Degradation of Organophosphates Promoted by 1,2,4-Triazole Anion: Exploring Scaffolds for Efficient Catalytic Systems

Abstract

Organophosphate (OP) pesticides are responsible for numerous human deaths every year. Nucleophilic substitution is an important method to mitigate the toxicity of obsolete stocks of OPs. Herein, the degradation of O,O-diethyl-2,4-dinitrophenyl phosphate (DEDNPP) and pesticide diethyl-4-nitrophenyl phosphate (Paraoxon) promoted by 1,2,4-triazole (TAZ) was investigated by means of kinetic studies, nuclear magnetic resonance (NMR) analyses, and theoretical calculations. Results showed fast degradation of OPs is promoted by the anionic form of the nucleophile (TAZ(−)) in pH > 8.5 (optimal at pH = 11). Rate enhancements of 106 and 105-fold in relation to neutral hydrolysis of DEDNPP and Paraoxon were observed, respectively, consistent with alpha-nucleophiles reactivity. TAZ(−) regioselectively promotes the degradation of DEDNPP via P–O bond break, forming a quickly hydrolyzable phosphorylated intermediate, regenerating the nucleophile. Calculations using M06-2X/6-311++G­(d,p) level of theory revealed that the equivalent nitrogen atoms of TAZ(−) are the main nucleophilic center of the molecule. This study expands the knowledge on the reactivity of iminic compounds as detoxificant agents of OPs, indicating the efficiency and selectivity of TAZ(−) in aqueous medium, encouraging the design of novel TAZ-based catalysts.

Nucleophilic Neutralization of Organophosphates: Lack of Selectivity or Plenty of Versatility?

“…Although, milder reaction conditions are more desirable, thus less basic conditions (lower pK a Nu ), sometimes a more basic nucleophile has an outstanding performance. For example, TAZ (pK a Nu = 10.10) carries out a catalytic and highly selective process via the phosphorus of DEDNPP (Table 4), with a t 1/2 of only 1 s. [101] Within the P=O organophosphates (Table 4), DEDNPP is the most reactive substrate (and one of the most studied) with a t 1/2 of 56 days in water. [38] Reactions with hydroxide, [38] imidazole derivatives (IMZ and 4(5)MEI), [38,54] NH 2 OH [73] and TAZ [101] are selective at the phosphorus center (that leads to less toxic products) and greatly reduce the t 1/2 , in comparison to the spontaneous reaction.…”

“…For example, TAZ (pK a Nu = 10.10) carries out a catalytic and highly selective process via the phosphorus of DEDNPP (Table 4), with a t 1/2 of only 1 s. [101] Within the P=O organophosphates (Table 4), DEDNPP is the most reactive substrate (and one of the most studied) with a t 1/2 of 56 days in water. [38] Reactions with hydroxide, [38] imidazole derivatives (IMZ and 4(5)MEI), [38,54] NH 2 OH [73] and TAZ [101] are selective at the phosphorus center (that leads to less toxic products) and greatly reduce the t 1/2 , in comparison to the spontaneous reaction. The imidazole derivatives stand out since they undergo a catalytic process (together with TAZ) and also guarantees milder reaction conditions due to its pK a Nu of 7.0.…”

“…BHA, another alphanucleophile, promotes among the fastest reaction (with Lcystein) with a t 1/2 of only 0.5 s but via two pathways (55 % at the desired P), non-catalytic. [76] The secondary alicyclic amines (i. e. piperidine and 1-formyl piperazine) and substituted pyridines (i. e. 4-hydroxy-and 3,4-dimethyl-pyridine) also exhibit fast reactions, but with varying selectivity (reaches 97 % at the phosphorus for 4-hydroxypyridine) and no [38] À 1.54 100 % P No 56 days À OH [76] 15.54 100 % P No 2 s IMZ [38] 7.00 100 % P Yes 39 s 4(5)MEI [54] 7.69 100 % P Yes 25 s NH 2 OH [73] 5.96 100 % P No 2 s BHA [76] 9.16 55 % P 45 % C Ar No 0.5 s Piperidine [81] 10.82 30 % P 70 % C Ar No 5 s 1-formyl piperazine [81] 7.63 15 % P 85 % C Ar No 1 h 4-hydroxypyridine [81] 11.50 97 % P 3 % C Ar No 3 s 3,4-dimethyl pyridine [81] 5.68 48 % P 52 % C Ar No 1 h L-cysteine [94] 8.10 100 % C Ar No 0.5 s TAZ [101] 10. H 2 O [38] À 1.54 100 % P No 7 years À OH [38] 15.54 100 % P No 4 min IMZ [38] 7.00 100 % P Yes 8 min NH 2 OH [70c] 5.96 100 % P No 3 min BHA [50] 9.…”

“…Although, milder reaction conditions are more desirable, thus less basic conditions (lower p K a Nu ), sometimes a more basic nucleophile has an outstanding performance. For example, TAZ (p K a Nu =10.10) carries out a catalytic and highly selective process via the phosphorus of DEDNPP (Table 4), with a t 1/2 of only 1 s [101] …”

“…The effectiveness of IMZ compounds in promoting the dephosphorylation of organophosphates [55,56] (vide supra) also encouraged a recent investigation centered on the reactivity of 1,2,4-triazole (TAZ). [101] Notable rate enhancements of 10 6 and 10 5 -fold were found for the degradation of DEDNPP and Paraoxon by the anionic form of TAZ (TAZ(-)) relative to neutral hydrolysis, respectively. Interestingly, based on pH-rate profiles such high nucleophilic activity was found equivalent to pralidoxime, a "suicide" nucleophile with alpha-effect.…”