PHOSPHONATES AS MIMICS OF PHOSPHATE BIOMOLECULES - ABINITIO CALCULATIONS ON TETRAHEDRAL GROUND-STATES AND PENTACOORDINATE INTERMEDIATES FOR PHOSPHORYL TRANSFER

The use of phosphonates as analogs of phosphate biomolecules was explored using ab initio SCF calculations at the 3-21G(*) and 3-21+G(*) levels. Fully optimized geometries were obtained for the tetrahedral ground-state monoanions CHF2PO3H-, CH2FPO3H-, CH3PO3H-, BH3PO3H2-, H2PO3-, and O-2 XCHCH2O (X = O, CFH) and torsional energy profiles obtained for CH2FPO3H- and H2PO3-. Comparison was made of (1) structure and conformational dependence for these species and (2) electrostatic potential maps for ethylene phosphate and its monofluoromethylene phosphonate analog. The results suggest that, despite the isopolar relationship of fluoromethyl phosphonates and the parent phosphates, binding at a receptor site may be considerably perturbed for the phosphonate analogs. Fully optimized geometries were located for isomers of the pentacoordinate trigonal bipyramidal species PH4X (X = CH3, CF3, CF2H, CFH2, BH3, BF3-, O-, OH) and H3PXCH2CH2O (X = O, CH2, CFH, CF2). Torsional energy profiles were explored for PH4X (X = CH3, CF3, CF2H, CFH2). The calculated relative apicophilicity scale in PH4X (CF3 > CF2H > CFH2 > CH3 > OH > O- much less than BF3- > BH3-) varies in the five-membered cyclic phosphoranes by reversal of CH3 and OH. It is concluded that mono- and difluoromethylene phosphonates have similar ligand preferences to the parent phosphates in the pentacoordinate state and by consideration of the fully optimized geometry of the pentacoordinate dianion HO32-PCFHCH2CH26 that these phosphonates are capable of forming transition-state analogs at the active site of phosphoryl transfer enzymes.