Variation of Surface Propensity of Halides with Droplet Size and Temperature: The Planar Interface Limit.

The radial number density profiles of halide and alkali ions in aqueous clusters with equimolar radius ≲1.4 nm, which correspond to ≲255 H2O molecules, have been extensively studied by computations. However, the surface abundance of Cl-, Br-, and I- relative to the bulk interior in these smaller clusters may not be representative of the larger systems. Indeed, here we show that the larger the cluster is, the lower the relative surface abundance of chaotropic halides is. In droplets with an equimolar radius of ≈2.45 nm, which corresponds to ≈2000 H2O molecules, the polarizable halides show a clear number density maximum in the droplet's bulk-like interior. A similar pattern is observed in simulations of the aqueous planar interface with halide salts at room temperature. At elevated temperature the surface propensity of Cl- decreases gradually, while that of I- is partially preserved. The change in the chaotropic halide location at higher temperatures than the room temperature may considerably affect photochemical reactivity in atmospheric aerosols, vapor-liquid nucleation and growth mechanisms, and salt crystallization via solvent evaporation. We argue that the commonly used approach of nullifying parameters in a force field in order to find the factors that determine the ion location does not provide transferable insight into other force fields.

Delayed pleuroperitoneal leak in an otherwise uncomplicated course of peritoneal dialysis.

Key Clinical Message: Pleuroperitoneal leaks are rare and normally arise as an early complication in peritoneal dialysis. This case illustrates the importance of considering pleuroperitoneal leaks as a cause for pleural effusions-even if peritoneal dialysis has been longstanding and uncomplicated. Abstract: A 66-year-old male on peritoneal dialysis for 15 months presented with dyspnoea and low ultrafiltration volumes. Chest radiography revealed a large right-sided pleural effusion. Pleural fluid sampling and peritoneal scintigraphy confirmed a pleuroperitoneal leak.

Limitations of Atomistic Molecular Dynamics to Reveal Ejection of Proteins from Charged Nanodroplets.

Atomistic molecular dynamics (MD) is frequently used to unravel the mechanisms of macroion release from electrosprayed droplets. However, atomistic MD is currently feasible for only the smallest window of droplet sizes appearing at the end steps of a droplet's lifetime. The relevance of the observations made to the actual droplet evolution, which is much longer than the simulated sizes, has not been addressed yet in the literature. Here, we perform a systematic study of the desolvation mechanisms of poly(ethylene glycol) (PEG), protonated peptides of different compositions, and proteins, to (a) obtain insight into the charging mechanism of macromolecules in larger droplets than those that are currently amenable to atomistic MD and (b) examine whether currently used atomistic MD modeling can establish the extrusion mechanism of proteins from droplets. To mimic larger droplets that are not amenable to MD modeling, we scale down the systems, by simulating a large droplet size relative to the macromolecule. MD of PEG charging reveals that, above a critical droplet size, ions are available near the backbone of the macromolecule, but charging occurs only transiently by transfer of ions from the solvent to the macroion, while below the critical size, the capture of the ion from PEG has a lifetime sufficiently long for the extrusion of a charged PEG from the aqueous droplet. This is the first report of the role of droplet curvature in the relation between macroion conformation and charging. Simulations of protonated peptides with a high degree of hydrophobicity show that partial extrusion of a peptide from the droplet surface is rare relative to desolvation by drying-out. Different from what has been presented in the literature, we argue that atomistic MD simulations have not sufficiently established the extrusion mechanism of proteins from droplets and their charging mechanism. We also argue that release of highly charged proteins can occur at an earlier stage of a droplet's lifetime than predicted by atomistic MD. In this earlier stage, we emphasize the key role of jets emanating from a droplet at the point of charge-induced instability in the release of proteins.

Salt Enrichment and Dynamics in the Interface of Supercooled Aqueous Droplets.

The interconversion reaction of NaCl between the contact-ion pair (CIP) and the solvent-separated ion pair (SSIP) as well as the free-ion state in cold droplets has not yet been investigated. We report direct computational evidence that the lower is the temperature, the closer to the surface the ion interconversion reaction takes place. In supercooled droplets the enrichment of the subsurface in salt becomes more evident. The stability of the SSIP relative to the CIP increases as the ion-pairing is transferred toward the droplet's outer layers. In the free-ion state, where the ions diffuse independently in the solution, the number density of Cl- shows a broad maximum in the interior in addition to the well-known maximum in the surface. In the study of the reaction dynamics, we find a weak coupling between the interionic NaCl distance reaction coordinate and the solvent degrees of freedom, which contrasts with the diffusive crossing of the free energy barrier found in bulk solution modeling. The H2O self-diffusion coefficient is found to be at least an order of magnitude larger than that in the bulk solution. We propose to exploit the enhanced surface ion concentration at low temperature to eliminate salts from droplets in native mass spectrometry ionization methods.

Conical Shape Fluctuations Determine the Rate of Ion Evaporation and the Emitted Cluster Size Distribution from Multicharged Droplets.

The ion evaporation mechanism (IEM) is perceived to be a major pathway for disintegration of multi-ion charged droplets found in atmospheric and sprayed aerosols. However, the precise mechanism of IEM and the effect of the nature of the ions in the emitted cluster size distribution have not yet been established despite its broad use in mass spectrometry and atmospheric chemistry over the past half century. Here, we present a systematic study of the emitted ion cluster distribution in relation to their spatial distribution in the parent droplet using atomistic modeling. It is found that in the parent droplet, multiple kosmotropic and weakly polarizable chaotropic ions (Cs+) are buried deeper within the droplet than polarizable chaotropic ions (Cl-, I-). This differentiation in the ion location is only captured by a polarizable model. It is demonstrated that the emitted cluster size distribution is determined by dynamic conical deformations and not by the equilibrium ion depth within the parent droplet as the IEM models assume. Critical factors that determine the cluster size distribution such as the charge sign asymmetry that have not been considered in models and in experiments are presented. We argue that the existing IEM analytical models do not establish a clear difference between IEM and Rayleigh fission. We propose a shift in the existing view for IEM from the equilibrium properties of the parent droplet to the chemistry in the conical shape fluctuations that serve as the centers for ion emission. Consequently, chemistry in the conical fluctuations may also be a key element to explain charge states of macromolecules in mass spectrometry and may have potential applications in catalysis due to the electric field in the conical region.

Low Density Interior in Supercooled Aqueous Nanodroplets Expels Ions to the Subsurface.

The interaction between water and ions within droplets plays a key role in the chemical reactivity of atmospheric and man-made aerosols. Here we report direct computational evidence that in supercooled aqueous nanodroplets a lower density core of tetrahedrally coordinated water expels the cosmotropic ions to the denser and more disordered subsurface. In contrast, at room temperature, depending on the nature of the ion, the radial distribution in the droplet core is nearly uniform or elevated toward the center. We analyze the spatial distribution of a single ion in terms of a reference electrostatic model. The energy of the system in the analytical model is expressed as the sum of the electrostatic and surface energy of a deformable droplet. The model predicts that the ion is subject to a harmonic potential centered at the droplet's center of mass. We name this effect "electrostatic confinement". The model's predictions are consistent with the simulation findings for a single ion at room temperature but not at supercooling. We anticipate this study to be the starting point for investigating the structure of supercooled (electro)sprayed droplets that are used to preserve the conformations of macromolecules originating from the bulk solution.

Relation between Ejection Mechanism and Ion Abundance in the Electric Double Layer of Droplets.

Charged droplets have been associated with distinct chemical reactivity. It is assumed that the composition of the surface layer plays a critical role in enhancing the reaction rates in the droplets relative to their bulk solution counterparts. We use atomistic modeling to relate the localization of ions in the surface layer to their ejection propensity. We find that ion ejection takes place via a two-stage process. First, a conical protrusion emerges as a result of a global droplet deformation that is insensitive to the locations of the single ions. The ions are subsequently ejected as they enter the conical regions. The study provides mechanistic insight into the ion-evaporation mechanism, which can be used to revise the commonly used ion-evaporation models. We argue that atomistic molecular dynamics simulations of minute nanodrops do not sufficiently distinguish the ion-evaporation mechanism from a Rayleigh fission. We explain mass spectrometry data on the charge state of small globular proteins and the existence of supercharged droplet states that have been detected in experiments.

Molecular Characterization of the Surface Excess Charge Layer in Droplets.

The surface excess charge layer (SECL) in droplets has often been associated with distinct chemistry. We examine the effect of the nature of ions in the composition and structure of SECL by using molecular dynamics. We find that in the presence of simple ions the thickness of SECL is invariant not only with respect to droplet size but also with respect to the nature of the ions. In the presence of simple ions, this layer has a thickness of ∼1.5-1.7 nm but in the presence of macroions it may extend to ∼2.0 nm. The proportion of ions contained in SECL depends on the nature of the ions and the droplet size. For the same droplet size, I- and model H3O+ ions show considerably higher concentration than Na+ and Cl- ions. We identify the maximum ion concentration region, which, in nanodrops, may partially overlap with SECL. As the relative shape fluctuations decrease when microdrop size is approached, the overlap between SECL and maximum ion concentration region increases. We suggest the extension of the bilayer droplet structure assumed in the equilibrium partitioning model of Enke to include the maximum ion concentration region that may not coincide with SECL in nanodrops. We compute the ion concentrations in SECL, which are those that should enter the kinetic equation in the ion-evaporation mechanism, instead of the overall drop ion concentration that has been used.

Where Do the Ions Reside in a Highly Charged Droplet?

Aqueous droplets in atmospheric and electrosprayed aerosols are charged due to presence of multiple ionic species. We examine the ion spatial distribution and the surface electric field in aqueous charged nanodrops by using atomistic modeling and analytical theory. We find that in nanoscopic liquid drops the concentration of simple ions is higher in the outer droplet shells, reduces gradually toward the drop center, and dies-off toward the vapor-droplet interface. The behavior of the ion spatial distribution is supported by a general analytical theory that takes into account a fluctuating droplet interface, an effective screening length of the charges and the finite size of a solvated ion. We compute the electric potential and the electric field near the droplet surface using a multipole expansion. We emphasize the significance of the fluctuations of the normal component of the electric field in ion evaporation via the Born model. In the presence of a highly charged peptide, we find that the peptide is situated mainly in the droplet interior and occasionally near the droplet surface. The simple ions are mainly near the droplet surface. The study provides insight into droplet chemistry and electrospray ionization mass spectrometry findings.

The Use of Anecdotal Information in a Hypothetical Lung Cancer Treatment Decision.

This mixed-methods study examined variables associated with use of experience-based (i.e., anecdotal) decisional strategies among 85 undergraduate students presented with 2 hypothetical lung cancer scenarios. Participants were asked to think aloud while they made their treatment choice. Eleven decisional strategies were identified and grouped into either data or experience-based strategies. Approximately, 25% of participants used experience-based strategies. Use of experience-based strategies was more likely if the participant reported involvement in the life of someone going through cancer treatment, and if they rated print-based media sources as less important. Use of experience-based strategies was associated with choosing surgery instead of radiation for lung cancer treatment.

Strengths and Weaknesses of Molecular Simulations of Electrosprayed Droplets.

The origin and the magnitude of the charge in a macroion are critical questions in mass spectrometry analysis coupled to electrospray and other ionization techniques that transfer analytes from the bulk solution into the gaseous phase via droplets. In many circumstances, it is the later stages of the existence of a macroion in the containing solvent drop before the detection that determines the final charge state. Experimental characterization of small (with linear dimensions of several nanometers) and short-lived droplets is quite challenging. Molecular simulations in principle may provide insight exactly in this challenging for experiments regime. We discuss the strengths and weaknesses of the molecular modeling of electrosprayed droplets using molecular dynamics. We illustrate the limitations of the molecular modeling in the analysis of large macroions and specifically proteins away from their native states. Graphical Abstract ᅟ.