Metalloporphyrins have been widely utilized as building blocks for molecular self-assembly in organic solvents, but their application in water is less common due to competition from water molecules for the metal center. However, Co(III) metalloporphyrins are notable for their strong binding to two aromatic amine ligands in aqueous buffers. In this study, we present a comprehensive investigation of the binding behavior of Co(III) tetraphenyl sulfonic acid porphyrin with selected aromatic and aliphatic amines in aqueous solution. Our findings reveal that the ligand affinity is influenced by the pKa values of both the ligand and the porphyrin, as well as the hybridization state of the nitrogen atom, with binding to sp3-hybridized nitrogen being significantly weaker than to sp2-hybridized nitrogen. DFT calculations further suggest that the variations in binding affinities are due to differences in the electrostatic potential at the nitrogen atoms, with aromatic ligands generally exhibiting stronger Co-N coordination due to greater electrostatic attraction. Moreover, our study and the binding model we developed demonstrate that changes in pH affect the affinity for each ligand to varying degrees, sometimes resulting in an allosteric cooperative effect. This effect is linked to electronic changes introduced by the binding of the first ligand. Our model provides a predictive tool for understanding the assembly behavior of these porphyrins in aqueous buffers, with potential applications in developing more efficient catalysts and in the creation of smart materials for fields ranging from catalysis to nanomedicine and optoelectronics.