Novel smart materials can be synthesized and designed at the molecular level by attaching well characterized and tailored functionalities to be used in in vitro and in vivo oximetry. A series of porphyrins and metalloporphyrins were synthesized and their EPR and UV-vis spectra studied. The steric hindrance and electronic effects of the substituted groups and the characteristics of different metal ions were the major contributors in influencing the properties of the compounds. As a result, their EPR and UV-vis spectra changed. Through studying the EPR spectroscopic properties of these compounds, we hope that novel EPR oximetry materials can be found and this will help to extend the applications of EPR oximetry in vivo.