyzing a 250 000 molecules simulated system, we provide evidence of the existence, upon supercooling, of a significant enhancement of spatially localized dynamic fluctuations stemming from regions of correlated mobile molecules. We show that both the magnitude of the departure from the value expected for the system-size dependence of an uncorrelated system and the system size at which such a trivial regime is finally recovered clearly increase upon supercooling.

Experimental and computational studies of the effects of free DHA on a model phosphatidylcholine membrane.

Docosahexaenoic acid (DHA, 22:6) is a natural active compound that has raised considerable interest due to its several biological effects. In this work, effects of free DHA on the physicochemical properties of dipalmitoylphosphatidylcholine (DPPC) liposomes are investigated in terms of lipid membrane structure, by means of temperature-dependent zeta potential measurements, density studies and molecular dynamics simulations. Experimental results predict, in good agreement with simulations that DHA readily incorporates into DPPC liposomes, localizing at the lipid headgroup region.

Spatiotemporal intermittency and localized dynamic fluctuations upon approaching the glass transition.

We introduce a robust approach for characterizing spatially and temporally heterogeneous behavior within a system based on the evolution of dynamic fluctuations averaged over different space lengths and timescales. We apply it to investigate the dynamics in two canonical systems as the glass transition is approached: simulated Lennard-Jones liquids and experimental dense colloidal suspensions. In both cases the onset of glassiness is marked by spatially localized dynamic fluctuations originating in regions of correlated mobile particles.

Theoretical models to predict the inhibitory effect of ligands of sphingosine kinase 1 using QTAIM calculations and hydrogen bond dynamic propensity analysis.

We report here the results of two theoretical models to predict the inhibitory effect of inhibitors of sphingosine kinase 1 that stand on different computational basis. The active site of SphK1 is a complex system and the ligands under the study possess a significant conformational flexibility; therefore for our study we performed extended simulations and proper clusterization process. The two theoretical approaches used here, hydrogen bond dynamics propensity analysis and Quantum Theory of Atoms in Molecules (QTAIM) calculations, exhibit excellent correlations with the experimental data.

Design, synthesis and biological evaluation of 1,3-dihydroxyxanthone derivatives: Effective agents against acetylcholinesterase.

The present work concerns the rational design and development of new inhibitors of acetylcholinesterase (AChE) based on the privileged xanthone scaffold. In order to understand and rationalize the mode of action of these target structures a theoretical study was initially conducted. From the results of rational design, a new variety of amphiphilic xanthone derivatives were synthesized, structurally characterized and evaluated as potential anti-Alzheimer agents.