The synthesis and characterization of combinatorial libraries of meso--tetraphenylporphyrin (H2TPP) derivatives - core structured libraries- is reported.  The libraries are readily further derivatized to create libraries of amphipathic porphyrins.  These amphipathic porphyrins are then screened for DNA binding, isolated, and examined for their ability to sensitize formation of singlet oxygen and cleave plasmid DNA.  Several novel porphyrins are identified and indicate multifunctional, amphipathic porphyrins bind more strongly than heretofore known homosubstituted porphyrins; thus, may be lead compounds for photodynamic therapeutics.