A novel target-promoted DNA alkylation system was designed, which consists of a DNA intercalating/alkylating quinone methide (QM) precursor, a removable amine linker, and a sequence-specific delivery. The QM in this system was regenerated by eliminating the amino linker promoted by the hydrophobic interaction between the target DNA and the intercalating QM precursor. Three alkylation model systems (methoxyl polycyclic system, intramolecular hydrogen bonding system and biaryl system) were proposed and synthesized. The potential DNA QM alkylation was investigated by deoxyadenosine (dA) and deoxyguanosine (dG) alkylation with the biaryl system. Only one deoxynucleoside adduct was observed when dA or dG reacted with quinoline or naphthalene QM precursor, in which both dA adducts degraded with time, while dG adducts remained unchanged after 72h at room temperature. The quinoline dG adduct was fully characterized as quinoline dG N1 adduct by NMR techniques. Naphthalene dG was found as a 1:1 mixture of diastereomers.

Thesis advisor: Amir H. Hoveyda / Chapter 1. Through the use of quantum theory of atoms in molecules (QTAIM) the similarities and differences between transition metal complexes ligated by phosphines and N-heterocyclic carbenes (NHC) were elucidated. Among the key findings, the phosphines were identified as stronger charge donors than NHCs; however, the latter class of ligands exhibits a weaker p-accepting character than the former. Furthermore, Tolman electronic parameter (TEP) was determined to be an inadequate gauge for the total electron donating ability of phosphines and NHCs; rather TEP can serve as a measurement of population of dp set of orbitals of a metal center in question. Computational and experimental studies of the mechanism of NHC-catalyzed boron and silicon addition to a,ß-unsaturated carbonyls reactions were carried out. Through the use of radical traps the mechanisms involving homolytic cleavage of B-B or B-Si bonds were ruled out. Computational (DFT) studies of the mechanism identified two pathways: (1) direct activation of diboron or borosilyl reagents through coordination of NHC to the B atom, (2) net oxidative addition of the diboron or borosilyl reagents to the carbon (II) of the NHC. The insights gained from the aforementioned studies were employed to rationalize the observed lack of reactivity of NHC-activated diboron complexes in the presence of aldehydes. Chapter 2. New C(1)-symmetric chiral monodentate N-heterocyclic carbenes were prepared, and corresponding chiral Ru-carbene complexes were synthesized. These complexes were employed to gain empirical understanding of factors that govern stereoselectivity in Ru-catalyzed enantioselective olefin ring-closing metathesis. The data thus obtained was employed to infer that syn-to-NHC reaction pathways are competitive and non-selective. One plausible mechanism, through which syn-to-NHC pathways can be accessed, involves Berry pseudorotations. Through the use of stereogenic-at-Ru complexes diastereomeric Ru-carbenes were isolated (silica gel chromatography) and spectroscopically characterized in solution phase. The diastereomeric Ru-carbenes were found to undergo non-metathesis stereomutations at Ru center, thereby providing additional support for the above hypothesis regarding accessibility of syn-to-NHC olefin metathesis pathways. Non-metathesis stereomutation at Ru was found to be accelerated in the presence of protic additives, suggesting the plausibility of hydrogen bonding between the acidic proton and the X-type ligands on Ru. Occurrence of hydrogen bonding was corroborated through the use of chiral allylic alcohols in Ru-catalyzed diastereoselective ring-opening/cross metathesis, which was developed into a versatile method for highly diastereoselective functionalization of terminal olefins. / Thesis (PhD) — Boston College, 2011. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

Nesse trabalho, foram obtidos bis-azofenóis (HO-(Azo-R)2) pela reação de sais de diazônio estáveis e fenol. As condições dessas reações foram analisadas, sendo que, pela primeira vez, a influência da temperatura foi investigada. Temperaturas mais altas aumentam o rendimento dos bis-azofenóis, o que reforça o modelo Droplet, e indicam um aumento na velocidade de reação da segunda reação de acoplamento. As propriedades espectroscópicas e fotoquímicas de HO-(Azo-Me)2 são essencialmente governadas pelo estabelecimento de uma ligação de hidrogênio intramolecular assistida por ressonância. Os rendimentos quânticos de fotoisomerização E-Z são baixos em decorrência, provavelmente, da formação de tautômeros no estado excitado, que desativam a isomerização. Foi obtida uma díade (Azo1-X-Azo2) contendo um azobenzeno da classe espectroscópica \"azobenzeno\" (Azo 1) e outro da classe \"aminoazobenzeno\'\' (Azo 2) conectados através de um espaçador (X). Não existe interação apreciável entre Azo 1 e Azo 2, sendo a separação entre os máximos de absorção dessas subunidades de mais de 60 nm. Observou-se que não foi possível fotoisomerizar (E-Z) seletivamente Azo 1, seja na região de seu isosbéstico, seja na região de seu máximo de absorção, sendo sempre observada a isomerização concomitante de Azo 2. O rendimento quântico de Azo 1 (0,22) é idêntico ao obtido para o modelo M-Azo 1, indicando que sua incorporação na díade não altera essa propriedade fotoquímica. A unidade Azo 2 pode ser fotoisomerizada (E-Z) seletivamente na região de seu máximo de absorção, não sendo observada isomerização significativa de Azo 1. É obtido um rendimento quântico (0,34) também idêntico ao do modelo M-Azo 2. Entretanto, na díade existe uma dependência do rendimento quântico de Azo 2 em função da região de excitação, sendo observado um rendimento quântico (0,54) quando excitado na região de 370 nm, que difere consideravelmente do rendimento quântico de M-Azo 2, que é independente do comprimento de onda (0,33). Um comportamento interessante foi observado ao se irradiar a díade na região de 370 nm, que corresponde ao ponto isosbéstico de Azo 2 e uma região de alta absorção da banda pi-pi* de Azo 1. Apesar da menor fração de luz absorvida por Azo 2 (44%), não se observa isomerização de Azo 1 até ser obtido o estado fotoestacionário (PSS) de Azo 2, indicando que existe um período de indução para que seja obtida a isomerização de Azo 1. Esse comportamento corresponde a um sistema do tipo neural, em que existe um estímulo durante um período de indução até que seja atingido um limiar para que ocorra uma determinada função. Considerando também os processos de isomerização Z-E, é possível realizar várias combinações a partir de estímulos luminosos diferentes e estados iniciais diferentes, que podem ser correlacionados com a lógica binária (byte [x,y]; x e y = 0 ou 1). Devido à combinação conveniente de grupos azo, essa díade é a primeira em que é possível uma caracterização fotoquímica dos processos fotoquímicos E-Z e Z-E e que se obtém uma seletividade, ao menos parcial, no controle desses processos. / In the studies herein proposed, bis-azophenols (HO-(Azo-R)2) were synthesized by the coupling reaction of stable diazonium salts and phenol. The reaction conditions were assessed and, for the first time, the influence of temperature was investigated in this type of reaction. Higher temperatures lead to increased yields of bis-azophenol, reinforcing the Droplet Model, and indicate an increase in the reaction rate for the second coupling step. Spectroscopic and photochemical properties of HO-(Azo-Me)2 are essentially directed by the establishment of a Resonance-Assisted Hydrogen Bond. The E-Z photoisomerization quantum yield is low, probably due to the formation of tautomers in the excited state that deactivate the isomerization process. A dyad (Azo1-X-Azo2) containing an azobenzene of the \"azobenzene\" spectroscopic group (Azo 1) and another azobenzene of the \"aminoazobenzene\" spectroscopic group (Azo 2), connected through a spacer (X), has been obtained. There is no appreciable interaction between Azo 1 and Azo 2 and the separation of the corresponding absorption maxima of these subunits is 60 nm. It was observed that selectively photoisomerization (E-Z) of Azo 1, either in the region of its isosbestic or in the region of its absorption maximum, was not feasible, being always observed the concomitant isomerization of Azo 2. The quantum yield of Azo 1 (0.22) is identical to that obtained for M-Azo 2, indicating that its incorporation into the dyad does not modify this photochemical property. The Azo 2 unit can be selectively photoisomerized (E-Z) in the region of its absorption maximum, without Azo 1 isomerization. A quantum yield of 0.34 was obtained, also the same to M-Azo 2 model. However, the dyad presents a dependence on the quantum yield of Azo 2 as a function of the excitation region , and a quantum yield of (0.54) was observed when excited in the region of 370 nm, which differs considerably from the quantum yield of M-Azo 2 since it is independent of the wavelength of excitation. An interesting behavior was observed by irradiating the dyad in the region of 370 nm, which corresponds to the isosbestic point of Azo 2 and a region of high absorption of the pi-pi* band of Azo 1. Despite the smaller fraction of light absorbed by Azo 2 (44%), isomerization of Azo 1 isn\'t observed until the photostationary state of Azo 2 is achieved, indicating that there is an induction period to obtain Azo 1 isomerization. This behavior corresponds to a neural type system, in which there is a stimulus during an induction period until a threshold is reached for a given function to occur. Considering also the Z-E isomerization processes, it is possible to perform several combinations from different light stimuli and different initial states that can be correlated with binary logic (byte [x, y] x and y = 0 or 1). Due to the convenient combination of azo groups, this dyad is the first in which a photochemical characterization of the photochemical processes E-Z and Z-E is obtained, and a partial selectivity is achieved in the control of these processes.

Over the past few decades, amorphous solid dispersions (ASDs) have been of great interest to pharmaceutical scientists to address bioavailability issues associated with poorly water-soluble drugs. ASDs consist of an active pharmaceutical ingredient (API) that is typically dispersed in an inert polymeric matrix. Despite promising advantages, a major concern that has resulted in limited marketed formulations is the physical instability of these complex formulations. Physical instability is often manifested as phase heterogeneity, where the drug and carrier migrate and generate distinct phases, which can be a prelude to recrystallization. One important factor that dictates the physical stability of ASDs is the spatial distribution of API in the polymeric matrix. It is generally agreed that intimate mixing of the drug and polymer is necessary to achieve maximum stabilization, and thus understanding the factors controlling phase mixing and nano-domain structure of ASDs is crucial to rational formulation design. The focus of this thesis work is to better understand the factors involved in phase mixing on the nanometric level and get insights on the role of excipients on overall stabilization of these systems. The central hypothesis of this research is that an intimately mixed ASD will have better physical stability as compared to a partially homogeneous or a non-homogeneous system. Our approach is to probe and correlate phase homogeneity and intermolecular drug-excipient interactions to better understand the physical stability of ASDs primarily using solid-state nuclear magnetic resonance (SSNMR) spectroscopy and other solid-state characterization tools. A detailed investigation was carried out to understand the role of hydrogen bonding on compositional homogeneity on different model systems. A comprehensive characterization of ternary ASDs in terms of molecular interactions and physical stability was studied. Finally, long-term physical stability studies were conducted in order to understand the impact of different grades of a cellulosic polymer on phase homogeneity for two sets of samples prepared via different methods. Overall, through this research an attempt has been made to address some relevant questions pertaining to nano-phase heterogeneity in ASDs and provide a molecular level understanding of these complex systems to enable rational formulation design.

This thesis is concerned with a range of chemical problems which are amenable to theoretical investigation via the application of current methods of computational quantum chemistry. These problems include the calculation of accurate thermochemical data, the prediction of reaction kinetics, the study of molecular potential energy surfaces, and the investigation of molecular structures and binding. The heats of formation (from both atomisation energies and isodesmic schemes) of a set of approximately 120 C1 and C2 fluorocarbons and oxidised fluorocarbons (along with C3F6 and CF3CHFCF2) were calculated with the Gaussian-3 (G3) method (along with several approximations thereto). These molecules are of importance in the flame chemistry of 2-H-heptafluoropropane, which has been proposed as a potential fire retardant with which to replace chloro- and bromofluorocarbons (CFC�s and BFC�s). The calculation of the data reported here was carried out in parallel with the modelling studies of Hynes et al.1-3 of shock tube experiments on CF3CHFCF3 and on C3F6 with either hydrogen or oxygen atoms. G3 calculations were also employed in conjunction with the experimental work of Owens et al.4 to describe the pyrolysis of CFClBr2 (giving CFCl) at a radiation wavelength of 265 nm. The theoretical prediction of the dissociation energy of the two C-Br bonds was found to be consistent with the energy at which carbene production was first observed, thus supporting the hypothesis that the pyrolysis releases two bromine radicals (rather than a Br2 molecule). On the basis of this interpretation of the experiments, the heat of formation of CFClBr2 is predicted to be 184 � 5 kJ mol-1, in good agreement with the G3 value of 188 � 5 kJ mol-1. Accurate thermochemical data was computed for 18 small phosphorus containing molecules (P2, P4, PH, PH2, PH3, P2H2, P2H4, PO, PO2, PO3, P2O, P2O2, HPO, HPOH, H2POH, H3PO, HOPO and HOPO2), most of which are important in the reaction model introduced by Twarowski5 for the combustion of H2 and O2 in the presence of phosphine. Twarowski reported that the H + OH recombination reaction is catalysed by the combustion products of PH3 and proposed two catalytic cycles, involving PO2, HOPO and HOPO2, to explain this observation. Using our thermochemical data we computed the rate coefficients of the most important reactions in these cycles (using transition state and RRKM theories) and confirmed that at 2000K both cycles have comparable rates and are significantly faster than the uncatalysed H + OH recombination. The heats of formation used in this work on phosphorus compounds were calculated using the G2, G3, G3X and G3X2 methods along with the far more extensive CCSD(T)/CBS type scheme. The latter is based on the evaluation of coupled cluster energies using the correlation consistent triple-, quadruple- and pentuple-zeta basis sets and extrapolation to the complete basis set (CBS) limit along with core-valence correlation corrections (with counterpoise corrections for phosphorus atoms), scalar relativistic corrections and spin-orbit coupling effects. The CCSD(T)/CBS results are consistent with the available experimental data and therefore constitute a convenient set of benchmark values with which to compare the more approximate Gaussian-n results. The G2 and G3 methods were found to be of comparable accuracy, however both schemes consistently underestimated the benchmark atomisation energies. The performance of G3X is significantly better, having a mean absolute deviation (MAD) from the CBS results of 1.8 kcal mol-1, although the predicted atomisation energies are still consistently too low. G3X2 (including counterpoise corrections to the core-valence correlation energy for phosphorus) was found to give a slight improvement over G3X, resulting in a MAD of 1.5 kcal mol-1. Several molecules were also identified for which the approximations underlying the Gaussian-n methodologies appear to be unreliable; these include molecules with multiple or strained P-P bonds. The potential energy surface of the NNH + O system was investigated using density functional theory (B3LYP/6-31G(2df,p)) with the aim of determining the importance of this route in the production of NO in combustion reactions. In addition to the standard reaction channels, namely decomposition into NO + NH, N2 + OH and H + N2O via the ONNH intermediate, several new reaction pathways were also investigated. These include the direct abstraction of H by O and three product channels via the intermediate ONHN, giving N2 + OH, H + N2O and HNO + N. For each of the species corresponding to stationary points on the B3LYP surface, valence correlated CCSD(T) calculations were performed with the aug-cc-pVxZ (x = Q, 5) basis sets and the results extrapolated to the complete basis set limit. Core-valence correlation corrections, scalar relativistic corrections and spin orbit effects were also included in the resulting energetics and the subsequent calculation of thermochemical data. Heats of formation were also calculated using the G3X method. Variational transition state theory was used to determine the critical points for the barrierless reactions and the resulting B3LYP energetics were scaled to be compatible with the G3X and CCSD(T)/CBS values. As the results of modelling studies are critically dependent on the heat of formation of NNH, more extensive CCSD(T)/CBS calculations were performed for this molecule, predicting the heat of formation to be 60.6 � 0.5 kcal mol-1. Rate coefficients for the overall reaction processes were obtained by the application of multi-well RRKM theory. The thermochemical and kinetic results thus obtained were subsequently used in conjunction with the GRIMech 3.0 reaction data set in modelling studies of combustion systems, including methane / air and CO / H2 / air mixtures in completely stirred reactors. This study revealed that, contrary to common belief, the NNH + O channel is a relatively minor route for the production of NO. The structure of the inhibitor Nd-(N'-Sulfodiaminophosphinyl)-L-ornithine, PSOrn, and the nature of its binding to the OTCase enzyme was investigated using density functional (B3LYP) theory. The B3LYP/6-31G(d) calculations on the model compound, PSO, revealed that, while this molecule could be expected to exist in an amino form in the gas phase, on complexation in the active site of the enzyme it would be expected to lose two protons to form a dinegative imino tautomer. This species is shown to bind strongly to two H3CNHC(NH2)2+ moieties (model compounds for arginine residues), indicating that the strong binding observed between inhibitor and enzyme is partially due to electrostatic interactions as well as extensive hydrogen bonding (both model Arg+ residues form hydrogen bonds to two different sites on PSO). Population analysis and hydrogen bonding studies have revealed that the intramolecular bonding in this species consists of either single or semipolar bonds (that is, S and P are not hypervalent) and that terminal oxygens (which, being involved in semipolar bonds, carry negative charges) can be expected to form up to 4 hydrogen bonds with residues in the active site. In the course of this work several new G3 type methods were proposed, including G3MP4(SDQ) and G3[MP2(Full)], which are less expensive approximations to G3, and G3X2, which is an extension of G3X designed to incorporate additional electron correlation. As noted earlier, G3X2 shows a small improvement on G3X; G3MP4(SDQ) and G3[MP2(Full)], in turn, show good agreement with G3 results, with MAD�s of ~ 0.4 and ~ 0.5 kcal mol-1 respectively. 1. R. G. Hynes, J. C. Mackie and A. R. Masri, J. Phys. Chem. A, 1999, 103, 5967. 2. R. G. Hynes, J. C. Mackie and A. R. Masri, J. Phys. Chem. A, 1999, 103, 54. 3. R. G. Hynes, J. C. Mackie and A. R. Masri, Proc. Combust. Inst., 2000, 28, 1557. 4. N. L. Owens, Honours Thesis, School of Chemistry, University of Sydney, 2001. 5. A. Twarowski, Combustion and Flame, 1995, 102, 41.

The structure, bonding and chemistry of water and hydroxyl on metal surfaces are presented. Synchrotron based x-ray photoelectron- and x-ray absorption spectroscopy along with density functional theory calculations mainly form the basis of the results. Conditions span the temperature range 35 - 520 K and pressures from ultra-high vacuum (~10 fAtm) to near ambient pressures (~1 mAtm). The results provide, e.g, new insights on the importance of hydrogen bonding for surface chemical kinetics. Water adsorbs intact on the Pt(111), Ru(001) and Cu(110) surfaces at low temperatures forming 2-dimensional wetting layers where bonding to the metal (M) mainly occurs via H2O-M and M-HOH bonds. Observed isotope differences in structure and kinetics for H2O and D2O adsorption on Ru(001) are due to qualitatively different surface chemistries. D2O desorbs intact but H2O dissociates in kinetic competition with desorption similar to the D2O/Cu(110) system. The intact water layers are very sensitive to x-ray and electron induced damage. The mixed H2O:OH phase on Ru(001) consists of stripe-like structures 4 to 6 Ru lattice parameters wide where OH decorates the edges of the stripes. On Pt(111), two different long-range ordered mixed H2O:OH structures are found to be inter-related by geometric distortions originating from the asymmetric H-bond donor-acceptor properties of OH towards H2O. Water adsorption on Cu(110) was studied at near ambient conditions and compared to Cu(111). Whereas Cu(111) remains clean, Cu(110) holds significant amounts of water in a mixed H2O:OH layer. The difference is explained by the differing activation barriers for water dissociation, leading to the presence of OH groups on Cu(110) which lowers the desorption kinetics of water by orders of magnitude due to the formation of strong H2O-OH bonds. By lowering the activation barrier for water dissociation on Cu(111) by pre-adsorbing atomic O, generating adsorbed OH, similar results to those on Cu(110) are obtained.

A refinement of a minimal model for protein folding originally proposed by Imamura is presented. The representation of the alpha-helix has been improved by adding in explicit modelling of the entire peptide unit. A four-helix bundle consisting of four alpha-helices and three loop regions is generated with the parallel tempering Monte Carlo scheme. Six native states are found for the given sequence, four U-bundle and two Z-bundle states. All six states have energies of E approx -218ε and all appear equally likely to occur in simulation. The highest probability of folding a native state is found to be at a hydrophobic strength of Ch = 0.8 which agrees with the value of Ch = 0.7 used by Imamura in his studies of alpha to beta structural conversions. Two folding stages are observed in the temperature spectrum dependent on the magnitude of the hydrophobic strength parameter. The two stages observed as temperature decreases are 1) the hydrophobic energy causes the random coil to collapse into a compact globule 2) the secondary structure starts forming below a temperature of about T = 0.52ε/kB. The temperature of the first stage, which corresponds to the characteristic collapse temperature Tθ, is highly dependent on the hydrophobic strength. The temperature of the second stage is constant with respect to hydrophobic strength. Attempts to measure the characteristic folding temperature, Tf , from the structural overlap function proved to be difficult due mostly to the presence of six minima and the complications that arose in the parallel tempering Monte Carlo scheme. However, a rough estimate of Tf is obtained at each hydrophobic strength from a native state density analysis. Tf is found to be significantly lower than Tθ.

A refinement of a minimal model for protein folding originally proposed by Imamura is presented. The representation of the alpha-helix has been improved by adding in explicit modelling of the entire peptide unit. A four-helix bundle consisting of four alpha-helices and three loop regions is generated with the parallel tempering Monte Carlo scheme. Six native states are found for the given sequence, four U-bundle and two Z-bundle states. All six states have energies of E approx -218ε and all appear equally likely to occur in simulation. The highest probability of folding a native state is found to be at a hydrophobic strength of Ch = 0.8 which agrees with the value of Ch = 0.7 used by Imamura in his studies of alpha to beta structural conversions. Two folding stages are observed in the temperature spectrum dependent on the magnitude of the hydrophobic strength parameter. The two stages observed as temperature decreases are 1) the hydrophobic energy causes the random coil to collapse into a compact globule 2) the secondary structure starts forming below a temperature of about T = 0.52ε/kB. The temperature of the first stage, which corresponds to the characteristic collapse temperature Tθ, is highly dependent on the hydrophobic strength. The temperature of the second stage is constant with respect to hydrophobic strength. Attempts to measure the characteristic folding temperature, Tf , from the structural overlap function proved to be difficult due mostly to the presence of six minima and the complications that arose in the parallel tempering Monte Carlo scheme. However, a rough estimate of Tf is obtained at each hydrophobic strength from a native state density analysis. Tf is found to be significantly lower than Tθ.

A fundamental characterization of hexafluoroalcohol substituted polynorbornene (HFAPNB) was completed to improve the final photoresist formulation using these materials. In this work, it was found that the dissolution behavior of these materials was controlled by the ability of polymer chains to form hydrogen bonds. This ability to form interchain hydrogen bonds was affected by stereochemical changes in the polynorbornene backbone as molecular weights increase. These observed changes in backbone polynorbornene stereochemistry were accurately modeled using the "helix-kink" theory, first described by Ahmed and Ludovice. It was found that several material properties altered the interchain hydrogen bonding within these materials, such as the polydispersity, polymerization catalyst, and the polymer film thickness. However, none of these material properties altered the unusual dissolution behavior observed in these materials. To improve the potential formulation of these materials, the interactions between HFAPNB and resist additives were studied. For all tested photoacid generators, it was found that some interchain hydrogen bonding occurred between resist additive molecules and HFA side groups, which retarded the dissolution rate in the formulated material. In particular, one can create a simple resist using unprotected HFAPNB polymer with an iodonium photoacid generator. Finally, a series of norbornene oligomers were evaluated as potential dissolution inhibitors for HFAPNB. It was found that the dissolution rate of HFAPNB can be completely inhibited with dissolution inhibitors at a loading of 15%.

This thesis describes original research aimed at the development of highly efficient polymer functionalization strategies by introducing orthogonal chemistry within polymeric systems. The primary hypothesis of this thesis is that the use of click chemistries or noncovalent interactions can provide new and easy pathways towards the synthesis of highly functionalized polymers thereby addressing the shortcomings of traditional covalent functionalization approaches. To verify the hypothesis, the work presented in the following chapters of this thesis further explores previous methods of either covalent or noncovalent polymer functionalization described in Chapter 1. Chapters 2 and 3 present advanced methods of covalent polymer functionalization based on high-yielding and orthogonal click reactions: 1,3-dipolar cycloaddition, hydrazone formation, and maleimide-thiol coupling. All three click reactions employed can be orthogonal to one another and conversions can be quantitative, leading to the easy and rapid synthesis of highly functionalized polymers without interference among functional handles along the polymer backbones. The next two chapters focus on the noncovalent functionalization strategies for creating supramolecular block copolymers via the main-chain self-assembly of telechelic polymers. Novel synthetic methods to prepare telechelic polymers bearing terminal recognition motifs were developed through a combination of ROMP using functionalized ruthenium initiators and functionalized chain-terminators, and the resulting polymers were self-assembled to form supramolecular block copolymers. Chapter 4 demonstrates the formation of supramolecular multiblock copolymers via self-assembly of symmetrical telechelic polymers using metal coordination, while Chapter 5 demonstrates that supramolecular ABC triblock copolymers can be prepared by the self-assembly of a heterotelechelic polymer as the central block with two other complementary monotelechelic polymers using two orthogonal hydrogen bonding interactions. Chapter 6 presents a unique application of noncovalent functionalization approaches. The ultimate goal of this research is to develop a controlled polymerization method based on noncovalent templation. The initial attempts at the metal coordination-based template polymerization are presented in this chapter. Finally, Chapter 7 summarizes the findings in each chapter and presents the potential extensions of the orthogonal functionalization strategies developed in this thesis.