title: UV-vis spectra of the anticancer camptothecin family drugs in aqueous solution: specific spectroscopic signatures unraveled by a combined computational and experimental study.
abstract: The ultraviolet-visible absorption spectrum of camptothecin (CPT) has been been recorded in aqueous solution at pH 5.3, where the equilibrium among the different CPT forms is shifted toward the lactonic one. Time-dependent density functional theory (TD-DFT) computations lead to a remarkable reproduction of the experimental spectrum only upon addition of explicit water molecules in interaction with specific moieties of the camptothecin molecule. Molecular dynamics (MD) simulations enforcing boundary periodic conditions for CPT embedded with 865 water molecules, with a force field derived from DFT computations, show that the experimental spectrum is due to the contributions of CPT molecules with different solvation patterns. A similar solvent effect is observed for several CPT derivatives, including the clinically relevant SN-38 and topotecan drugs. The quantitative agreement between TD-DFT/MD computations and experimental data allow us to identify specific spectroscopic signatures diagnostic of the drug environment and to develop procedures that can be used to monitor the drug-DNA/protein interaction.
authors.affiliation: CASPUR, Consortium for Supercomputing in Research, Via dei Tizii 6, 00185 Roma, Italy. sanna@caspur.it
authors.forename: Nico
authors.initials: N
authors.lastname: Sanna
authors.forename: Giovanni
authors.initials: G
authors.lastname: Chillemi
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Gontrani
authors.forename: Andrea
authors.initials: A
authors.lastname: Grandi
authors.forename: Giordano
authors.initials: G
authors.lastname: Mancini
authors.forename: Silvia
authors.initials: S
authors.lastname: Castelli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Zagotto
authors.forename: Costantino
authors.initials: C
authors.lastname: Zazza
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Barone
authors.forename: Alessandro
authors.initials: A
authors.lastname: Desideri