Phosphorolytic Cleavage of Phosphate and Phosphonoformate Diesters by Cetyltrimethylammonium Iodosobenzoate

Abstract

Micellar cetyltrimethylammonium iodosobenzoate (4) cleaves P-O ester linkages of bis(p-nitrophenyl) phosphate (3), methoxycarbonyl phenyl phosphonoformate (6), and hexyloxycarbonyl phenyl phosphonoformate (7). Kinetic advantages of several orders of magnitude are obtained relative to the unassisted hydrolyses.o-Iodosobenzoate (1, IBA) is a potent catalyst for the cleavage of neutral P-O substrates, 1,2 including phosphotriesters, 3 thiophosphates and phosphonothioates, 4 phosphonofluoridate nerve agents, 5 and phosphate or thiophosphate pesticides, such as paraoxon or parathion. 6 For these applications, IBA is often deployed in cetyltrimethylammonium (CTA) micellar solutions, where the cationic micelles solubilize both the anionic IBA and the neutral substrate, concentrating the reactants in the micellar phase and providing a significant kinetic advantage. 3,7 Although IBA in micellar (CTA)Cl is an exceptional facilitator of the hydrolysis of neutral, activated phosphotriesters such as bis(p-nitrophenyl) methyl phosphate (2), it is much less reactive toward anionic phosphodiester substrates: even the "activated" bis(p-nitrophenyl) phosphate 3 (BNPP) is not readily cleaved. 3 Thus, 1 × 10 -4 M IBA in 2.5 mM aqueous (CTA)Cl at pH 8 cleaved 1 × 10 -5 M phosphotriester 2 with k ) 0.074 s -1 , whereas phosphodiester 3 initially appeared not to cleave with IBA at various (CTA)Cl concentrations under similar conditions. 3,8 Presumably, attack of the anionic IBA is inhibited at the phosphorus center of the anionic O-P-O triad of BNPP.Recently we reported that cetyltrimethylammonium iodosobenzoate 9 (4, (CTA)IBA) is 20-30% more reactive than a 1:1 (CTA)Cl-IBA blend in the micellar hydrolyses of paraoxon and parathion. 6 In holomicellar (CTA)IBA, where there are no chloride ions to compete for the cationic CTA binding sites, the reactive IBA anions may bind more strongly at the CTA cationic sites, affording more efficient reaction with the hydrophobically bound (neutral) substrate.These results led us to restudy the reaction between IBA and BNPP. We imagined that in holomicellar (CTA)-IBA the CTA cations might support stronger electrostatic interactions with the (O-P-O) -units of nBNPP, mitigating the negative charge and potentiating the attack of IBA on what would effectively be CTA-BNPP ion pairs. We now find that (CTA)IBA, and (CTA)Cl/IBA, lyse the P-O bond of BNPP. This is the initial report of phosphodiester hydrolysis mediated by IBA. Additionally, we describe the cleavage of several phosphonoformate diester substrates by (CTA)IBA, noting two further instances of P-O scission. Results and DiscussionSubstrates. The substrates we employed included BNPP (3), dimethyl phosphonoformate (5, DMPF), methoxycarbonyl phenyl phosphonoformate (6), hexyloxycarbonyl phenyl phosphonoformate (7), phenoxycarbonyl methyl phosphonoformate (8), and diphenyl phosphonoformate (9, DPPF). Substates 3 and 5-9 were used as sodium salts. BNPP was commercially available from Sigma Chemical Co. DMPF (5) was prepared by the NaI demethylation of ...

Metal-Cation-Mediated Hydrolysis of Phosphonoformate Diesters: Chemoselectivity and Catalysis1

“…18,51 Additionally, the slow cleavage of DMPF (k obs ) 7.6 × 10 -7 s -1 at pH 8.4) by cetyltrimethylammonium iodosobenzoate also occurs with only C-OMe cleavage. 52 However, the scission of 8, as might be expected, occurs with 90:10 P-OPh/C-OMe cleavage. S1 in the Supporting Information and Figure 3).…”

“…Similarly, 10 mM DMPF was hydrolyzed at pD 6.8 by 25 mM of the monomeric Co(III)cyclen complex 28 , with k obs = 9.5 × 10 -4 s -1 to yield only 15 by C−OMe cleavage. , Additionally, the slow cleavage of DMPF ( k obs = 7.6 × 10 -7 s -1 at pH 8.4) by cetyltrimethylammonium iodosobenzoate also occurs with only C−OMe cleavage . However, the scission of 8 , as might be expected, occurs with 90:10 P−OPh/C−OMe cleavage …”