Rational Design of Advanced Photosensitizers Based on Orthogonal BODIPY Dimers to Finely Modulate Singlet Oxygen Generation.
The synthesis, photophysical characterization, and modeling of a new library of halogen-free photosensitizers (PS) based on orthogonal boron dipyrromethene (BODIPY) dimers are reported. Herein we establish key structural factors in order to enhance singlet oxygen generation by judiciously choosing the substitution patterns according to key electronic effects and synthetic accessibility factors. The photosensitization mechanism of orthogonal BODIPY dimers is demonstrated to be strongly related to their intrinsic intramolecular charge transfer (ICT) character through the spin-orbit charge-transfer intersystem crossing (SOCT-ISC) mechanism. Thus, singlet oxygen generation can be effectively modulated through the solvent polarity and the presence of electron-donating or withdrawing groups in one of the BODIPY units. The photodynamic therapy (PDT) activity is demonstrated by in vitro experiments, showing that selected photosensitizers are efficiently internalized into HeLa cells, exhibiting low dark toxicity and high phototoxicity, even at low PS concentration (0.05-5×10-6m).
Departamento de Química Física, Universidad del País Vasco-EHU, Apartado 644, 48080, Bilbao, Spain.
Nerea
N
Epelde-Elezcano
Departamento de Química Orgánica I, Facultad de CC. Químicas, Universidad Complutense de Madrid, Ciudad Universitaria s/n, 28040, Madrid, Spain.
Eduardo
E
Palao
Departamento de Física de la Materia Condensada, Universidad del País Vasco-EHU, Apartado 644, 48080, Bilbao, Spain).
Hegoi
H
Manzano
Departamento de Química Orgánica I, Facultad de CC. Químicas, Universidad Complutense de Madrid, Ciudad Universitaria s/n, 28040, Madrid, Spain.
Alejandro
A
Prieto-Castañeda
Departamento de Química Física, Universidad del País Vasco-EHU, Apartado 644, 48080, Bilbao, Spain.
Antonia R
AR
Agarrabeitia
Departamento de Biología, Universidad Autónoma de Madrid, Darwin 2, 28049, Madrid, Spain.
Andrea
A
Tabero
Departamento de Biología, Universidad Autónoma de Madrid, Darwin 2, 28049, Madrid, Spain.|Instituto Madrileño de Estudios Avanzados (IMDEA) Nanociencia, Ciudad Universitaria de Cantoblanco, 28049, Madrid, Spain.
Angeles
A
Villanueva
Departamento de Química Orgánica I, Facultad de CC. Químicas, Universidad Complutense de Madrid, Ciudad Universitaria s/n, 28040, Madrid, Spain.
Santiago
S
de la Moya
Departamento de Química Física, Universidad del País Vasco-EHU, Apartado 644, 48080, Bilbao, Spain.
Íñigo
Í
López-Arbeloa
Departamento de Química Física, Universidad del País Vasco-EHU, Apartado 644, 48080, Bilbao, Spain.
Virginia
http://orcid.org/0000-0001-7551-3714
V
Martínez-Martínez
Departamento de Química Orgánica I, Facultad de CC. Químicas, Universidad Complutense de Madrid, Ciudad Universitaria s/n, 28040, Madrid, Spain.
María J
MJ
Ortiz
biological activity; charge transfer; singlet oxygen; solvent effects; substituent effects