Ab initio investigation of the molecular structure of methyl methoxymethyl phosphonate, a promising nuclease-resistant alternative of the phosphodiester linkage.

Conformational flexibility of the methyl methoxymethyl phosphonate anion (CH3-O-PO2-CH2-O-CH3)-, a nuclease resistant alternative to the phosphodiester linkage in DNA, have been investigated by ab initio quantum mechanical calculations. The potential of backbone torsional degrees of freedom of methyl methoxymethyl phosphonate anion (MMP) was determined at the Hartree-Fock (HF) 3-21G* level using the adiabatic mapping technique. Energies, geometries, and effective atomic charges of different conformers were calculated at HF/6-31G* and MP2/6-31G* levels of theory. These were compared to the results obtained for dimethyl phosphate calculated at the same level. The impact on DNA structure from inserting a methylene group between phosphorus and oxygen of the nucleoside sugar moiety was examined via distance and angle-constrained geometry optimizations. Due to its high flexibility, MMP has been shown to be compatible with both A and B forms of DNA.