| Affiliation: | 1. Departamento de Química/Instituto de Tecnología Química UPV-CSIC, Universitat Politècnica de València, Camino de Vera s/n, 46022 València, Spain;2. Departamento de Química/Instituto de Tecnología Química UPV-CSIC, Universitat Politècnica de València, Camino de Vera s/n, 46022 València, Spain Unidad Mixta de Investigación UPV-Instituto de Investigación Sanitaria (IIS), La Fe, Hospital Universitari i Politècnic La Fe, Avenida de Fernando Abril Martorell 106, 46026 Valencia, Spain;3. Centro Singular de Investigación en Química Biolóxica e Materiais, Moleculares (CiQUS), Departamento de Química Orgánica, Universidade de Santiago de Compostela, Jenaro de la Fuente s/n, 15782 Santiago, de Compostela, Spain;4. Instituto de Ciencia Molecular, Universitat de València, P.O. Box 22085, 46071 València, Spain |
| Abstract: | Lapatinib (LAP) is an anticancer drug, which is metabolized to the N- and O-dealkylated products (N-LAP and O-LAP, respectively). In view of the photosensitizing potential of related drugs, a complete experimental and theoretical study has been performed on LAP, N-LAP and O-LAP, both in solution and upon complexation with human serum albumin (HSA). In organic solvents, coplanar locally excited (LE) emissive states are generated; they rapidly evolve towards twisted intramolecular charge-transfer (ICT) states. By contrast, within HSA only LE states are detected. Accordingly, femtosecond transient absorption reveals a very fast switching (ca. 2 ps) from LE (λmax=550 nm) to ICT states (λmax=480 nm) in solution, whereas within HSA the LE species become stabilized and live much longer (up to the ns scale). Interestingly, molecular dynamics simulation studies confirm that the coplanar orientation is preferred for LAP (or to a lesser extent N-LAP) within HSA, explaining the experimental results. |
