Spin–Orbit Charge‐Transfer Intersystem Crossing (ISC) in Compact Electron Donor–Acceptor Dyads: ISC Mechanism and Application as Novel and Potent Photodynamic Therapy Reagents

Abstract

Spin-orbit charge-transfer intersystem crossing (SOCT-ISC) is useful for the preparation of heavy atom-free triplet photosensitisers( PSs). Herein, as eries of perylene-Bodipy compact electrond onor/acceptor dyads showing efficient SOCT-ISC is prepared. The photophysical properties of the dyads were studiedw ith steady-state and time-resolved spectroscopies. Efficient triplet state formation (quantum yield F T = 60 %) waso bserved, with at riplets tate lifetime (t T = 436 ms) much longert han that accessed with the conventional heavy atom effect (t T = 62 ms). The SOCT-ISC mechanism wasu nambiguously confirmed by direct excitation of the charget ransfer (CT) absorption band by using nanosecond transienta bsorption spectroscopy and time-resolved electronp aramagnetic resonance (TREPR) spectroscopy.T he factors affecting the SOCT-ISC efficiency include the geometry,t he potential energy surfaceo ft he torsion, the spin density for the atoms of the linker,s olvent polarity,a nd the energym atchingo ft he 1 CT/ 3 LE states. Remarkably,t hese heavya tom-free triplet PSs were demonstrated as an ew type of efficient photodynamic therapy (PDT) reagents (phototoxicity,E C 50 = 75 nm), with an egligibled ark toxicity (EC 50 = 78.1 mm)c ompared with the conventionalh eavy atom PSs (dark toxicity,E C 50 = 6.0 mm, light toxicity, EC 50 = 4.0 nm). This study provides in-depthu nderstanding of the SOCT-ISC, unveils the design principles of triplet PSs based on SOCT-ISC, andu nderlines their applicationa sanew generationo fp otent PDT reagents.[a] Dr.[h] Prof. M. Di Donato INO, Istituto Nazionale di Ottica Largo Enrico Fermi 6, 50125F lorence (Italy)[ + + ] These authorscontributed equally to this work.Supporting information and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.

Quantitative Structure‐Property Relationship Modelling for the Prediction of Singlet Oxygen Generation by Heavy‐Atom‐Free BODIPY Photosensitizers**

“…On the other hand, the remaining two BODIPY compounds (BDP-5 and BDP-6) presented two multiplets at ~-144 and -146 ppm (Figures S8 and S13), which can be attributed to the single ortho-methoxy substituent forming an inequivalent environment for the Fatoms. 58,62 Finally, all compounds showed a typical triplet peak (~0.3 ppm) in their 11 B NMR spectra, as expected. 60 Furthermore, the structures of all four newly synthesized donoracceptor dyads (BDP 4-7) were analyzed through single crystal X-ray crystallography.…”

“…Mono-methoxy substituted BODIPY derivatives (BDP-1, BDP-2 and BDP-3) were prepared as reference compounds following previously published procedures. 59 All BODIPY compounds (BDP 1-7) were fully characterized through 1 H, 13 C, 19 F, 11 B NMR spectroscopy and HRMS (see ESI). The spectroscopic data of the three reference derivatives (BDP 1-3) were identical with those reported previously.…”

“…Singlet oxygen quantum yields were calculated based on the equation: (11) where ΦΔ is the singlet oxygen quantum yield; the superscript ref stands for 2,6-diiodoBODIPY (0.85 in toluene) 81 ; k is the slope of the curves of DMA absorption (376 nm) change vs. irradiation time; Iabs represents the absorption correction factor which is given by I = 1-10 -OD (OD is the optical density at 514 nm).…”

“…Instrumentation: Melting points are uncorrected and were measured on a Reichert Thermovar Apparatus. NMR spectra were recorded on a Bruker Advance III 400 MHz spectrometer for 1 H (400 MHz), 13 C (101 MHz), 19 F (377 MHz) and 11 UV-Vis spectra were recorded in solutions using a PerkinElmer Lambda 900 UV/VIS/NIR Spectrometer (1 cm path length quartz cell). Emission spectra were measured using a PerkinElmer LS 55 Luminescence Spectrometer.…”

“…5 Moreover, the presence of heavy atoms can also result in shortening the triplet state lifetimes. 6 The replacement of costly transition metal complexes in industrial-scale photocatalytic processes with organic PSs has drawn considerable attention, 7 and has stimulated a search for alternative methods to promote ISC, not relying on the heavy atom effect, e.g., using a spin converter, 8 exciton coupling, 9 doubly-substituted excited states, 10 twisting of the aromatic systems 11 and radical-induced ISC have been very actively studied in recent years. The formation of triplet excited states in electron donor-acceptor dyads via the process of spin-orbit charge transfer intersystem crossing (SOCT-ISC) does not require introduction of transition metals or other heavy atoms into the molecule.…”