Two-photon absorption (2PA) is a nonlinear optical process which requires a high light intensity and leads to the simultaneous absorption of two photons. The use of low-energy (near-infrared) focused light allows deeper penetration into the material or tissue being analyzed while causing less damage. Therefore, 2PA has widespread applications in microscopy, 3D data storage, microfabrication, bioimaging and photodynamic therapy. However, the design of efficient molecular light absorbers still poses challenges, and, as such, computational prediction of 2PA [1,2] can play an important role in understanding and predicting absorption properties of new synthetic targets. I will discuss our recent computational research examining two-photon absorption (2PA) cross-sections [1-4] in small fluorescent molecules and fluorescent protein chromophores. I will introduce 2PA including the use of two- (or few-) level models for interpreting 2PA cross-sections, based on transition dipole moments (oscillator strengths), permanent dipole moments, and excitation energies. I will also emphasize differences between degenerate 2PA, where both absorbed photons have equal energies, and non-degenerate 2PA, where absorbed photons have different energies. Results presented are determined using both time-dependent density functional theory (TD-DFT) and the approximate second-order coupled cluster (RI-CC2) approaches. I will show the importance of the choice of functional for predicting 2PA cross-sections [1] but also hioghlight alternative approaches such as GW/BSE [2].

[1] I.A. Elayan, L. Rib, R.A. Mendes, and A. Brown, 2024, Beyond Explored Functionals: A Computational Journey of Two-Photon Absorption, J. Chem. Theory Comput., 20(9) 3879–3893. DOI: 10.1021/acs.jctc.4c00133
[2] A. Henderson, I.A. Elayan, and A. Brown, 2025, Beyond TD-DFT: Assessing the Bethe–Salpeter Equation within the GW Approximation for Absorption Properties, J. Phys. Chem. Lett, 16, 12137–12145. DOI: 10.1021/acs.jpclett.5c02447
[3] I.A. Elayan and A. Brown, 2024, Non-Degenerate Two-Photon Absorption of Fluorescent Protein Chromophores, J. Phys. Chem. A, 128, 36, 7511–7523. DOI: 10.1021/acs.jpca.3c08402. DOI: 10.1021/acs.jpca.3c08402
[4] I.A. Elayan and A. Brown, 2023, Degenerate and Non-Degenerate Two-Photon Absorption of Coumarin Dyes, Phys. Chem. Chem. Phys., 25, 16772-16780. DOI: 10.1039/D3CP00723E