Conjugates of oligonucleotides with chlorin-type photosensitizers were prepared. Two chlorin moieties, CPP and CHEVP, characterized by a modified pyrrole unit bearing an aldehyde chain, were photochemically prepared from protoporphyrin and heptaethylvinylporphyrin, respectively. These chlorin moieties were coupled through the carboxylic acid side-chain (CPP) or aldehyde side-chain (CHEVP) to the 3’-activated phosphate of oligodeoxy-nucleotides. Diamine or dihydrazide were used as linkers. The resulting conjugates were purified by HPLC and characterized by electrophoresis, UV-visible spectroscopy, and mass spectrometry. The photosensitizing properties of the conjugate of CHEVP with the 14-mer oligodeoxynucleotide TTCTTCTCCTTTCT were investigated using three different targets. A single-stranded 25-mer containing the complementary sequence of the 14-mer formed a double helix with the chlorin-14-mer conjugate. A 24 base-pair duplex and a 41-mer hairpin with 18 base pairs and a five nucleotide loop formed triple helices with the conjugate. In all cases, upon irradiation with visible light (428 or 658 nm), piperidine-labile sites at guanine positions were produced. The reaction required oxygen and was inhibited to some extent by sodium azide. The cleavage sites were correlated with the chlorin position in both the duplex and tripler structures. In the 41-mer hairpin, the most reactive guanines were those located in the loop region. The quantum yield for cleavage of the hairpin structure was determined to be about 10(-3), independent of the excitation wavelength. This modest value is largely compensated by the high absorption of the chlorin in the red, making the conjugate highly efficient even under low light fluence. No effect was found with a noncomplementary chlorin-oligonucleotide conjugate. These results show that site-directed damages to nucleic acid structures can be achieved using oligonucleotide-chlorin conjugates and red light irradiation.