Modeling the ionization mechanism of amorphous solid particles without an external energy source coupled to mass spectrometry.

Ionization desorption of charged analytes from the surface of solid amorphous glutaric acid particles, without the assistance of an external energy source, has been shown to be a promising method that can be coupled to mass spectrometry. We conduct mechanistic studies of the later stages of this ionization process using atomistic molecular dynamics. Our analysis focuses on the hydrogen bonding, diffusion, and ion desorption from nano-aggregates of glutaric acid.

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 HO 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.

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.

Atomistic Modeling of Jet Formation in Charged Droplets.

The first atomistic simulations that reveal the mechanism of Rayleigh fission are presented. It is demonstrated that simple ion or macroion ejection takes place through droplet deformation from a spherical into a distinct "tear" shape that contains a conical protrusion. We assert that the latter state is a free-energy minimum along an order parameter that measures the degree of droplet asphericity.

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.

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.

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.

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.

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.

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.

Effect of the chemical environment of the DNA guanine quadruplex on the free energy of binding of Na and K ions.

Guanine quadruplex (G-quadruplex) structures play a vital role in stabilizing the DNA genome and in protecting healthy cells from transforming into cancer cells. The structural stability of G-quadruplexes is greatly enhanced by the binding of monovalent cations such as Na or K into the interior axial channel. We computationally study the free energy of binding of Na and K ions to two intramolecular G-quadruplexes that differ considerably in their degree of rigidity and the presence or absence of terminal nucleotides.

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.

Macroion-Solvent Interactions in Charged Droplets.

Macroion-droplet interactions play a critical role in many settings such as ionization techniques of samples in mass spectrometry analysis and atmospheric aerosols. The droplets under investigation are composed of a polar solvent, primarily water, a charged macroion, and, possibly, buffer ions. We present highlights of our research on the relation between the charge state of a macroion and the droplet morphologies.

"Star" morphologies of charged nanodrops comprised of conformational isomers.

We study the spatial distribution of conformational isomers surrounding a central macroion in a charged droplet with linear dimensions in the nanometer range. Dimethyl carbonate and formic acid are selected as typical solvents that undergo isomerization and a charged buckyball (C) is selected as a representative example of a macroion. The study is performed by atomistic molecular dynamics simulations.

What factors determine the stability of a weak protein-protein interaction in a charged aqueous droplet?

Maintaining the interface of a weak transient protein complex transferred from bulk solution to the gaseous state via evaporating droplets is a critical question in the detection of the complex association (dissociation) constant by using electrospray ionization mass spectrometry (ESI-MS). Here we explore the factors that may affect the stability of a protein-protein interaction (PPI) using atomistic molecular dynamics (MD) modelling of a complex of ubiquitin (Ub) and the ubiquitin-associated domain (UbA) (RCSB PDB code ) and a non-covalent complex of diubiquitin (RCSB PDB code ) in aqueous droplets. A general method is presented to determine the protonation states of the complexes we investigate in particular, and that of a protein in general, under various pH conditions that an evaporating droplet acquires due to its change in size.

When droplets become stars: charged dielectric droplets beyond the Rayleigh limit.

When a nano-drop comprising a single spherical central ion and dielectric solvent is charged above a well-defined threshold, it acquires a stable star morphology. In contrast, conducting droplets, will undergo fission. Here we report combined atomistic molecular dynamics and continuum modelling study of star formation of droplets that contain a highly charged ion.

Charging and Release Mechanisms of Flexible Macromolecules in Droplets.

We study systematically the charging and release mechanisms of a flexible macromolecule, modeled by poly(ethylene glycol) (PEG), in a droplet by using molecular dynamics simulations. We compare how PEG is solvated and charged by sodium Na ions in a droplet of water (HO), acetonitrile (MeCN), and their mixtures. Initially, we examine the location and the conformation of the macromolecule in a droplet bearing no net charge.

Advances in Modeling the Stability of Noncovalent Complexes in Charged Droplets with Applications in Electrospray Ionization-MS Experiments.

Electrospray ionization mass spectrometry is used extensively to measure the equilibrium constant of noncovalent complexes. In this Perspective, we attempt to present an accessible introduction to computational methodologies that can be applied to determine the stability of weak noncovalent complexes in their journey from bulk solution into the gaseous state. We demonstrate the usage of the methods on two typical examples of noncovalent complexes drawn from a broad class of nucleic acids and transient protein complexes found in aqueous droplets.

Stability of a Transient Protein Complex in a Charged Aqueous Droplet with Variable pH.

Electrospray ionization mass spectrometry (ESI-MS) has the potential to become a high-throughput robust experimental method for the detection of protein-protein equilibrium constants. Poorly understood processes that affect the stability of weak noncovalent protein complexes in the intervening droplet environment are a significant factor that precludes the advancement of the method. We use molecular dynamics to study the stability of a ubiquitin and ubiquitin-associated domain complex (RCSB PDB code 2MRO ) in an aqueous droplet with changing size and charge concentration.

Characterization of "Star" Droplet Morphologies Induced by Charged Macromolecules.

"Star" morphologies of charged liquid droplets are distinct droplet conformations that, for a certain charge squared to volume ratio, have lower energy than their spherically shaped analogues. For these shapes to appear, the charge should be carried by a single ionic species. A typical example of a charge carrier that we employ in this study is a fully charged double-stranded oligodeoxynucleotide (dsDNA) in an aqueous and an acetonitrile droplet.

How do non-covalent complexes dissociate in droplets? A case study of the desolvation of dsDNA from a charged aqueous nanodrop.

We present the desolvation mechanism of a double-stranded oligodeoxynucleotide (dsDNA) from an aqueous nanodrop studied by using atomistic molecular dynamics methods. The central theme of this study is the stability of a non-covalently bound complex, in general, and that of a dsDNA in particular, in a droplet environment. Among the factors that may affect the stability of a complex in an evaporating droplet we examine the increase in ion concentration and the distinct droplet morphologies arising from the charge-induced instability.

Effect of solvent on the charging mechanisms of poly(ethylene glycol) in droplets.

We examine the effect of solvent on the charging mechanisms of a macromolecule in a droplet by using molecular dynamics simulations. The droplet contains excess charge that is carried by sodium ions. To investigate the principles of the charging mechanisms of a macromolecule in a droplet, we simulate aqueous and methanol droplets that contain a poly(ethylene glycol) (PEG) molecule.

Effect of counterions on the charging mechanisms of a macromolecule in aqueous nanodrops.

We report the first molecular dynamics study of the effect of counterions on the charging mechanisms of a macromolecule found in an aqueous droplet that contains excess charge. To investigate the principles of the charging mechanisms of a macromolecule in a droplet, we simulate aqueous droplets that contain a poly(ethylene glycol) (PEG) molecule, sodium, and chloride ions. We study the effect of counterions by varying the concentration of the chloride ions and the temperature of the droplets.

Variation of droplet acidity during evaporation.

Variation of acidity and associated chemical changes of macromolecules in evaporating droplets is of central importance in electrosprayed aerosols. We study changes in acidity during evolution of a droplet that is composed of solvent and a charge binding macromolecule. We analyze the acidity of the droplet using analytical theory and stochastic modeling.