Theoretical 14N and 17O nuclear quadrupole resonance parameters for tirapazamine and related metabolites

Density functional theory (DFT) calculations were performed to realize the effects of the N-O group on the reactivity and electronic properties of 3-amino-1,2,4-benzotriazines. The electric field gradient, EFG, tensors of N-14 and O-17 nuclei and natural bond orbital (NBO) analysis in the tirapazamine (TPZ) and its four derivatives were calculated at the B3LYP/6-311+G(d,p)//B3LYP/6-31G(d) method in the gas phase. The NBO analysis reveal that the bond strength, proton affinity and position of N-O group in the heterocyclic ring have major influence on the reactivity of considered molecules. Accordingly, we suggest that the TPZ and 4-oxide (d) structures due to having a weaker N-O bond with larger negative charge on the oxygen atom at the 4-position are more active than the other ones. Calculated N-14 and O-17 EFG tensors were used to evaluate nuclear quadrupole coupling tensors, chi, and asymmetry parameters, eta (Q) . Results showed that oxidation of a nitrogen atom at any position have significant influence on its N-14 nuclear quadrupole resonance (NQR) parameters. Also, the occupancy of nitrogen lone pair plays an important role in determination of the q (zz) and chi values of mentioned nuclei. It is found that the eta (Q) and chi are appropriate parameters to study the contribution of lone pair electrons of nitrogen atom in the formation of chemical bond or conjugation with the aromatic system. Finally, a linear correlation is observed between the chi(N-14) and chi(O-17) values in the N-O bond which may be associated with the reactivity of these compounds.