AbstractA classical methodology to design free‐basemeso‐tetra‐(1‐pyrenyl)porphyrin (H2TPyrP) and their corresponding metalloporphyrins containing Zn(II), Cu(II), Ni(II), Co(III), and Mn(III) was described. These porphyrins were characterized in terms of structure, photophysical, and interactions profile withcalf‐thymusdeoxyribonucleic acid (CT‐DNA) and bovine serum albumin (BSA).H2TPyrPexhibited five characteristic bands in the visible wavelength: Soret (432 nm) and Q‐bands (520–650 nm range), while the metalloporphyrins showed some spectrum shifts according to the nature of the ion, which were also explored by time‐dependent density functional theory (TD‐DFT) calculations. The fluorescence and singlet oxygen quantum yield (Φfl, ΦΔ, respectively) decreased with the presence of metal species in the porphyrin core. The porphyrins interact spontaneously via a ground‐state association in the minor groove of CT‐DNA following the increasing order of binding:CuTPyrP<H2TPyrP<CoTPyrP<MnTPyrP<NiTPyrP<ZnTPyrP, while for BSA the suitable complex geometry for Co(III) and Mn(III) complexes increased the binding capacity.