The primary focus of this dissertation is the advancement of the correlation consistent composite approach (ccCA) methodology from its original formulation to the current implementation. Although for large main group test sets which contained both first- (Li-Ne) and second-row (Na-Ar) species ccCA produced chemical accuracy (generally estimated as a deviation of ~1 kcal mol-1 from reliable experiment), the second-row species were smaller in molecular size in comparison to their corresponding first-row species. Previous theoretical work has shown that the accuracy for theoretical calculations involving second-row species (specifically sulfur-containing species) are more basis set dependent than first-row species. Therefore, an analysis of the accuracy of ccCA for sulfur-containing species is warranted. The ccCA methodology is used to evaluate both enthalpies of formation and bond dissociation energies of sulfur-containing species as well as examine isomerization energies for three sets of sulfur-containing isomers. During the testing of ccCA for sulfur-containing species two observations were made which led to further investigations. First, there is no agreement between different theoretical methodologies on the lowest energetic isomer between SNO and NSO. In fact, G3 and G3B3 which differ only by the geometry of the single-point calculations do not agree on the lowest isomer. For this reason, larger, more complete theoretical treatments of SNO and NSO are investigated. Second, for open-shell sulfur-containing systems the accuracy of the ccCA methodology begins to degrade when spin-contamination becomes non-negligible. Therefore, we investigate the accuracy of the ccCA methodology when spin-contamination is removed from the wavefunction. Finally, the ccCA methodology is utilized in a multilayer ONIOM approach as the high level of theory in conjunction with density functional theory as the low level for the C-H bond dissociation energies of anthracene and fluorene analogues.
The reaction of 1-(diphenylphosphino)-2-(diphenylphosphito)benzene (PP*) and Os3(CO)10(ACN) has been investigated. A combined experimental and computational study on the isomerization of 1,2-Os3(CO)10[μ-1,2-Ph2P(C6H4)P(OPh)2] (A) and 1,1-Os3(CO)10[μ-1,2-Ph2P(C6H4)P(OPh)2] (B) and reversible ortho-metalation exhibited by the triosmium cluster B are reported. The subsequent conversion of cluster B to the hydrido cluster HOs3(CO)9[μ-1,2-PhP(C6H4-η1)C6H4P(OPh)2] (E) and the benzyne-substituted cluster HOs3(CO)8(µ3-C6H4)[μ-1,2-PhP(C6H4)P(OPh)2] (N) has been established. All of these new clusters have been isolated and fully characterized in solution by IR and NMR spectroscopy; in addition, X-ray diffraction analyses have been performed on the clusters A, B, J, and N. The ortho-metalation reaction that gives cluster E is shown to be reversible, and the mechanism has been probed using selectively deuterated PP* isotopomers. Kinetic and thermodynamic isotope data, in conjunction with DFT calculations, are presented that support the existence of an intermediate unsaturated cluster in the ortho-metalation reaction. Due to interest in the coordination chemistry of formamidines, the non-symmetric amidine ligands PhNC(Me)NHPri, PhNC(Et)NHPri, and (2,4,6-Me3C6H2)NC(Me)NHPri, have been synthesized, and their reaction with Os3(CO)10(MeCN)2 has been investigated. Of the twelve new clusters prepared in section, seven have been structurally characterized by X-ray crystallography.
The potential use of polymeric, functionalized nanoparticles (NPs) as drug delivery vectors was explored. Covalent conjugation of albumin to the surface of NPs via maleimide chemistry proved problematic. However, microwave assisted synthesis of NPs was not only time efficient, but enabled the exploration of size control by changing the following parameters: temperature, microwave power, reaction time, initiator concentration, and percentage of monomer used. About 1.5 g of fluorescently-labeled, carboxylic acid-functionalized NPs (100 nm diameter) were synthesized for a total cost of less than $1. Future work will address further functionalization of the NPs for the coupling of albumin (or other targeted proteins), and tests for in vivo biodistribution.
The reaction between the formamidine ligand PriN=CHNHPri and the activated cluster Os3(CO)10(MeCN)2 has been studied. A rapid reaction is observed at room temperature, yielding the hydride clusters HOs3(CO)9[μ-OCNPriC(H)NPri] and HOs3(CO)10[μ-NPriC(H)NPri] as the principal products. The spectroscopic data and X-ray diffraction structures of those formamidinate-substituted clusters will be present. The thermal reactivity of the clusters has been investigated, with the face-capped cluster HOs3(CO)9[μ-NPriC(H)NPri] found as the sole observable product. The relationship between these three clusters has been established by kinetic studies, the results of which will be discussed.
Combinatorial libraries are used in the search for ligands that bind to target proteins. Fmoc solid-phase peptide synthesis is routinely used to generate such libraries. Microwave-assisted peptide synthesis was employed here to decrease reaction times by 80-90%. Two One-Bead-One-Compound combinatorial libraries were synthesized on 130μm beads (one containing 750 members and the other 16, 807). The use of smaller solid supports would have many important practical advantages including; increased library diversity per unit mass, smaller quantities of library needed to generate hits, and screening could be conducted by using a standard flow cytometer. To this end, a miniaturized peptide library was synthesized on 20 μm beads to demonstrate proof of principle. A small sample from the 16,807-member library was screened against transferrin-AlexaFluro 647, a protein responsible for iron transport in vivo. A number of hits were identified and sequenced using techniques coupling nanomanipulation with nanoelectrospray mass spectrometry.
Nonlinear organic liquids that exhibit two-photon absorption (TPA) function as good optical limiters for sensor protection from laser pulses. L34 (4-butyl-4'-propyl-diphenylethyne) is a liquid organic compound exhibiting nonlinear optical absorption. A thiol- derivatized analog of L34 (“thiol-L34”) was prepared to bind the molecules to the surface of gold nanoparticles. Surface binding is necessary to investigate synergy between nonlinear optical absorption of gold nanoparticles and thiol-L34. Thiol-L34 was prepared in a six-step organic synthesis starting from 3-(4-bromophenyl) propionic acid. Au nanoparticles with <15 nm diameter have been prepared and sensitized with the thiol-L34 compound for assessment of their nonlinear optical behavior. Diazolylmethenes a class of metal-coordinating dyes that are similar to dipyrrins with some substitutions of nitrogen atoms in place of carbon atoms. Modification in the framework of dipyrrinoid dyes via this replacement of nitrogen for carbon atoms may lead to compounds that serve as effective agents for bioimaging and/or photodynamic therapy. Several routes to the synthesis of di-(1,2,3)-triazolylmethenes, di-(1,2,4)-triazolylmethenes, and ditetrazolylmethenes are presented.
A combined experimental and computational study on the reversible ortho-metalation exhibited by the triosmium cluster Os3(CO)10(dppm) (dppm = 1,1-bis(diphenylphosphino)methane is reported. The conversion of nonacarbonyl cluster HOs3(CO)9[-PhP(C6H4)CH2PPh2] to Os3(CO)10(dppm) is independent of added CO and exhibits a significant inverse equilibrium isotope effect (EIE). Reductive coupling of the C-H bond in HOs3(CO)9[-PhP(C6H4)CH2PPh2] leads to the formation of agostic C-H and two distinct aryl-π species prior to the rate-limiting formation of the unsaturated cluster Os3(CO)9(dppm). Heating the unsaturated dimer H2Re2(CO)8 with Cp*Rh(CO)2 (Cp* = 1,2,3,4,5-pentamethylcyclopentadiene) at elevated temperature affords the new trimetallic clusters H2RhRe2Cp*(CO)9 and HRh2ReCp*2(CO)6, and the spiked-triangular cluster HRhRe3Cp*(CO)14. H2Re2(CO)8 reacts with Cp*2Rh2(CO)2 under identical conditions to furnish H2RhRe2Cp*(CO)9 and HRh2ReCp*2(CO)6 as the principal products, in addition to the tetrahedral cluster H2Rh2Re2Cp*2(CO)8. H2RhRe2Cp*(CO)9 undergoes facile fragmentation in the presence of halogenated solvents and the thiols RSH (where R = H, C6H4Me-p) to afford the structurally characterized products Cp*Rh(-Cl)3Re(CO)3, S2Rh3Cp*(CO)4, Cp*Rh(-Cl)(-SC6H4Me-p)2Re(CO)3, and Cp*Rh(-SC6H4Me-p)3Re(CO)3. The new hydrazido-substituted compounds TaCl(NMe2)3[N(TMS)NMe2] (TMS = tetramethylsilyl) and Ta(NMe2)4[N(TMS)NMe2] have been synthesized and their structures established by X-ray crystallography. The latter product represents the first structurally characterized octahedral tantalum(V) complex containing a single hydrazido(I) ligand in an all-nitrogen coordinated environment about the metal center. The fluxional properties of the amido and hydrazido ligands in these new compounds have been established by VT 1H NMR spectroscopy (VT = variable temperature). Preliminary data using Ta(NMe2)4[N(TMS)NMe2] as an ALD (ALD = atomic layer deposition) precursor for the preparation of tantalum nitride and tantalum oxide thin films are presented.