Conformational Analysis and Electronic Structure of Folic Acid: A Theoretical Study

Abstract Folic acid decomposes when exposed to UV light so understanding of photochemical behavior of this biomolecule is very important. In this study, sixty conformers of folic acid were investigated by two methods of DFT calculations. The three most stable conformers were selected for study of their electronic structure and photoelectron spectra. The valence photoelectron spectra were simulated by two high level ab initio computational methods: general-R symmetry adapted cluster-configuration interaction (general-R-SAC-CI) method and outer-valence Green's function (OVGF). The SAC-CI computations were performed with two different basis sets: D95 (df,pd) and 6-311G(d,p). Because of the size of the folic acid molecule, OVGF calculations were only performed with 6-311G(d,p) basis set. The simulated photoelectron spectrum of folic acid was obtained by the superposition of weighted photoelectron spectra of individual conformers. natural bonding orbitals (NBO) calculations were performed for the assignment of simulated photoelectron spectra. The lowest energy ionizations occurs mostly from the orbitals localized on p -aminobenzoyl moiety in folic acid. Koopmans' approximation is only valid for describing the five lowest energy orbital ionizations (photoelectron bands). The in-situ molecular structures of two bio-active conformers were extracted from X-ray diffraction data obtained for folic acid bound to folate receptor protein. These molecular structures were then used for calculating ionization energies. We discuss the consequences for ligand-receptor binding of switching from the most stable conformation to bioactive conformation in FA.