Quantifying Additive Interactions of the Osmolyte Proline with Individual Functional Groups of Proteins: Comparisons with Urea and Glycine Betaine, Interpretation of <i>m</i>‑Values

To quantify interactions of the osmolyte l-proline with protein functional groups and predict their effects on protein processes, we use vapor pressure osmometry to determine chemical potential derivatives dμ₂/d<i>m</i>₃ = μ₂₃, quantifying the preferential interactions of proline (component 3) with 21 solutes (component 2) selected to display different combinations of aliphatic or aromatic C, amide, carboxylate, phosphate or hydroxyl O, and amide or cationic N surface. Solubility data yield μ₂₃ values for four less-soluble solutes. Values of μ₂₃ are dissected using an ASA-based analysis to test the hypothesis of additivity and obtain α-values (proline interaction potentials) for these eight surface types and three inorganic ions. Values of μ₂₃ predicted from these α-values agree with the experiment, demonstrating additivity. Molecular interpretation of α-values using the solute partitioning model yields partition coefficients (<i>K</i>_p) quantifying the local accumulation or exclusion of proline in the hydration water of each functional group. Interactions of proline with native protein surfaces and effects of proline on protein unfolding are predicted from α-values and ASA information and compared with experimental data, with results for glycine betaine and urea, and with predictions from transfer free energy analysis. We conclude that proline stabilizes proteins because of its unfavorable interactions with (exclusion from) amide oxygens and aliphatic hydrocarbon surfaces exposed in unfolding and that proline is an effective in vivo osmolyte because of the osmolality increase resulting from its unfavorable interactions with anionic (carboxylate and phosphate) and amide oxygens and aliphatic hydrocarbon groups on the surface of cytoplasmic proteins and nucleic acids

A Computational Re-examination of the Criegee Intermediate–Sulfur Dioxide Reaction

The atmospheric oxidation of sulfur dioxide by the parent and dimethyl Criegee intermediates (CIs) may be an important source of sulfuric acid aerosol, which has a large impact on radiative forcing and therefore upon climate. A number of computational studies have considered how the CH₂OOS­(O)­O heteroozonide (HOZ) adduct formed in the CI + SO₂ reaction converts SO₂ to SO₃. In this work we use the CBS-QB3 quantum chemical method along with equation-of-motion spin-flip CCSD­(dT) and MCG3 theories to reveal new details regarding the formation and decomposition of the <i>endo</i> and <i>exo</i> conformers of the HOZ. Although ∼75% of the parent CI + SO₂ reaction is initiated by formation of the <i>exo</i> HOZ, hyperconjugation preferentially stabilizes many of the <i>endo</i> intermediates and transition structures by 1–5 kcal mol^–1. Our quantum chemical calculations, in conjunction with statistical rate theory models, predict a rate coefficient for the parent CI + SO₂ reaction of 3.68 × 10^–11 cm³ molecule^–1 s^–1, in good agreement with recent experimental measurements. RRKM/master equation simulations based on our quantum chemical data predict a prompt carbonyl + SO₃ yield of >95% for the reaction of both the parent and dimethyl CI with SO₂. The existence of concerted cycloreversion transition structures 10–15 kcal mol^–1 higher in energy than the HOZ accounts for most of the predicted SO₃ formation