Local Solvent Environment Research Articles

The effect of fluorination on the physical properties and the free energies of hydration of 1-alcohols

Because of the widespread use of fluorinated compounds and their subsequent release into the environment, these chemicals have been subjected to a great deal of scrutiny in the past years to determine the extent of their toxicity. In order to better understand the interactions of perfluorinated alcohols and fluorotelomer alcohols in aqueous environments, molecular dynamics simulations are utilized to determine environmental predictors, such as the free energy of hydration. In this work, the predictions of two different force fields, the united-atom Transferable Potentials for Phase Equilibria (TraPPE) and the all-atom Optimized Potentials for Liquid Simulations (OPLS) are compared against available experimental data. Both force fields yield reliable predictions for liquid densities, heats of vaporization and hydration free energies. Investigation of the local solvation environment around the hydroxyl group reveals that fluorination of carbons closest to the hydroxyl group has the greatest effect on the overall hydration free energy.

Ultrafast vibrational spectroscopy (2D-IR) of CO2 in ionic liquids: Carbon capture from carbon dioxide's point of view.

The CO2ν3 asymmetric stretching mode is established as a vibrational chromophore for ultrafast two-dimensional infrared (2D-IR) spectroscopic studies of local structure and dynamics in ionic liquids, which are of interest for carbon capture applications. CO2 is dissolved in a series of 1-butyl-3-methylimidazolium-based ionic liquids ([C4C1im][X], where [X](-) is the anion from the series hexafluorophosphate (PF6 (-)), tetrafluoroborate (BF4 (-)), bis-(trifluoromethyl)sulfonylimide (Tf2N(-)), triflate (TfO(-)), trifluoroacetate (TFA(-)), dicyanamide (DCA(-)), and thiocyanate (SCN(-))). In the ionic liquids studied, the ν3 center frequency is sensitive to the local solvation environment and reports on the timescales for local structural relaxation. Density functional theory calculations predict charge transfer from the anion to the CO2 and from CO2 to the cation. The charge transfer drives geometrical distortion of CO2, which in turn changes the ν3 frequency. The observed structural relaxation timescales vary by up to an order of magnitude between ionic liquids. Shoulders in the 2D-IR spectra arise from anharmonic coupling of the ν2 and ν3 normal modes of CO2. Thermal fluctuations in the ν2 population stochastically modulate the ν3 frequency and generate dynamic cross-peaks. These timescales are attributed to the breakup of ion cages that create a well-defined local environment for CO2. The results suggest that the picosecond dynamics of CO2 are gated by local diffusion of anions and cations.

Ab Initio Characterization of the Electrochemical Stability and Solvation Properties of Condensed-Phase Ethylene Carbonate and Dimethyl Carbonate Mixtures

A central challenge in the refinement of lithium-ion batteries is to control cathode-induced oxidative decomposition of electrolyte solvents, such as ethylene carbonate (EC) and dimethyl carbonate (DMC). We study the oxidation potentials of neat EC, neat DMC, and 1:1 mixtures of EC and DMC using the newly developed projection-based embedding method, which we demonstrate to be capable of correcting qualitative inaccuracies in the electronic densities and ionization energies obtained from conventional Kohn–Sham density functional theory (DFT) methods. Our wave function-in-DFT embedding approach enables accurate calculation of the vertical ionization energy (IE) of individual molecules at the CCSD(T) level of theory while explicitly accounting for the solvent using a combination of DFT and molecular mechanics interactions. We find that the ensemble-averaged distributions of vertical IEs are consistent with a linear response interpretation of the statistics of the solvent configurations, enabling determination of both the intrinsic oxidation potential of the solvents and the corresponding solvent reorganization energies. Interestingly, we reveal that large contributions to the solvation properties of DMC originate from quadrupolar interactions, resulting in a much larger solvent reorganization energy than that predicted using simple dielectric continuum models. Demonstration that the solvation properties of EC and DMC are governed by fundamentally different intermolecular interactions provides insight into key aspects of lithium-ion batteries, with relevance to electrolyte decomposition processes, solid–electrolyte interphase formation, and the local solvation environment of lithium cations.

Solvation of a Cellulose Microfibril in Imidazolium Acetate Ionic Liquids: Effect of a Cosolvent.

The solvation and the onset of dissolution of a cellulose I(β) microcrystal in ionic liquid media are studied by molecular simulation. Ionic liquids can dissolve large amounts of cellulose, which can later be regenerated from solution, but their high viscosity is an inconvenience. Hydrogen bonding between the anion of the ionic liquid and cellulose is the main aspect determining dissolution. Here we try to elucidate the role of a molecular cosolvent, dimethyl sulfoxide (DMSO), which is an aprotic polar compound, in the system composed of cellulose and the ionic liquid 1-butyl-3-methylimidazolium acetate. We calculated quantities related to specific interactions (mainly hydrogen bonds), conformations, and the structure of local solvation environments, both for a solvated oligomer chain of cellulose and for a model microfibril composed of 36 chains in the I(β) crystal structure. We compare two solvent systems: the pure ionic liquid and a mixed solvent with an equimolar composition in ionic liquid and DMSO. All entities are represented by detailed all-atom, fully flexible force fields. The main conclusions are that DMSO behaves as an "innocent" cosolvent, lowering the viscosity and accelerating mass transport in the system, but without interacting specifically with cellulose or disrupting the interactions between cellulose with the anions of the ionic liquid. An understanding of solvation in mixed solvents composed of ionic liquids and molecular compounds can enable the design of high-performance media for the use of biomass materials.

PH Effects on Molecular Adsorption and Solvation of p-Nitrophenol at Silica/Aqueous Interfaces

Resonance-enhanced second-harmonic generation (SHG) was used to examine the effects of solution pH and surface charge on para-nitrophenol (pNP) adsorption to silica/aqueous interfaces. During the early stages of monolayer formation, SHG spectra of interfacial pNP showed a single resonant excitation wavelength at approximately 313 nm regardless of solution pH. This resonance wavelength of adsorbed species is lower than the 318 nm excitation maximum of pNP in bulk aqueous solution. Experiments were performed at pHs of 1.0, 5.0, 7.0, and 10.5. Under these conditions, the silica surface carried a surface charge that ranged from slightly positive (pH = 1) to strongly negative (pH = 10.5) due to protonation/deprotonation of surface silanol groups. Over the course of 1-3 h, SHG spectra of pNP evolved so that spectra from interfaces fully equilibrated with solution pH showed two clear resonance features with wavelengths of approximately 310 and 330 nm. These wavelengths imply that adsorbed pNP samples two discrete local solvation environments at the silica/aqueous interface. On the basis of the solvatochromic behavior of pNP in different bulk solvents, the shorter-wavelength feature corresponds to a local environment having an effective dielectric constant of 9.5 (similar to that of dichloromethane), while the longer-wavelength feature lies outside of pNP's standard solvatochromic window. This longer-wavelength result implies an effective dielectric constant greater than that of bulk water or an adsorption mechanism that has pNP adsorbates sharing a proton with surface silanol groups (and adopting an electronic structure that begins to resemble that of its deprotonated form, p-nitrophenoxide). The longer-wavelength feature is weakest in the low-pH systems when the surface is either neutral or slightly positively charged and most prominent at the negatively charged silica/aqueous (pH = 10.5) interface. pNP adsorption isotherms for all systems showed approximate Langmuir behavior. Using concentration-dependent data from both low and intermediate pH led to calculated adsorption energies of -19 ± 2 kJ/mol for all pH values except pH 10.5 where ΔG(ads) was -6 ± 2 kJ/mol. Taken together, these spectroscopic and adsorption studies of pNP adsorption to silica/aqueous interfaces as a function of aqueous pH show that interfacial acid/base chemistry can require hours to reach equilibrium and that the silica surface presents hydrogen-bonding solutes such as pNP with two distinct adsorption sites. The invariance of pNP's SHG spectra to bulk solution pH suggests that pNP solvation is dominated by substrate-solute interactions, with the adjacent solvent having very little influence on adsorbed solute properties.

The Effects of Chloride Binding on the Behavior of Cellulose-Derived Solutes in the Ionic Liquid 1-Butyl-3-methylimidazolium Chloride

The structure and diffusion of various linear and ringed solutes are examined in two different solvents, the ionic liquid 1-butyl-3-methylimidazolium chloride ([BMIM]Cl) and SPC/E water, using molecular dynamics (MD) simulations. The formation of distinctly ordered local solvent environments around these solutes is observed. Specifically, spatial distribution functions reveal significant ordering of the solvents around the solutes with chloride-hydroxyl group interactions largely dictating these arrangements. Further, a breakdown of the hydrogen bonds that develop between the solute and solvent is provided, showing a relationship between the presence of additional functional groups and the distribution of hydrogen bonds. The diffusivities of the solutes were determined in water at 298 K, 1 bar and [BMIM]Cl at 400 K, 1 bar. The results show that the solutes were approximately 10-100 times more diffusive in water than in [BMIM]Cl. Within [BMIM]Cl, diffusivity appears to decrease with increasing strength of the hydroxyl groups present. Additionally, the free energies of solvation of the solutes are determined with COSMO-RS, providing information about their tendencies in forming aggregates. These results are then compared with MD results in which aggregation is quantified through the use of a dispersion measure. Though all solutes remained relatively dispersed in each of the solvents, those with hydroxyl groups were seen to be the most highly dispersed in the solvent [BMIM]Cl. Further, the dynamic dispersal of a large solute aggregate into [BMIM]Cl was studied, finding that solutes with hydroxyl groups tend to form complexes with the chloride ions. If strong enough, these chlorides can actually bind multiple solutes together into long chains, inhibiting their dispersal in solvent. It is believed that the formation of these chloride-solute complexes is largely responsible for the decreased diffusivity and elevated dispersion seen in simulations with [BMIM]Cl.

Conformational distributions of denatured and unstructured proteins are similar to those of 20 × 20 blocked dipeptides

Understanding intrinsic conformational preferences of amino-acids in unfolded proteins is important for elucidating the underlying principles of their stability and re-folding on biological timescales. Here, to investigate the neighbor interaction effects on the conformational propensities of amino-acids, we carried out (1)H NMR experiments for a comprehensive set of blocked dipeptides and measured the scalar coupling constants between alpha protons and amide protons as well as their chemical shifts. Detailed inspection of these NMR properties shows that, irrespective of amino-acid side-chain properties, the distributions of the measured coupling constants and chemical shifts of the dipeptides are comparatively narrow, indicating small variances of their conformation distributions. They are further compared with those of blocked amino-acids (Ac-X-NHMe), oligopeptides (Ac-GGXGG-NH(2)), and native (lysozyme), denatured (lysozyme and outer membrane protein X from Escherichia coli), unstructured (Domain 2 of the protein 5A of Hepatitis C virus), and intrinsically disordered (hNlg3cyt: intracellular domain of human NL3) proteins. These comparative investigations suggest that the conformational preferences and local solvation environments of the blocked dipeptides are quite similar to not only those of other short oligopeptides but also those of denatured and natively unfolded proteins.

Normal modes for probing the local solvation environment of nitrate anion during step wise hydration: A theoretical study

We investigate structural, energetic and spectroscopic aspects of the finite size hydrated NO3-·nH2O (n=1–8) clusters based on the first principles electronic structure calculations. It is observed that the geometrical parameters at MP2/6-311++G(d,p) level are almost equal to that of calculated at B3LYP/6-311++G(d,p) level for the higher size of clusters (n>3). Our results reveal that total interaction energy and its components do vary linearly with the size of the clusters. Two types of scaling factors are implemented in two different regions to account the effect of anharmonic vibrations. The degeneracy of in-plane bending and asymmetric NO stretching mode in nitrate system is lifted due to hydration. An excellent agreement is observed between the present calculated H2O bending and asymmetric NO stretching frequencies with the experimental results (within 4% w.r.t. experimentally measured values). Understanding the nature of normal modes of vibration at the molecular level provides information of the local hydration environment during stepwise solvation.

Application of Split-GFP System in Biophysical Research and in Cell Biology

Truncated green fluorescent protein (GFP) that is refolded after removing the 10th beta strand can readily bind to a synthetic strand to fully recover the absorbance and fluorescence of the whole protein. 1) The spontaneous reassembly allows rigorous experimental determination of thermodynamic and kinetic parameters of the split system including the equilibrium constant and the association/dissociation rates, which enables residue-specific analysis of peptide-protein interactions. 2) Furthermore, the split-GFP scheme, with its complete synthetic control over the split peptide, is ideal to study the biophysics of color tuning in fluorescent proteins by gradually changing the local solvation environment of the chromophore to selectively stabilize or destabilize a certain resonance contributor that leads to different degree of color shift. 3) The dissociation rate of the noncovalently-bound strand is observed through the strand exchange process that is accompanied by a color change, and surprisingly, the rate is greatly enhanced by light irradiation. This peptide-protein photodissociation is a very unusual phenomenon and can potentially be useful for introducing spatially and temporally well-defined perturbations to biological systems as a genetically encoded caged protein.View Large Image | View Hi-Res Image | Download PowerPoint Slide

Encapsulation Influence on EPR Parameters of Spin-Labels: 2,2,6,6-Tetramethyl-4-methoxypiperidine-1-oxyl in Cucurbit[8]uril.

Encapsulation of a nitroxide spin label into a host cavity can prolong the lifetime of the spin label in biological tissues and other environments. Although such paramagnetic supramolecular complexes have been extensively studied experimentally, there is yet little understanding of the role of the encapsulation on the magnetic properties of the spin labels and their performance at the atomistic level. In this work, we approach this problem by modeling encapsulation induced changes of the magnetic properties of spin labels for a prototypical paramagnetic guest-host complex, 2,2,6,6-tetramethyl-4-methoxypiperidine-1-oxyl, enclosed in the hydrophobic cavity of cucurbit[8]uril, using state-of-the-art hybrid quantum mechanics/molecular mechanics methodology. The results allow a decomposition of the encapsulation shift of the electronic g-tensor and the nitrogen isotropic hyperfine coupling constant of nitroxide radical into a set of distinct contributions associated with the host cavity confinement and with changes of the local solvent environment of the spin label upon encapsulation. It is found that the hydrophobic cavity of cucurbit[8]uril only weakly influences the electronic g-tensor of the 2,2,6,6-tetramethyl-4-methoxypiperidine-1-oxyl but induces a significant encapsulation shift of the nitrogen hyperfine coupling constant. The latter is caused by the change of topology of the hydrogen bonding network and the nature of the hydrogen bonds around the spin label induced by the hydrophobic cavity of the inclusion host. This indirect effect is found to be more important than the direct influence of the cavity exerted on the radical. The ramification of this finding for the use of approximate methods for computing electron paramagnetic resonance spectra of spin labels and for designing optimal spin labels based on guest-host templates is discussed.

Characterization of the 6-methyl isoxanthopterin (6-MI) base analog dimer, a spectroscopic probe for monitoring guanine base conformations at specific sites in nucleic acids

We here characterize local conformations of site-specifically placed pairs of guanine (G) residues in RNA and DNA, using 6-methyl isoxanthopterin (6-MI) as a conformational probe. 6-MI is a base analog of G and spectroscopic signals obtained from pairs of adjacent 6-MI residues reflect base–base interactions that are sensitive to the sequence context, local DNA conformation and solvent environment of the probe bases. CD signals show strong exciton coupling between stacked 6-MI bases in double-stranded (ds) DNA; this coupling is reduced in single-stranded (ss) DNA sequences. Solvent interactions reduce the fluorescence of the dimer probe more efficiently in ssDNA than dsDNA, while self-quenching between 6-MI bases is enhanced in dsDNA. 6-MI dimer probes closely resemble adjacent GG residues, in that these probes have minimal effects on the stability of dsDNA and on interactions with solvent additive betaine. They also serve as effective template bases, although further polymerase-dependent extension of DNA primers past 6-MI template bases is significantly inhibited. These probes are also used to monitor DNA ‘breathing’ at model replication forks. The 6-MI dimer probe can serve in many contexts as a useful tool to investigate GG conformations at specific sites within the nucleic acid frameworks of functioning macromolecular machines in solution.

Molecular Origin of Electron Paramagnetic Resonance Line Shapes on β-Barrel Membrane Proteins: The Local Solvation Environment Modulates Spin-Label Configuration

In this work, electron paramagnetic resonance (EPR) spectroscopy and X-ray crystallography were used to examine the origins of EPR line shapes from spin-labels at the protein-lipid interface on the β-barrel membrane protein BtuB. Two atomic-resolution structures were obtained for the methanethiosulfonate spin-label derivatized to cysteines on the membrane-facing surface of BtuB. At one of these sites, position 156, the label side chain resides in a pocket formed by neighboring residues; however, it extends from the protein surface and yields a single-component EPR spectrum in the crystal that results primarily from fast rotation about the fourth and fifth bonds linking the spin-label to the protein backbone. In lipid bilayers, site 156 yields a multicomponent spectrum resulting from different rotameric states of the labeled side chain. Moreover, changes in the lipid environment, such as variations in bilayer thickness, modulate the EPR spectrum by modulating label rotamer populations. At a second site, position 371, the labeled side chain interacts with a pocket on the protein surface, leading to a highly immobilized single-component EPR spectrum that is not sensitive to hydrocarbon thickness. This spectrum is similar to that seen at other sites that are deep in the hydrocarbon, such as position 170. This work indicates that the rotameric states of spin-labels on exposed hydrocarbon sites are sensitive to the environment at the protein-hydrocarbon interface, and that this environment may modulate weak interactions between the labeled side chain and the protein surface. In the case of BtuB, lipid acyl chain packing is not symmetric around the β-barrel, and EPR spectra from labeled hydrocarbon-facing sites in BtuB may reflect this asymmetry. In addition to facilitating the interpretation of EPR spectra of membrane proteins, these results have important implications for the use of long-range distance restraints in protein structure refinement that are obtained from spin-labels.

Swelling the Hydrophobic Core of Surfactant-Suspended Single-Walled Carbon Nanotubes: A SANS Study

Localized solvent environments form around single-wall carbon nanotubes (SWCNTs) because of the ability of surfactant molecules to solubilize immiscible organic solvents. Although these microenvironments around SWCNTs have already been used for fundamental and applied studies, small-angle neutron scattering (SANS) was used here to assess the size and shape of the solvent domains, their uniformity and distribution on the sidewalls, and the effect of solvent swelling on the aggregation state of the suspension. SANS measurements confirm both the formation of local solvent environments and that no irreversible aggregation of the nanotube suspension occurs after the SDS molecules are swollen in solvent. The results also corroborate prior conclusions based on photoluminescence that the structure formed is dependent of the nature of the solvent-surfactant combination; SWCNTs suspended with SDS and swelled with benzene have a more uniform coating on the sidewall than those swelled with o-dichlorobenzene. These differences can be important to understanding the effect of the local environment on the photoluminescence properties and the interaction of SWCNTs with interfaces.

Initial structure of cetyltrimethylammonium bromide micelles in aqueous solution from molecular dynamics simulations

A series of molecular dynamics simulations were performed in order to explore the initial (10.5 ns) structure of CTAB micelles formed in aqueous solutions. The determination of the aggregation number of CTAB is a long-standing and fundamental problem. Therefore we simulated eight model systems of micelles in aqueous solution. Some micellar structural characteristics, local solvation environments, and counter ion distributions are described. Topological and geometrical concepts are used to characterize the resulting micelle structures. Our findings indicate that for certain aggregation numbers micelles are formed by layered spherical structures.

Are Short, Low-Barrier Hydrogen Bonds Unusually Strong?

In a symmetric hydrogen bond (H-bond), the hydrogen atom is perfectly centered between the two donor atoms. The energy diagram for hydrogen motion is thus a single-well potential, rather than the double-well potential of a more typical H-bond, in which the hydrogen is covalently bonded to one atom and H-bonded to the other. Examples of symmetric H-bonds are often found in crystal structures, and they exhibit the distinctive feature of unusually short length: for example, the O-O distance in symmetric OHO H-bonds is found to be less than 2.5 Å. In comparison, the O-O distance in a typical asymmetric H-bond, such as ROH···OR(2), ranges from about 2.7 to 3.0 Å. In this Account, we briefly review and update our use of the method of isotopic perturbation to search for a symmetric, centered, or single-well-potential H-bond in solution. Such low-barrier H-bonds are thought to be unusually strong, owing perhaps to the resonance stabilization of two identical resonance forms [A-H···B ↔ A···H-B]. This presumptive bond strength has been invoked to explain some enzyme-catalyzed reactions. Yet in solution, a wide variety of OHO, OHN, and NHN H-bonds have all been found to be asymmetric, in double-well potentials. Examples include the monoanion of (±)-2,3-di-tert-butylsuccinic acid and a protonated tetramethylnaphthalenediamine, even though these two ions are often considered prototypes of species with strong H-bonds. In fact, all of the purported examples of strong, symmetric H-bonds have been found to exist in solution as pairs of asymmetric tautomers, in contrast to their symmetry in some crystals. The asymmetry can be attributed to the disorder of the local solvation environment, which leads to an equilibrium among solvatomers (that is, isomers that differ in solvation). If the disorder of the local environment is sufficient to break symmetry, then symmetry itself is not sufficient to stabilize the H-bond, and symmetric H-bonds do not have an enhanced stability or an unusual strength. Nor are short H-bonds unusually strong. We discuss previous evidence for "short, strong, low-barrier" H-bonds and show it to be based on ambiguous comparisons. The role of such H-bonds in enzyme-catalyzed reactions is then ascribed not to any unusual strength of the H-bond itself but to relief of "strain."

Easy Access to a Family of Polymer Catalysts from Modular Star Polymers

We report a versatile and scalable synthesis of a water-dispersible modular star polymer platform with an enzyme-inspired hydrophobic interior. The cores of the stars can be functionalized at will, independently from the modification of the polymer structure. We explored the use of this material for the creation of a local hydrophobic solvent environment in water and for site isolation of incompatible catalytic entities.

Peptide-Membrane and Peptide-Peptide Interactions between Myelin Basic Protein and Myelin-Like Lipids Revealed by Covalently Attached Vibrational Labels

Cyanylation of cysteine reveals the local solvent environment of the modified side chain and the ps-time scale dynamics of membrane-protein interactions via the infrared absorbance of the covalently attached CN probe vibration. Single-cysteine mutants of the primary membrane binding sequence from the myelin basic protein, were synthesized and cyanylated. A combination of transmission and horizontal attenuated total reflectance (HATR) infrared spectra are used to investigate the dynamics of the membrane-peptide interactions.

Is DNA a worm-like chain in Couette flow? In search of persistence length, a critical review.

Persistence length is the foremost measure of DNA flexibility. Its origins lie in polymer theory which was adapted for DNA following the determination of BDNA structure in 1953. There is no single definition of persistence length used, and the links between published definitions are based on assumptions which may, or may not be, clearly stated. DNA flexibility is affected by local ionic strength, solvent environment, bound ligands and intrinsic sequence-dependent flexibility. This article is a review of persistence length providing a mathematical treatment of the relationships between four definitions of persistence length, including: correlation, Kuhn length, bending, and curvature. Persistence length has been measured using various microscopy, force extension and solution methods such as linear dichroism and transient electric birefringence. For each experimental method a model of DNA is required to interpret the data. The importance of understanding the underlying models, along with the assumptions required by each definition to determine a value of persistence length, is highlighted for linear dichroism data, where it transpires that no model is currently available for long DNA or medium to high shear rate experiments.

Comparative PCET Study of a Donor−Acceptor Pair Linked by Ionized and Nonionized Asymmetric Hydrogen-Bonded Interfaces

A Zn(II) amidinium porphyrin is the excited-state electron donor (D) to a naphthalene diimide acceptor (A) appended with either a carboxylate or sulfonate functionality. The two-point hydrogen bond (...[H(+)]...) formed between the amidinium and carboxylate or sulfonate functionalities establishes a proton-coupled electron transfer (PCET) pathway for charge transfer. The two D...[H(+)]...A assemblies differ only by the proton configuration within the hydrogen-bonding interface. Specifically, the amidinium ion transfers a proton to the carboxylate to form a nonionized amidine-carboxylic acid two-point hydrogen network, whereas the amidinium retains both protons when bound to the sulfonate functionality, forming an ionized amidinium-sulfonate two-point hydrogen bond network. These two interface configurations within the dyads thus allow for a direct comparison of the PCET kinetics for the same donor and acceptor juxtaposed by ionized and nonionized hydrogen-bonded interfaces. Analysis of the PCET kinetics ascertained from transient absorption and transient emission spectroscopy reveals that the ionized interface is more strongly impacted by the local solvent environment, thus establishing that the initial static configuration of the proton interface is a critical determinant in the kinetics of PCET.

Effects of Solute Structure on Local Solvation and Solvent Interactions: Results from UV/Vis Spectroscopy and Molecular Dynamics Simulations

Solvation of heterocyclic amines in CO(2)-expanded methanol (MeOH) has been explored with UV/vis spectroscopy and molecular dynamics (MD) simulations. A synergistic study of experiments and simulations allows exploration of solute and solvent effects on solvation and the molecular interactions that affect absorption. MeOH-nitrogen hydrogen bonds hinder the n-pi* transition; however, CO(2) addition causes a blue shift relative to MeOH because of Lewis acid/base interactions with nitrogen. Effects of solute structure are considered, and very different absorption spectra are obtained as nitrogen positions change. MD simulations provide detailed solvent clustering behavior around the solute molecules and show that the local solvent environment and ultimately the spectra are sensitive to the solute structure. This work demonstrates the importance of atomic-level information in determining the structure-property relationships between solute structure, local salvation, and solvatochromism.