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Synthesis of chemically modified or ion-substituted hydroxyapatite (HA) as a bioactive bone replacement material is of great interest since the main component of hard tissues in vertebrates is a substituted apatite. The most abundant species in natural bone mineral other than calcium and phosphate ions is carbonate ions. Carbonate ions can be substituted at 2 distinct sites in the HA lattice; the hydroxide (OH) site and the phosphate (PO4) site. Synthetic silicate substituted HA (SiHA) and carbonate-substituted HA (CHA) have each previously been shown to enhance new bone formation when compared to HA in vivo. The positive bioactive properties that result, individually, from carbonate or silicate substitution led to the hypothesis that simultaneous co-substitution of these two ions in to the HA lattice would lead to further improved bioactivity. A range of novel silicate and carbonate co-substituted HA (SiCHA) materials were prepared with silicate substitution of up to 12.5 wt% (3.8 wt% Si) and carbonate substitution up to 8.2 wt%. These compositions were characterised extensively, examining both their chemical and physical attributes. These compositions were single phase after sintering in a wet CO2 atmosphere to near-theoretical density, and contained carbonate ions on both hydroxide and phosphate sites. The grain sizes of these ceramic specimens of these compositions were intermediate between those of CHA and SiHA controls. Further controlled synthesis demonstrated that carbonate and silicate ions could be substituted in non-equimolar quantities, and increased amounts of carbonate could be substituted independently on to the hydroxide site of the SiCHA samples. The biological response to these materials was assessed by completing direct and indirect cell culture experiments using both the MG-63 osteoblast-like cell line and primary human osteoblast (pHOB) cells. The silicate and carbonate co-substituted materials and their dissolution products were not toxic to either of the cell lines, and cell proliferation was observed with all materials studied. The effect of the synthesis route on the purity of silicate-substituted hydroxyapatite (SiHA) was also assessed, with a particular focus on the role of tetraethyl orthosilicate (TEOS) as the source of silicate. The outcomes of this study showed that the final composition of SiHA was strongly dependent on how and when the tetraethyl orthosilicate (TEOS) solution was incorporated during the precipitation reaction.

Phosphate esters and their hydrolysis reactions underpin many of the most important reactions in biology and have therefore been the focus of continued research. In this thesis, a range of theoretical studies on two phosphate ester hydrolysis reactions is presented. Particular attention is paid to the role of solvent in these reactions. The first reaction studied is the hydrolysis of dimethyl phosphate. A study using density functional theory examines three possible mechanisms for this reaction in the gas phase and the presence of solvent is also considered through the use of reaction field methods. The base-catalysed mechanism for this reaction receives further attention and the reaction energy profile in solution is adiabatically mapped using two different hybrid QM/MM potentials. The use of a QM/MM potential facilitates an atomistic representation of the solvent. Another study determines the potential of mean force for this reaction by simulating the reaction using QM/MM molecular dynamics simulations in conjunction with umbrella sampling methods. Both QM/MM studies demonstrate that, in solution, the rate-determining step for the base-catalysed reaction is the cleavage of the bond between the phosphorous and the leaving group. The QM/MM studies also established that the reaction proceeds via the formation of a short-lived pentacoordinated intermediate species. The second reaction studied was the base-catalysed hydrolysis of methyl ribose phosphate, a realistic model of the nonenzymatic hydrolysis of RNA. Since the hydrolysis of thio-substituted analogues of RNA have been the study of many experimental studies probing the mechanism of RNA hydrolysis, theoretical studies of the hydrolysis of two thio analogues of methyl ribose phosphate are also presented. The results of these studies provide valuable insight into the mechanism of RNA hydrolysis and concludes that the cleavage of P-O5' bond corresponds to the reaction transition state.

Thesis (M.S.)--University of Michigan, 1979.

Thesis (M.S.)--Duquesne University, 2004. / Title from document title page. Abstract included in electronic submission form. Includes bibliographical references (p. 50-57) and index.

Thesis (M.S.)--University of Michigan, 1979.

Thesis (M.S.)--University of Wisconsin--Madison, 1965. / eContent provider-neutral record in process. Description based on print version record. Bibliography: l. 51-52.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1965. / Vita. Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (Ph. D.)--University of Virginia, 2000. / Includes bibliographical references (leaves 141-154). Also available online through Digital Dissertations.

Thesis (Ph. D.)--Michigan State University. Dept. of Chemistry, 2008. / Title from PDF t.p. (viewed Sept. 10, 2009). Includes bibliographical references. Also issued in print.