Theoretical Evaluation of pK_a in Phosphoranes:  Implications for Phosphate Ester Hydrolysis

Abstract

Knowledge of the pK(a) of phosphoranes is important for the interpretation of phosphate ester hydrolysis. Calculated pK(a)'s of the model phosphorane, ethylene phosphorane, are reported. The method of calculation is based on the use of dimethyl phosphate as a reference state for evaluating relative pK(a) values, and on the optimization of the oxygen and acidic hydrogen van der Waals radii to give reasonable pK(1)(a), pK(2)(a), and pK(3)(a) for phosphoric acid in solution. Density functional theory is employed to calculate the gas-phase protonation energies, and continuum dielectric methods are used to determine the solvation corrections. The calculated pK(1)(a) and p(2)(a) for the model phosphorane are 7.9 and 14.3, respectively. These values are within the range of proposed experimental values, 6.5-11.0 for pK(1)(a), and 11.3-15.0 for pK(2)(a). The mechanistic implications of the calculated pK(a)'s are discussed.

Coupling of Protonation, Reduction, and Conformational Change in azurin from Pseudomonas aeruginosa Investigated with Free Energy Measures of Cooperativity

“…19,40 The intrinsic energies for the model compounds of deprotonated arginine could not be simply computed from the macroscopic pK a value of the model compounds, since the different tautomeric forms are not equivalent. The relative intrinsic energies of the tautomers were computed from their relative free energies in aqueous solution.…”

Electron capture dissociation and infrared multiphoton dissociation of oligodeoxynucleotide dications

“…In our experiments with protonated oligonucleotides, the phosphate groups are neutral before electron capture but a hydrogen bond between a terminal 5'-or 3'-sugar hydroxyl hydrogen and a neutral backbone phosphate oxygen could still facilitate their interaction (see Scheme 2 for the 5'-case). Formation of fragment ions corresponding to (w/d ϩ H 2 O) could possibly proceed through a pentavalent phosphorane structure (see Scheme 2), which is known to be involved in RNA hydrolysis [75][76][77]. Nucleoside-like fragment ions with a structure complementary to (w n /d n ϩ H 2 O) (molecule II in Scheme 3) are commonly observed in CID of protonated oligonucleotides, indicating that such ions are relatively stable [50,51].…”

Calculation of the Solvation Free Energy of the Proton in Methanol

“…1 Examples 1-24 include carboxylic acids, [7][8][9]11,14,[17][18][19] alcohols, 11 thiols, 11 phenols, 21 pyrone derivatives, 12 amines, 3 imidazoles, 5,24 hydrated transition metal cations, 2 transition metal complexes, 16 phosphoranes, 22 and DNA (RNA) bases. 6,15,23 Recent applications are extended to the evaluation of pK a values of 1) intermediate species that are not easily measured experimentally, 22 2) weak organic acids with high pK a values, 13 which cannot be measured experimentally in aqueous phase, and 3) molecules having multiple protonation sites.…”

“…6,15,23 Recent applications are extended to the evaluation of pK a values of 1) intermediate species that are not easily measured experimentally, 22 2) weak organic acids with high pK a values, 13 which cannot be measured experimentally in aqueous phase, and 3) molecules having multiple protonation sites. 23 Since the computation of pK a involves quantum chemical calculations of the deprotonation events at the gas phase and the evaluations of the solvation free energies of the various species, 20 the accuracy relies on the methods for evaluating the gas phase acidity (or basicity), and for the solvation free energies.…”