Probing the Catalytically Active Species in POM‐Catalysed DNA‐Model Hydrolysis**

Abstract

Phosphoester hydrolysis is an important chemical step in DNA repair. One archetypal molecular model of phosphoesters is para-nitrophenylphosphate (pNPP). It has been shown previously that the presence of molecular metal oxide [Mo 7 O 24 ] 6À may catalyse the hydrolysis of pNPP through the partial decomposition of polyoxomolybdate framework resulting in a [(PO 4 ) 2 Mo 5 O 15 ] 6À product. Real-time monitoring of the catalytic system using electrospray ionisation mass spectrometry (ESI-MS) provided a glance into the species present in the reaction mixture and identification of potential catalytic candidates. Following up on the obtained spectrometric data, Density Functional Theory (DFT) calculations were carried out to characterise the hypothetical intermediate [Mo 5 O 15 (pNPP) 2 (H 2 O) 6 ] 6À that would be required to form under the hypothesised transformation. Surprisingly, our results point to the dimeric [Mo 2 O 8 ] 4À anion resulting from the decomposition of [Mo 7 O 24 ] 6À as the active catalytic species involved in the hydrolysis of pNPP rather than the originally assumed {Mo 5 O 15 } species. A similar study was carried out involving the same species but substituting Mo by W. The mechanism involving W species showed a higher barrier and less stable products in agreement with the non-catalytic effect found in experimental results.

Computational Modelling of the Interactions Between Polyoxometalates and Biological Systems

“…The phosphoester bond hydrolysis catalysed by molybdate anions as artificial phosphoesterases has been also studied computationally. ( Martins et al, 2021 ; Lanuza et al, 2021 ; Sа´nchez-Gonzа´lez et al, 2021 ). In combination with electrospray ionization mass spectroscopy (ESI-MS) experiments, the obtained results provided a different picture of the mechanism compared to previous experimental studies based on NMR, RAMAN and UV-Vis spectroscopy, obtained for [Mo 7 O 24 ] 6− species.…”

New Insights on the Interaction of Phenanthroline Based Ligands and Metal Complexes and Polyoxometalates with Duplex DNA and G-Quadruplexes

“…Such transition state was very close in energy to the associative one. On the other hand, in our other study, [44] experimental data pointed towards the existence of a dinuclear system that could be related to RDD1 through a protonation of RDD1. For this reason, we calculated the same pathway starting from RDD1prot, where both bridging O atoms were protonated.…”

“…In this section, we incorporate (in our computational studies) the reactivity of DNA model targets addressing the hydrolysis of the phosphoester bond in the presence of Mooxo species. Indeed, during the last years our team has studied POMs (see one example in Figure 32) and simpler oxides as promoters and catalysts of the phosphoester bond hydrolysis (that is, the use of metal-oxo species as artificial phosphoesterases) [44,45]. The phosphoester bond plays a major role in biological systems and is associated with several biomolecules such as DNA, RNA, ATP, ADP, etc.…”

“…Refs. [36][37][38][39][40][41][42][43][44][45][46][47][48] The general goal of this focused review on our team is to address our new insights on the modelling of the interactions and the behavior of some selected systems, namely phen derivatives and oxo-Mo species with several targets based on canonical and non-canonical DNA to improve antitumoral chemotherapy treatments and to fight against antibiotic resistance.…”

Mechanistic Insights into Promoted Hydrolysis of Phosphoester Bonds by MoO2Cl2(DMF)2

“…In a recent study, experimental data pointed to the existence of a dimeric structure that can be related to RDD1 through the protonation of RDD1. Because of this, we calculated the same pathway starting from RDD1 prot , in which both bridging oxygens are protonated.…”