The Solvation of Acetonitrile

Reimers, Jeffrey R.; Hall, Lachlan E.

doi:10.1021/ja983878n

Cited by 251 publications

(365 citation statements)

References 92 publications

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“…Similar shifts of the peak position were reported for the SFG spectrum of CH 3 symmetric stretching mode at the vapor/water-methanol mixture [19,33] or at the vapor/water-acetone mixture interface [20]. It is well accepted that the stretching frequency depends on the electron density localized in the CN bond, which suggests that higher electron density generally weakens the CN bond strength [17,34]. As a consequence, the vibrational frequency becomes red-shifted.…”

Section: Resultssupporting

confidence: 74%

Adsorption of benzonitrile at the air/water interface studied by sum frequency generation spectroscopy

et al. 2013

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Section: Resultssupporting

confidence: 74%

Adsorption of benzonitrile at the air/water interface studied by sum frequency generation spectroscopy

et al. 2013

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“…The corresponding experiment would be difficult with the hALR2/1/NADP + complex because of the relatively smaller Stark tuning rate and absorptivity of the nitrile. Previous theoretical analysis of vibrational spectroscopy of acetonitrile dissolved in alcohol solvents has shown that, when the CtN group's nitrogen atom acts as a hydrogen bond acceptor, the absorption energy of the CtN bond is perturbed independently of electrostatic effects (48). The proximity of the CtN bond of inhibitor 1 to the hydroxyl group of T113 (modeled at <2 Å for the N‚‚‚O distance, Figure 3) is therefore a possible complication for measuring electrostatic fields in this region of hALR2 with a nitrile probe.…”

Section: Resultsmentioning

confidence: 99%

Electrostatic Fields Near the Active Site of Human Aldose Reductase: 1. New Inhibitors and Vibrational Stark Effect Measurements

2008

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Vibrational Stark effect spectroscopy was used to measure electrostatic fields in the hydrophobic region of the active site of human aldose reductase (hALR2). A new hALR2 inhibitor was designed and synthesized that contains a nitrile probe with a Stark tuning rate of 0.77 cm -1 /(MV/cm). Mutations to amino acid residues in the vicinity of the nitrile functional group were selected based on electrostatics calculations, possible complications from hydrogen bonds near the nitrile, and comparison with the active site of human aldehyde reductase, whose structure is very similar. Changes in the absorption energy of the nitrile probe when bound to those mutated proteins were then used to quantify perturbations to the protein's electrostatic field. Electrostatic field changes as large as -10 MV/cm were observed. Measured electrostatic fields were compared to predictions based on continuum electrostatics calculations, revealing that substantial modifications to the calculation strategy are necessary. The effects of hydrogen bonding of amino acid side chains to the nitrile probe are considered, and applications of vibrational Stark effect spectroscopy to investigations of ligand binding and biological function are discussed.The highly organized three-dimensional structure of a protein can support large variations in internal electrostatic fields that influence every aspect of the protein's function (1-3) including folding (4), chemical reactivity and kinetics (5-7), and protein-protein interactions (8). Measurements of the strength and direction of these fields are therefore of great importance, and represent a long-standing biophysical challenge (9-16). One strategy that has been developed in recent years is vibrational Stark effect (VSE 1 ) spectroscopy, which describes the influence of an electric field on a molecular vibrational frequency and can be observed through infrared spectroscopy (17,18). VSE spectroscopy is a twostep experiment. In the first step, a vibrational probe is selected and the effect of a known external applied electric field on the infrared absorption frequency is used to calibrate sensitivity of the oscillator's vibrational frequency to an electric field. The magnitude of this effect is called the Stark tuning rate, and is taken as an intrinsic property of the oscillator. In the second step, the calibrated vibrational probe is inserted into a protein of interest and used as a highly local, sensitive, and directional reporter of changes of the protein's electrostatic field as perturbations are made to the protein, for example by amino acid mutagenesis. We use the term "vibrational Stark effect" to describe both the effect of a known applied external electric field on an oscillator's vibrational frequency and the absorption frequency shifts in the IR spectrum of the calibrated spectator vibrational probe when it is exposed to a perturbation inside a protein.Here we introduce an ideal vibrational Stark probe, the nitrile (CtN) functional group (19), into the active site of the protein human...

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“…The common, linear electric field sensitivity of the IR and NMR observables leads to a correlation between them in the absence of specific interactions with the probe. Direct hydrogen bond formation to a nitrile leads to a departure from this linear correlation, ascribed to anomalous behavior in the IR but not the NMR dimension (41)(42)(43). By comparing tandem IR and NMR measurements for KSI-CN probes to a previously determined correlation of IR stretching frequency versus 13 C NMR chemical shift of ethyl thiocyanate in aprotic solvents, such departures can be identified.…”

Section: Tandem Measurement Of Ir Stretch Frequency and 13 C Nmr Chemmentioning

confidence: 89%

Quantitative, directional measurement of electric field heterogeneity in the active site of ketosteroid isomerase

Fafarman¹,

Sigala²,

Schwans³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

216

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Understanding the electrostatic forces and features within highly heterogeneous, anisotropic, and chemically complex enzyme active sites and their connection to biological catalysis remains a longstanding challenge, in part due to the paucity of incisive experimental probes of electrostatic properties within proteins. To quantitatively assess the landscape of electrostatic fields at discrete locations and orientations within an enzyme active site, we have incorporated site-specific thiocyanate vibrational probes into multiple positions within bacterial ketosteroid isomerase. A battery of X-ray crystallographic, vibrational Stark spectroscopy, and NMR studies revealed electrostatic field heterogeneity of 8 MV∕cm between active site probe locations and widely differing sensitivities of discrete probes to common electrostatic perturbations from mutation, ligand binding, and pH changes. Electrostatic calculations based on active site ionization states assigned by literature precedent and computational pK a prediction were unable to quantitatively account for the observed vibrational band shifts. However, electrostatic models of the D40N mutant gave qualitative agreement with the observed vibrational effects when an unusual ionization of an active site tyrosine with a pK a near 7 was included. UV-absorbance and 13 C NMR experiments confirmed the presence of a tyrosinate in the active site, in agreement with electrostatic models. This work provides the most direct measure of the heterogeneous and anisotropic nature of the electrostatic environment within an enzyme active site, and these measurements provide incisive benchmarks for further developing accurate computational models and a foundation for future tests of electrostatics in enzymatic catalysis. E xtensive structural studies of enzymes have revealed that biological catalysis occurs within sequestered active site crevices that solvate reacting substrates with an anisotropic and chemically complex constellation of charged, polar, and hydrophobic groups. But beyond visualization of the chemical composition and architecture of active sites permitted by the rich library of available protein structures, our understanding of the electrostatic nature and properties of this highly heterogeneous environment and its role in molecular recognition and catalysis is largely based on simulations. Computations using three-dimensional structures routinely provide electrostatic potentials, as in Fig. 1A. These potentials have been used to identify and characterize protein-protein and protein-ligand binding sites, and interaction energies derived from these calculations have suggested key contributions from the electrostatic environment to enzymatic rate enhancement and specificity (1-5). However, even the most sophisticated computational methods have multiple approximations and limitations (6-8) and, most importantly, have not been rigorously evaluated through cycles of nontrivial computational predictions and experimental tests. Incisive and quantitative experimental measures o...

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The Solvation of Acetonitrile

Cited by 251 publications

References 92 publications

Adsorption of benzonitrile at the air/water interface studied by sum frequency generation spectroscopy

Adsorption of benzonitrile at the air/water interface studied by sum frequency generation spectroscopy

Electrostatic Fields Near the Active Site of Human Aldose Reductase: 1. New Inhibitors and Vibrational Stark Effect Measurements

Quantitative, directional measurement of electric field heterogeneity in the active site of ketosteroid isomerase

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