For porphyrinic enediynes to function as anti-tumor agents in hypoxic environments, the Bergman cyclization reactivity in these highly absorbing macrocyclic constructs must be understood and controlled. Towards this end, the synthesis of a new series of free base, Ni(II), and Zn(II) 2,3,12,13-tetraethynyl-5,10,15,20-tetraphenylporphyrins is described featuring enhanced local diradical reactivity. Upon heating, two of the four ethynyl moieties undergo Bergman cyclization to afford the mono-cyclized 2,3-diethynyl-5,20-diphenylpiceno[10,11,12,13,14,15-jklmn]porphyrin in 30%, 10%, and trace yields, respectively. However, no fully cyclized bis-piceno-[20,1,2,3,4,5,10,11,12,13,14,15-fghij]porphyrin was isolated from the reaction mixture. To elucidate this reactivity, the Bergman cyclization reaction coordinates were examined using density functional theory at the PWPW91/cc-pVTZ(-f), and the barrier to the second cyclization event was found to be 5.5 kcal/mol higher than the first, suggesting a negative cooperative effect and significantly slower rate for the second cyclization. However, the second enediyne functionality can be activated by the metal-mediated cyclization with PtCl2, which generates a unique class of phenanthroporphyrins. This occurs through a 6-endo-dig type mechanism in good yields and at modest reaction temperatures to produce bathochromatically shifted π-fused exocyclic porphyrins, characterized by both 2D NMR and X-ray crystallographic spectroscopy. Reduced activation barriers were also seen in (2,3-diethynyl-5,10,15,20-tetraphenylporphyrinato)platinum(II). A series of Pt(II) dialkynylporphyrins and derivatives were synthesized, and Bergman cyclization of the deprotected dialkynylporphyrin progressed at a lower temperature than the free base and Zn(II), suggesting that the Pt(II) derivative is more reactive towards the thermal cyclization. Bench top cyclization experiments, both in air and under N2, showed that the (2,3-diethynyl-5,10,15,20-tetraphenylporphyrinato)platinum(II) begins the conversion to the picenoporphyrin compound at RT in as little as 4 days, and light and dark reactions proceed at comparable rates. Possible activation pathways to explain the low thermal energy cyclization activation are currently being computationally analyzed. To elucidate the excited state reactivity of these constructs, transient absorption spectra for both the singlet and triplet states was collected and analyzed for the free base, Zn(II), and Pt(II) dialkynylporphyrin series. The spectral traces of the controls were not found to be different than the reactive dialkynylporphyrins. To further reduce the Bergman cyclization barrier, a porphyrinic-enediyne with conjugated in-plane π system that has a metal-binding moiety was also developed, and the ongoing work towards ([5-{(Z)-2-((chloropent-4-en-2-ynyloxy)methyl}pyridine]-10,15,20-triphenylporphyrin)zinc(II) is presented. Together, this work progresses the understanding of Bergman cyclization reactivity in porphyrinic enediynes and the synthesis of molecules that have higher reactivity and toxicity towards malignant tissue in a hypoxic biological environment.