Browsing by Subject "hydrogen bonding"

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    Computational and experimental investigations of forces in protein folding
    (Texas A&M University, 2005-02-17) Schell, David Andrew
    Properly folded proteins are necessary for all living organisms. Incorrectly folded proteins can lead to a variety of diseases such as Alzheimer?s Disease or Bovine Spongiform Encephalitis (Mad Cow Disease). Understanding the forces involved in protein folding is essential to the understanding and treatment of protein misfolding diseases. When proteins fold, a significant amount of surface area is buried in the protein interior. It has long been known that burial of hydrophobic surface area was important to the stability of the folded structure. However, the impact of burying polar surface area is not well understood. Theoretical results suggest that burying polar groups decreases the stability, but experimental evidence supports the belief that polar group burial increases the stability. Studies of tyrosine to phenylalanine mutations have shown the removal of the tyrosine OH group generally decreases stability. Through computational investigations into the effect of buried tyrosine on protein stability, favorable van der Waals interactions are shown to correlate with the change in stability caused by replacing the tyrosine with phenylalanine to remove the polar OH group. Two large-scale studies on nearly 1000 high-resolution x-ray structures are presented. The first investigates the electrostatic and van der Waals interactions, analyzing the energetics of burying various atom groups in the protein interior. The second large-scale study analyzes the packing differences in the interior of the protein and shows that hydrogen bonding increases packing, decreasing the volume of a hydrogen bonded backbone by about 1.5 ?3 per hydrogen bond. Finally, a structural comparison between RNase Sa and a variant in which five lysines replaced five acidic groups to reverse the net charge is presented. It is shown that these mutations have a marginal impact on the structure, with only small changes in some loop regions.
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    The Development of Werner-type Cobalt Complexes in Enantioselective Hydrogen Bond Mediated Catalysis
    (2013-12-03) Lewis, Kyle
    Chiral-at-metal Werner complexes of the type (?/?)-[Co(1,2-diamine)_(3)]^(3+) 3X^(?)have long been a cornerstone of coordination chemistry. However, despite being inexpensive and readily available in enantiopure form, they have had no applications in enantioselective organic synthesis. This derives from their poor solubility in organic solvents and the fact that the chelating ligands are non-labile, preventing metal based substrate activation. However, it was conceived that the abundant nitrogen-hydrogen bonds of the diamine ligands could activate Lewis basic substrates towards nucleophilic addition via hydrogen bonding. Towards this end, the diastereomeric trications ?-[Co((S,S)-dpen)_(3)]^(3+) and ?-[Co((S,S)-dpen)_(3)]^(3+) (dpen = diphenyl ethylenediamine) were prepared by stereoselective syntheses. Incorporation of the lipophilic Bar_(f)^(?) (B(3,5-CF_(3)-C_(6)H_(3))_(4)^(?)) anion, among others, afforded the organic-soluble mixed salts ?-[Co((S,S)-dpen)_(3)]^(3+) 2X^(?) BAr_(f)^(-) and ?-[Co((S,S)-dpen)_(3)]^(3+) 2X^(?) Bar^( ?)(X = Cl^(?), BF_(4)^(?), PF_(6)^(?)). These Werner complexes were then applied as hydrogen bond mediating catalysts for enantioselective Michael additions of dialkyl malonates to nitroolefins. The catalyzed Michael addition of dimethyl malonate (15a) to trans-?- nitrostyrene was optimized with respect to solvent, temperature, and catalyst counteranion and then extended to a range of nitroolefin substrates. Under optimized ? conditions, ?-(S,S)-3^(3+) 2BF_(4)^(?) Bar_(f)^(-) (10 mol%) catalyzes the Michael addition of 15a to 2-benzyloxy-trans-?-nitrostyrene in acetone at 0 ?C in the presence of Et_(3)N (1.0 equiv) to afford dimethyl 2-(2-nitro-1-(2 benzyloxyphenyl)ethyl)malonate in 95% isolated yield and 96% ee. This work marks the first time that a Werner-type complex has been applied as a catalyst for organic transformations with high enantioselectivities. The unique stereochemistry of the Werner complex, which features a chiral metal center, is primarily responsible for the stereoselectivity of the catalyzed reactions.