Charles G. Fry

Glyoxal in Aqueous Ammonium Sulfate Solutions: Products, Kinetics and Hydration Effects

Reactions and interactions between glyoxal and salts in aqueous solution were studied. Glyoxal was found to react with ammonium to form imidazole, imidazole-2-carboxaldehyde, formic acid, N-glyoxal substituted imidazole, and minor products at very low concentrations. Overall reaction orders and rates for each major product were measured. Sulfate ions have a strong and specific interaction with glyoxal in aqueous solution, which shifts the hydration equilibria of glyoxal from the unhydrated carbonyl form to the hydrated form. This ion-specific effect contributes to the observed enhancement of the effective Henrys law coefficient for glyoxal in sulfate-containing solutions. The results of UV-vis absorption and NMR spectroscopy studies of solutions of glyoxal with ammonium, methylamine, and dimethylamine salts reveal that light absorbing compounds require the formation of nitrogen containing molecules. These findings have implications on the role of glyoxal in the atmosphere, both in models of the contribution of glyoxal to form secondary organic aerosol (SOA), the role of nitrogen containing species for aerosol optical properties and in predictions of the behavior of other carbonyls or dicarbonyls in the atmosphere.

Influence of Strand Number on Antiparallel β-Sheet Stability in Designed Three- and Four-stranded β-Sheets

We describe experiments that probe whether antiparallel beta-sheet secondary structure becomes more stable as the number of strands increases. Several groups, including ours, have explored this issue with peptides designed to adopt three-stranded beta-sheet conformations, but the conclusions have not been consistent. In this study, we examine the effect on conformational stability of beta-sheet lengthening perpendicular to the strand direction via analysis of designed peptides that adopt three-stranded or four-stranded antiparallel beta-sheet conformations in aqueous solution. The findings reported here, along with the context provided by earlier studies, suggest that antiparallel beta-sheet does, in general, become more stable when the number of strands is increased from two to three. We show that this conclusion is not influenced by the rigidity of the loop segment used to link adjacent beta-strands (D-Pro-Gly versus Asn-Gly). We show that further extension, from three strands to four, leads to a further increase in antiparallel beta-sheet stability.

Structurally Diverse Diazafluorene-Ligated Palladium(II) Complexes and Their Implications for Aerobic Oxidation Reactions

4,5-Diazafluoren-9-one (DAF) has been identified as a highly effective ligand in a number of Pd-catalyzed oxidation reactions, but the mechanistic basis for its utility has not been elucidated. Here, we present the complex coordination chemistry of DAF and palladium(II) carboxylate salts. Multiple complexes among an equilibrating mixture of species have been characterized by (1)H and (15)N NMR spectroscopy and X-ray crystallography. These complexes include monomeric and dimeric Pd(II) species, with monodentate (κ(1)), bidentate (κ(2)), and bridging (μ:κ(1):κ(1)) DAF coordination modes. Titration studies of DAF and Pd(OAc)2 reveal the formation of two dimeric DAF/Pd(OAc)2 complexes at low [DAF] and four monomeric species at higher [DAF]. The dimeric complexes feature two bridging acetate ligands together with either a bridging or nonbridging (κ(1)) DAF ligand coordinated to each Pd(II) center. The monomeric structures consist of three isomeric Pd(κ(1)-DAF)2(OAc)2 complexes, together with Pd(κ(2)-DAF)(OAc)2 in which the DAF exhibits a traditional bidentate coordination mode. Replacing DAF with the structurally related, but more-electron-rich derivative 9,9-dimethyl-4,5-diazafluorene (Me2DAF) simplifies the equilibrium mixture to two complexes: a dimeric species in which the Me2DAF bridges the two Pd centers and a monomeric species with a traditional κ(2)-Me2DAF coordination mode. The use of DAF in combination with other carboxylate ligands (CF3CO2(-) or tBuCO2(-)) also results in a simplified collection of equilibrating Pd(II)-DAF complexes. Collectively, the results highlight the ability of DAF to equilibrate rapidly among multiple coordination modes, and provide valuable insights into the utility of DAF as a ligand in Pd-catalyzed oxidation reactions.

Solwaric acids A and B, antibacterial aromatic acids from a marine Solwaraspora sp.

Two novel trialkyl-substituted aromatic acids, solwaric acids A and B, were isolated from a marine Solwaraspora sp. cultivated from the ascidian Trididemnum orbiculatum. Solwaric acids A and B were isotopically labeled with U-13C glucose, and analysis of a 13C–13C COSY allowed for unambiguous determination of the location of the phenyl methyl group. The two novel compounds demonstrated antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive Staphylococcus aureus (MSSA).

In Situ Monitoring of Backbone Thioester Exchange by 19F NMR

backbone thioester exchange; coiled coil; fluorine; NMR spectroscopy; protein foldingBackbone thioester exchange (BTE) is a new technique for assessing the stability of foldingpatterns adopted by polypeptides.[1–5] Implementation of this method requires thereplacement of a single backbone amide group in the polypeptide of interest with a thioester;this replacement is an approximately isostructural substitution.[ 6,7] Combining the backbone-modified polypeptide analogue (a thiodepsipeptide) with a small thiol in pH 7 aqueous bufferinitiates a thiol–thioester exchange reaction.[8] The equilibrium constant for this exchange isstrongly influenced by the stability of the folded conformation adopted by the full-lengththiodepsipeptide. We have shown that BTE enables examination of sequence–stabilityrelationships for a variety of small folding motifs under native conditions including β-hairpins,coiled coils and a small protein, the chicken villin headpiece subdomain.[1–5] BTE analysisis complementary to traditional methods of assessing protein conformational stability, in whichthe folding pattern is disrupted with heat or chemical additives.[ 9] The traditional approachesrequire extrapolation to obtain folding parameters that apply under native conditions, whileBTE enables direct measurement under native conditions. BTE has provided new insights oncommon protein folding motifs[ 1,3–5] and on contributions of unnatural side chains to tertiarystructural stability,[2] but continued development is necessary to maximize the utility of thisnew tool.Here we report that quantitative BTE analysis can be conducted in situ by using

Kinetic and thermodynamic characterization of C-N bond rotation by N-methylacetohydroxamic acid in aqueous media.

Hydroxamic acids (HAs) perform tasks in medicine and industry that require bidentate metal binding. The two favored conformations of HAs are related by rotation around the C(=O)–N bond. The conformations are unequal in stability. Recently, we reported that the most stable conformation of a small secondary HA in water places the oxygen atoms anti to one another. The barrier to C–N bond rotation may therefore modulate metal binding by secondary HAs in aqueous media. We have now determined the activation barrier to C–N rotation from major to minor conformation of a small secondary HA in D2O to be 67.3 kJ/mol. The HA rotational barrier scales with solvent polarity, as is observed in amides, although the HA barrier is less than that of a comparable tertiary amide in aqueous solution. Successful design of new secondary HAs to perform specific tasks requires solid understanding of rules governing HA structural behavior. Results from this work provide a more complete foundation for HA design efforts. Copyright

Corrigendum to “Influence of Strand Number on Antiparallel β-Sheet Stability in Designed Three- and Four-Stranded β-Sheets”: J. Mol. Biol. (2003) 326, 553–568

In the original paper, we compared our results with the previous findings of Griffiths-Jones & Searle. However, we inadvertantly misquoted those previous results. We indicated that this reference suggested a b-hairpin stabilization of 0.1 kcal/mol from addition of a third strand to a b-sheet. However, the data of Griffiths-Jones & Searle actually suggests a b-hairpin stabilization of 0.26 kcal/mol from addition of a third strand, which is closer to our observed value of 0.4 kcal/mol. This correction does not affect the conclusions drawn in our paper.