Silica-bound copper(ii)triazacyclononane as a phosphate esterase: effect of linker length and surface hydrophobicity

Abstract

A series of silica-bound Cu(ii) triazacyclononane materials was prepared to study the effect of linker length and surface hydrophobicity on the hydrolysis of phosphate esters. The general synthetic approach for these heterogeneous reagents was rhodium-catalyzed hydrosilation between an alkenyl-modified triazacyclononane and hydride-modified silica followed by metallation with a Cu(ii) salt. Elemental analysis confirmed that organic functionalization of the silica gel was successful and provided an estimate of the surface concentration of triazacyclononane. EPR spectra were consistent with square pyramidal Cu(ii), indicating that Cu(ii) ions were bound to the immobilized macrocycles. The hydrolytic efficacies of these heterogeneous reagents were tested with bis(p-nitrophenyl)phosphate (BNPP) and diethyl 4-nitrophenyl phosphate (paraoxon). The agent that performed best was an octyl-linked, propanol-blocked material. This material had the most hydrophilic surface and the most accessible active site, achieving a rate maximum on par with the other materials, but in fewer cycles and without an induction period.

Recent Advances in Heterogeneous Catalytic Systems Containing Metal Ions for Phosphate Ester Hydrolysis

“…In some cases, the supported catalysts were investigated with a number of substrates. Examples include the lanthanum complex of 15 with ENPMP and E3,5DCPMPT [78] and the copper complex of 11 with 4‐BNPP and paraoxon [75] . Tables 1 and 2 list numerous examples that illustrate the diversity of substrates tested, solvents used, temperature and pH conditions, as well as metal ions and solid supports employed.…”

“…These studies are not always straightforward; in one case, leaching of zinc above pH 8 was reported for the Zn II complex immobilised on a 1 % cross‐linked Merrifield resin [101] and, in another case, a diffusion‐related process and product partitioning were observed for a zinc complex of 1,4,7‐triazacyclononane immobilised on Tentagel (mixed polystyrene–polyethylene glycol) resin, necessitating adaptations to the model kinetics [100] . It was suggested that inorganic materials, such as silica, offered advantages, including durability, over organic polymers, such as polymers synthesised with DVB [75] . By employing both N ‐(4‐but‐1‐ene)(TACN) and N ‐(8‐oct‐1‐ene)(TACN) (TACN=1,4,7‐triazacyclononane) in a reaction with hydride‐modified silica, followed by metallation, it was possible to prepare immobilised Cu II complexes of TACN [75] .…”

“…By employing both N ‐(4‐but‐1‐ene)(TACN) and N ‐(8‐oct‐1‐ene)(TACN) (TACN=1,4,7‐triazacyclononane) in a reaction with hydride‐modified silica, followed by metallation, it was possible to prepare immobilised Cu II complexes of TACN [75] . These immobilised complexes ( 11 – 14 ; Figure 3) permitted the study of the effect of linker length and hydrophobicity of the surface on the rate of hydrolysis of the activated ester substrate 4‐BNPP [75] . For these resins, diffusion‐related phenomena and product partitioning were observed in the kinetic studies, and these effects were considered in the kinetic treatment [100] .…”

“…Some data in Tables 1 and 2 deserve additional attention, in particular, those studies with the substrates paraoxon [75] and fenitrothion [99] . The latter is a broad spectrum insecticide, whereas the former is a cholinesterase inhibitor and active metabolite of the insecticide 6 .…”

Metal‐coordinated Hydroxide as a Nucleophile: a Brief History

“…The following references provide selected examples of other model metal complexes, which are capable of cleaving both activated phosphate esters and DNA, while reviews are also available. ,…”