New water-soluble cationic meso-tetraarylporphyrins (TArP, Ar = 4-C6H4) and some metal derivatives have been synthesized and characterized. One main goal was to assess if N-methylpyridinium (N-Mepy) groups must be directly attached to the porphyrin core for intercalative binding of porphyrins to DNA. The new porphyrins have the general formula, [T((RRNSO2Ar)-R-2-N-1)P]X-4/8 (R-1 = CH3 or H and R-2 = N-Mepy-n-CH2 with n = 2, 3, or 4; or R-1 = R-2 = Et3NCH2CH2). Interactions of selected porphyrins and metalloporphyrins (Cu(II), Zn(II)) with calf thymus DNA were investigated by visible circular dichroism (CD), absorption, and fluorescence spectroscopies. The DNA-induced changes in the porphyrin Soret region (a positive induced CD feature and, at high DNA concentration, increases in the Soret band and fluorescence intensities) indicate that the new porphyrins interact with DNA in an outside, non-self-stacking binding mode. Several new metalloporphyrins did not increase DNA solution viscosity and thus do not intercalate, confirming the conclusion drawn from spectroscopic studies. Porphyrins known to intercalate typically bear two or more N-Mepy groups directly attached to the porphyrin ring, such as the prototypical meso-tetra(N-Mepy)porpyrin tetracation (TMpyP(4)). The distances between the nitrogens of the N-Mepy group are estimated to be similar to 11 angstrom (cis) and 16 angstrom (trans) for the relatively rigid TMpyP(4). For the new flexible porphyrin, [T(N-Mepy-4-CH2(CH3)NSO2Ar)P]Cl-4, the distances between the nitrogens are estimated to be able to span the range from similar to 9 to similar to 25 angstrom. Thus, the N-Mepy groups in the new porphyrins can adopt the same spacing as in known intercalators such as TMpyP(4). The absence of intercalation by the new porphyrins indicates that the propensity for the N-Mepy group to facilitate DNA intercalation of cationic porphyrins requires direct attachment of N-Mepy groups to the porphyrin core.