Combining cyclic peptides with metal coordination

This thesis targets cyclic peptide supramolecular structures for biomaterial applications. The introduction gives a brief insight into supramolecular interactions, peptides, and their application in biomaterials. These supramolecular interactions range from the weak forces of electrostatics and van der Waals interactions, to hydrogen bonding and metal-coordination. The application of peptides and supramolecular interactions has become a highly studied area of chemistry, which has quickly gotten attention in the area of biomaterials. The use of peptides in biomaterials seems obvious since in vivo rejection of this material might be limited. Nature can be used as a blue print to direct the path for hydrogen bonding motifs and metal-coordinating interactions and can be applied potentially towards supramolecular biomaterials. Finally, the introduction reviews the use of cyclic peptides and accounts for the synthetic design of the cyclic octapeptide to be used throughout the thesis work. The second chapter of the thesis provides the details by which the synthetic scheme for creating the linear peptides of interest and ultimately the cyclic peptides is described in detail. Many synthetic challenges were met and overcome during this thesis work; the most notable was overcoming purification challenges and poor amino acid coupling reactions that resulted in low yields. This thesis focuses primarily on the di-substituted pyridylalanine cyclic octapeptide, however much of the initial work on the mono-substituted cyclic octapepide was carried out in tandem allowing for comparison of the two peptides necessary for future work.M.S.Committee Chair: Weck, Marcus; Committee Member: Collard, David; Committee Member: Kubanek, Juli

The Preparation, Characterization and X-Ray Structural Analysis of Tetrakis[1-methyl-3-(2-propyl)-2(3H)-imidazolethione]zinc(II) Tetrafluoroborate and Tetrakis[1-methyl-3-(1-butyl)-2(3H)-imidazolethione]zinc(II) Tetrafluoroborate

[Zn(mipit) 4][BF4]2 (1) and [Zn(mnbit)4][BF4]2 (2) were synthesized and characterized via std. solid and soln. state methods including single crystal x-ray crystallog. (mipit = 1-methyl-3-(2-propyl)-2(3H)-imidazolethione and mnbit = 1-methyl-3-(1-butyl)-2(3H)-imidazolethione). Compd. 1 crystallizes in monoclinic space group P21/n with a 11.804(2), b 16.710(3), c 25.763(5) Å, γ 90.14(3)° and Z = 4, whereas compd. 2 crystallizes in tetragonal space group I.hivin.4 with a = b 11.6517(16), c 16.820(3) Å, and Z = 2. Both complexes are high melting, colorless water sol. 2:1 electrolyte solids that state have flattened tetrahedral ZnS4 coordination geometry. The iso-Pr analog is slightly more distorted than the Bu analog, and the degree of distortion is not directly related to the steric bulk of the ligand

The Preparation, Characterization, X-ray Structural Analysis, and Thermogravimetric Analysis of Tetrakis[1,3-Dimethyl-2(3H)-Imidazolethione]Zinc(II) Nitrate and Tetrafluoroborate

Two new compds., [Zn(dmit) 4][BF4]2 (1) and [Zn(dmit)4][NO3]2 (2), were synthesized and characterized via std. solid and soln. state methods including single crystal x-ray crystallog. (dmit = 1,3-dimethyl-2(3H)-imidazolethione). [Zn(dmit)4][BF4]2 crystallizes in space group Pbcn with a 11.954(2), b 21.260(4), c 12.749(3) Å, Z = 4. [Zn(dmit)4][NO3]2 crystallizes in space group I41/a with a = b 11.091(4), c 22.713(5) Å, Z = 4. Both structures display a compressed tetrahedral geometry in the zinc coordination sphere similar to previously reported iso-Pr and Bu analogs. The degree of distortion is closer to that noted for the recently reported Me iso-Pr analog than to the Me Bu complex. There are no significant differences between the nitrate and tetrafluoroborate coordination spheres, and the source of distortion appears to be close intramol. contacts. TGA results suggest that both complexes decomp. to yield ZnS2 instead of ZnS

CCDC 273152: Experimental Crystal Structure Determination

Related Article: D.J.Williams, J.J.Concepcion, M.C.Koether, K.A.Arrowood, A.L.Carmack, T.G.Hamilton, S.M.Luck, M.Ndomo, C.R.Teel, D.VanDerveer|2006|J.Chem.Cryst.|36|453|doi:10.1007/s10870-005-9054-4,An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures

CCDC 273153: Experimental Crystal Structure Determination

Related Article: D.J.Williams, J.J.Concepcion, M.C.Koether, K.A.Arrowood, A.L.Carmack, T.G.Hamilton, S.M.Luck, M.Ndomo, C.R.Teel, D.VanDerveer|2006|J.Chem.Cryst.|36|453|doi:10.1007/s10870-005-9054-4,An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures

CCDC 704290: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.,Related Article: D.J.Williams, K.A.Arrowood, L.M.Bloodworth, A.L.Carmack, D.Gulla, M.W.Gray, I.Maasen, F.Rizvi, S.L.Rosenbaum, K.P.Gwaltney, D.VanDerveer|2010|J.Chem.Cryst.|40|1074|doi:10.1007/s10870-010-9797-

CCDC 621659: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.,Related Article: D.J.Williams, K.A.Arrowood, L.M.Bloodworth, A.L.Carmack, D.Gulla, M.W.Gray, I.Maasen, F.Rizvi, S.L.Rosenbaum, K.P.Gwaltney, D.VanDerveer|2010|J.Chem.Cryst.|40|1074|doi:10.1007/s10870-010-9797-

CCDC 742462: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.,Related Article: D.J.Williams, D.Gulla, K.A.Arrowood, L.M.Bloodworth, A.L.Carmack, T.J.Evers, M.S.Wilson, J.J.Concepcion, C.A.S.Brevett, B.E.Huck, D.VanDerveer|2009|J.Chem.Cryst.|39|581|doi:10.1007/s10870-009-9528-

The Preparation, Characterization and X-ray Structural Analysis of Tetrakis[1-Methyl-3-(2-Propyl)-2(3H)-Imidazolethione]Cadmium(II) Hexafluorophosphate

A new compd., [Cd(mipit)4][PF6]2 was synthesized and characterized via std. solid and soln. state methods including single crystal x-ray crystallog. (mipit = 1-methyl-3-(2-propyl)-2(3H)-imidazolethione). The title compd. crystallizes in tetragonal space group I41/a with a 12.478(2), b 12.478(2), c 28.806(6) Å, and Z = 4. The complex is a high melting, colorless solid that has a distorted tetrahedral CdS4 coordination geometry. TGA results for the title compd. as well as for another potential CdS synthon and two potential CdSe synthons are reported

Cloning and Characterization of the Acidic Ribosomal Protein P2 of Cryptosporidium parvum, a New 17-Kilodalton Antigen▿

Cryptosporidium infection is commonly observed among children and immunocompromised individuals in developing countries, but large-scale outbreaks of disease among adults have not been reported. In contrast, outbreaks of cryptosporidiosis in the United States and Canada are increasingly common among patients of all ages. Thus, it seems likely that residents of regions where Cryptosporidium is highly endemic acquire some level of immunity, while residents of the developed world do not. A new immunodominant Cryptosporidium parvum antigen in the 15- to 17-kDa size range was identified as the Cryptosporidium parvum 60S acidic ribosomal protein P2 (CpP2). We developed a recombinant protein-based enzyme-linked immunosorbent assay for serologic population surveillance for antibodies that was 89% sensitive and 92% specific relative to the results of the large-format Western blot assay. The human IgG response is directed almost exclusively toward the highly conserved, carboxy-terminal 15 amino acids of the protein. Although IgG antibody cross-reactivity was documented with sera from patients with acute babesiosis, the development of an anti-CpP2 antibody response in our Peru study population correlated better with Cryptosporidium infection than with infection by any other parasitic protozoan. In Haiti, the prevalence of antibodies to CpP2 plateaus at 11 to 20 years of age. Because anti-CpP2 IgG antibodies were found only among residents of countries in the developing world where Cryptosporidium infection occurs early and often, we propose that this response may be a proxy for the intensity of infection and for acquired immunity