Analysis of Gas Nanoclusters in Water Using All-Atom Molecular Dynamics.

The Young-Laplace equation suggests that nanosized gas clusters would dissolve under the effects of perturbation. The fact that nanobubbles are observed raises questions as to the mechanism underlying their stability. In the current study, we used all-atom molecular dynamics simulations to investigate the gas-water interfacial properties of gas clusters. We employed the instantaneous coarse-graining method to define the fluctuating boundaries and analyze the deformation of gas clusters. Fourier transform analysis of the cluster morphology revealed that the radius and morphology deformation variations exhibit power law relationships with the vibrational frequency, indicating that the surface energy dissipated through morphology variations. Increasing pressure in the liquid region was found to alter the network of water molecules at the interface, whereas increasing pressure in the gas region did not exhibit this effect. The overall gas concentration was oversaturated and proportional to the gas density inside the clusters. However, the result of comparison with Henry's law reveals that the gas pressure at the interface reduced by the interfacial effects is much lower than that inside the gas region, thus reducing the demanding degree of oversaturation. Originating from the interfacial charge allocation, the magnitude of the electrostatic stress is greater than that of the gas pressure inside the cluster. However, the magnitude of the reversed tension induced by electrostatic stress is far below the value of interfacial tension. The potential of mean force (PMF) profiles revealed that a barrier potential at the interface hindered gas particles from escaping the cluster. Several effects contribute to stabilizing the gas clusters in water, including high-frequency morphological deformation, electrostatic stress, reduced interfacial tension, and gas oversaturation conditions. Our results suggest that gas clusters can exist in water under gas oversaturation conditions in the absence of hydrophobic contaminants or pinning charges at interfaces.

Effects of Gas Adsorption and Surface Conditions on Interfacial Nanobubbles.

Gas aggregation and formation of interfacial nanobubbles (INBs) provide challenges and opportunities in the operation of micro-/nanofluidic devices. In the current study, we used molecular dynamics(MD) simulations to investigate the effects of hydrophobicity and various homogeneous surface conditions on gas aggregation and INB stability with a series of 3D argon-water-solid and water-solid systems. Among various signatures of surface hydrophobicity, the potential of mean force (PMF) minima exhibited the strongest correlation with the water molecular orientation at the liquid-solid interface, compared to the depletion layer width and the droplet contact angle. Our results indicated that argon aggregation on the substrate was a function of hydrophobicity as well as competition between gas-solid and water-solid PMFs. Thus, one precondition for gas aggregation on a surface is that the free energy minima of gas induced by the surface be much lower than that induced by water. We found that although the presence of gas molecules had little effect on the measures of wettability, it enhanced density fluctuations near liquid-solid interfaces. The PMF of gas along the surface tangential plane exhibited a small energy barrier between the epitaxial gas layer (EGL) in the bubble and the gas enrichment layer (GEL) in the liquid, which may benefit nanobubble stability. Much lower PMF in the EGL compared to that in the GEL indicated that gas molecules could migrate from the GEL to the nanobubble basement. However, density fluctuations enhanced by the GEL could reduce the energy barrier, thus reducing the stability of INBs.

Investigating Interfacial Effects on Surface Nanobubbles without Pinning Using Molecular Dynamics Simulation.

We investigated how the stability of aqueous argon surface nanobubbles on hydrophobic surfaces depends on gas adsorption, solid-gas interaction energy, and the bulk gas concentration using molecular dynamics simulation with the SPC/E water solvent. We observed stable surface nanobubbles without surface pinning sites for longer than 160 ns, contrary to previous findings using monoatomic Lennard-Jones solvent. In addition, the hydrophobicity of a substrate has an effect to reduce the requirement degree of oversaturation on water bulk. We found that the gas enrichment layer, gas adsorption monolayer on the hydrophobic substrate, and water hydrogen bonding near the interface are likely necessary conditions for nanobubble stability. We concluded that gas nanobubble stability does not necessarily require three-phase pinning sites.

Hybrid Cassie-Wenzel model for droplets on surfaces with nanoscale roughness.

Several models have been developed to predict the contact angle of a droplet sitting on a roughened surface; however, no such model has been developed for substrates with nanoscale surface structures. In this paper we propose a hybrid Cassie-Wenzel model, which considers two factors attributed to the breakdown of macroscopic predictions, including the width of the wall-fluid depletion region and the coexistence of Cassie and Wenzel states in cases where the wall-fluid interface presents nanoscale structures. At the molecular scale, the parameter of surface roughness can be corrected by treating the wall-fluid interface as a hybrid Cassie-Wenzel state in which the fraction in the Wenzel state depends on fluid density within the cavities. A more general model developed using data fitted to fluid density is able to account for deviating tendencies induced by nanoscale surface features. A comparison of predicted results obtained in this study with those from previous works demonstrates that the proposed hybrid Cassie-Wenzel model is applicable to the evaluation of wettability in a wide range of substrates with nanoscale surface structures, corresponding to a Cassie state, a Wenzel state, and a mixed state. More importantly, the present work provides a quantitative approach to the estimation of wettability even amidst nanoscale effects, which can have a significant influence in cases with surface features at the molecular scale.

2-[3-[2-[(2S)-2-Cyano-1-pyrrolidinyl]-2-oxoethylamino]-3-methyl-1-oxobutyl]- 1,2,3,4-tetrahydroisoquinoline: a potent, selective, and orally bioavailable dipeptide-derived inhibitor of dipeptidyl peptidase IV.

Dipeptidyl peptidase IV (DPP-IV) inhibitors are expected to become a new type of antidiabetic drugs. Most known DPP-IV inhibitors often resemble the dipeptide cleavage products, with a proline mimic at the P1 site. As off-target inhibitions of DPP8 and/or DPP9 have shown profound toxicities in the in vivo studies, it is important to develop selective DPP-IV inhibitors for clinical usage. To achieve this, a new class of 2-[3-[[2-[(2S)-2-cyano-1-pyrrolidinyl]-2-oxoethyl]amino]-1-oxopropyl]-based DPP-IV inhibitors was synthesized. SAR studies resulted in a number of DPP-IV inhibitors, having IC(50) values of <50 nM with excellent selectivity over both DPP8 (IC(50) > 100 microM) and DPP-II (IC(50) > 30 microM). Compound 21a suppressed the blood glucose elevation after an oral glucose challenge in Wistar rats and also inhibited plasma DPP-IV activity for up to 4 h in BALB/c mice. The results show that compound 21a possesses in vitro and in vivo activities comparable to those of NVP-LAF237 (4), which is in clinical development.

Glutamic acid analogues as potent dipeptidyl peptidase IV and 8 inhibitors.

To find potent and selective inhibitors of dipeptidyl peptidase IV (DPP-IV), we synthesized a series of 2-cyanopyrrolidine with P2-site 4-substituted glutamic acid derivatives and tested their activities against DPP-IV, DPP8, and DPP-II. Analogues that incorporated a bulky substituent at the first carbon position of benzylamine or isoquinoline showed over 30-fold selectivity for DPP-IV over both DPP8 and DPP-II. From structure-activity relationship studies, we speculate that the S2 site of DPP8 might be similar to that of DPP-IV, while DPP-IV inhibitor with N-substituted glycine in the P2 site and/or with a moiety involving in hydrophobic interaction with the side chain of Phe357 might provide a better selectivity for DPP-IV over DPP8.