title: Phosphate ester hydrolysis of biologically relevant molecules by cerium oxide nanoparticles.
abstract: In an effort to characterize the interaction of cerium oxide nanoparticles (CNPs) in biological systems, we explored the reactivity of CNPs with the phosphate ester bonds of p-nitrophenylphosphate (pNPP), ATP, o-phospho-l-tyrosine, and DNA. The activity of the bond cleavage for pNPP at pH 7 is calculated to be 0.860 ± 0.010 nmol p-nitrophenol/min/μg CNPs. Interestingly, when CNPs bind to plasmid DNA, no cleavage products are detected. While cerium(IV) complexes generally exhibit the ability to break phosphorus-oxygen bonds, the reactions we report appear to be dependent on the availability of cerium(III) sites, not cerium(IV) sites. We investigated the dephosphorylation mechanism from the first principles and find the reaction proceeds through inversion of the phosphate group similar to an S(N)2 mechanism. The ability of CNPs to interact with phosphate ester bonds of biologically relevant molecules has important implications for their use as potential therapeutics.
authors.affiliation: Cancer Research Institute, M. D. Anderson Cancer Center Orlando, Orlando, Florida, USA. melissa.kuchma@orlandohealth.com
authors.forename: Melissa Hirsch
authors.initials: MH
authors.lastname: Kuchma
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Komanski
authors.forename: Jimmie
authors.initials: J
authors.lastname: Colon
authors.forename: Andrew
authors.initials: A
authors.lastname: Teblum
authors.forename: Artëm E
authors.initials: AE
authors.lastname: Masunov
authors.forename: Beatrice
authors.initials: B
authors.lastname: Alvarado
authors.forename: Suresh
authors.initials: S
authors.lastname: Babu
authors.forename: Sudipta
authors.initials: S
authors.lastname: Seal
authors.forename: Justin
authors.initials: J
authors.lastname: Summy
authors.forename: Cheryl H
authors.initials: CH
authors.lastname: Baker
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry; D002563:Cerium / Q000737:chemistry*; D004247:DNA / Q000737:chemistry; D006868:Hydrolysis; D053758:Nanoparticles / Q000737:chemistry*; D009596:Nitrophenols / Q000737:chemistry; D010755:Organophosphates / Q000737:chemistry*; D009943:Organophosphorus Compounds / Q000737:chemistry; D019000:Phosphotyrosine / Q000737:chemistry
chemical_list: D009596:Nitrophenols; D010755:Organophosphates; D009943:Organophosphorus Compounds; D019000:Phosphotyrosine; D002563:Cerium; C008644:nitrophenylphosphate; C030583:ceric oxide; D000255:Adenosine Triphosphate; D004247:DNA