The synthesis and biological properties of tetra-substituted zinc and cobalt phthalocyanines bearing ethynylpyridine units on the periphery and their quaternized derivatives have been reported. The binding of quaternized ZnPc and CoPc (Q-ZnPc and Q-CoPc) with calf thymus DNA was investigated by UV-Vis spectrophotometric methods and thermodynamics. The mixtures of Q-ZnPc or Q-CoPc and DNA solutions were used to determine the change in the thermal melting temperature of DNA with the thermal denaturation profile. Thermodynamic parameters that show the spontaneity of the reactions between DNA and the quaternized phthalocyanines were investigated. K-b binding constants at a degree of 10(5) and 10(6) for Q-ZnPc and Q-CoPc, respectively, showed that the phthalocyanines bound to DNA fragments efficiently and thermodynamic data proved that the binding process was spontaneous and entropy-driven. The interactions between Q-ZnPc and Q-CoPc and DNA in an aqueous environment corresponded to electrostatic attractions and nonspecific binding.