Solvation Energy Difference Research Articles

Ions Speciation at the Water–Air Interface

In typical aqueous systems, including naturally occurring sweet and salt water and tap water, multiple ion species are co-solvated. At the water-air interface, these ions are known to affect the chemical reactivity, aerosol formation, climate, and water odor. Yet, the composition of ions at the water interface has remained enigmatic. Here, using surface-specific heterodyne-detected sum-frequency generation spectroscopy, we quantify the relative surface activity of two co-solvated ions in solution. We find that more hydrophobic ions are speciated to the interface due to the hydrophilic ions. Quantitative analysis shows that the interfacial hydrophobic ion population increases with decreasing interfacial hydrophilic ion population at the interface. Simulations show that the solvation energy difference between the ions and the intrinsic surface propensity of ions determine the extent of an ion's speciation by other ions. This mechanism provides a unified view of the speciation of monatomic and polyatomic ions at electrolyte solution interfaces.

Ionization and structural properties of mRNA lipid nanoparticles influence expression in intramuscular and intravascular administration

Lipid Nanoparticles (LNPs) are used to deliver siRNA and COVID-19 mRNA vaccines. The main factor known to determine their delivery efficiency is the pKa of the LNP containing an ionizable lipid. Herein, we report a method that can predict the LNP pKa from the structure of the ionizable lipid. We used theoretical, NMR, fluorescent-dye binding, and electrophoretic mobility methods to comprehensively measure protonation of both the ionizable lipid and the formulated LNP. The pKa of the ionizable lipid was 2-3 units higher than the pKa of the LNP primarily due to proton solvation energy differences between the LNP and aqueous medium. We exploited these results to explain a wide range of delivery efficiencies in vitro and in vivo for intramuscular (IM) and intravascular (IV) administration of different ionizable lipids at escalating ionizable lipid-to-mRNA ratios in the LNP. In addition, we determined that more negatively charged LNPs exhibit higher off-target systemic expression of mRNA in the liver following IM administration. This undesirable systemic off-target expression of mRNA-LNP vaccines could be minimized through appropriate design of the ionizable lipid and LNP.

In Vivo Detection of Redox-Inactive Neurochemicals in the Rat Brain with an Ion Transfer Microsensor.

Electrochemical tracking of redox-inactive neurochemicals remain a challenge due to chemical inertness, almost no Faraday electron transfer for these species, and the complex brain atmosphere. In this work, we demonstrate a low-cost, simple-making liquid/liquid interface microsensor (LLIM) to monitor redox-inactive neurochemicals in the rat brain. Taking choline (Ch) as an example, based on the difference in solvation energies of Ch in cerebrospinal fluid (aqueous phase) and 1,2-dichloroethane (1,2-DCE; organic phase), Ch is recognized in the specific ion-transfer potential and distinctive ion-transfer current signals. The LLIM has an excellent response to Ch with good linearity and selectivity, and the detection limit is 0.37 μM. The LLIM can monitor the dynamics of Ch in the cortex of the rat brain by both local microinfusion and intraperitoneal injection of Ch. This work first demonstrates that the LLIM can be successfully applied in the brain and obtain electrochemical signals in such a sophisticated system, allowing one new perspective of sensing at the liquid/liquid interface for nonelectrically active substances in vivo to understand the physiological function of the brain.

A Practical Prediction of LogPo/w through Semiempirical Electronic Structure Calculations with Dielectric Continuum Model

Abstract We examined various combinations of semiempirical and polarizable continuum methods and found that SMD/PM7 provides the highest accuracy in calculating LogPo/w. The correlation between the experimental and calculated LogPo/w is approximately R2 = 0.74. However, this result is not sufficiently accurate for achieving a practical prediction. To clarify the details of the calculation results, a linear fitting was conducted for each functional group and each atom. The results showed a large variation, indicating a large error. We then conducted a multiple regression analysis using the number of atoms in the molecule, the number of multiple bonds, the ring structure, and the indicator for aromatic nature as explanatory variables and the experimental value of LogPo/w as the objective variable; finally, we incorporated a correction to the calculated value of LogPo/w. We showed that the accuracy was significantly improved to approximately R2 = 0.95 when adopting the difference in solvation energy, along with four additional explanatory variables.

Beyond Size Complementary Factors in Anion-Tetralactam Macrocycle Complexes: From Intrinsic Gas-Phase to Solvent-Predicted Stabilities.

The gas-phase affinities of different types of anions X– (halogen anions, oxoanions, and hydrogenated anions) toward a model tetralactam-based macrocycle receptor (1), defined in terms of stability of an anion–receptor complex (1 + X–) against its disintegration, were evaluated by dissociation studies using a mass spectrometry-based methodology and supported by theoretical calculations (density functional theory–PBE0). The gas-phase complex with Cl– was found to be tailor-made for the macrocycle 1, while 1 + SA– (SA– = salicylate anion) and 1 + HSO4– were the weakest ones. Other complexes displayed a relatively low-stability dispersion (<1.2 kcal·mol–1). The 1/εr approach of the electrostatic contribution scaling method was used to predict the stability trends in a dimethyl sulfoxide solvent from the gas-phase binding energy partition using the symmetry-adapted perturbation theory. High deformation energy and differences in solvation energies were suggested to be the main sources of inconsistency in the predicted and experimental stabilities of 1 + F– and 1 + H2PO4– complexes.

Quantum Mechanical Modeling of Reaction Rate Acceleration in Microdroplets.

Organic reactions in microdroplets can be orders of magnitude faster than their bulk counterparts. We hypothesize that solvation energy differences between bulk and interface play a key role in the intrinsic rate constant increase and test the hypothesis with explicit solvent calculations. We demonstrate for both the protonated phenylhydrazine reagent and the hydrazone transition state (TSB) that molecular orientations which place the charge sites at the surface confer high energy. A pathway in which this high-energy form transforms into a fully solvated TSB has a lower activation energy than bulk by some 59 kJ/mol, a result that is consistent with experimental rate acceleration studies.

Microhydration Structures of Protonated Oxazole

The initial microhydration structures of the protonated pharmaceutical building block oxazole (Ox), H+Ox-Wn≤4, are determined by infrared photodissociation (IRPD) spectroscopy combined with quantum chemical dispersion-corrected density functional theory calculations (B3LYP-D3/aug-cc-pVTZ). Protonation of Ox, achieved by chemical ionization in a H2-containing plasma, occurs at the most basic N atom. The analysis of systematic shifts of the NH and OH stretch vibrations as a function of the cluster size provides a clear picture for the preferred cluster growth in H+Ox-Wn. For n = 1-3, the IRPD spectra are dominated by a single isomer, and microhydration of H+Ox with hydrophilic protic W ligands occurs by attachment of a hydrogen-bonded (H-bonded) Wn solvent cluster to the acidic NH group via an NH···O H-bond. Such H-bonded networks are stabilized by strong cooperativity effects. This is in contrast to previously studied hydrophobic ligands, which prefer interior ion solvation. The strength of the NH···O ionic H-bond increases with the degree of hydration because of the increasing proton affinity (PA) of the Wn cluster. At n = 4, proton-transferred structures of the type Ox-H+Wn become energetically competitive with H+Ox-Wn structures, because differences in solvation energies can compensate for the differences in the PAs, and barrierless proton transfer from H+Ox to the Wn solvent subcluster becomes feasible. Indeed, the IRPD spectrum of the n = 4 cluster is more complex suggesting the presence of more than one isomer, although it lacks unequivocal evidence for the predicted intracluster proton transfer.

Volcano Plots Emerge from a Sea of Nonaqueous Solvents: The Law of Matching Water Affinities Extends to All Solvents.

The properties of all electrolyte solutions, whether the solvent is aqueous or nonaqueous, are strongly dependent on the nature of the ions in solution. The consequences of these specific-ion effects are significant and manifest from biochemistry to battery technology. The “law of matching water affinities” (LMWA) has proven to be a powerful concept for understanding and predicting specific-ion effects in a wide range of systems, including the stability of proteins and colloids, solubility, the behavior of lipids, surfactants, and polyelectrolytes, and catalysis in water and ionic liquids. It provides a framework for considering how the ions of an electrolyte interact in manifestations of ion specificity and therefore represents a considerable conceptual advance on the Hofmeister or lyotropic series in understanding specific-ion effects. Underpinning the development of the law of matching water affinities were efforts to interpret the so-called “volcano plots”. Volcano plots exhibit a stark inverted “V” shape trend for a range of electrolyte dependent solution properties when plotted against the difference in solvation energies of the ions that constitute the electrolyte. Here we test the hypothesis that volcano plots are also manifest in nonaqueous solvents in order to investigate whether the LMWA can be extended to nonaqueous solvents. First we examine the standard solvation energies of electrolytes in nonaqueous solvents for evidence of volcano trends and then extend this to include the solubility and the activity/osmotic coefficients of electrolytes, in order to explore real electrolyte concentrations. We find that with respect to the solvent volcano trends are universal, which brings into question the role of solvent affinity in the manifestation of specific-ion effects. We also show that the volcano trends are maintained when the ionic radii are used in place of the absolute solvation energies as the abscissa, thus showing that ion sizes, rather than the solvent affinities, fundamentally determine the manifestation of ion specificity. This leads us to propose that specific-ion effects across all solvents including water can be understood by considering the relative sizes of the anion and cation, provided the ions are spherical or tetrahedral. This is an extension of the LMWA to all solvents in which the “water affinity” is replaced with the relative size of the anion and cation.

Quantitative Analysis of Aqueous Two Phase Separation of DNA-SWCNT Hybrids

Carbon nanotubes have attracted considerable interest due to their outstanding physical, electronical and optical properties. Since those properties depends on the chirality, sorting single walled carbon nanotubes (SWCNT) by chirality is essential. Hybrids of DNA and SWCNTs have been used successfully to solve tje long-standing recalcitrant problem of structure-based sorting of complex mixtures of SWCNTs. Recently, it is shown that single stranded DNA coated SWCNTs could be separated effectively into various chiralities using an aqueous two phase system. SWCNT partition in the ATP system is determined by the SWCNT solvation energy difference between the two phases. In this way, we suggest that the ATP process is both a technique for separation and a method by which to evaluate and rank hydration or solvation free energy. In this study, we performed a systematic study of various DNA sequences on different species of SWCNT in ATP systems of two different polymer composition. We observe strong sequence-dependent of partitioning. We developed a model that can phenomenologically describe the experimental observation well and be used to extract a quantitative measure of relative solvation free energy of various DNA/SWCNT hybrids. Furthermore, to investigate a structural basis for experimental findings, we have employed molecular dynamics to examine a few of the ssDNA/CNT combinations.

Origin of Solvent-independent Optical Property of Unsubstituted BODIPY Revisited

An unsubstituted BODIPY is revisited to clarify the origin of its characteristic nearly solvent-independent optical property based on the calculated results of the density functional theory (DFT) and time-dependent (TD)-DFT methods. Using the Kirkwood model, we provide a simple origin of the negligible difference in solvation energies between the S0 and S1 states based on their negligible variation in electric dipole moments, which are associated with the HOMO–LUMO transition and solvation effects on their structures.

Electrochemical properties and radical anions of carbocycle-fluorinated quinoxalines and their substituted derivatives

Electrochemical reduction (ECR) and oxidation (ECO) of 5,6,7,8-tetrafluoroquinoxaline (1) and its derivatives bearing various substituents R (7-H (2), 7,8-H2 (3), 6-CF3 (4), 6-Cl (5), 5,7-Cl2 (6), 5-NH2 (7), 6-OCH3 (8), 6,7-(OCH3)2 (9), 6,7,8-(OCH3)3 (10), 5,6,7,8-(OCH3)4 (11), 6-OCH3,7-N(CH3)2 (12), 6-N(CH3)2 (13), 6,7-(N(CH3)2)2 (14), 5,6,7-(N(CH3)2)3 (15), and 7,8-cyclo-(=CF-CF = CF-CF=) (16)) in the carbocycle have been studied by cyclic voltammetry in MeCN. For 1–4 and 7–15, the first reduction peaks have been found to be 1-electron and reversible, thus corresponding to the formation of their radical anions (RAs), which are long lived at 295 K except those of 4–6 and 15, 16. Irreversible hydrodechlorination has been observed for 5 and 6 at the first step of their ECR confirmed by EPR detection of corresponding RAs of 2 and 5,7-H2 derivative of 1 (17) at the next steps. Electrochemically generated RAs of 1–3, 7–14, and 17 have been characterized in MeCN by EPR spectroscopy together with DFT calculations at the (U)B3LYP/6-31 + G(d) level of theory using PCM to describe the solvent. A noticeable alternation of spin density on the –NCCN– moiety of quinoxaline has been observed for all RAs possessing R-substitution asymmetry. The comparative electron-accepting ability of 1–15 has been analyzed in terms of their experimental reduction peak potentials and the (U)B3LYP/6-31 + G(d)-calculated gas-phase first adiabatic electron affinities (EAs). The differences in electron transfer solvation energies for 1–15 have been evaluated on the basis of ECR peaks' potentials and calculated gas-phase EAs. The ECO of 1–5 and 7–14 has been found to be irreversible.

The α-Effect in Nucleophilic Substitution Reactions of Y-Substituted-Phenyl X-Substituted-Cinnamates with Butane-2,3-dione Monoximate

Second-order rate constants (<TEX>$k_{Ox^-}$</TEX>) have been measured spectrophotometrically for nucleophilic substitution reactions of 4-nitrophenyl X-substituted-cinnamates (7a-7e) and Y-substituted-phenyl cinnamates (8a-8e) with butane-2,3-dione monoximate (<TEX>$Ox^-$</TEX>) in 80 mol % <TEX>$H_2O$</TEX>/20 mol % DMSO at <TEX>$25.0{\pm}0.1^{\circ}C$</TEX>. The Hammett plot for the reactions of 7a-7e consists of two intersecting straight lines while the Yukawa-Tsuno plot exhibits an excellent linearity with <TEX>${\rho}_X$</TEX>=0.85 and r=0.58, indicating that the nonlinear Hammett plot is not due to a change in the rate-determining step but is caused by resonance stabilization of the ground state (GS) of the substrate possessing an electron-donating group (EDG). The Br<TEX>${\o}$</TEX>nsted-type plot for the reactions of Y-substituted-phenyl cinnamates (8a-8e) is linear with <TEX>${\beta}_{lg}$</TEX> = -0.64, which is typical of reactions reported previously to proceed through a concerted mechanism. The <TEX>${\alpha}$</TEX>-nucleophile (<TEX>$Ox^-$</TEX>) is more reactive than the reference normal-nucleophile (<TEX>$4-ClPhO^-$</TEX>). The magnitude of the <TEX>${\alpha}$</TEX>-effect (i.e., the <TEX>$k_{Ox^-}/k_{4-ClPhO^-}$</TEX> ratio) is independent of the electronic nature of the substituent X in the nonleaving group but increases linearly as the substituent Y in the leaving group becomes a weaker electron-withdrawing group (EWG). It has been concluded that the difference in solvation energy between <TEX>$Ox^-$</TEX> and <TEX>$4-ClPhO^-$</TEX> (i.e., GS effect) is not solely responsible for the <TEX>${\alpha}$</TEX>-effect but stabilization of transition state (TS) through a cyclic TS structure contributes also to the Y-dependent <TEX>${\alpha}$</TEX>-effect trend (i.e., TS effect).

Polarization effects on the solvation dynamics of coumarin C153 in ionic liquids: Components and their cross-correlations

The solvation dynamics of coumarin C153 dissolved in three selected molecular ionic liquids - EMIM(+)BF4(-), EMIM(+)TfO(-), and BMIM(+)BF4(-) - was studied by molecular dynamics simulations including polarization forces. The solvation response function was decomposed with respect to permanent and induced charge distributions, cationic and anionic contributions, and translational and non-translational motions. The latter decomposition was accomplished by an appropriate multipole expansion. Furthermore, the difference in solvation energy was resolved radially. The dynamics in the sub-picosecond regime was elucidated as the mutual translational motion of the solute and the cage formed by the first solvation shell. For a qualitative interpretation, solvent molecules can be reduced to "quasi-atomic" ions carrying a net charge at their molecular center of mass. Towards a quantitative description, the dipole moment serves as a measure of charge anisotropy.

General Methodology of Using Oil-in-Water and Water-in-Oil Emulsions for Coiling Nanofilaments

Hydrophobic carbon nanotubes (CNTs) and hydrophilic nanofilaments such as oxidized CNTs, Pd nanowires (NWs), and MnO(2) NWs are transformed from wires to rings by a general methodology. We show that both oil-in-water and water-in-oil emulsions, so long as their droplet size is sufficiently small, can exert significant force to the entrapped nanostructures, causing their deformation. This effect can be easily achieved by simply mixing a few solutions in correct ratios. Even preformed oil droplets can take in CNTs from the aqueous solution converting them into rings, indicating the important role of thermodynamics: The question here is not if the droplets can exert sufficient force to bend the nanofilaments, because their random vibration may be already doing it. As long as the difference in solvation energy is large enough for a nanofilament, it would "want" to move away from the bulk solution and fit inside tiny droplets, even at the cost of induced strain energy. That said, the specific interactions between a droplet and a filament are also of importance. For example, when an oil droplet rapidly shrinks in size, it can compress the entrapped CNTs in multiple stages into structures with higher curvatures (thus higher strain) than that of a circular ring, which has minimal induced strain inside a spherical droplet.

Acid and Alkali Effects on the Decomposition of HMX Molecule: A Computational Study

The stored and wasted explosives are usually in an acid or alkali environment, leading to the importance of exploring the acid and alkali effects on the decomposition mechanism of explosives. The acid and alkali effects on the decomposition of HMX molecule in gaseous state and in aqueous solution at 298 K are studied using quantum chemistry and molecular force field calculations. The results show that both H(+) and OH(-) make the decomposition in gaseous state energetically favorable. However, the effect of H(+) is much different from that of OH(-) in aqueous solution: OH(-) can accelerate the decomposition but H(+) cannot. The difference is mainly caused by the large aqueous solvation energy difference between H(+) and OH(-). The results confirm that the dissociation of HMX is energetically favored only in the base solutions, in good agreement with previous HMX base hydrolysis experimental observations. The different acid and alkali effects on the HMX decomposition are dominated by the large aqueous solvation energy difference between H(+) and OH(-).

Toward robust computational electrochemical predicting the environmental fate of organic pollutants

A number of density functionals was utilized for the calculation of electron attachment free energy for nitrocompounds, quinones and azacyclic compounds. Different solvation models have been tested on the calculation of difference in free energies of solvation of oxidized and reduced forms of nitrocompounds in aqueous solution, quinones in acetonitrile, and azacyclic compounds in dimethylformamide. Gas-phase free energies evaluated at the mPWB1K/tzvp level and solvation energies obtained using SMD model to compute solvation energies of neutral oxidized forms and PCM(Pauling) to compute solvation energies of anion-radical reduced forms provide reasonable accuracy of the prediction of electron attachment free energy, difference in free solvation energies of oxidized and reduced forms, and as consequence yield reduction potentials in good agreement with experimental data (mean absolute deviation is 0.15 V). It was also found that SMD/M05-2X/tzvp method provides reduction potentials with deviation of 0.12 V from the experimental values but in cases of nitrocompounds and quinones this accuracy is achieved due to the cancelation of errors. To predict reduction ability of naturally occurred iron containing species with respect to organic pollutants we exploited experimental data within the framework of Pourbaix (Eh - pH) diagrams. We conclude that surface-bound Fe(II) as well as certain forms of aqueous Fe(II)aq are capable of reducing a variety of nitroaromatic compounds, quinones and novel high energy materials under basic conditions (pH > 8). At the same time, zero-valent iron is expected to be active under neutral and acidic conditions.

Pathologically Activated Neuroprotection via Uncompetitive Blockade of N-Methyl-d-aspartate Receptors with Fast Off-rate by Novel Multifunctional Dimer Bis(propyl)-cognitin

Uncompetitive N-methyl-d-aspartate (NMDA) receptor antagonists with fast off-rate (UFO) may represent promising drug candidates for various neurodegenerative disorders. In this study, we report that bis(propyl)-cognitin, a novel dimeric acetylcholinesterase inhibitor and gamma-aminobutyric acid subtype A receptor antagonist, is such an antagonist of NMDA receptors. In cultured rat hippocampal neurons, we demonstrated that bis(propyl)-cognitin voltage-dependently, selectively, and moderately inhibited NMDA-activated currents. The inhibitory effects of bis(propyl)-cognitin increased with the rise in NMDA and glycine concentrations. Kinetics analysis showed that the inhibition was of fast onset and offset with an off-rate time constant of 1.9 s. Molecular docking simulations showed moderate hydrophobic interaction between bis(propyl)-cognitin and the MK-801 binding region in the ion channel pore of the NMDA receptor. Bis(propyl)-cognitin was further found to compete with [(3)H]MK-801 with a K(i) value of 0.27 mum, and the mutation of NR1(N616R) significantly reduced its inhibitory potency. Under glutamate-mediated pathological conditions, bis(propyl)-cognitin, in contrast to bis(heptyl)-cognitin, prevented excitotoxicity with increasing effectiveness against escalating levels of glutamate and much more effectively protected against middle cerebral artery occlusion-induced brain damage than did memantine. More interestingly, under NMDA receptor-mediated physiological conditions, bis(propyl)-cognitin enhanced long-term potentiation in hippocampal slices, whereas MK-801 reduced and memantine did not alter this process. These results suggest that bis(propyl)-cognitin is a UFO antagonist of NMDA receptors with moderate affinity, which may provide a pathologically activated therapy for various neurodegenerative disorders associated with NMDA receptor dysregulation.

Exploration of density functional methods for one-electron reduction potential of nitrobenzenes

Performance of the set of density functional approaches for calculation of one-electron reduction potentials of nitroaromatic compounds was investigated. To select the most precise and affordable method, we selected a set of model molecules and investigated effects of basis set, density functional, and solvation model on the calculation of reduction potentials. It was found that the mPWB1K/TZVP method provides the most accurate gas phase electron affinity values (RMS error is 0.1 eV). This method in conjunction with the PCM (Bondi) method yields also the most accurate difference in solvation energies of neutral oxidized form and anion-radical reduced form. The final E0 values were calculated with RMS error of 0.10 V, compared with experimental values.

Toward basic understanding of the partition coefficient log P and its application in QSAR 1

The log P value has been the first choice for the molecular hydrophobicity descriptor in QSAR studies. However, it is still now difficult to understand the partitioning phenomenon in terms of physical chemistry. First, an attempt to understand and predict log P is addressed. We formulated a simple model that expressed by the solvent accessible surface area and the solvation energy difference between aqueous and solvent phases. Next, an application of log P in QSAR analyses of ligand-CYP (Cytochrome P450) interaction was described. Azole compounds are widely used as antifungal agents. We showed that the binding affinity of 18 azole compounds with CYP2B and CYP3A were nicely expressed by the bilinear model of log P. These results suggest that molecular hydrophobicity plays a major role in the binding affinity. The binding mechanism was discussed based on the correlation equations. 1Presented at CMTPI 2007: Computational Methods in Toxicology and Pharmacology Integrating Internet Resources (Moscow, Russia, September 1–5, 2007).

Reduction Energy of 1 M Aqueous Ruthenium(III) Hexaammine in the Gas Phase: A Route toward Establishing an Absolute Electrochemical Scale

The internal energy deposited into gas-phase Ru(NH3)6(H2O)n3+ when reduced by thermal electrons is investigated as a function of cluster size. For n ≥ 40, reduction results exclusively in the loss of water molecules from the reduced precursor ion; loss of water is accompanied by the loss of a single ammonia molecule for smaller clusters. The average number of ligands lost from the reduced precursor decreases with cluster size for n ≤ 31, presumably because of increased binding energy of the ligands to the smaller, doubly charged clusters. For Ru(NH3)6(H2O)553+, which corresponds to a concentration or activity of about 1 M, reduction results in a mean loss of 18.2 water molecules, from which an average and maximum energy deposition of 7.9 and ∼8.2 to 8.7 eV, respectively, is determined. To the extent that the dissociation is statistical, the internal energy deposited corresponds to the reduction energy of the hydrated precursor ion by a thermal electron in the gas phase. This measured value is combined with the electron affinity of water and the difference in solvation energies of the precursor and reduced cluster ions to provide an absolute value for the reduction energy for 1 M Ru(NH3)63+ by a solvated electron in bulk water of about −3.8 eV at 0 K. This route toward establishing absolute half-cell reduction potentials has the advantages that effects of counterions, solvent, and chemical form can be easily controlled and quantified, and redox reactions not readily observed in solution can be measured.