NMR and MRI are non-invasive and ionizing-radiation free techniques that have been widely used in various applications such as chemical and pharmaceutical industries, clinical setups, and various biotechnological and materials-science settings. However, these versatile spectroscopic and imaging techniques suffer from notoriously low detection sensitivity. The sensitivity of NMR or MRI is limited by the low spin polarization during thermal equilibrium as determined by the Boltzmann distribution. For example, even at high magnetic field such as 9.4 T (~400 MHz proton resonance frequency), the polarization value Pt is approximately 10-5, which means only one out of a hundred thousand spins is contributing to the net NMR signal—while the others remain undetected. To overcome this inherent NMR sensitivity, issue a number of techniques have been utilized that basically exploit the selection rules of quantum mechanics and statistical mechanics to obtain the highly non thermal or strongly polarized nuclear spin state. This process of driving spin populations into specific nuclear (spin) quantum states is termed “Hyperpolarization”, and it can be used to enhance the NMR detection sensitivity by several orders of magnitude. Parahydrogen (p-H2) Induced Polarization (PHIP) is such a NMR hyperpolarization technique that has been developed over the last few decades that has gained particular excitement inrecent years. PHIP utilizes pure nuclear spin order from p-H2 gas to generate non-Boltzmann distributions (i.e., hyperpolarization) on a growing range of substrates and eventually improves the NMR SNR (signal-to-noise ratio) by orders of magnitude. SABRE (Signal Amplification by Reversible Exchange) is a cheap and scalable extension of the PHIP technique that transfers the p-H2 spin order to the target substrates upon reversible binding to the catalyst center, with properly matched applied fields. SABRE enhances the signal of the substrates during the lifetime of the transient complex without changing them chemically. Even though SABRE has proved to be versatile and easily adaptable NMR signal enhancement technique, key challenges remain that stand in the way of widespread efficacy of SABRE and its applications, includes limited ranges of substrates, the use of organic solvents, and most importantly—the need for rapid and effective separation of the catalyst from the hyperpolarized (HP) substrate-solvent mixture, allowing the preparation of “pure” (free-from-catalyst) HP agents and ultimate recycling/reuse of the catalyst. To address these issues and to better understand the SABRE hyperpolarization process for various molecules of interest (i.e., metronidazole, pyruvate, etc.) our primary objective is to develop a new approach that will dramatically enhance the NMR sensitivity alongside increasing the effective separation of catalyst from the solvent-substrate mixture. More specifically, one effort described in this dissertation focuses on establishing and optimizing synthetic routes for novel metal organic framework (MOF)-based heterogeneous SABRE catalysts that will enable us to prepare pure HP target substrates. For example, zirconium-based NU1000 with eight connected Zr6(μ3-O)4(μ3- OH)4(H2O)4(OH)4 nodes at each vertex and tetratopic 1,3,6, 8-(p-benzoate)pyrene linkers are strongly bound, which provides the MOF with strong thermal stability and high porosity for the faster diffusion of the soluble species within the pores. As part of this effort, we synthesized NU1000 solid support-based IrIMes heterogeneous catalyst and over the course of our initial SABRE studies made a strange discovery—that exposure of parahydrogen to the MOF-SABRE catalyst led to the creation of anomalous signatures of hyperpolarized orthohydrogen in solution. These very strong, antiphase orthohydrogen signals indicated the population of an unexpected quantum state; taken together, they embody a seemingly paradoxical observation since the antiphase signals “should” cancel each other out by symmetry (and thus should have given no signal at all). We characterized these unexpected phenomena to help provide at least a partial explanation of their origin and discuss the possible ramifications of these effects. In the next project, the chemical equilibria of the SABRE reaction products and potential intermediates based on the IrIMes-pyridine and IrIMes-DMSO-pyruvate systems are computationally analyzed using DFT (Density Functional Theory). Through computational methods, a minimum energy pathway, reaction barrier, chemical potential, and equilibrium constants were computed to elucidate the potential SABRE reaction network with the traditional hexacoordinated Ir-SABRE complex utilizing pyridine and pyruvate as substrates. These efforts can help provide explanations of SABRE phenomena and help lay the groundwork for future studies of SABRE, particularly in less-well-understood interactions between the Ir-IMes SABRE catalyst and substrates with carbonyl/carboxyl groups. Additionally, this dissertation explores the validation and optimization of two key SABRE-hyperpolarized agents: hyperpolarized [15N3]-metronidazole and [1-13C] pyruvate. Here, the effort is to develop cell-free assays (using, e.g., enzymes like in the presence of CYPYA (a variant of cytochrome P450 enzyme) nitro-reductase and LDH (Lactate dehydrogenase) that can metabolize the substrates of interest), ultimately aiming to develop protocols for evaluating HP agents prior to use in envisioned in-vivo applications, including hypoxia sensing and quantification of aberrant metabolism associated with inflammation, neurodegeneration, and cancer. Next, this dissertation discusses SABRE hyperpolarization studies of another class of agents that are currently being considered for an entirely different application: fundamental physics experiments for testing universal symmetries. Here, our long-term intellectual pursuit is to investigate the possible existence of time-reversal violation in strongly-interacting particle systems. Such an experiment would involve the careful quantification of polarized neutron transmission through hyperpolarized nuclear targets that possess low-energy (~eV) neutron resonances with particular features. Given that one isotope identified to possess such a neutron resonance is 117Sn, this work investigates the R&D needed to develop the required polarized 117Sn target and provides some of the preliminary NMR experiments to support the feasibility of this approach, including the first demonstration of SABRE-hyperpolarized 117Sn in 5-tributylstannylpyrimidine. Indeed, suppression of the precipitation of this molecule with the IrIMes catalyst allowed experiments to be performed over extended periods, enabling both 117Sn SABRE hyperpolarization and nuclear spin relaxation to be observed as functions of various experimental parameters.