QUANTUM-CHEMICAL STUDIES OF PYROPHOSPHATE HYDROLYSIS

The hydrolysis of pyrophosphate to form two orthophosphates is coupled to virtually all biosynthetic reactions. Despite numerous experiments , a detailed understanding of the energetic factors contributing to th is reaction energy is still lacking. In this paper we describe large b asis set ab initio calculations of the reaction energy for pyrophospha te hydrolysis. These calculations were performed using second-order Mo ller-Plesset perturbation theory at the Hartree-Fock/6-311++G* optimi zed geometries. We find that in the gas phase the hydrolysis of the fu lly-protonated pyrophosphate is unfavored by 5 kcal/mol. The origin of this unfavorable free energy is a pair of intramolecular hydrogen bon ds that link the two phosphate moieties. For the anionic forms of pyro phosphate that exist near neutral pH, the gas-phase hydrolysis energie s are strongly negative due to electrostatic repulsion. We have also p redicted the aqueous phase hydration energy using several methods base d on a dielectric continuum model of the aqueous solvent. Aqueous solv ation acts to cancel this repulsion; the ab initio aqueous phase resul t, which we expect to be most reliable; predicts hydrolysis energies o f 3 to 7 kcal/mol for the protonation states predominant near physiolo gical pH.