A QM/MM study on triplet decay of 6-thioguanine and 6-selenoguanine with explicit solvent.

contextMotivated by their potential use as a photosensitizer in photodynamic therapy, we report an electrostatic embedding quantum mechanics/molecular mechanics (QM/MM) study of 6-selenoguanine and 6-thioguanine in water. We analyzed triplet-state nonradiative decay within quasi-Marcus theory and assessed the influence of solvation by comparing QM/MM with previous microsolvation and PCM models. Both molecules follow similar deactivation pathways, involving torsional distortion around the chalcogen center and decay through a T₁/S₀ crossing point. Experimental studies show that triplet decay of 6-selenoguanine (6SeGua) is 835 times faster than 6-thioguanine (6tGua) in water. The shorter T₁ lifetime of 6SeGua is due to its higher spin-orbit coupling (SOC) and lower activation barrier to reach the T

methodAll molecular dynamics simulations of 6SeGua and 6tGua were performed using AMBER 2023 with GAFF2 and the TIP3P water model. Representative equilibrated structures were used for QM/MM calculations within the COBRAMM framework using electrostatic embedding. The QM region was treated using TD-DFT within the Tamm-Dancoff approximation (TDA) at the CAM-B3LYP/6-311G* level, with electronic structure calculations performed using Gaussian 16. T₁/S₀ crossing points were optimized using an in-house CIOpt program. Spin-orbit coupling (SOC) matrix elements were calculated using the PySOC program based on the Breit-Pauli spin-orbit Hamiltonian with the effective charge approximation. Nonradiative ISC rates were estimated using a quasi-Marcus approach, and noncovalent interactions were analyzed using QTAIM and IGMH methods with Multiwfn.