In-layer inhomogeneity of molecular dynamics in quasi-liquid layers of ice.

Quasi-liquid layers (QLLs) are present on the surface of ice and play a significant role in its distinctive chemical and physical properties. These layers exhibit considerable heterogeneity across different scales ranging from nanometers to millimeters. Although the formation of partially ice-like structures has been proposed, the molecular-level understanding of this heterogeneity remains unclear. Here, we examined the heterogeneity of molecular dynamics on QLLs based on molecular dynamics simulations and machine learning analysis of the simulation data. We demonstrated that the molecular dynamics of QLLs do not comprise a mixture of solid- and liquid water molecules. Rather, molecules having similar behaviors form dynamical domains that are associated with the dynamical heterogeneity of supercooled water. Nonetheless, molecules in the domains frequently switch their dynamical state. Furthermore, while there is no observable characteristic domain size, the long-range ordering strongly depends on the temperature and crystal face. Instead of a mixture of static solid- and liquid-like regions, our results indicate the presence of heterogeneous molecular dynamics in QLLs, which offers molecular-level insights into the surface properties of ice.

Supramolecular copolymerization of hydrophobic and hydrophilic monomers in liquid crystalline media.

In the case of covalent polymers, immiscible polymers can be integrated by covalently linking them together, but such a strategy is not possible in supramolecular polymers. Here we report the supramolecular copolymerization of two porphyrin-based monomers, C10P2H and TEGPCu with side chains bearing cyanobiphenyl (CB) groups at the ends of hydrophobic alkyl or hydrophilic tetraethylene glycol chains, respectively. These monomers undergo self-sorting supramolecular polymerization in highly diluted solutions ([monomer] = 3.4 × 10-9 mol% (2.0 × 10-8 mol L-1)) in nonpolar media due to the incompatibility of the side chains. Surprisingly, these monomers undergo supramolecular copolymerization under high concentration conditions ([monomer] = 7.7 mol%) in the medium of 4-cyano-4'-pentyloxybiphenyl (5OCB) to form a columnar liquid crystalline phase under thermodynamic conditions, where the individual columns are composed of supramolecular block copolymers. The combination of CB ends of both monomers and the 5OCB medium is essential for the two monomers to form an integrated structure in a condensed system without phase separation.

Design strategy for blends of biodegradable polyester and thermoplastic starch based on a molecular dynamics study of the phase-separated interface.

Molecular insight into the phase-separated interface formed when biodegradable polyesters and thermoplastic starch (TPS) are melt-blended is valuable for the design of composites. In this study, eight different interfaces combining four major biodegradable polyesters (PLA, PBS, PHB and PBAT) and two TPSs [unmodified TPS (nTPS) and citrate-modified TPS (cTPS)] were investigated by using molecular dynamics (MD) simulations. According to the MD simulation results, PBS, PHB and PBAT diffuse readily into the TPS and form compatible interfaces, whereas PLA is less compatible with the TPS. The results of tensile simulations show that PBS and PBAT adhere well to TPS; in particular, PBS/cTPS and PBAT/cTPS exhibit high interfacial-fracture energy (G). Both PLA and PHB blended with TPS exhibit low G because PLA is less compatible with TPS and PHB and TPS have low electrostatic interaction. The reason for the high G of PBS/cTPS and PBAT/cTPS is thought to be a combination of three factors: (i) formation of a deep compatible interface, (ii) suppression of void growth by electrostatic interactions and (iii) absorption of strain energy by a change in the conformation of the molecular chains. These three interfacial adhesion mechanisms should be considered when designing biodegradable polyester/TPS blends with good mechanical properties.

Asymmetric Hydrogenation of α-Alkyl-Substituted ß-Keto Esters and Amides through Dynamic Kinetic Resolution.

Asymmetric hydrogenation of α-alkyl-substituted ß-keto esters and amides with the DIPSkewphos/3-AMIQ-Ru(II) catalyst system through dynamic kinetic resolution was examined. A series of ß-keto esters and amides with a simple or functionalized α-alkyl group were applicable to this reaction, affording the α-substituted ß-hydroxy esters and amides in ≥99% ee (anti/syn ≥ 99:1) in many cases. The 5 g scale reaction was readily achieved. The mode of enantio- and diastereoselection in the transition state model was proposed.

Predicting the Performance of Functional Materials Composed of Polymeric Multicomponent Systems Using Artificial Intelligence-Formulations of Cleansing Foams as an Example.

Cleansing foam is a common multicomponent polymeric functional material. It contains ingredients in innumerable combinations, which makes formulation optimization challenging. In this study, we used artificial intelligence (AI) with machine learning to develop a cleansing capability prediction system that considers the effects of self-assembled structures and chemical properties of ingredients. Over 500 cleansing foam samples were prepared and tested. Molecular descriptors and Hansen solubility index were used to estimate the cleansing capabilities of each formulation set. We used five machine-learning models to predict the cleansing capability. In addition, we employed an in silico formulation by generating virtual formulations and predicting their cleansing capabilities using an established AI model. The achieved accuracy was R2 = 0.770. Our observations revealed that mixtures of cosmetic ingredients exhibit complex interactions, resulting in nonlinear behavior, which adds to the complexity of predicting cleansing performance. Nevertheless, accurate chemical property descriptors, along with the aid of in silico formulations, enabled the identification of potential ingredients. We anticipate that our system will efficiently predict the chemical properties of polymer-containing blends.

Unsupervised deep learning for molecular dynamics simulations: a novel analysis of protein-ligand interactions in SARS-CoV-2 Mpro.

Molecular dynamics (MD) simulations, which are central to drug discovery, offer detailed insights into protein-ligand interactions. However, analyzing large MD datasets remains a challenge. Current machine-learning solutions are predominantly supervised and have data labelling and standardisation issues. In this study, we adopted an unsupervised deep-learning framework, previously benchmarked for rigid proteins, to study the more flexible SARS-CoV-2 main protease (Mpro). We ran MD simulations of Mpro with various ligands and refined the data by focusing on binding-site residues and time frames in stable protein conformations. The optimal descriptor chosen was the distance between the residues and the center of the binding pocket. Using this approach, a local dynamic ensemble was generated and fed into our neural network to compute Wasserstein distances across system pairs, revealing ligand-induced conformational differences in Mpro. Dimensionality reduction yielded an embedding map that correlated ligand-induced dynamics and binding affinity. Notably, the high-affinity compounds showed pronounced effects on the protein's conformations. We also identified the key residues that contributed to these differences. Our findings emphasize the potential of combining unsupervised deep learning with MD simulations to extract valuable information and accelerate drug discovery.

The Relationship between Nanostructured Bio-Inspired Material Surfaces and the Free Energy Barrier Using Coarse-Grained Molecular Dynamics.

Bio-inspired (biomimetic) materials, which are inspired by living organisms, offer exciting opportunities for the development of advanced functionalities. Among them, bio-inspired superhydrophobic surfaces have attracted considerable interest due to their potential applications in self-cleaning surfaces and reducing fluid resistance. Although the mechanism of superhydrophobicity is understood to be the free energy barrier between the Cassie and Wenzel states, the solid-surface technology to control the free energy barrier is still unclear. Therefore, previous studies have fabricated solid surfaces with desired properties through trial and error by measuring contact angles. In contrast, our study directly evaluates the free energy barrier using molecular simulations and attempts to relate it to solid-surface parameters. Through a series of simulations, we explore the behavior of water droplets on surfaces with varying values of surface pillar spacing and surface pillar height. The results show that the free energy barrier increases significantly as the pillar spacing decreases and/or as the pillar height increases. Our study goes beyond traditional approaches by exploring the relationship between free energy barriers, surface parameters, and hydrophobicity, providing a more direct and quantified method to evaluate surface hydrophobicity. This knowledge contributes significantly to material design by providing valuable insights into the relationship between surface parameters, free energy barriers, and hydrophilicity/hydrophobicity.

Aggregation of amphiphilic nanocubes in equilibrium and under shear.

We investigate the self-assembly of amphiphilic nanocubes into finite-sized aggregates in equilibrium and under shear, using molecular dynamics (MD) simulations and kinetic Monte Carlo (KMC) calculations. These patchy nanoparticles combine both interaction and shape anisotropy, making them valuable models for studying folded proteins and DNA-functionalized nanoparticles. The nanocubes can self-assemble into various finite-sized aggregates ranging from rods to self-avoiding random walks, depending on the number and placement of the hydrophobic faces. Our study focuses on suspensions containing multi- and one-patch cubes, with their ratio systematically varied. When the binding energy is comparable to the thermal energy, the aggregates consist of only few cubes that spontaneously associate/dissociate. However, highly stable aggregates emerge when the binding energy exceeds the thermal energy. Generally, the mean aggregation number of the self-assembled clusters increases with the number of hydrophobic faces and decreases with increasing fraction of one-patch cubes. In sheared suspensions, the more frequent collisions between nanocube clusters lead to faster aggregation dynamics but also to smaller terminal steady-state mean cluster sizes. The results from the MD and KMC simulations are in excellent agreement for all investigated two-patch cases, whereas the three-patch cubes form systematically smaller clusters in the MD simulations compared to the KMC calculations due to finite-size effects and slow aggregation kinetics. By analyzing the rate kernels, we are able to identify the primary mechanisms responsible for (shear-induced) cluster growth and breakup. This understanding allows us to tune nanoparticle and process parameters to achieve desired cluster sizes and shapes.

Molecular insight into toughening induced by core-shell structure formation in starch-blended bioplastic composites.

Binary and ternary blends with poly(lactic acid) (PLA), poly(butylene succinate) (PBS), and thermoplastic starch (TPS) were prepared by a melt process to produce biodegradable biomass plastics with both economical and good mechanical properties. The mechanical and structural properties of each blend were evaluated. Molecular dynamics (MD) simulations were also conducted to examine the mechanisms underlying the mechanical and structural properties. PLA/PBS/TPS blends showed improved mechanical properties compared with PLA/TPS blends. The PLA/PBS/TPS blends with a TPS ratio of 25-40 wt% showed higher impact strength than PLA/PBS blends. Morphology observations showed that in the PLA/PBS/TPS blends, a structure similar to that of core-shell particles with TPS as the embedding phase and PBS as the coating phase was formed, and that the trends in morphology and impact strength changes were consistent. The MD simulations suggested that PBS and TPS tightly adhered to each other in a stable structure at a specific intermolecular distance. From these results, it is clear that PLA/PBS/TPS blends are toughened by the formation of a core-shell structure in which the TPS core and the PBS shell adhered well together and stress concentration and energy absorption occurred in the vicinity of the core-shell structure.

Wetting hysteresis induces effective unidirectional water transport through a fluctuating nanochannel.

We propose a water pump that actively transports water molecules through nanochannels. Spatially asymmetric noise fluctuations imposed on the channel radius cause unidirectional water flow without osmotic pressure, which can be attributed to hysteresis in the cyclic transition between the wetting/drying states. We show that the water transport depends on fluctuations, such as white, Brownian, and pink noises. Because of the high-frequency components in white noise, fast switching of open and closed states inhibits channel wetting. Conversely, pink and Brownian noises generate high-pass filtered net flow. Brownian fluctuation leads to a faster water transport rate, whereas pink noise has a higher capability to overcome pressure differences in the opposite direction. A trade-off relationship exists between the resonant frequency of the fluctuation and the flow amplification. The proposed pump can be considered as an analogy for the reversed Carnot cycle, which is the upper limit of the energy conversion efficiency.

Effect of temperature on the structure and drug-release behaviour of inclusion complex of ß-cyclodextrin with cyclophosphamide: a molecular dynamics study.

Cyclodextrins (CDs) are suitable drug carriers because of their doughnut-shaped cavities with hydrophilic outer and hydrophobic inner surfaces. Temperature-responsive CD-based drug carriers are expected to be one of the most promising candidates for drug delivery systems. In this study, we performed molecular dynamics simulations of the inclusion complex of ß-CD with cyclophosphamide (CP) at temperatures from 300 K to 400 K to investigate the temperature dependency of the release behaviour of CP and structural changes of ß-CD in an aqueous solution. We analysed the distance between the centres of mass of ß-CD and CP and the radius of gyration of ß-CD. The CP molecule was released from the ß-CD cavity at 400 K, whereas two different inclusion complexes, partially and completely, were observed at T < 400 K. ß-CD encapsulating a CP molecule had a more spherical shape and rigidity than ß-CD without a CP, and the rigidity of their inclusion complex decreased with increasing temperature. Our findings provide fundamental insights into the behaviours of the ß-CD/CP complex and drug release at the molecular level and can facilitate the development of new temperature-responsive drug delivery systems with CD nanocarriers triggered by localised temperature increases using focused ultrasound.

Intramolecular [2 + 2] Cycloaddition of Isocarbostyrils Catalyzed by an Iridium Visible-Light Photocatalyst.

Irradiation on N-(ω-alkenyl)isocarbostyrils in the presence of an iridium photocatalyst by LEDs emitting 455 nm light gave the corresponding cyclobutane-fused benzo[b]quinolizine derivatives stereoselectively in high yields. Loading 1 mol % of the catalyst was enough to obtain high yields of the products in convenient reaction time in many cases. The reaction likely proceeds through stepwise [2 + 2] cycloaddition via a triplet biradical intermediate.

Asymmetric Hydrogenation of α-Amino Esters into Optically Active ß-Amino Alcohols through Dynamic Kinetic Resolution Catalyzed by Ruthenabicyclic Complexes.

Racemic α-substituted α-amino esters were hydrogenated into enantioenriched ß-amino alcohols through dynamic kinetic resolution with chiral ruthenabicyclic complexes. The reaction was carried out with a substrate/catalyst molar ratio of 200-1000 under 15 atm of H2 at 25 °C to afford a variety of ß-substituted ß-aminoethanols in up to 96% ee (24 examples). The mechanistic studies including deuteration experiments suggested that the reaction proceeds with 1,2-hydride migration of the α-amino acetalate intermediate into the α-hydroxy imine followed by the continuous reduction of the imino compound, affording the amino alcohol product.

Combining Molecular Dynamics and Machine Learning to Analyze Shear Thinning for Alkane and Globular Lubricants in the Low Shear Regime.

Lubricants with desirable frictional properties are important in achieving an energy-saving society. Lubricants at the interfaces of mechanical components are confined under high shear rates and pressures and behave quite differently from the bulk material. Computational approaches such as nonequilibrium molecular dynamics (NEMD) simulations have been performed to probe the molecular behavior of lubricants. However, the low-shear-velocity regions of the materials have rarely been simulated owing to the expensive calculations necessary to do so, and the molecular dynamics under shear velocities comparable with that in the experiments are not clearly understood. In this study, we performed NEMD simulations of extremely confined lubricants, i.e., two molecular layers for four types of lubricants confined in mica walls, under shear velocities from 0.001 to 1 m/s. While we confirmed shear thinning, the velocity profiles could not show the flow behavior when the shear velocity was much slower than thermal fluctuations. Therefore, we used an unsupervised machine learning approach to detect molecular movements that contribute to shear thinning. First, we extracted the simple features of molecular movements from large amounts of MD data, which were found to correlate with the effective viscosity. Subsequently, the extracted features were interpreted by examining the trajectories contributing to these features. The magnitude of diffusion corresponded to the viscosity, and the location of slips that varied depending on the spherical and chain lubricants was irrelevant. Finally, we attempted to apply a modified Stokes-Einstein relation at equilibrium to the nonequilibrium and confined systems. While systems with low shear rates obeyed the relation sufficiently, large deviations were observed under large shear rates.

Correlation between ordering and shear thinning in confined OMCTS liquids.

Despite decades of extensive research, the behavior of confined liquids, particularly in the mixed/boundary lubrication regime, remains unelucidated. This can be attributed to several factors, including the difficulty to make direct experimental observations of the behavior of lubricant molecules under nonequilibrium conditions, the high computational cost of molecular simulations to reach steady state, and the low signal-to-noise ratio at extremely low shear rates corresponding to actual operating conditions. In this regard, we studied the correlation between the structure formation and shear viscosity of octamethylcyclotetrasiloxane confined between two mica surfaces in a mixed/boundary lubrication regime. Three different surface separations-corresponding to two-, three-, and five-layered structures-were considered to analyze the effect of confinement. The orientational distributions with one specific peak for n = 2 and two distributions, including a parallel orientation with the surface normal for n > 2, were observed at rest. The confined liquids exhibited a distinct shear-thinning behavior independent of surface separations for a relatively low shear rate, γ̇≲108s-1. However, the shear viscosities at γ̇≲108s-1 depended on the number of layered structures. Newtonian behavior was observed with further increase in the shear rate. Furthermore, we found a strong correlation between the degree of molecular orientation and the shear viscosity of the confined liquids. The magnitude of the shear viscosity of the confined liquids can primarily be determined by the degree of molecular orientation, and shear thinning originates from the vanishing of specific orientational distributions with increasing shear rate.

Theoretical Design of a Janus-Nanoparticle-Based Sandwich Assay for Nucleic Acids.

Nanoparticles exhibit diverse self-assembly attributes and are expected to be applicable under unique settings. For instance, biomolecules can be sandwiched between dimer nanoparticles and detected by surface-enhanced Raman scattering. Controlling the gap between extremely close dimers and stably capturing the target molecule in the gap are crucial aspects of this strategy. Therefore, polymer-tethered nanoparticles (PTNPs), which show promise as high-performance materials that exhibit the attractive features of both NPs and polymers, were targeted in this study to achieve stable biomolecule sensing. Using coarse-grained molecular dynamics simulations, the dependence of the PTNP interactions on the length of the grafted polymer, graft density, and coverage ratio of a hydrophobic tether were examined. The results indicated that the smaller the tether length and graft density, the smaller was the distance between the PTNP surfaces (Rsurf). In contrast, Rsurf decreased as the coverage ratio of the hydrophobic surface (ϕ) increased. The sandwiching probability of the sensing target increased in proportion to the coverage ratio. At high ϕ values, the PTNPs aggregated into three or more particles, which hindered their sensing attributes. These results provide fundamental insight into the sensing applications of NPs and demonstrate the usefulness of PTNPs in sensing biomolecules.

Molecular Insight into the Possible Mechanism of Drag Reduction of Surfactant Aqueous Solution in Pipe Flow.

The phenomenon of drag reduction (known as the "Toms effect") has many industrial and engineering applications, but a definitive molecular-level theory has not yet been constructed. This is due both to the multiscale nature of complex fluids and to the difficulty of directly observing self-assembled structures in nonequilibrium states. On the basis of a large-scale coarse-grained molecular simulation that we conducted, we propose a possible mechanism of turbulence suppression in surfactant aqueous solution. We demonstrate that maintaining sufficiently large micellar structures and a homogeneous radial distribution of surfactant molecules is necessary to obtain the drag-reduction effect. This is the first molecular-simulation evidence that a micellar structure is responsible for drag reduction in pipe flow, and should help in understanding the mechanisms underlying drag reduction by surfactant molecules under nonequilibrium conditions.

Effect of chemical design of grafted polymers on the self-assembled morphology of polymer-tethered nanoparticles in nanotubes.

There is a clear relationship between the self-assembling architecture of nanoparticles (NPs) and their physical properties, and they are currently used in a variety of applications, including optical sensors. Polymer-tethered NPs, which are created by grafting polymers onto NPs to control the self-assembly of NPs, have attracted considerable attention. Recent synthetic techniques have made it possible to synthesize a wide variety of polymers and thereby create NPs with many types of surfaces. However, self-assembled structures have not been systematically classified because of the large number of tuning parameters such as the polymer length and graft density. In this study, by using coarse-grained molecular simulation, we investigated the changes in the self-assembled structure of polymer-tethered NP solutions confined in nanotubes due to the chemical properties of polymers. Three types of tethered polymer NP models were examined: homo hydrophilic, diblock hydrophilic-hydrophobic (HI-HO), and diblock hydrophobic-hydrophilic. Under strong confinement, the NPs were dispersed in single file at low axial pressure. As the pressure increased, multilayered lamellar was observed in the HI-HO model. In contrast, under weak confinement, the difference in the pressure at which the phases emerge, depending on the model, was significant. By changing the chemical properties of the grafted polymer, the thermodynamic conditions (the axial pressure in this study) under which the phases appear is altered, although the coordination of NPs remains almost unchanged. Our simulation offers a theoretical guide for controlling the morphologies of self-assembled polymer-tethered NPs, a novel system that may find applications in nanooptical devices or for nanopatterning.

Self-assembly of polymer-tethered nanoparticles with uniform and Janus surfaces in nanotubes.

In this study, a coarse-grained molecular simulation was performed to investigate the morphologies and phase diagrams of self-assembled polymer-tethered nanoparticles (NPs) confined in nanotubes (NTs). Unlike ordinary NPs, polymer-tethered NPs have two distinct characteristic lengths, which are key factors that determine their self-assembly. Herein, two distinct types of NT walls and three types of polymer-tethered NPs were considered: hydrophilic and hydrophobic walls, and hydrophilic, hydrophobic, and Janus surfaces. First, the qualitative phase diagrams of the axial pressure, Pz, versus the ratio of the NT radius to the NP radius, L, were derived. The results revealed that diverse self-assembled morphologies, which are not formed in non-tethered NPs, were observed in the polymer-tethered NPs. For example, three types of ordered structures with different structural characteristic lengths, depending on Pz, were obtained. In addition, the effect of the chemical nature of the polymer-tethered NP surface on the self-assembled morphology confined in NTs was investigated. Clusters of water molecules were formed, particularly in the hydrophobic polymer-tethered NPs, and these clusters caused the structural distortion of the NP. Moreover, in the polymer-tethered NPs with the Janus amphiphilic surface, the hydrophobic and hydrophilic polymer tethered NPs assembled in the axial direction to form an ordered structure, and a double-helix structure was formed at L = 3.0 in the hydrophobic NT. The results of these simulations indicate that the self-assembly behaviours of polymer-tethered NPs can be qualitatively predicted based on the chemical nature of the NT walls and the surface design of the polymer-tethered NP.

Nanotube Active Water Pump Driven by Alternating Hydrophobicity.

Water transport must be efficiency controlled for the future sustainability of life. Various water transport systems using carbon nanotubes have been proposed in recent years. Although these systems are more permeable than aquaporins, their water transport is passive. In this study, we successfully demonstrate an active water pump driven by simple hydrophobic interaction through computer simulation. Even in the absence of a pressure- or density-gradient, the proposed pump can actively transport water molecules by alternately switching the hydrophobicity of the pump surface. The water transport rate can be easily controlled by varying the time interval of switching. The pump with optimized switching time exhibits prominent water permeance. The results obtained herein can be applied in various water transport technologies because of the simple mechanics. The proposed water pump has the potential to realize an effective device such as a low-energy artificial purification system.