Cammers' Group Research Interests:      

We study and design functional molecular recognition on the basis of "predictable" conformational preferences in water. The primary design parameters in the control of conformation and function are hydrophobic, hydrogen bonding and coulombic interactions. We are interested in how competitive solvation affects these parameters. The following outlines some research areas under current exploration. The research is drawing our attention toward the particularities of aqueous solvation.

Water Soluble Organic Molecules for the Molecular Recognition of Oxo-anions

      Water is the most competitive solvent in its solvation of anions. The selective extraction of anions from aqueous media by organic molecules presents the organic chemist with a hardy challenge. Cations are usually discriminated on the basis of charge and size. A hypothetical molecular process which discriminates between similar multiatomic anions in aqueous solution, has more demands placed upon it. In general, anions of interest are more charge-diffuse and topologically more complex than the corresponding heavy metal cations with which water quality specialists concern themselves. Topological complexity and varied physical properties should enable the design of molecular systems to selectively recognize anions. The main obstacle to this hypothesis is the competitive stabilizing interaction established between water and these anions.

      We are seeking structures which segregate hydrophilic strcture from aqueous solution and make cites to stabilize anionic species. This concept has recently gone nanometric.[-1-]

Polypeptoid Design and Protein Folding

      Due to cooperative stabilizing contributions, proteins can display two-state behavior: the folded native state and random coil states. We aim to harness the factors that spawn cooperativity in the design of minimalist peptide sequences. <>       While the mechanisms of protein folding and predictability from primary structure are still mysterious, nature has afforded us a few clues from which to work. There are over 400 protein structures known by X-ray diffraction. From solution and solid state morphology and denaturation studies, we know proteins pay a high price for charge burial. Reverse turns, hairpins and loops are places about which polypeptide structures separate domains in proteins. Increased frequency of hydrophobic residues about b-sheets implies that sheets have hydrophobic faces. Helices can pack with enough energy to drive dimerization. Furthermore, domains excised from native conformations of proteins that are spatially related, often tend to dimerize in solution.

Condensed Phase p-Stacking

      Aromatic surfaces in aqueous media aggregate. This phenomenon is often cited in the conformational control of many biological molecules. Controversy remains whether the cohesion between aromatic surfaces in water is more a function of the hydrophobic effect or a function of dispersion forces between hydrocarbons. Other studies have pointed tentatively to favorable electrostatic (dipole and quadrupole) interactions between aromatic surfaces giving rise to cohesive forces. Work still remains to be done to enrich human understanding of p-stacking in order to use it more effectively as a molecular design tool. We have devised a model for water-soluble, face-to-face, center-to-edge (FFCE) p-stacking that implicates enthalpic interactions between solvent molecules and the edges of the aromatic rings versus interactions between solvent and the faces of the aromatic ring. In this model aromatic rings interact to minimize interactions between solvent and the aromatic faces of the solute. [-2-] [-3-] [-4-] [-5-] [-6-]

The Fluoroalkanol Effect on Peptide Structure

      We are pursuing an understanding of the factors that enable TFE and other fluorinated alcohols at low concentrations in water to affect changes in peptide structure. The marked effect that these small molecules have on the secondary structure of short peptides has been a mystery to peptide chemists for years. Understanding the role fluoroalcohol plays is potentially important to the protein folding mechanism and to the role of solvent and excluded solvent in the protein folding process. There have been many studies in this direction with medium sized peptides. We have compared the behavior of a few small organic probes with that of peptide conformation in an attempt to unveil the solvent-born impact on peptide structure. On the basis of these studies we have been able to revise the current mechanism for fluoroalkanols at low concentration.[-7-]

Much of the work thus far has been supported by the NSF.