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 ani on (CH3-O-PO2-CH2-O-CH3)(-), a nuclease resistant alternative to the p hosphodiester linkage in DNA, have been investigated by ab initio quan tum mechanical calculations. The potential of backbone torsional degre es of freedom of methyl methoxymethyl phosphonate anion (MMP) was dete rmined at the Hartree-Fock (HF) 3-21G level using the adiabatic mappi ng technique. Energies, geometries, and effective atomic charges of di fferent conformers were calculated at HF/6-31G and MP2/6-31G* levels of theory. These were compared to the results obtained for dimethyl ph osphate calculated at the same level. The impact on DNA structure from inserting a methylene group between phosphorus and oxygen of the nucl eoside sugar moiety was examined via distance- and angle-constrained g eometry optimizations. Due to its high flexibility, MMP has been shown to be compatible with both A and B forms of DNA.