La3+-catalyzed methanolysis of O,O-diethyl S-(p-nitrophenyl) phosphorothioate and O,O-diethyl S-phenyl phosphorothioate. Millions-fold acceleration of the destruction of V-agent simulants

Abstract

The La3+-catalyzed methanolysis of two phosphorothioate derivatives, O,O-diethyl S-(p-nitrophenyl) phosphorothioate (4a) and O,O-diethyl S-phenyl phosphorothioate (4b) were studied as a function of [La3+] and pH in methanol solvent. In both cases the kinetics of catalyzed methanolysis maximize at pH 9.1 and a detailed analysis indicates that the dominant species responsible for catalysis are dimers formulated as La3+(2)(-OCH3)2 and La3+(2)(-OCH3)4. The catalysis is compared with that seen for the corresponding phosphate esters, namely paraoxon (3a) and O,O-diethyl phenyl phosphate (3b) for which La3+ catalysis is slightly better and markedly worse than for 4a and 4b respectively. Overall, at s(s)pH 9.1, a 2 mmol dm-3 solution of La(OTf)3 with equimolar NaOCH3 provides accelerations of 2.2x10(8)-fold, 9.7x10(6)-fold and 9.3x10(6)-fold for methanolysis of 3a, 4a and 4b, relative to the background reaction of methoxide reacting with the three substrates. In each case, the P-containing product of the reactions is exclusively diethyl methyl phosphate. Turnover experiments with 6-fold and 100-fold excesses of 4a and 4b respectively, methanolyzed in the presence of approximately 10 mmol dm-3 La3+ and equimolar NaOCH3, indicate that the reactions are essentially complete within 103 s and 70 min respectively. The latter turnover experiment with 4b corresponded to 100 turnovers in 70 min and an overall reaction t1/2 of 8 min. A common mechanism of reaction is postulated for each of the substrates which involves Lewis acid coordination of one of the La3+ to the P=O unit, followed by nucleophilic attack by the second La3+-(-)OCH3.

Exploiting parameter space in MOFs: a 20-fold enhancement of phosphate-ester hydrolysis with UiO-66-NH2

“… 21 Given that early row transition metals are often found in biological materials due to bioavailability, researchers such as Brown have utilized coordination complexes with more Lewis-acidic centres such as La III and Zr IV as catalysts for phosphate-ester hydrolysis. 11 , 14 , 22 …”

“…Transition-metal, or rather Lewis-acid, hydrolysis is ubiquitous in the eld of phosphate-hydrolysis. [10][11][12][13][14][15][16] Taking a lesson from nature, many transition-metal complexes employ hydroxide bridged dimers as catalysts. 10,11,[17][18][19][20] For example, the family of phosphoesterase enzymes utilize a Zn II -OH-Zn II active site which is oen further supported by a bridging carboxylate.…”

Nanomaterial-Enabled Sensors and Therapeutic Platforms for Reactive Organophosphates

“…It is because without such OP removal from the skin surface, the exposed surface serves as a depot for extended OP absorption which causes sustained toxicity [115]. Several types of decontaminants [96,[116][117][118][119][120][121] have been developed for skin decontamination that include most notably reactive skin decontamination lotion (RSDL) [122,123]. Its active ingredient consists of Dekon 139, a potassium salt of diacetyl monooxime (DAM).…”

“…However, Dekon 139 can induce adverse systemic effects such as skeletal muscle paralysis due to its rapid skin and wound absorption [125]. Recently, several types of molecular scaffolds are designed and tested as effective chemical decontaminants for OP pesticides and nerve agents [119,121,[126][127][128]. These include α-nucleophile scaffolds prepared by conjugation with oxime [16,124], pyridinium aldoxime (PAM) [120,129,130] or hydroxamic acid (HA) [16,129,131].…”

“…Other scaffolds such as those prepared by PAM conjugation to a glucose [2] or βcyclodextrin [132,133] unit have shown potent reactivity in OP (POX, cyclosarin) inactivation in vitro [132,133] or preventing POX-induced hypothermia in vivo [2]. Non-αnucleophile scaffolds are similarly validated as OP-reactive constructs that include alkali metal alkoxides [126], lanthanide (La 3+ ) ions [121], nitrogen-containing bases [127] and imidazolium-based ionic liquids [119].…”