Modern nitramines TNAZ and CL-20 (HNIW): their electron-accepting potency, enzymatic reactivity and cytotoxicity

摘要

Energetic nitrocompounds are widely used in various industrial and military areas. Environmental contamination by these materials is an acute problem, and nitramine compounds are one of the major groups of such type contaminants. One of the initial stages of biodegradation and/or toxic action of such compounds is frequently related to their 1e-/2e-(4e-) reduction catalyzed by redox-active flavoenzymes. In this work the enzymatic reactivity of the newest nitramine compounds - TNAZ and CL-20 (HNIW) - was examined towards single- and two-electron transferring flavoenzymes and their electron-accepting potency was assessed by electrochemical and quantum mechanical methods. The standard nitramine RDX was also used in this work for comparison. The first peak potentials of volt-ammetric reduction (E_(p,7)) vs. Ag/AgCl of CL-20 and TNAZ were -612 mV to -390 mV, respectively, while E_(p,7) of RDX was -554 mV. The same trend of the electron accepting potency of the compounds was obtained by means of quantum mechanical calculation. The enzymatic reactivity of the nitramines, expressed as apparent second-order rate constants (k_(cat)/K_m) of their reduction, towards single-electron transferring flavoenzyme P-450R as well as two-electron transferring flavoenzymes PETN-reductase (PETNR), nitroreductase (NR) and DT-diaphorase (NQO1) varied in the range of TNAZ ＞ CL-20 ≥ RDX, and reactivity of TNAZ was almost one order of magnitude higher than that of CL-20 and RDX. This reactivity increased with an increase in the electron-accepting potency of the compounds. TNAZ and CL-20 were found to be much more toxic compounds for mice spleno-cytes than RDX; the CL_(50) values (the concentration of the compounds causing 50 % cell death) of TNAZ and CL-20 were defined to be equal to 15.6 and 21.9μM, respectively, while CL_(50) of RDX was 140 μM. The toxicity of the former compounds was much higher than that of relatively new nitramine representative TEX and bicyclic structure energetic nitramine BCHMX. This work demonstrates that the cytotoxicity of the compounds is caused mainly by their electron-accepting potency and might be influenced by their structural peculiarities.