The solution chemistry and crystal structure of nickel tetrakis(2,3,5,6-tetrafluoro-N,N,N-trimethyl-4-aniliniumyl)porphyrin (NiTF(4)TMAP(4+)) are reported and compared with analogous chemistry for nickel tetrakis(N-methyl-4-pyridiniumyl)porphyrin (NiT4-N-MePyP(4+)). NiTF(4)TMAP(4+) binds axial ligands more strongly than most other reported porphyrins. For stronger-field ligands such as 1-methylimidazole and tris(n-butyl)phosphine two sequential binding equilibria are observed, whereas with weaker ligands binding of two axial ligands appears to occur simultaneously. The four coordinate NiTF(4)TMAP(4+) is in equilibrium with the six coordinate Ni(H2O)(2)TF(4)TMAP(4+) in aqueous solution ([6 coordinate]/[4 coordinate] = 1.6), but the axial waters are readily lost in the presence of organic substrates such as aromatics (anionic and neutral) and aliphatic ligands (anionic and neutral). The interactions are best explained as being predominantly due to the hydrophobic effect. While this effect is exacerbated in this fluorinated porphyrin, these results indicate that hydrophobic effects should be considered in any study of porphyrin interactions in aqueous solution. The buffers HEPES and MES cause the porphyrin to be 4-coordinate in their basic form, but the zwitterionic forms do not interact with the porphyrin. In contrast, hydrogen phthalate displaces the coordinated water more strongly than the dibasic phthalate. These observations are probably due to increased hydration of the substrate. The crystal structure of Ni(TF(4)TMAP)(CF3SO3)(4) . 2CH(3)CN . 2(CH3)(2)-CO (R = 7.59%, R(w) = 7.91%, P ($) over bar 1, Z = 2, a = 14.090(3) Angstrom, b = 15.725(3) Angstrom, c = 19.554(4) Angstrom, alpha = 78.43(3)degrees, beta = 77.26(3)degrees, gamma = 83.14(3)degrees) showed that the nickel(II) was four coordinate, with no interactions with the anions or lattice solvent.