Effects of the Metal Ion on the Mechanism of Phosphodiester Hydrolysis Catalyzed by Metal-Cyclen Complexes

Abstract

In this study, mechanisms of phosphodiester hydrolysis catalyzed by six di- and tetravalent metal-cyclen ( M-C ) complexes ( Zn-C, Cu-C, Co-C, Ce-C, Zr-C and Ti-C ) have been investigated using DFT calculations. The activities of these complexes were studied using three distinct mechanisms: (1) direct attack ( DA ), (2) catalyst-assisted ( CA ), and (3) water-assisted ( WA ). All divalent metal complexes ( Zn-C, Cu-C and Co-C ) coordinated to the BNPP substrate in a monodentate fashion and activated its scissile phosphoester bond. However, all tetravalent metal complexes ( Ce-C, Zr-C , and Ti-C ) interacted with BNPP in a bidentate manner and strengthened this bond. The DA mechanism was energetically the most feasible for all divalent M-C complexes, while the WA mechanism was favored by the tetravalent complexes, except Ce-C . The divalent complexes were found to be more reactive than their tetravalent counterparts. Zn-C catalyzed the hydrolysis with the lowest barrier among all M-C complexes, while Ti-C was the most reactive tetravalent complex. The activities of Ce-C and Zr-C , except Ti-C , were improved with an increase in the coordination number of the metal ion. The structural and mechanistic information provided in this study will be very helpful in the development of more efficient metal complexes for this critical reaction.

Mechanisms of peptide and phosphoester hydrolysis catalyzed by two promiscuous metalloenzymes (insulin degrading enzyme and glycerophosphodiesterase) and their synthetic analogues

“…Based on the experimental data, the hydrolysis of BNPP by I C was studied using two types of metal ions, divalent [Zn (II), Cu(II), and Co(II)] and tetravalent [Ce(IV), Zr(IV), and Ti(IV)], through three different mechanisms: direct attack (DA, Figure 8b), catalyst-assisted (CA, Figure 8b), and water-assisted (WA, Figure 8c). 164 In the DA mechanism, [165][166][167] the metal ion was bound to the cyclen ligand, a hydroxyl ion and a water molecule in the initial reactant (R i ). The active complex (R) was created by replacing the water molecule with the BNPP substrate.…”

A Novel Alkaline Phosphatase/Phosphodiesterase, CamPhoD, from Marine Bacterium Cobetia amphilecti KMM 296

“…The Ca 2+ dependence of the phosphatase/phosphodiesterase from Aphanothece halophytica [9] as well as the activation of the alkaline phosphatase from Pyrococcus abyssi in the presence of Mg 2+ , Zn 2+ , and Co 2+ ions have already been shown [43]. In addition, the alkaline phosphatase of the hyperthermophilic bacterium Termatoga maritima was shown to contain Co 2+ and Mg 2+ in the active center [44], while the active center of an E. coli alkaline phosphatase possessing the phosphodiesterase activity contained two Zn 2+ and one Mg 2+ [51], similar to most of the PhoA alkaline phosphatases, for example CmAP from C. amphilecti KMM 296 [6,24,52].…”

One-pot synthesis of α-aminophosphonates by yttrium-catalyzed Birum–Oleksyszyn reaction

“… 21 However, under the reaction conditions, hydrolysis proceeds with the help of the Lewis acid. 32 With prolonged reaction time ( i.e. , 24 h) we noticed a decrease in the yield of product 4 almost in half compared to the yield obtained in the reaction performed for 4 h and formation of acid 10 as the major side product.…”

“…36,37 As reported in literature, phosphodiesters can be hydrolyzed by Lewis acids. 32,38 Paracetamol-containing phosphorus esters are much more sensitive to the presence of water compared to their alkyl analogs. Therefore, analysis of the catalyst efficiency can be carried out by using an additional parameterselectivity for the formation of the target diester 4 compared to the proportion of the hydrolyzed monoester side product 10.…”