title: Density functional calculations on the effect of sulfur substitution for 2'-hydroxypropyl-p-nitrophenyl phosphate: C-O vs. P-O bond cleavage.
abstract: Density functional theory calculations have been used to investigate the intra-molecular attack of 2'-hydroxypropyl-p-nitrophenyl phosphate (HPpNP) and its analogous compound 2-thiouridyl-p-nitrophenyl phosphate (s-2'pNP). Bulk solvent effect has been tested at the geometry optimization level with the polarized continuum model. It is found that the P-path involving the intra-molecular attack at the phosphorus atom and C-path involving the attack at the beta carbon atom proceed through the S(N)2-type mechanism for HPpNP and s-2'pNP. The calculated results indicate that the P-path with the free energy barrier of about 11 kcal/mol is more accessible than the C-path for the intra-molecular attack of HPpNP, which favors the formation of the five-membered phosphate diester. While for s-2'pNP, the C-path with the free energy barrier of about 21 kcal/mol proceeds more favorably than the P-path. The calculated energy barriers of the favorable pathways for HPpNP and s-2'pNP are both in agreement with the experimental results.
authors: School of Chemistry, Sichuan University, Chengdu 610064, China.
authors: Futing
authors: F
authors: Xia
authors: School of Chemistry, Sichuan University, Chengdu 610064, China; State Key Laboratory of Biotherapy, Sichuan University, Chengdu 610064, China. Electronic address: zhuhua@scu.edu.cn.
authors: Hua
authors: H
authors: Zhu
mesh_terms: D002244:Carbon / Q000737:chemistry; D008956:Models, Chemical; D009596:Nitrophenols / Q000737:chemistry*; D010755:Organophosphates / Q000737:chemistry*; D009943:Organophosphorus Compounds / Q000737:chemistry*; D010100:Oxygen / Q000737:chemistry; D010758:Phosphorus / Q000737:chemistry; D012997:Solvents / Q000737:chemistry; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D013455:Sulfur / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: C436487:2-(hydroxypropyl)-4-nitrophenyl phosphate; D009596:Nitrophenols; D010755:Organophosphates; D009943:Organophosphorus Compounds; D012997:Solvents; D013438:Sulfhydryl Compounds; D010758:Phosphorus; C008644:nitrophenylphosphate; D013455:Sulfur; D002244:Carbon; D010100:Oxygen