Nanometer patterning of water by tetraanionic ferrocyanide stabilized in aqueous nanodrops.

Formation of the small, highly charged tetraanion ferrocyanide, Fe(CN)64-, stabilized in aqueous nanodrops is reported. Ion-water interactions inside these nanodrops are probed using blackbody infrared radiative dissociation, infrared photodissociation (IRPD) spectroscopy, and molecular modeling in order to determine how water molecules stabilize this highly charged anion and the extent to which the tetraanion patterns the hydrogen-bonding network of water at long distance. Fe(CN)64-(H2O)38 is the smallest cluster formed directly by nanoelectrospray ionization. Ejection of an electron from this ion to form Fe(CN)63-(H2O)38 occurs with low-energy activation, but loss of a water molecule is favored at higher energy indicating that water molecule loss is entropically favored over loss of an electron. The second solvation shell is almost complete at this cluster size indicating that nearly two solvent shells are required to stabilize this highly charged anion. The extent of solvation necessary to stabilize these clusters with respect to electron loss is substantially lower through ion pairing with either H+ or K+ (n = 17 and 18, respectively). IRPD spectra of Fe(CN)64-(H2O) n show the emergence of a free O-H water molecule stretch between n = 142 and 162 indicating that this ion patterns the structure of water molecules within these nanodrops to a distance of at least ∼1.05 nm from the ion. These results provide new insights into how water stabilizes highly charged ions and demonstrate that highly charged anions can have a significant effect on the hydrogen-bonding network of water molecules well beyond the second and even third solvation shells

Long distance ion-water interactions in aqueous sulfate nanodrops persist to ambient temperatures in the upper atmosphere.

The effect of temperature on the patterning of water molecules located remotely from a single SO42- ion in aqueous nanodrops was investigated for nanodrops containing between 30 and 55 water molecules using instrument temperatures between 135 and 360 K. Magic number clusters with 24, 36 and 39 water molecules persist at all temperatures. Infrared photodissociation spectroscopy between 3000 and 3800 cm-1 was used to measure the appearance of water molecules that have a free O-H stretch at the nanodroplet surface and to infer information about the hydrogen bonding network of water in the nanodroplet. These data suggest that the hydrogen bonding network of water in nanodrops with 45 water molecules is highly ordered at 135 K and gradually becomes more amorphous with increasing temperature. An SO42- dianion clearly affects the hydrogen bonding network of water to at least ∼0.71 nm at 135 K and ∼0.60 nm at 340 K, consistent with an entropic drive for reorientation of water molecules at the surface of warmer nanodrops. These distances represent remote interactions into at least a second solvation shell even with elevated instrumental temperatures. The results herein provide new insight into the extent to which ions can structurally perturb water molecules even at temperatures relevant to Earth's atmosphere, where remote interactions may assist in nucleation and propagation of nascent aerosols

Structural and electrostatic effects at the surfaces of size- and charge-selected aqueous nanodrops.

The effects of ion charge, polarity and size on the surface morphology of size-selected aqueous nanodrops containing a single ion and up to 550 water molecules are investigated with infrared photodissociation (IRPD) spectroscopy and theory. IRPD spectra of M(H2O) n where M = La3+, Ca2+, Na+, Li+, I-, SO42- and supporting molecular dynamics simulations indicate that strong interactions between multiply charged ions and water molecules can disrupt optimal hydrogen bonding (H-bonding) at the nanodrop surface. The IRPD spectra also reveal that "free" OH stretching frequencies of surface-bound water molecules are highly sensitive to the ion's identity and the OH bond's local H-bond environment. The measured frequency shifts are qualitatively reproduced by a computationally inexpensive point-charge model that shows the frequency shifts are consistent with a Stark shift from the ion's electric field. For multiply charged cations, pronounced Stark shifting is observed for clusters containing ∼100 or fewer water molecules. This is attributed to ion-induced solvent patterning that extends to the nanodrop surface, and serves as a spectroscopic signature for a cation's ability to influence the H-bond network of water located remotely from the ion. The Stark shifts measured for the larger nanodrops are extrapolated to infinite dilution to obtain the free OH stretching frequency of a surface-bound water molecule at the bulk air-water interface (3696.5-3701.0 cm-1), well within the relatively wide range of values obtained from SFG measurements. These cluster measurements also indicate that surface curvature effects can influence the free OH stretching frequency, and that even nanodrops without an ion have a surface potential that depends on cluster size

Modeling the maximum charge state of arginine-containing peptide ions formed by electrospray ionization

A model for the gas-phase proton transfer reactivity of multiply protonated molecules is used to quantitatively account for the maximum charge states of a series of arginine-contain- ing peptide ions measured by Downard and Biemann (Int. J. Mass Spectrom. Ion Processes 1995, 148, 191–202). We find that our calculations account exactly for the maximum charge state for 7 of the 10 peprides and are off by one charge for the remaining 3. These calculations clearly predict the trend in maximum charge states for these peptides and provide further evidence that the maximum charge state of ions formed by electrospray ionization is determined by their gas-phase proton transfer reactivity. (J Am Soc Mass Spectrom 1996, 7, 972–976

High-Throughput Single-Particle Characterization of Aggregation Pathways and the Effects of Inhibitors for Large (Megadalton) Protein Oligomers

Protein aggregation is involved in many human diseases, but characterizing the sizes and shapes of intermediate oligomers (∼10-100 nm) that are important to the formation of macroscale aggregates like amyloid fibrils is a significant analytical challenge. Here, charge detection mass spectrometry (CDMS) is used to characterize individual conformational states of bovine serum albumin oligomers with up to ∼225 molecules (15 MDa). Elongated, partially folded, and globular conformational families for each oligomer can be readily distinguished based on the extent of charging. The abundances of individual conformers vary with changes in the monomer concentration or by adding aggregation inhibitors, such as SDS, heparin, or MgCl2. These results show the potential of CDMS for investigating intermediate oligomers in protein aggregation processes that are important for understanding aggregate formation and inhibition mechanisms and could accelerate formulation buffer development to prevent the aggregation of biotherapeutics