The study of ionic liquids that may be compatible with the type of radiation chemistry events occurring in nuclear separation processes is a topic of high current interest. In this article, we focus on two ionic liquids based on the benzylpyridinium cation. This cation has been proposed to be able to capture either an excess electron or hole without undergoing fast dissociation. Shkrob, Wishart, and collaborators ( J. Phys. Chem. B 2013, 117 (46), 14385–−14399) have indicated that the stabilization is likely in the form of dimers in solution with the excess electron localized on adjacent pyridinium rings and the excess hole localized on phenyl rings. Our first-principles dynamical studies support these ideas but present a more nuanced view of the time-dependent behavior that is likely to occur at short time for systems at room temperature.

The behavior in the bulk and at interfaces of biphilic ionic liquids in which either the cation or anion possesses moderately long alkyl tails is to a significant degree well understood. Less clear is what happens when both the cation and anion possess tails that are not apolar, such as in the case of ether functionalities. The current article discusses the structural characteristics of C2OC2OC2-mim+/C2OC2OC2-OSO3– in the bulk and at the vacuum interface. We find that the vacuum interface affects only the nanometer length scale. This is in contrast to what we have recently found in ( J. Phys. Chem. Lett., 2016, 7 (19), 3785––3790) for isoelectronic C[8]-mim+/C[8]-OSO3–, where the interface effect is long ranged. Interestingly, ions with the diether tail functionality still favor the tail-outward orientation at the vacuum interface and the bulk phase preserves the alternation between charged networks and tails that is commonly observed for biphilic ionic liquids. However, such alternation is less well-defined and results in a significantly diminished first sharp diffraction peak in the bulk liquid structure function.

Mutations in the hinge region of cyanovirin-N (CVN) dictate its preferential oligomerization state. Constructs with the Pro51Gly mutation preferentially exist as monomers, whereas wild-type cyanovirin can form domain-swapped dimers under certain conditions. Because the hinge region is an integral part of the high-affinity binding site of CVN, we investigated whether this mutation affects the shape, flexibility, and binding affinity of domain B for dimannose. Our studies indicate that the capability of monomeric wild-type CVN to resist mechanical perturbations is enhanced when compared to that of constructs in which the hinge region is more flexible. Our computational results also show that enhanced flexibility leads to blocking of the binding site by allowing different rotational isomeric states of Asn53. Moreover, at higher temperatures, this observed flexibility leads to an interaction between Asn53 and Asn42, further hindering access to the binding site. On the basis of these results, we predicted that binding affinity for dimannose would be more favorable for cyanovirin constructs containing a wild-type hinge region, whereas affinity would be impaired in the case of mutants containing Pro51Gly. Experimental characterization by isothermal titration calorimetry of a set of cyanovirin mutants confirms this hypothesis. Those possessing the Pro51Gly mutation are consistently inferior binders.

Modern room temperature ionic liquids are structurally defined by symmetries on different length scales. Polar–apolar alternation defines their nanoscale structural heterogeneity, whereas positive–negative charge alternation defines short length scale order. Much progress has been made in the past few years as it pertains to the theoretical interpretation of X-ray scattering experiments for these liquids. Our group has contributed to the development of theoretical interpretation guidelines for the analysis of their structure function. Perhaps less well developed is our understanding of how transport and dynamics in general couple to the very unique structure of ionic liquids which are often dynamically and structurally heterogeneous. This article attempts to present our most current understanding of ionic liquid structure in general and its coupling to transport and dynamics in minimally technical terms for the benefit of the broadest audience.

The deviations from Stokes–Einstein hydrodynamics of small solutes are more pronounced in ionic liquids than in conventional solvents (J. Phys. Chem. B 2013 117 (39), 11697). Small neutral solutes diffuse much faster than expected, whereas small charged solutes diffuse much slower. This article attempts to establish a link between the local friction experienced by tracer solutes and the polar/apolar structure of ionic liquids. We find that small neutral solutes probe locally “stiff” (mostly charged, high electrostriction) regions and locally “soft” (mostly apolar, low electrostriction) regions. These regions of high and low friction are associated with cage and jump regimes. Enhanced neutral tracer mobility in the low friction regions associated with the cationic apolar component has an important bearing on the large positive deviations from Stokes–Einstein behavior. In contrast, diminished charged tracer mobility involves long caging dynamics separated by jump events often triggered by the loss and recovery of counterions.

In a recent article [ J. Am. Chem. Soc. 2011, 133, 20186], we described the nature of the “dry” excess electron in a variety of different ionic liquids. We found that this could delocalize over cations or anions depending on the nature of the ions involved. A second article [ J. Am. Chem. Soc. 2013, 135, 17528] explored the nature of the “dry to trapped” excess electron transition, the early localization dynamics, and associated spectroscopic signatures in alkylamonium and pyrrolidinium bis(trifluoromethylsulfonyl)amide based ionic liquids. In this study we predicted that the trapped electron localizes on an anion, resulting in fragmentation that is undesirable for photochemical, electrochemical, and radiation chemistry applications. The current work focuses instead on an ionic liquid based on the dicyanamide anion that on a time scale relevant to electron transfer and solvation dynamics does not appear to undergo facile fragmentation. Although electrochemical cathodic and anodic limits were correctly predicted by our recent study, it is unclear whether the reaction channels explored are necessarily those responsible for the observed near-infrared (NIR) band typical of excess electrons at long time. Could it be possible that the electrochemically relevant reaction channel is not necessarily the one giving rise to the NIR signal? This work attempts to approach such structural and dynamical aspects relevant to photodegradation, radiation chemistry, and electrochemistry in the case of pyrrolidinium dicyanamide based ionic liquids.

The carbohydrate binding protein, Cyanovirin-N, obtained from cyanobacteria, consists of high-affinity and low-affinity binding domains. To avoid the formation of a domain swapped structure in solution and also to better focus on the binding of carbohydrates at the high-affinity site, the Ghirlanda group (Biochemistry, 46, 2007, 9199–9207) engineered the P51G-m4-CVN mutant which does not dimerize nor binds at the low-affinity site. This mutant provides an excellent starting point for the experimental and computational study of further transformations to enhance binding at the high-affinity site as well as to retool this site for the possible binding of different sugars. However, before such endeavors are pursued, detailed understanding of apparently key interactions both present in wild-type and P51G-m4-CVN at the high-affinity site must be derived and controversies about the importance of certain residues must be resolved. One such interaction is that of Glu41, a charged residue in intimate contact with 2′OH of dimannose at the nonreducing end. We do so computationally by performing two mutations using the thermodynamic integration formalism in explicit solvent. Mutations of P51G-m4-CVN Glu41 to Ala41 and Gly41 reveal that whereas the loss of Coulomb interactions result in a free energy penalty of about 2.1 kcal/mol, this is significantly compensated by favorable contributions to the Lennard-Jones portion of the transformation, resulting in almost no change in the free energy of binding. At least in terms of free energetics, and in the case of this particular CVN mutant, Glu41 does not appear to be as important as previously thought. This is not because of lack of extensive hydrogen bonding with the ligand but instead because of other compensating factors.

Triphilic ionic liquids (containing polar, apolar, and fluorinated components) that can hydrogen bond present a new paradigm in ionic liquid structural morphology. In this study we show that butylammonium pentadecafluorooctanoate and its nonfluorinated analogue butylammonium octanoate form disordered bicontinuous phases where a network of charge alternating hydrogen bonds continuously percolate through the whole liquid. These systems show order on multiple length scales, the largest length scale given by the percolating network. Separation between filaments in the network gives rise to a prepeak or first sharp diffraction peak. In the case of the fluorinated system, shorter range order occurs due to apolar-fluorinated alternation that decorates the surface of each individual filament. The backbone of the filaments is the product of the shortest organized length scale, namely, charge alternating hydrogen bonds. Liquid structure obtained via molecular dynamics simulations is used to compute coherent X-ray scattering intensities, and a full picture of the liquid landscape is developed. A careful mathematical analysis of the simulation data proposed here reveals individual molecular correlations that importantly contribute to each feature of the experimental structure function.

In a recent article (J. Am. Chem. Soc. 2011, 133, 20186) we investigated the initial spatial distribution of dry excess electrons in a series of room-temperature ionic liquids (RTILs). Perhaps unexpectedly, we found that in some alkylammonium-based systems the excess negative charge resided on anions and not on the positive cations. Following on these results, in the current paper we describe the time evolution of an excess electronic charge introduced in alkylammonium- and pyrrolidinium-based ionic liquids coupled with the bis(trifluoromethylsulfonyl)amide ([Tf2N–]) anion. We find that on a 50 fs time scale an initially delocalized excess electron localizes on a single [Tf2N–] anion which begins a fragmentation process. Low-energy transitions have a very different physical origin on the several femtoseconds time scale when compared to what occurs on the picosecond time scale. At time zero, these are intraband transitions of the excess electron. However after 40 fs when the excess electronic charge localizes on a single anion, these transitions disappear, and the spectrum is dominated by electron-transfer transitions between the fragments of the doubly charged breaking anion.

X-ray scattering experiments and molecular dynamics simulations have been performed to investigate the structure of four room temperature ionic liquids (ILs) comprising the bis(trifluoromethylsulfonyl)amide (NTf2–) anion paired with the triethyloctylammonium (N2228+) and triethyloctylphosphonium (P2228+) cations and their isoelectronic diether analogs, the (2-ethoxyethoxy)ethyltriethylammonium (N222(2O2O2)+) and (2-ethoxyethoxy)ethyltriethylphosphonium (P222(2O2O2)+) cations. Agreement between simulations and experiments is good and permits a clear interpretation of the important topological differences between these systems. The first sharp diffraction peak (or prepeak) in the structure function S(q) that is present in the case of the liquids containing the alkyl-substituted cations is absent in the case of the diether substituted analogs. Using different theoretical partitioning schemes for the X-ray structure function, we show that the prepeak present in the alkyl-substituted ILs arises from polarity alternations between charged groups and nonpolar alkyl tails. In the case of the diether substituted ILs, we find considerable curling of tails. Anions can be found with high probability in two different environments: close to the cationic nitrogen (phosphorus) and also close to the two ether groups. For the two diether systems, anions are found in locations from which they are excluded in the alkyl-substituted systems. This removes the longer range (polar/nonpolar) pattern of alternation that gives rise to the prepeak in alkyl-substituted systems.

X-ray scattering and molecular dynamics simulations have been carried out to investigate structural differences and similarities in the condensed phase between pyrrolidinium-based ionic liquids paired with the bis(trifluoromethylsulfonyl)amide (NTf2–) anion where the cationic tail is linear, branched, or cyclic. This is important in light of the charge and polarity type alternations that have recently been shown to be present in the case of liquids with cations of moderately long linear tails. For this study, we have chosen to use the 1-alkyl-1-methylpyrrolidinium, Pyrr1,n+ with n = 5 or 7, as systems with linear tails, 1-(2-ethylhexyl)-1-methylpyrrolidinium, Pyrr1,EtHx+, as a system with a branched tail, and 1-(cyclohexylmethyl)-1-methylpyrrolidinium, Pyrr1,ChxMe+, as a system with a cyclic tail. We put these results into context by comparing these data with recently published results for the Pyrr1,n+/NTf2– ionic liquids with n = 4, 6, 8, and 10.1,2 General methods for interpreting the structure function S(q) in terms of q-dependent natural partitionings are described. This allows for an in-depth analysis of the scattering data based on molecular dynamics (MD) trajectories that highlight the effect of modifying the cationic tail.

In this work we compare the role that different anions play in the structure function S(q) for a set of liquids with the same cation. It is well established that because of their amphiphilic nature and their often larger size, cations play a fundamental role in the structural landscape of ionic liquids. On the other hand, it is often atoms in the anions that display the largest X-ray form factors and therefore play a very significant role as reporters of structure in small- and wide-angle X-ray scattering (SAXS/WAXS)-type experiments. For a set of liquids with similar topological landscape, how does S(q) change when the anionic scattering is deemphasized? Also, how do we computationally recover the typical length scale of important and perhaps universal ionic liquid structural features such as charge alternation when these are experimentally inaccessible from S(q) because of interference cancellations? We answer these questions by studying three different tetrapentylammonium-based liquids with the I–, PF6– and N(CN)2– anions.Keywords: anionic effect on structure; ionic liquids; structure function; X-ray;

Structural patterns that have the same spatial periodicity but a phase offset give rise to peaks and anti-peaks (negative-going peaks) at the same q value in the SAXS structure function S(q). As an example, in ionic liquids we often find charge alternation, and at the distance where one finds a density enhancement of charges of the same type one also finds a depletion of charges of opposite sign. Another such situation arises with polar–apolar densities. At distances where there is enhancement of same-type (polar–polar or apolar–apolar) densities there is also a depletion of opposite-type (polar–apolar) density. This gives rise to prepeaks and what we call same spatial periodicity anti-prepeaks.

In this article, we describe general trends to be expected at short times when an excess electron is generated or injected in different room-temperature ionic liquids (RTILs). Perhaps surprisingly, the excess electron does not localize systematically on the positively charged cations. Rather, the excess charge localization pattern is determined by the cation and anion HOMO/LUMO gaps and, more importantly, by their relative LUMO alignments. As revealed by experiments, the short-time (ps/ns) transient UV spectrum of excess electrons in RTILs is often characterized by two bands, a broad band at low energies (above 1000 nm) and another weaker band at higher energies (around 400 nm). Our calculations show that the dry or presolvated electron spectrum (fs) also has two similar features. The broad band at low energies is due to transitions between electronic states with similar character on ions of the same class but in different locations of the liquid. The lower-intensity band at higher energies is due to transitions in which the electron is promoted to electronic states of different character, in some cases on counterions. Depending on the chemical nature of the RTIL, and especially on the anions, excess electrons can localize on cations or anions. Our findings hint at possible design strategies for controlling electron localization, where electron transfer or transport across species can be facilitated or blocked depending on the alignment of the electronic levels of the individual species.

In this article we show that, analyzed in a barycentric reference frame, the deviation in conductivity measured directly from impedance experiments with respect to that estimated indirectly from NMR diffusion experiments has different origins in electrolyte solutions and pure salts. In the case of electrolyte solutions, the momentum conservation law is satisfied by solvent + ions. Instead, in a molten salt or ionic liquid momentum conservation must be satisfied solely by the ions. This has significant implications. While positively correlated motion of ions of opposite charge is a well justified explanation for the reduction in impedance conductivity in the case of electrolyte solutions, it is not so in the case of ionic liquids and molten salts. This work presents a set of equations that in the case of ionic liquids and molten salts can be used to obtain from direct measurements of impedance and NMR the distinct part of the diffusion coefficient matrix in the barycentric reference frame. In other words, by using experimentally measurable quantities, these equations allow us to access the motional coupling between ions for which there is no single direct experimental measurement technique. While equations of this type have been proposed before, the ones presented here can be easily derived from the momentum conservation law and linear response theory. Our results indicate that the decrease in the impedance conductivity with respect to NMR conductivity in ionic liquids and molten salts is due to anticorrelated motion of ions of same charge. This scenario is different in electrolyte solutions, where the positively correlated motion of ions of opposite charge makes a significant contribution to the decrease in the impedance conductivity. In contrast, in a system comprising a single binary salt (a room temperature ionic liquid or a molten salt), the cation–anion distinct diffusion coefficient is negative definite and opposes the contribution from the cation–cation and anion–anion distinct diffusion coefficients. This property of the cation–anion distinct diffusion coefficient in systems comprising just two ion-constituents holds true not just in the barycentric reference frame but also in any of the internal reference frames of nonequilibrium thermodynamics.

In this study, we present a general-purpose methodology for deriving the three-dimensional (3D) arrangement of multivalent transmembrane complexes in the presence of their ligands. Specifically, we predict the most likely families of structures of the experimentally intractable trimeric asialoglycoprotein receptor (ASGP-R), which consists of human hepatic subunits (two subunits of H1 and one subunit of H2), bound to a triantennary oligosaccharide (TA). Because of the complex nature of this multivalent type-II transmembrane hetero-oligomeric receptor, structural studies have to date been unable to provide the 3D arrangement of these subunits. Our approach is based on using the three-pronged ligand of ASGP-R as a computational probe to derive the 3D conformation of the complex and then using this information to predict the relative arrangement of the protein subunits on the cell surface. Because of interprotein subunit clashes, only a few families of TA conformers are compatible with the trimeric structure of ASGP-R. We find that TA displays significant flexibility, matching that detected previously in FRET experiments, and that the predicted complexes derived from the viable TA structures are asymmetric. Significant variation exists with respect to TA presentation to the receptor complex. In summary, this study provides detailed information about TA−ASGP-R interactions and the symmetry of the complex.

The observation of a first sharp diffraction peak (FSDP) at low frequency in the X-ray and neutron scattering spectra of different imidazolium-based room-temperature ionic liquids (RTILs) (the so-called prepeak) has often been experimentally interpreted as indicative of mesoscopic organization leading to nanoscale segregation and the formation of domains of different morphologies. This interpretation that has permeated the analysis of many recently published articles deserves an in depth theoretical analysis. In this article, we use several different computational techniques to thoroughly dissect the atomistic components giving rise to the low-frequency FSDP as well as other features in the structure function (S(q)). By understanding how S(q) changes as imidazolium-based ionic systems undergo solid−liquid phase transition, and by artificially perturbing the liquid structure in a way that directly couples to the intensity of the FSDP, we are able to identify in a rigorous way its geometric origin. Similar to the solid phase, the liquid phase is characterized by two typical length scales between polar groups. The shorter length scale gives rise to a shoulder peak in S(q) at about 0.9 Å−1 whereas the longer one gives rise to the prepeak.

In this article, we investigate the excited state intramolecular electron transfer (ET) reaction of crystal violet lactone (CVL) in the room temperature ionic liquid (RTIL) N-propyl-N-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide [Pr31+][Tf2N−]. This system was chosen in light of recent experimental observations by Maroncelli and co-workers (J. Phys. Chem. B 2007, 111, 13473), in which the kinetics of electron transfer between S1 (commonly referred as LE) and S2 (commonly referred as CT) emission states and, therefore, the ratio of emitting populations were shown to be absorption-wavelength-dependent. Our computational studies indicate that the kinetics of the intramolecular ET between S1 and S2 states of CVL in [Pr31+][Tf2N−] is local solvent-environment-dependent. Because emission time scales are smaller than solvent relaxation time scales, this behavior is characteristic of RTILs but uncommon in conventional solvents. Therefore, RTILs open a window of opportunity for manipulating the outcome of chemical reactions simply by tunning the initial excitation wavelength. Our studies show that when acetonitrile is used as a solvent instead of [Pr31+][Tf2N−] the ratio of populations of emission states is independent of excitation wavelength, eliminating the opportunity for influencing the outcome of reactions.

This article reports on the implementation of J coupling calculations in our recently developed Fast Sugar Structure Prediction Software (FSPS). The FSPS combines a smart and exhaustive algorithm to search through conformational space with the calculation of different experimental nuclear magnetic resonance observables to establish the conformation of saccharides in solution. Using our algorithm in combination with NMR data, we investigate the solution structure of three simple disaccharides (methyl α-sophoroside, methyl α-laminarabioside, and methyl α-cellobioside) and one complex bacterial polysaccharide (Shigella flexneri 5a).

The difference in lifetime with respect to hydrolysis of two covalent syalosyl−enzyme intermediates of two difluorinated sialic acid analogues (1 and 2) bound to Trypanosoma rangeli sialidase is rationalized based on quantum mechanical calculations. The two intermediates differ only in a single functional group, acetamide in the sialidase−1 complex and hydroxyl in the sialidase−2 complex. It is shown that the acetamide group, which is also present in the natural substrate, increases the pKa of a catalytic base (Asp60) through electrostatic repulsion with the carbonyl oxygen on the ligand. This oxygen is absent in 2, resulting in a less basic Asp60 residue and, hence, a longer lifetime of the silaidase−2 complex. Presumably, the lifetime of a sialidase inhibitor complex could be increased further by substituents that stabilize the negative charge on (and lowers the pKa value of) Asp60 in T. rangeli sialidase.

Ionic liquids (ILs) have recently attracted significant attention from academic and industrial sources. This is because, while their vapor pressures are negligible, many of them are liquids at room temperature and can dissolve a wide range of polar and nonpolar organic and inorganic molecules. In this Account, we discuss the progress of our laboratory in understanding the dynamics, spectroscopy, and fluid dynamics of selected imidazolium-based ILs using computational and analytical tools that we have recently developed. Our results indicate that the red edge effect, the non-Newtonian behavior, and the existence of locally heterogeneous environments on a time scale relevant to chemical and photochemical reactivity are closely linked to the viscosity and highly structured character of these liquids.

In this work, we investigate the slow dynamics of 1-butyl-3-methylimidazolium hexafluorophosphate, a very popular room-temperature ionic solvent. Our study predicts the existence of heterogeneity in the liquid and shows that this heterogeneity is the underlying microscopic cause for the recently reported “red-edge effect” (REE) observed in the study of fluorescence of the organic probe 2-amino-7-nitrofluorene. This theoretical work explains in microscopic terms the relation between REE and dynamic heterogeneity in a room-temperature ionic liquid (IL). The REE is typical of micellar or colloidal systems, which are characterized by microscopic environments that are structurally very different. In contrast, in the case of this room-temperature IL, the REE occurs because of the long period during which molecules are trapped in quasistatic local solvent cages. This trapping time, which is longer than the lifetime of the excited-state probe, together with the inability of the surroundings to adiabatically relax, induces a set of site-specific spectroscopic responses. Subensembles of fluorescent molecules associated with particular local environments absorb and emit at different frequencies. We describe in detail the absorption wavelength-dependent emission spectra of 2-amino-7-nitrofluorene and show that this dependence on λex is characteristic of the IL and, as is to be expected, is absent in the case of a normal solvent such as methanol.

Structural patterns that have the same spatial periodicity but a phase offset give rise to peaks and anti-peaks (negative-going peaks) at the same q value in the SAXS structure function S(q). As an example, in ionic liquids we often find charge alternation, and at the distance where one finds a density enhancement of charges of the same type one also finds a depletion of charges of opposite sign. Another such situation arises with polar–apolar densities. At distances where there is enhancement of same-type (polar–polar or apolar–apolar) densities there is also a depletion of opposite-type (polar–apolar) density. This gives rise to prepeaks and what we call same spatial periodicity anti-prepeaks.