Porphyrins incorporating heterocyclic N-oxides:: (oxidopyridyl)porphyrins, porphyrin-N-oxides, and a tirapazamine-porphyrin conjugate

Porphyrins containing one to four 3-pyridyl groups as meso-substituents were synthesized via a mixed aldehyde condensation, and then "N-oxidized" with m-chloroperbenzoic acid to produce five novel (oxidopyridyl) porphyrins and seven porphyrin-N-oxides which were characterized by analysis and spectroscopic methods, especially NMR; an X-ray crystal structure of 5-(1-oxido-4-pyridyl)-10, 15,20-triphenylporphyrin was also obtained. Crystals of (oxidopyridyl)triphenylporphyrin are tetragonal, a = b = 15.174(1), c = 13.709(1) Angstrom, Z = 4, space group 12d. The structure was solved by direct methods and refined by full-matrix least-squares procedures to R = 0.031 (R-w = 0.026) for 685 reflections with I greater than or equal to 3 sigma(I). Sulfonation of two of the (oxidopyridyl)porphyrins was achieved readily with no loss of oxygen from the oxidopyridyl groups. Tirapazamine (3-amino-1,2,4-benzotriazine-1,4-di-N-oxide) was treated with triphosgene to yield the previously reported 2H-[1,2,3]oxadiazolo[3,2-c][ 1,2,3]benzotriazin-2-one-5-oxide (1); this reacts like an isocyanate and with 5-(4-aminophenyl)-10,15,20-triphenylporphyrin yields a tirapazamine-porphyrin conjugate (2).