Interaction of propargyl cation with tetrahydrofuran: Thermodynamics, kinetics, and biological relevance

Ab initio calculations have been carried out for the reaction of propargyl cation and tetrahydrofuran, a model for the novel stereoselective reductive dimerization of cobalt-complexed propargyl cations, mimicking, on a molecu lar level, DNA damage inflicted by electrophilic carcinogenic agents. The o ptimized geometries derived from semiempirical calculations (AM1) have been employed in ab initio calculations using Hartree-Fock (3-21G* and 6-31G* b asis sets) and density functional theory (DFT) methods. The highly exotherm ic character of the major mechanistic pathways, a hydride-ion transfer towa rd the carbocationic center and a direct coordination of the latter with an oxygen atom in tetrahydrofuran, has been revealed (-49.74 to -72.85 kcal/m ol). A two-electron, three-membered "late" transition state was found for t he hydride-ion transfer pathway with an activation energy of +24.69 kcal/mo l. A direct one-electron oxidation of tetrahydrofuran by propargyl cation i s the mechanistic pathway most sensitive toward the calculation technique u sed: ab initio method employing 3-21G* and 6-31G* basis sets suggests exoth ermicity for the process in question, whereas DFT calculation using the num erical polarization basis sets indicates moderate endothermicity (+7.74 kca l/mol). The mechanistically distinct pathways thus identified-"ionic", "bin ding", and "radical"-imply that structural alteration of DNA caused by elec trophilic carcinogenic agents may occur by (a) a delivery of hydride-ion or iginating from 1' and 4' positions of the sugar moiety toward the electroph ilic center, (b) binding of the electron-deficient species to an oxygen ato m in a ribose ring, and (c) a single-electron transfer toward the electroph ile with a ribose ring acting as a reducing moiety.