Chromatographic resolution of diastereomeric pyranosides prepared from enantiomerically pure α-hydroxy esters was shown to be a reliable method of obtaining a variety of potentially useful chiral substrates. Several enantiomerically pure α-hydroxy esters are commercially available and lead to chromatographically separable pyranosides. The methyl esters of lactic and mandelic acid are inexpensive, available in both enantiomeric forms, and were easily incorporated into readily available racemic pyran substrates. The resolutions were performed on a preparative scale using gravity driven silica gel column chromatography. Phenylselenyl substituted tetrahydropyranosides were prepared using the alkoxy-selenation reaction and were subjected to elimination under mild oxidative conditions to afford dihydropyranosides. The resolved chirality of the anomeric center permitted diastereoselective functionalization of the alkene moiety in these compounds. The dihydropyranosides possessing lactate or mandelate ester appendages preferentially underwent epoxidation with peroxy acids and cis-dihydroxylation with catalytic osmium tetroxide on the face of the alkene anti to the appendage. Reduction of the ester with lithium aluminum hydride converted the sterically demanding ester appendage into a polar primary alcohol. This enabled the appendage to participate in the delivery of electrophilic reagents such as peroxy acids and mercuric acetate preferentially to the syn-face of the dihydropyranoside alkene. Utilization of these general principles permitted the asymmetric syntheses of 4-deoxyribose, (R)-mevalonolactone, a protected mevinic acid precursor, and the calicheamicin ethylamino sugar.

A novel glucose oxidase based needle-type glucose microsensor has been developed for subcutaneous glucose monitoring. The new configuration greatly facilitates the deposition of uniform enzyme and polymer films so that sensors with satisfactory in vitro characteristics (upper limit of linear range (>15 mM) and response time (<5 min) can be prepared in high yield (>60%). The sensor is equivalent in size to a 26 gauge needle (0.45 mm o.d.) and can be implanted with ease without any incision. The insertion of the sensor causes minimal trauma to the tissue and to the sensor itself. The multilayer structure of the sensor ensures satisfactory performance in subcutaneous tissue over extended periods of time (up to 20 days). The sensor response is largely independent of oxygen tension in the normal physiological range. It also exhibits the desired sensitivity and selectivity. A two-point in vivo calibration procedure is adapted for in vivo evaluation of the sensors. Both short-term and long-term implantation experiments are described. The methods of cell culture toxicity testing are modified and applied to locate the source of toxicity in a multi-component glucose sensor. It is shown that a non-toxic sensor can be readily obtained by removing the leachable toxic substances through extraction in phosphate buffer. A nonenzymatic glucose sensor that utilizes permselective membranes to achieve the selectivity required for screening glucose in biological fluids has been described. Interference from endogenous oxidizable substances such as amino acids, urea, ascorbic acid, and uric acid, as well as the effect of chloride and proteins on glucose response, is studied by using flow injection analysis. A set of membranes made of Nafion perfluorinated membrane and collagen, when arranged in front of the working electrode (gold), result in significant improvement in the system selectivity and sensitivity.

Some space-constraining amino acid-containing oxytocin analogues were synthesized, of which the biological activities were found to be remarkably consistent with the predictions based on molecular mechanics calculations using the CHARMM program. Correlations of the biological activities and computer modeling studies of the conformational properties of Tyr², Phe², eBmp² (agonists), Pen¹, and Tic² (antagonists) oxytocin analogs revealed that a g+ conformation for the aromatic ring in the 2-position is important for the oxytocin-uterus receptor transduction. Examination of the topographical features of the energy minimized conformations of these analogs shows that a parallel aromatic surface over the top of the 20-membered disulfide containing ring of the molecule is equally important for the transduction. Though the Tic compound may exclusively exist as the g+ conformation for the aromatic ring in the 2-position, possible backbone changes and particularly the perpendicularly located aromatic ring on the top of the 20-membered ring may be the reason for its antagonism. Calculations shows that (erythro(2S, 3S)-β-methyltyrosine²) OXT has all the requirements for being an highly active compound, while the isomer (threo-L-(2S, 3R)-β-methyltyrosine²) OXT, which differs only in the configuration of the β carbon, is unlikely to be an agonist according to our calculations. Both compounds were synthesized together with other analogs by the solid-phase peptide synthesis techniques on p-methyl-benzhydrylamine resin. The biological activities of these two compounds were consistent with the predictions.

The aim of this work was to study the solution conformation of dimeric and polymeric 1actams. In a first part of this work, the synthesis of bicyc1odi1actams as precursors of the polymers was explored. A new preparation for the 2, 5-diazabicyc1o [2,2,2] octa-3, 6-dione was developed. The dimers and polymers were obtained from the N-protected cis- and trans- 3-amino-6-carboxy-2-piperidone for which an improved synthesis was found. Base treatment of the trans activated ester led to the polymer. Using the methods of solution phase peptide synthesis, the four possible dimers were prepared. After transformation to the paranitrophenyl esters, they polymerized to oligomeric species under the same treatment. The solution conformation of the monomeric, dimeric and polymeric species was determined by 1- and 2-dimensional NMR techniques. The 1actam rings have a chair-like conformation in solution. The cis- 1actam is a powerful β-turn- inducer when incorporated in synthetic peptides. The cis- lactam was found, however, to have a very similar conformation in DMSO solution, without hydrogen bonding to stabilize the turn. No evidence was found for the β-turn in the dimers and polymers using 2-dimensional NMR techniques. The dimers were found to exist in an extended conformation in DMSO. The fact that every other amide bond is in the cis configuration, as well as the steric crowding due to the rings may not allow the existence of the β-turn.

The trivalent metallophthalocyanines, GaPc-Cl and InPc-Cl, have been investigated with respect to: (1) their possible application as gas-phase chemical sensor coatings for the detection of O₂, NH₃ and NO₂; and (2) the development of a new class of molecular electronic materials based upon the epitaxial growth of these large organic molecules. UHV analyses of InPc-Cl coated interdigitated array transducers have indicated that impurity phthalocyanines (such as FePc, MnPc and CuPc) have a dramatic impact upon the electrical nature and responsivity of these devices toward various gas analytes. Each of the different gas analytes examined, O₂, NH₃ and NO₂, were found to possess at least two different types of chemisorption sites on the surface of these organic films. Chemical sensor devices prepared and characterized under vacuum (including quartz crystal microbalance, surface acoustic wave and interdigitated array transducer devices), were also examined within an atmospheric sensing chamber in order to assess their ultimate feasibility as chemical sensors. The simultaneous monitoring of both electrical and microgravimetric changes within these devices allowed for complimentary information to be obtained concerning the chemisorption events taking place on the surface of these materials. Photoelectrochemical metal modification of the surface of these phthalocyanines provided a means for further enhancing the response of the chemical sensors toward NH₃, while a modification of the phthalocyanine surface with reducing agents such as polyvinyl ferrocene and MnPc provided an analogous enhancement in sensitivity to NO₂. The epitaxial growth of InPc-Cl has been demonstrated on both bulk SnS₂(0001) and MBE grown SnS₂ on muscovite. The optical absorbance and photoaction spectra obtained from these highly ordered phthalocyanine films have, in some cases, been found to be as narrow as the solution absorption spectra for these materials (FWHM = 40-60 nm). The epitaxial growth of CuPc, perylene tetracarboxylic dianhydride, C₆₀ and coronene were demonstrated on the MoS₂(0001) surface, with specific models developed to explain the nature of these organic overgrowths on the metal dichalcogenide surface. The formation of highly ordered heterojunctions or bilayer films based upon various combinations of these organic semiconductor materials has also been investigated as a precursor to the development of organic superlattice structures.

The electronic structures of disilenes and tungstenocene complexes of disilenes, silenes, and alkenes are studied by gas phase valence photoelectron spectroscopy (PES). PES is reported for three stable disilenes: Mes2Si=SiMes2' (Mes)(ᵗBu)Si=Si(ᵗBu)(Mes), and [(Me₃Si)₂CH]Si=Si[CH(SiMe₃)₂] [Mes = 2,4,6- C₆H₃(CH₃)₃, Me = CH₃]. The PES of tetramesityldisilene is compared to that of tetraphenylethylene. Fenske-Hall calculations are also reported. This comparison shows that the primary difference between the interaction of a C=C bond and a Si=Si bond with aryl substituents is the direction of the "push" of the filled-filled interaction with the π orbitals of the aryl. While for an olefin, interaction with aryl groups stabilizes the C=C π ionization, for a disilene this interaction destabilizes the Si=Si π ionization. This is the direct influence of the difference in energy between the C=C π bond and Si=Si π bond. The PES of the two alkyl substituted disilenes indicates that some type of decomposition is occurring in the gas phase, possibly forming silylene. More study is needed to confirm the gas phase process that is occurring. The PES of the complexes CP₂W(η ²-H₂C=CH2), CP₂W(η²-Me₂Si=CH₂), and CP₂W(η²-Me₂Si=SiMe₂) are also reported (Cp = η⁵-C₅H₅). The overall amount of electron donation by the alkene, silene, and disilene ligands appears to be approximately the same. For the alkene and silene complexes, the highest occupied molecular orbital (HOMO) is the a₁, metal based orbital associated with the d² metal center, and contains little to no contribution from the olefinic ligand. The HOMO of the disilene complex is the same molecular orbital, but contains a significant amount of silicon character due to increased interaction with the disilene π orbital. This additional interaction is due to greater overlap and better energy matching of the ligand P and metal fragment a₁ orbitals. The relationship between these differences in bonding and differences between the reactivity of the disilene complex and the reactivity of the alkene and silene complexes is also discussed.

Dendrimers incorporating a green emitter, quinacridone, for organic light emitting diodes (OLEDs) were synthesized and their photophysical and electrochemical properties were explored. Quinacridone dendrimers were synthesized for site isolation, intramolecular energy transfer, and photocrosslinking.Site-isolation of quinacridone at the core of a dendrimer was achieved by attaching bulky poly(aryl ether) dendrons to the quinacridone at the amino functional groups. Both benzyl- and t-butyl-terminated dendrimers were synthesized up to the third generation. These dendrimers showed enhanced solubility in organic solvents due to reduced aggregation and hydrogen bonding. Increased photoluminescence intensity was observed for the denderimers in the solid state indicating reduced self-quenching due to enhanced site-isolation. Preliminary incorporation of these dendrimers as dopants into OLEDs showed increased emission from the dendrimers as the doping percentage increases.When high-energy host absorbing groups, such as oligo(p-phenylene vinylene)s (oPPVs) were placed at the periphery of poly (aryl ether) dendrimers with quinacridone guest cores, intramolecular energy transfer occurs when the host periphery groups were excited. These dendrimers showed high efficiency energy transfer yields in both solution and the solid state, as well as an antennae effect which resulted in increased emission when the oPPVs were excited versus direct excitation of the quinacridone. For comparison, poly (methyl methacrylate) polymers with pendant oPPV groups were synthesized and combined both in solution and in thin films with the site-isolated dendrimers to investigate the architectural requirements for energy transfer. These mixtures showed no energy transfer in solution from the polymer to the dendrimers. However, in the solid state, energy transfer increaseed with decreasing generation due to the host/guest chromophores decreased separation.Finally, poly (aryl ether) dendrimers containing photocrosslinkable cinnamate groups at the periphery and quinacridone cores were synthesized. Thin films of the higher generation dendrimers were photopolymerized via ultraviolet irradiation. The films were resistant to solvent after the polymerization step indicating a stable crosslinked network. Standard photolithography was performed on the higher generation dendrimers to achieve feature sizes as small as 5 microns as observed by fluorescence and atomic force microscopy.

Molecular level understanding of solid-liquid interfaces in ambient condition is still a challenging, but exciting area. The work presented here demonstrates the effectiveness of emersion IRRAS as a new tool in our arsenal to expand our understanding of solid-liquid interfaces through the investigation of model solvent/organically modified interfaces and electrochemically relevant interfaces using novel emersion spectroscopy. The emersion approach effectively isolates the molecularly-thin emersed liquid layer under ambient conditions by physically removing bulk liquid from the interface. Without the interferences from bulk liquid, the emersed layer is accessible with conventional spectroscopic methods.In this work, development and implementation of emersion IRRAS is first described. Emersion IRRAS was used to investigate the model solvents water and methanol at three w-terminated-SAM-modified Ag surfaces (11-MUA, 11-MUD, and UDT-modified Ag) possessing a range of surface energies. These surfaces had been previously characterized with emersion Raman spectroscopy and/or ellipsometry. Furthermore, solvation of CO on Pt by three solvents (methanol, acetonitrile, and water) was investigated in an effort to attain molecular-level insight into electrochemically-relevant interfaces.Experimental results presented show successful implementation of emersion IRRAS. For each of the systems studied, interfacial solvent spectra clearly differed from those of bulk solvents indicating unique molecular structures of emersed liquids.

The studies presented in this dissertation focus on elucidating key aspects of the interaction of metals and dithiolenes. The interaction is probed in a series of metallocene-dithiolene compounds (CpML where Cp = cyclopentadienyl, M = Mo, V, Ti and L = benezedithiolato and quinoxalinedithiolato) that have relatively simple electronic structures. The straightforward electronic structures were selected for assigning spectral features and correlating changes in electronic structure with changes in geometry, specifically the dithiolene fold angle. The experimental methods used to investigate the electronic structures include gas-phase photoelectron spectroscopy, X-ray absorption spectroscopy (XAS), resonance Raman (rR), and cyclic voltammetry (CV). Results from the experiment were supported by computational modeling with density functional theory.Results from the first part of the dissertation attempt to quantify the orbital interaction energy of the metal and dithiolene by comparing gas-phase X-ray and UV photoelectron (XPS/UPS) ionization energies. However, it was found that the metallocene compounds exhibit significant mixing of cyclopentadienyl orbital character with the frontier metal and dithiolene orbitals, which affects the orbital energies. Though unexpected, the implications for observing mixing between the dithiolene and other ligand orbitals can impact the understanding of Mo enezyme active sites as well as other synthetic systems.The next set of experiments looked at the effects of altering the electronic nature of the dithiolene ligand. The effect on the orbital energies of the molecules was probed by gas-phase UPS and CV. These results show no overall effect on the interaction between the dithiolene and the metal despite definite differences in the ligand electronic structure. Further experiments to probe the metal-ligand covalency using XAS also showed little change in the metal-ligand interaction.Finally, the relationship between geometric and electronic structure was investigated by comparing results from UPS vibrational structure with those from rR data. These data sets suggest that a metal-sulfur core breathing mode maybe active in electron transfer to and from the metal center in these types of compounds. The vibrational mode assigned to a dithiolene folding motion was shown to have a significant dependence on the metal electron count of the complexes as expected from basic molecular orbital theory.

Structure-activity relationships (SAR) of opioid peptide analogues related to endorphin or dynorphin have provided rational and powerful approaches toward the design of peptide therapeutics. A series of glycosylated β-endorphin analogues were designed by modifying the N-terminal “message domain,” the C-terminal “address domain,” and the “linkage domain” between the two, and by altering the intrinsic helix stability of the amphipathic helix that comprises the “address domain.” Further changes were accomplished by altering the charged groups on the side chains of the “address region.” The unglycosylated peptide homologues and variations of the saccharide moieties (monosaccharides vs disaccharides) were also studied. The β- endorphin glycopeptide analogue ¹Tyr- ᵐD-Thr- ³Gly- ⁴Phe- ⁵Leu- ᴸPro- ⁷Asn- ⁸Leu- ʰAib ᶜGlu- ᶜLys- ʰAla- ¹³Leu- ᶜLys-¹⁵Ser[β-O-Glucose]- ¹⁶Leu-NH2, was modified at the indicated positions (m, h, c), and in collaboration with the Bidlack Lab at the Rochester Medical Center, binding affinities Kᵢ were measured using human opioid receptors expressed in CHO cells. All the peptides and glycopeptides were panagonists, showing low nanomolar affinity for the μ, δ and κ-opioid receptors. Helix stability was varied by substituting ʰAib, ʰAla, and ʰGly, which altered membrane affinity, which was correlated with helix stability. Charges on the address side chains were varied by substituting ᶜAsn, ᶜGlu, and ᶜLys. The 15Ser residue bore either a β- Lactoside, a β-D-glucoside or was unglycosylated. These peptides and glycopeptides were studied by circular dichroism (CD) and by 2D-NMR in H₂O buffer (pH = 5.5), in 30% trifluoroethanol in H₂O, and in H₂O containing SDS micelles as a model for biological membranes. In H₂O the glycopeptides and peptides showed only nascent helix behavior and random coil conformations. Chemical Shift Indices (CSI) and nuclear Overhauser effects (NOE) confirmed the helical nature of the “address domains” in the presence of SDS micelles (membrane mimics). Detailed backbone conformations were determined using distance constraints provided by NOE volumes. Based on the CD experiments, most of the β-endorphin analogues showed substantial amounts of helicity in the presence of membrane bilayer models. Several glycopeptides demonstrated penetration of the Blood Brain Barrier (BBB), and produced potent antinociceptive effects in mice after intravenous (i.v.) injection. The amphipathic address domain played a major role in BBB penetration, as reflected by the i.v. activities. The linker also had profound effects on the SAR, and it was possible to produce antinociceptive glycopeptides. In summary, we suggest that this biousian nature is essential for glycopeptides to maintain bioactivities, and the longer, more flexible linkages GABA and DAVA were able to mediate two interactions having lower energy, one interaction between the message segment and opioid receptor’s binding pocket, and another one between the address segment and the cell membrane, to result in higher binding affinities to all three opioid receptors, and significantly increasing analgesia after both i.c.v and i.v. administration. The cyclic linkers restricted D- and L-Pro on the orientation of message segment, relative to the membrane.