## 2 Materials and Methods
### General Procedures for Synthesis of TPZs
HRMS (ESI) _m/z_ [M+H]\({}^{+}\) = 251.0772 (calculated: 251.0775). _3-Trifluoroacetylamino-1,2,4-benzotriazine 1,4-dioxide_ (compound **7**): yield: 52%, melting point: 135 \({}^{\circ}\)C, \({}^{1}\)H NMR (CDC\({}_{3}\)): \(\delta\) 9.22 (bs, 1H, NH), 8.73 (d, 2H, H5 and H8, J = 7.9 Hz), 8.65 (t, 1H, H6, J = 4.7 Hz), 7.39 (t, 1H, H6, J = 4.7 Hz). HRMS (ESI) _m/z_ [M+H]\({}^{+}\) = 275.0384). _3-Trifluoromethyl-sulfonylamino-1,2,4-benzotriazine 1,4-dioxide_ (compound **8**): yield: 74%; melting point: 214 \({}^{\circ}\)C; \({}^{1}\)H NMR (CDC\({}_{3}\)): \(\delta\) 9.80 (bs, 1H, NH), 8.81 (d, 2H, H5 and H8, J = 7.8 Hz), 8.45 (t, 1H, H6, J = 4.9 Hz), 7.69 (t, 1H, H6, J = 4.9 Hz); HRMS (ESI) _m/z_ [M+H]\({}^{+}\) = 311.0058 (calculated: 311.0056). _3-Methylsulfonylamino-1,2,4-benzotriazine 1,4-dioxide_ (compound **9**): yield 62%, melting point 241 \({}^{\circ}\)C, \({}^{1}\)H NMR (CDC\({}_{3}\)): \(\delta\)9.57 (bs, 1H, NH), 8.63 (d, 2H, H5 and H8, J = 7.8 Hz), 8.29 (t, 1H, H6, J = 4.8 Hz), HRMS (ESI) _m/z_ [M+H]\({}^{+}\) = 257.0340 (calculated: 257.0339). _3-Ethoxycarbonylamino-1,2,4-benzotriazine 1,4-dioxide_ (compound **6**) was obtained following virtually the same synthetic procedure as described for compound **5**. Yield: 62%. Melting point: 183 \({}^{\circ}\)C. \({}^{1}\)H NMR (CDC\({}_{3}\)): \(\delta\)8.66 (bs, 1H, NH), 8.51 (d, 2H, H5 and H8, J = 7.9 Hz), 8.35 (t, 1H, H6, J = 4.7 Hz), 7.18 (t, 1H, H6, J = 4.7 Hz),2.30 (q, 2H, OCH\({}_{2}\)), 1.02 (t, 3H, CH\({}_{3}\)). HRMS (ESI) _m/z_ [M+H]\({}^{+}\) = 251.0772 (calculated: 251.0775). _3-n-Propylthiocarbamoylamino-1,2,4-benzotriazine 1,4-dioxide_ (compound **10**) was synthesized by prolonged heating of a mixture of TPZ (**1**) with 1.2 molar equivalents of 1-propylisothiocyanate in dioxane medium at 100 \({}^{\circ}\)C for approximately 12 h. All volatiles were removed in vacuoandthe resultant product was crystallized from the methylacetate and 2-propanol mixture (1:2). Yield: 43%. Melting point: 292 \({}^{\circ}\)C. \({}^{1}\)HNMR ((CD\({}_{3}\))\({}_{2}\)SO) \(\delta\) 9.23 (brs., 2H, NH-CS-NH); 7.47-8.43 (m, 4H, arom); 3.55 (t, 2H, CH\({}_{3}\)CH\({}_{2}\)CH\({}_{2}\), J = 6.8 Hz); 1.57 (m, 2H, CH\({}_{3}\)CH\({}_{2}\)CH\({}_{2}\)), 0.90 (t, 3H, CH\({}_{3}\), J = 7.6 Hz). HRMS (ESI) _m/z_ [M+H]\({}^{+}\) = 280.0861 (calculated: 280.0863). _2.3. Computational Details of TPZs_  
All quantum mechanical computations of TPZs were performed using the Spartan 10\({}^{\prime}\) (Wavefunction Inc., version 1.1.0, 2011, Irvine, CA, USA) software package. To define more stable conformers (compounds **2-10**), a systematic conformational search was conducted by the Merck Molecular Force Field (MMFF)method by applying the conformational distribution module implemented into Spartan 10' package. The most stable conformers were subjected to further geometric optimization by the restricted Hartree-Fock method (RHF) with a 6-31 G(d,p) basis set. The final optimization and computation of the compounds were carried out by the restricted DFT-B3 LYP method coupled with a 6-311+G(d,p) basis set. At each calculation stage, the structures of the compounds were globally optimized without symmetry restrictions and their stationary points were confirmed by frequency analysis. For all the optimized structures, no imaginary frequencies were defined.