Gibbs energy of solvation of organic ions in aqueous and dimethyl sulfoxide solutions

Pliego, Josefredo R.; Riveros, José M.

doi:10.1039/b109595a

Cited by 222 publications

(264 citation statements)

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“…The adjacent cysteines, poorly conserved in other ALDHs, might also help stabilize the thiolate but they are observed to be hydrogen bonded to Asp457 in our simulations. These direct interactions and the polar environment of the active site accounts for the different energetics calculated in the gas phase (40). In the presence of propanal, the direct interactions direct that help stabilize the thiolate anion in the holo form have been replaced by interactions with the substrate which are weaker.…”

Section: Cys302 Addition To Nad+mentioning

confidence: 99%

Mechanistic Implications of the Cysteine−Nicotinamide Adduct in Aldehyde Dehydrogenase Based on Quantum Mechanical/Molecular Mechanical Simulations

2007

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Recent computer simulations of the cysteine nucleophilic attack on propanal in human mitochondrial Aldehyde Dehydrogenase (ALDH2) yielded an unexpected result; the chemically reasonable formation of a dead-end cysteine-cofactor adduct when NAD+ was in the "hydride transfer" position. More recently, this adduct found independent crystallographic support in work on formyltetrahydrofolate dehydrogenase, work which further found evidence of the same adduct on re-examination of deposited electron densities of ALDH2. Although the experimental data showed this adduct was reversible, several mechanistic questions arise from the fact that it forms at all. Here, we present results from further Quantum Mechanical/Molecular Mechanical (QM/MM) simulations toward understanding the mechanistic implications of adduct formation. These simulations revealed that formation of the oxyanion thiohemiacetal intermediate only when the nicotinamide ring of NAD + is oriented away from the active site, contrary to prior arguments. In contrast, and in seeming paradox, when NAD is oriented to receive the hydride, disassociation of the oxyanion intermediate to form the dead-end adduct is more thermodynamically-favored than maintaining the oxyanion intermediate necessary for catalysis to proceed. However, this disassociation to the adduct could be avoided through proton transfer from the enzyme to the intermediate. Our results continue to indicate that the unlikely source of this proton is the Cys302 main chain amide.The overall mechanism of aldehyde dehydrogenase (E.C. 1.2.1.3) shown in Figure 1 involves 1) nucleophilic attack on the aldehyde to form a thiohemiacetal intermediate from which 2) the hydride is transferred to NAD+, to yield NADH and the thioester which 3) hydrolyses to yield the product carboxylic acid followed by 4) release of the cofactor. Specific atomic level details about each of these steps have been obtained from x-ray crystallography and NMR. The side chain of the conserved Asn169 (ALDH2 numbering) and the main chain amide of Cys302 are positioned to form hydrogen bonds to a negatively charged thiohemiacetal intermediate structure. This configuration is often called the "oxyanion hole".In the human mitochondrial ALDH2 structure (1), the Asn169 Nδ-to-crotonaldehyde carbonyl oxygen is 4.1 Å while the main chain amide nitrogen of Cys302 is 3.8 Å away. Three *To whom correspondence should be addressed: Pittsburgh Supercomputing Center 300 S. Craig Street Pittsburgh, PA 15213 e-mail: wymore@psc.edu Phone: 412−268−4960 FAX: 412−268−8200. Supporting Information Available Coordinates of optimized product structures presented in Figure 3 are given in XYZ format. This material is available free of charge via the Internet at http://pubs.acs.org. NIH Public Access Author ManuscriptBiochemistry. Author manuscript; available in PMC 2008 September 5. . The other NAD+ conformation shows the nicotinamide more removed from the active site and is likely the position of the coenzyme during thioester hydrolysis. In this conformation,...

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Section: Cys302 Addition To Nad+mentioning

confidence: 99%

Mechanistic Implications of the Cysteine−Nicotinamide Adduct in Aldehyde Dehydrogenase Based on Quantum Mechanical/Molecular Mechanical Simulations

2007

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“…Through the use of thermochemical cycle 6 (illustrated in Scheme 6) 132 the conventional solvation free energy of clustered cations and anions can be written in terms of the conventional solvation free energy of their analogous unclustered ions according to (19) where M ± is the same as M + , X − , BH + and A − , is the free energy associated with moving the solute from the gas phase into its own pure liquid phase (often, we refer to this free energy as a "self solvation free energy" 166 ) and is the sum of the stepwise clustering free energies of M ± with n solvent (S) molecules in the gas-phase (20) where (21) Note that the concentration of the pure liquid does not appear in eq 19 because we use as a standard state an ideal dilute solution, for which the activity of the pure liquid is very nearly equal to unity. 167 In this standard-state, the free energy associated with the following reaction (22) which we have also used in previous work 7,56,111 and is shown in the bottom leg of thermochemical!…”

Section: Conventional Solvation Free Energies Of Clustered Ionsmentioning

confidence: 99%

Single-Ion Solvation Free Energies and the Normal Hydrogen Electrode Potential in Methanol, Acetonitrile, and Dimethyl Sulfoxide

2006

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The division of thermodynamic solvation free energies of electrolytes into ionic constituents is conventionally accomplished by using the single-ion solvation free energy of one reference ion, conventionally the proton, to set the single-ion scales. Thus the determination of the free energy of solvation of the proton in various solvents is a fundamental issue of central importance in solution chemistry. In the present article, relative solvation free energies of ions and ion-solvent clusters in methanol, acetonitrile, and dimethyl sulfoxide (DMSO) have been determined using a combination of experimental and theoretical gas-phase free energies of formation, solution-phase reduction potentials and acid dissociation constants, and gas-phase clustering free energies. Applying the cluster pair approximation to differences between these relative solvation free energies leads to values of −263.5, −260.2, and −273.3 kcal/mol for the absolute solvation free energy of the proton in methanol, acetonitrile, and DMSO, respectively. The final absolute proton solvation free energies are used to assign absolute values for the normal hydrogen electrode potential and the solvation free energies of other single ions in the above solvents.

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“…These results are unexpected considering that it is well documented that continuum models work better for anions in aprotic solvents than in protic solvents. 51,52 In fact, several theoretical studies of anion-molecule S N 2 reactions in DMSO using the PCM method and the Pliego and Riveros 45 atomic cavities have led to reliable activation barriers. 24,53,54 In part, the reason for this high deviation can be attributed to reaction of the PhS -nucleophile in DMF, with a deviation of 8.3 kcal mol -1 for TS4.…”

Section: Resultsmentioning

confidence: 99%

“…Considering that previous studies on anion-molecule S N 2 reactions in DMSO using the PCM method with the Pliego and Riveros 45 cavities has worked fine, this approach was also tested. The results are presented in Table 2, with the values in parenthesis.…”

Section: Resultsmentioning

confidence: 99%

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How Accurate is the SMD Model for Predicting Free Energy Barriers for Nucleophilic Substitution Reactions in Polar Protic and Dipolar Aprotic Solvents?

Miguel¹,

Santos²,

Silva³

et al. 2016

Journal of the Brazilian Chemical Society

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In the past seven years, the SMD (Solvent Model Density) method has been widely used by computational chemists. Thus, assessment on the reliability of this model for modeling chemical process in solution is worthwhile. In this report, it was investigated six anion-molecule nucleophilic substitution reactions in methanol and dipolar aprotic solvents. Geometry optimizations have been done at SMD/X3LYP level and single point energy calculations at CCSD(T)/TZVPP + diff level. Our results have indicated that the SMD model is not adequate for dipolar aprotic solvents, with a root of mean squared (RMS) error of 5.6 kcal mol . The classical protic to dipolar aprotic solvent rate acceleration effect was not predicted by the SMD model for the tested systems.Keywords: continuum solvation model, ion solvation, solvent effect, aromatic nucleophilic substitution, M11 functional IntroductionIn the middle of the twentieth century, several experimental studies have led to foundation of empirical rules for qualitative prediction of solvent effects on chemical reactions, authoritatively reviewed by Parker 1 in a classical paper. Nevertheless, a deeper view on solvent effects was only possible with experimental studies of gas phase ion-molecule reactions [2][3][4][5][6] and theoretical modeling of these processes. [7][8][9] It was evident from theoretical studies that solute-solvent interactions can be very strong and produce a profound effect on chemical reactivity. [10][11][12][13][14][15][16][17] On the other hand, gas phase dynamic of chemical reactions can open new mechanistic possibilities. 18,19 Among the different solvents used to conduct ionic chemical reactions, polar protic and dipolar aprotic solvents are paramount due to their property of solubilize ionic species. 20 Methanol is a polar protic solvent and its ability to solvate ions is similar to water. 21,22 In addition, it has the advantage of solubilize many organic molecules not soluble in water. Some usual dipolar aprotic solvents are dimethyl sulfoxide (DMSO), dimethylformamide (DMF) and acetonitrile. Because anions are less solvated in these solvents, anion-molecule reactions are accelerated when transferred from protic to dipolar aprotic solvents. Our ability to describe theoretically this effect is an important goal and a challenge for continuum solvation models once requires these models be able to describe specific solutesolvent interactions. 23 Considering that the Born formula for solvation of a spherical ion of charge q and radius R into a solvent with dielectric constant ε is given by:(1) it could be noted that the use of the same "molecular cavity" for an ionic solute into a protic and dipolar aprotic solvent with high dielectric constant would lead to very similar solvation free energy of ions. A possibility to overcome this problem would be to use different molecular cavity for protic and dipolar aprotic solvents. This approach has reached some successful ten years ago using the polarizable continuum model (PCM) in the study of anion-molecule reaction...

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Gibbs energy of solvation of organic ions in aqueous and dimethyl sulfoxide solutions

Cited by 222 publications

References 53 publications

Mechanistic Implications of the Cysteine−Nicotinamide Adduct in Aldehyde Dehydrogenase Based on Quantum Mechanical/Molecular Mechanical Simulations

Mechanistic Implications of the Cysteine−Nicotinamide Adduct in Aldehyde Dehydrogenase Based on Quantum Mechanical/Molecular Mechanical Simulations

Single-Ion Solvation Free Energies and the Normal Hydrogen Electrode Potential in Methanol, Acetonitrile, and Dimethyl Sulfoxide

How Accurate is the SMD Model for Predicting Free Energy Barriers for Nucleophilic Substitution Reactions in Polar Protic and Dipolar Aprotic Solvents?

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