This work presents a systematic investigation of the electronic and conformational properties of five new fluorescent nucleobases belonging to the alphabet based on the isothiazole[4,3-d]pyrimidine molecule, very recently synthesized. This is of particular importance in the characterization of the main electronic aspects of these fluorescent nucleosides. The solvent effects of 1,4-dioxane and water were included combining the Sequential Monte Carlo/CASPT2 and the Free Energy Gradient (FEG) methods. For comparison, the Polarizable Continuum method was also used. The geometries of all compounds were optimized in solvent with the largest effects observed in water using the average solvent electrostatic configuration (ASEC) and the FEG approaches. Statistical analysis of the solute-solvent hydrogen bonds is performed and their effect on the absorption spectra analyzed. The dipole moments were calculated and the value obtained from the ASEC-FEG method in water follows the same trend as the natural canonical bases (adenine → uracil → guanine → cytosine). The theoretical results for the absorption spectra obtained from CASPT2(18,13) calculations using the geometries obtained with the ASEC-FEG procedure are in very good agreement with the experimental data. A detailed elucidation of the main aspects of the absorption spectra of the five new fluorescent nucleoside analogues is successfully attempted.

The photophysical relaxation pathways of tz A, tz G, and tz I luminescent nucleobases were investigated with the MS-CASPT2 quantumchemical method and double-ζ basis sets (cc-pVDZ) in gas and condensed phases (1,4-dioxane and water) with the sequential Monte Carlo/CASPT2 and free energy gradient (FEG) methods. Solvation shell structures, in the ground and excited states, were examined with the pairwise radial distribution function (G(r)) and solute−solvent hydrogen-bond networks. Site-specific hydrogen bonding analysis evidenced relevant changes between both electronic states. The three luminescent nucleobases share a common photophysical pattern, summarized as the lowest-lying 1 (ππ*) bright state that is populated directly after the absorption of radiation and evolves barrierless to the minimum energy structure, from where the excess of energy is released by fluorescence.From the 1 (ππ*) min region, the conical intersection with the ground state ((ππ*/GS) CI ) is not accessible due to the presence of high energetic barriers. By combining the present results with those reported earlier by us for the pyrimidine fluorescent nucleobases, we present a comprehensive description of the photophysical properties of this important class of new fluorescent nucleosides.

The tz C and tz U emissive properties were investigated with the MS-CASPT2 method and CASSCF/CASPT2 protocol, with inclusion of solvent effects with the aid of the PCM and Sequential QM/MM, the Free Energy Gradient methods. Theoretical vertical emission energies and Stokes shifts, using the ASEC-FEG method, are in a good agreement with the experimental data, within the expected accuracy of CASPT2 method. Their emissive properties can be understood in analogy to the photophysical behaviour of the canonical uracil and cytosine pyrimidine nucleobases, for which the twisting of the C 5 C 6 bond is the key for understanding their ultrashort radiationless decay times. For both tz C and tz U, the computed photophysical deactivation pathway, shows that the bright state 1 ðpp * Þ goes directly to a minimum structure on its potential energy hypersurface ð 1 ðpp * Þ min Þ, from where no conical intersection with the ground state can be reached, due to the steric hindrance of the C 5 C 6 position, which forms the bridge between the rings in both molecules. Solvent effects place the conical intersection in higher energy region, reinforcing their emissive nature.

The photochemical reaction path approach, the MS-CASPT2 quantum-chemical method, and double-ζ basis sets (cc-pVDZ) were used to study 9H-8-azaguanine and 8H-8-azaguanine relaxation pathways. Several potential energy hypersurfaces were characterized by means of equilibrium geometries, surface crossings (conical intersections and singlet–triplet intersystem crossings), minimum energy paths, and linear interpolation in internal coordinates. The 9H-8-azaguanine main photochemical event begins with the direct population of the 1(ππ* La) state, which evolves toward a conical intersection with the ground state after surmounting a small energy barrier, explaining why it is nonfluorescent. For 8H-8-azaguanine, two relaxation mechanisms are possible, depending on the excitation energy. If the S1 1(ππ*) state is initially populated (lower-energy region), the system evolves barrierless to the S1 1(ππ*)min region, from where the excess energy is released. If the 1(ππ* La) state is populated (higher-energy radiation), the system will encounter conical intersections with the S2 1(nOπ*) and S1 1(ππ*) states before evolving to the 1(ππ* La)min region, from where a conical intersection with the ground state is accessible, favoring radiationless deactivation to the ground state. However, because a fraction of the population can be transferred from 1(ππ* La) to the S1 1(ππ*) state, emission from the S1 1(ππ*)min region is also expected, although weaker than it would be if the S1 1(ππ*) state were populated directly. Irrespective of the excitation energy, the emissive state is the same and a single fluorescence band is observed, with the strongest emission occurring upon excitation in the lower-energy region, as observed experimentally. Therefore, our computational study corroborates experimental results, attributing the emission of the neutral form of 8-azaguanine in solution to the presence of the minor 8H-8-azaguanine tautomer, while the 9H-8-azaguanine major tautomer is nonfluorescent.

The population and depopulation mechanisms leading to the lowest-lying triplet states of the 2-Se-Thymine were studied at the MS-CASPT2/cc-pVDZ level of theory. Several critical points on different potential energy hypersurfaces...