Using Quantum Mechanics to Investigate the Photophysical Properties of the DNA and RNA Bases and their Fluorescent Analogs

Abstract

The ability of the nucleic acids to absorb ultraviolet light and remain relatively photostable is a property upon which life depends. The nucleobases, which are the primary chromophores, when irradiated display rapid radiationless decay back to the ground state, in general faster than is needed for photoreaction. Fluorescent analogs of these bases have structures similar to the nucleic acid bases, but display much longer excited state lifetimes. Theoretical investigations using quantum mechanical methods can provide insight into the precise mechanisms of these decay processes, and to the molecular specifics that contribute to them. The results of multi-reference configuration interaction (MRCI) ab initio investigations into these mechanisms are presented, with emphasis on cytosine and its fluorescent analog 5-methyl-2-pyrimidinone (5M2P). A comprehensive picture of the potential energy surfaces of these two bases is given, including stationary points and conical intersections, where radiationless transitions are promoted, between up to three state surfaces, as well as pathways connecting these points for each base. Cytosine is shown to have two different energetically accessible radiationless decay channels. The fluorescence of 5M2P is also demonstrated theoretically, with mechanism proposed. The potential energy surfaces of the two bases have many close similarities, with the different photophysical properties being attributed to subtle energetic differences between the two bases. Nonadiabatic coupling and the geometric phase effect are analyzed in detail near conical intersections in cytosine, including in a region close to a three-state conical intersection. A substituent effect study on the 2-pyrimidinone ring system shows that the presence, position and orientation of the amino group in cytosine is central to its photophysical properties, particularly its high absorption energy, and can be explained with a simple Frontier Molecular Orbital model. The effects of water solvent on the excitation energies of cytosine and uracil are theoretically investigated using two multi-reference ab initio methods, a quantum mechanical molecular mechanics method using MRCI (MRCI-QM/MM), and the fragment molecular orbital multiconfiguration self-consistent field method (FMO-MCSCF). The solvatochromic shifts calculated from both methods agree well with other more expensive methods and experimental data. The effects of water on the photophysical pathways of cytosine is also investigated using MRCI-QM/MM, including considerations of solvent reorganization. Results show that the overall effect of water on the decay mechanisms is small, with neither decay channel being significantly blocked or favored.