Photocrosslinking studies use sulfur- and halogen-substituted nucleobases to investigate protein binding to nucleic acids. They also find use in crosslinking secondary structure in nucleic acids (such as hairpin loops, pseudoknots, etc.) in RNA and DNA. These substituted bases create covalent bonds with adjacent amino acids or nucleobases upon irradiation with ultraviolet light. These adducts may be analyzed by immunological and mass spectrometry techniques to identify locations of macromolecule interaction.