Chapter 1: This chapter presented the introduction to the structural design and functionalization of reticular chemistry and pore chemistry of metal-organic frameworks (MOFs). The pores in MOFs can be functionalized by placing chemical entities along the backbone and within the backbone. This chemistry is enabled by the architectural, thermal and chemical robustness of the frameworks and the ability to characterize them by many diffraction and spectroscopic techniques. Pore chemistry, functionalization chemistry and strategies, their applications, and reading and writing functionality sequences in MOFs are discussed.Chapter 2: In this chapter, I described a new post-synthetic functionalization strategy of MOFs: a metal docking strategy utilizing the precise spatial arrangement of organic struts as metal chelating sites in MOF-303 [Al(OH)(C5H2O4N2)]. Pairs of uncoordinated N-atoms on adjacent pyrazole dicarboxylate linkers distributed along the rod-shaped Al–O secondary building units in MOF-303 were used to chelate Cu(I) and Ag(I) with atomic precision and yield the metalated Cu- and Ag-MOF-303 compounds [(CuCl)0.50-Al(OH)(C5H2O4N2) and (AgNO3)0.49-Al(OH)(C5H2O4N2)]. The coordination geometries of Cu(I) and Ag(I) were examined using 3D electron diffraction and extended X-ray absorption fine structure spectroscopy techniques. The resulting metalated MOFs showed pore sizes matching the size of Xe, thus allowing for binding of Xe from Xe/Kr mixtures with high capacity and selectivity. In particular, Ag-MOF-303 exhibited Xe uptake of 59 cm3 cm-3 at 298 K and 0.2 bar with a selectivity of 10.4, placing it among the highest performing MOFs. It also gave up to 100% improvement of the dynamic separation performance in comparison to pristine MOF-303. This metalation strategy represents a new strategy for engineering MOFs to give high-performance gas separations. Chapter 3: MOFs with absolute structures are of particular interest as the asymmetry of their crystal structures enables wide applications from asymmetric catalysis to enantioselective separation. Previous reports on the synthetic strategies toward MOFs with absolute structures always required the use of chiral precursors or chiral templates, however, it is not always easy to obtain enantiopure starting materials. In this chapter, a new non-centrosymmetric MOF, MOF-829, synthesized from aluminium salt and achiral organic linker was described. Further comparisons are made between MOF-829 and a reported Al-based chiral MOF (MOF-520) that is composed of the same metal ion and linker, and similarly synthesized without using chiral compounds. The configurations of the building units, the absolute structures of both MOFs, and their topologies were investigated in detail. I found that (i) topology is one of the determining factors in the formation of non-centrosymmetric MOFs; (ii) the formation of chiral MOFs further requires the directionality of chiral linkers but more importantly chiral secondary building units (SBUs), which can be realized by fine tuning of the synthetic conditions. I envision that both synthetic exploration of chiral SBUs and the design of non-centrosymmetric topologies will open a new direction in the design of MOFs with absolute structures. Chapter 4: Zeolitic imidazolate frameworks (ZIFs) is a subclass of MOFs, built from tetrahedral nodes connected through imidazolate linkers. The structures of ZIFs are characteristic of a variety of large, zeolite-like cages that are covalently connected with neighboring cages and fused in 3-dimensional space. In contrast to molecular cages, the fuse of cages results in extraordinary architectural and chemical stability for the passage of gases and molecules throughout cages and for carrying out chemical reactions within these cages while keeping the cages intact. While the field of ZIFs has seen rapid development over the past decade, with hundreds of ZIF structures built from dozens of different cages of varying composition, size, and shapes reported, rational approaches to their design are largely unknown. This chapter summarized a vast number of cages formed in reported ZIFs, then demenstrated how the thermodynamic factors and traditional guest-templating strategies from zeolites influence the formation of cages. I also highlight how the link-link interactions perform in the ZIF formation mechanism and serve as a means to target the formation of frameworks containing cages of specific sizes with structures exhibiting a level of complexity as yet unachieved in discrete coordination cages. Chapter 5: When applying sorption isotherms to the study of crystalline materials, it is often assumed that the measured bulk sample represents each individual crystal, and thus the performance of the powder as a whole describes the intrinsic properties of a unit cell. However, crystals are not all equivalent, even if they are synthesized from the same materials in the same batch; crystallites exhibit a distribution of sizes, morphologies, surface textures, and defect levels, all contributing in an unknown way to adsorption behavior. This chapter presented a spectroscopic and imaging approach to sorption isotherms at the single-crystal level for the first time. A metal-organic framework, MOF-801, was chosen as the object of the study, which has shown great performance in water harvesting from atmosphere in arid climates. The uptake of water by MOF-801 is recorded for single crystals and quantified as a function of vapor pressure (isotherms), time (kinetics), and location (imaging), through the combination of in situ Raman spectroscopy and polarization-sensitive coherent anti-Stokes Raman scattering (pCARS) imaging. The results showed that in MOF-801 crystal, water moves ~20 times faster than in the bulk. This represents the upper limit for water harvesting devices containing MOF-801 could produce up to 3.8 L of water per hour per kilogram of MOF, a vast improvement over the previously reported 2.8 L per day. Chapter 6: MOFs are typically viewed as solids that have fixed volumes and shapes with atoms that are bound tightly to each other that makes them resistant to change. This chapter presented that MOFs can respond to the external environments and change. Building units of MOFs can move in and out of MOFs freely just like in the “solution” system. The composition, pore chemistry, and even structure of MOFs will change accordingly. Thus, the MOFs can be viewed as living solids and the evolution of MOFs can happen.