Mapping the influence of ligand electronics on the spectroscopic and 1O2 sensitization characteristics of Pd(ii) biladiene complexes bearing phenyl–alkynyl groups at the 2- and 18-positions

Abstract

Photodynamic therapy (PDT) is a promising treatment for certain cancers that proceeds via sensitization of ground state ³O₂ to generate reactive ¹O₂. Classic macrocyclic tetrapyrrole ligand scaffolds, such as porphyrins and phthalocyanines, have been studied in detail for their ¹O₂ photosensitization capabilities. Despite their compelling photophysics, these systems have been limited in PDT applications because of adverse biological side effects. Conversely, the development of non-traditional oligotetrapyrrole ligands metalated with palladium (Pd[DMBil1]) have established new candidates for PDT that display excellent biocompatibility. Herein, the synthesis, electrochemical, and photophysical characterization of a new family of 2,18-bis(phenylalkynyl)-substituted Pd^II 10,10-dimethyl-5,15-bis(pentafluorophenyl)-biladiene (Pd[DMBil2-R]) complexes is presented. These second generation biladienes feature extended conjugation relative to previously characterized Pd^II biladiene scaffolds (Pd[DMBil1]). We show that these new derivatives can be prepared in good yield and, that the electronic nature of the phenylalkynyl appendages dramatically influence the Pd^II biladiene photophysics. Extending the conjugation of the Pd[DMBil1] core through installation of phenylacetylene resulted in a ∼75 nm red-shift of the biladiene absorption spectrum into the phototherapeutic window (600–900 nm), while maintaining the Pd^II biladiene's steady-state spectroscopic ¹O₂ sensitization characteristics. Varying the electronics of the phenylalkyne groups via installation of electron donating or withdrawing groups dramatically influences the steady-state spectroscopic and photophysical properties of the resulting Pd[DMBil2-R] family of complexes. The most electron rich variants (Pd[DMBil2-N(CH₃)₂]) can absorb light as far red as ∼700 nm but suffer from significantly reduced ability to sensitize formation of ¹O₂. By contrast, Pd[DMBil2-R] derivatives bearing electron withdrawing functionalities (Pd[DMBil2-CN] and Pd[DMBil2-CF₃]) display ¹O₂ quantum yields above 90%. The collection of results we report suggest that excited state charge transfer from more electron-rich phenyl-alkyne appendages to the electron deficient biladiene core circumvents triplet sensitization. The spectral and redox properties, as well as the triplet sensitization efficiency of each Pd[DMBil2-R] derivative is considered in relation to the Hammett value (σ_p) for each biladiene's R-group. More broadly, the results reported in this study clearly demonstrate that biladiene redox properties, spectral properties, and photophysics can be perturbed greatly by relatively minor alterations to biladiene structure.