Photochemistry of Matrix Isolated Isoniazid

A. BORBA, A. GóMEZ ZAVAGLIA, R. FAUSTO

Granada

Congreso; 5th EuCheMS Conference on Nitrogen Ligands in Coordination Chemistry, Metal-organic Chemistry,; 2011

Isoniazid (or isonicotinic acid hydrazide, INH; see Figure 1) has a high activity against Mycobacterium tuberculosis (the microorganism responsible for the tuberculosis disease) and is still the most widely used drug in antituberculous regimens [1,2].   In this study [3], the structure, spectroscopy, and photochemistry of INH were studied by low-temperature infrared spectroscopy and quantum chemistry calculations. According to DFT(B3LYP)/6-311++G(d,p)  calculations,  12  minima  were  found  on  the  potential  energy  surface  of  the  molecule, corresponding to two cis conformers about the O=C-N-N axis (C1, C2) and one form trans about this axis (T), all being 4‑fold degenerate by symmetry. The C1 conformer was predicted to be more stable than T and C2, by 20.4 and 22.6 kJ mol-1, respectively.   After UV (ë > 235 nm) irradiation of the matrix-isolated isoniazid, the compound was found to undergo photolysis through two different pathways: a Norrish type I a-cleavage leading to production of isonicotinaldehyde and N2H2 and a concerted sigmatropic reaction with production of pyridine, CO and N2H2. The latter reaction was found to be nearly two times faster than the former in both argon and xenon matrixes. In addition, both reactions were found to be disfavored in a xenon matrix, which is in consonance with the involvement of (n, ð*) excited states in both photochemical processes.