Confined environments can be used to alter the selectivity of a reaction by influencing the organization of the reactants, altering the mobility of trapped molecules, facilitating one reaction pathway or selectively stabilizing the products. This manuscript utilizes a series of potentially photoreactive guests to interrogate the utility of the one-dimensional nanochannels of a porous host to absorb and facilitate the reaction of encapsulated guests. The host is a columnar self-assembled phenylethynylene bis-urea macrocycle, which absorbs guests, including coumarin, 6-methyl coumarin, 7-methyl coumarin, 7-methoxy coumarin, acenaphthylene, cis-stilbene, trans-stilbene, and trans-b-methylstyrene to afford crystalline inclusion complexes. We examine the structure of the host:guest complexes using powder X-ray diffraction, which suggests that they are well-ordered highly crystalline materials. Investigations using solid-state cross-polarized magic angle spinning C-13{H-1}CP-MAS NMR spectroscopy indicate that the guests are mobile relative to the host. Upon UV-irradiation, we observed selective photodimerization reactions for coumarin, 6-methyl coumarin, 7-methyl coumarin, and acenaphthylene, while the other substrates were unreactive even under prolonged UV-irradiation. Grand Canonical Monte Carlo simulations suggest that the reactive guests were close paired and preorganized in configurations that facilitate the photodimerization with high selectivity while the unreactive guests did not exhibit similar close pairing. A greater understanding of the factors that control diffusion and reaction in confinement could lead to the development of better catalysts.