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

Spin–orbit charge-transfer intersystem crossing (SOCT-ISC) is useful for the preparation of heavy atom-free triplet photosensitisers (PSs). Herein, a series of perylene-Bodipy compact electron donor/acceptor dyads showing efficient SOCT-ISC is prepared. The photophysical properties of the dyads were studied with steady-state and time-resolved spectroscopies. Efficient triplet state formation (quantum yield Φ_T=60 %) was observed, with a triplet state lifetime (τ_T=436 μs) much longer than that accessed with the conventional heavy atom effect (τ_T=62 μs). The SOCT-ISC mechanism was unambiguously confirmed by direct excitation of the charge transfer (CT) absorption band by using nanosecond transient absorption spectroscopy and time-resolved electron paramagnetic resonance (TREPR) spectroscopy. The factors affecting the SOCT-ISC efficiency include the geometry, the potential energy surface of the torsion, the spin density for the atoms of the linker, solvent polarity, and the energy matching of the ¹CT/³LE states. Remarkably, these heavy atom-free triplet PSs were demonstrated as a new type of efficient photodynamic therapy (PDT) reagents (phototoxicity, EC₅₀=75 nm ), with a negligible dark toxicity (EC₅₀=78.1 μm ) compared with the conventional heavy atom PSs (dark toxicity, EC₅₀=6.0 μm, light toxicity, EC₅₀=4.0 nm ). This study provides in-depth understanding of the SOCT-ISC, unveils the design principles of triplet PSs based on SOCT-ISC, and underlines their application as a new generation of potent PDT reagents.     

Long-Lived Triplet Excited State Accessed with Spin–Orbit Charge Transfer Intersystem Crossing in Red Light-Absorbing Phenoxazine-Styryl BODIPY Electron Donor/Acceptor Dyads

Orthogonal phenoxazine-styryl BODIPY compact electron donor/acceptor dyads were prepared as heavy atom-free triplet photosensitizers (PSs) with strong red light absorption (ϵ=1.33×10⁵ M⁻¹ cm⁻¹ at 630 nm), whereas the previously reported triplet photosensitizers based on the spin-orbit charge transfer intersystem crossing (SOCT-ISC) mechanism show absorption in a shorter wavelength range (<500 nm). More importantly, a long-lived triplet state (τ_T=333 μs) was observed for the new dyads. In comparison, the triplet state lifetime of the same chromophore accessed with the conventional heavy atom effect (HAE) is much shorter (τ_T=1.8 μs). Long triplet state lifetime is beneficial to enhance electron or energy transfer, the primary photophysical processes in the application of triplet PSs. Our approach is based on SOCT-ISC, without invoking of the HAE, which may shorten the triplet state lifetime. We used bisstyrylBodipy both as the electron acceptor and the visible light-harvesting chromophore, which shows red-light absorption. Femtosecond transient absorption spectra indicated the charge separation (109 ps) and SOCT-ISC (charge recombination, CR; 2.3 ns) for BDP-1 . ISC efficiency of BDP-1 was determined as Φ_T=25 % (in toluene). The dyad BDP-3 was used as triplet PS for triplet-triplet annihilation upconversion (upconversion quantum yield Φ_UC=1.5 %; anti-Stokes shift is 5900 cm⁻¹).     

Engineering the Charge-Transfer State to Facilitate Spin–Orbit Charge Transfer Intersystem Crossing in Spirobis[anthracene]diones

Spiro conjugation has been proposed to dictate the efficiency of charge transfer, which could directly affect the spin–orbit charge transfer intersystem crossing (SOCT-ISC) process. However, this process has yet to be exemplified. Herein, we prepared three spirobis[anthracene]diones, in which two benzophenone moieties are locked in close proximity and differentially functionalized to fine-tune the charge transfer state. Its feasibility for SOCT-ISC was theoretically predicted, then experimentally evaluated. Through fine-tuning the spiro conjugation coupling and varying the solvent dielectric constants, ISC rate constants were engineered to vary in a dynamic range of three orders of magnitude, from 7.8×10⁸ s⁻¹ to 1.0×10¹¹ s⁻¹, which is the highest ISC rate reported for SOCT-ISC system to our knowledge. Our findings substantiate the key factors for effective SOCT-ISC and offer a new avenue for the rational design of heavy atom free triplet sensitizers.     

Intersystem Crossing in Naphthalenediimide–Oxoverdazyl Dyads: Synthesis and Study of the Photophysical Properties

Oxoverdazyl (Vz) radical units were covalently linked to the naphthalenediimide (NDI) chromophore to study the effect of the radical on the photophysical properties, especially the radical enhanced intersystem crossing (REISC), which is a promising approach to develop heavy-atom-free triplet photosensitizers. Rigid phenyl or ethynylphenyl linkers between the two moieties were used, thus REISC and formation of doublet (D₁, total spin quantum number S=1/2) and quartet states (Q₁, S=3/2) are anticipated. The photophysical properties of the dyads were studied with steady-state and femtosecond/nanosecond transient absorption (TA) spectroscopies and DFT computations. Femtosecond transient absorption spectra show a fast electron transfer (<150 fs), and ISC (ca. 1.4–1.85 ps) is induced by charge recombination (CR, in toluene). Nanosecond transient absorption spectra demonstrated a biexponential decay of the triplet state of the NDI moiety. The fast component (lifetime: 50 ns; population ratio: 80 %) is assigned to the D₁→D₀ decay, and the slow decay component (2.0 μs; 20 %) to the Q₁→D₀ ISC. DFT computations indicated ferromagnetic interactions between the radical and chromophore (J=0.07–0.13 eV). Reversible formation of the radical anion of the NDI moiety by photoreduction of the radical-NDI dyads in the presence of sacrificial electron donor triethanolamine (TEOA) is achieved. This work is useful for design of new triplet photosensitizers based on the REISC effect.     

Geometrical Changes and Their Energies in the Formation of Donor–Acceptor Complexes

We have mapped the energy demands of the geometrical changes in donor–acceptor complexes BH₃NH₃ and AlCl₃NH₃ and in the course of their formation from their monomers. We have varied the individual geometrical parameters systematically and performed ab initio quantum chemical calculations for these structures. We investigated the energy requirements to change bond lengths and bond angles in both the monomers and complexes and the angles of torsion in the complexes. The changes of bond lengths require more energy in the monomers than in the complexes. The energies to change the acceptor bond angles in the monomers are markedly higher than in the complexes. The changes in the geometrical parameters during the complexation process are more moderate in donors than in acceptors, in agreement with prior experimental observations. The geometry versus energy variations related to the process of complexation are in agreement with the notion of relative rigidity of the donor parts and the more compliant nature of the acceptor parts as well as with the notion of competing effects in the structures of the complexes.     

Radical-Enhanced Intersystem Crossing in a Bay-Substituted Perylene Bisimide−TEMPO Dyad and the Electron Spin Polarization Dynamics upon Photoexcitation**

A 4-amino-2,2,6,6-tetramethyl-1-piperidinyloxyl (TEMPO) radical was attached to the bay position of perylene-3,4 : 9,10-bis(dicarboximide) (perylenebisimide, PBI) to study the radical-enhanced intersystem crossing (REISC) and electron spin dynamics of the photo-induced high-spin states. The dyads give strong visible light absorption (ϵ=27000 M⁻¹ cm⁻¹at 607 nm). Attaching a TEMPO radical to the PBI unit transforms the otherwise non-radiative decay of S₁ state (fluorescence quantum yield: Φ_F=2.9 %) of PBI unit to ISC (singlet oxygen quantum yield: Φ_Δ=31.8 %, Φ_F=1.6 %). Moreover, the REISC is more efficient as compared to the heavy atom effect-induced ISC (Φ_Δ=17.8 % for 1,8-dibromoPBI). For the dyad, ISC takes 245 ps and triplet state lifetime is 1.5 μs, much shorter than the native PBI (τ_T=126.6 μs). X- and Q-band time-resolved electron paramagnetic resonance spectroscopy shows that the exchange interaction in the photoexcited radical-chromophore dyad is larger than the triplet zero-field splitting (ZFS) and the difference of Zeeman energies of the radical and chromophore. The inversion of electron spin polarization from emissive to absorptive was observed and attributed to the initial completion of the quartet state population and the subsequent depopulation processes induced by the zero-field splitting.     

Formation of Highly Efficient,Long-Lived Charge Separated States in Star-Shaped Ferrocene-Diketopyrrolopyrrole-Triphenylamine Donor–Acceptor–Donor Conjugates

The significance of multiple number of donor–acceptor entities on a central electron donor in a star-shaped molecular system in improving light energy harvesting ability is reported. For this, donor–acceptor–donor type conjugates comprised up to three entities ferrocenyl (Fc)-diketopyrrolopyrrole (DPP) onto a central triphenylamine (TPA), ( 4 – 6 ) by the Pd-catalyzed Sonogashira cross-coupling reactions have been newly synthesized and characterized. Donor–acceptor conjugates possessing diketopyrrolopyrrole (1 to 3 entities) onto the central triphenylamine, ( 1 – 3 ) served as reference dyads while monomeric DPP and Fc-DPP served as control compounds. Both DPP and Fc-DPP carrying conjugates exhibited red-shifted absorption compared to their respective control compounds revealing existence of ground state interactions. Furthermore, DPP fluorescence in 4 – 6 was found to be quantitatively quenched while for 1 – 3 , this property varied between 73–65 % suggesting occurrence moderate amounts of excited state events. The electrochemical investigations exhibited an additional low potential oxidation in the case of Fc-DPP-TPA based derivatives ( 4 – 6 ) owing to the presence of ferrocene unit(s). This was in addition to DPP and TPA redox peaks. Using spectral, electrochemical and computational studies, Gibbs free-energy calculations were performed to visualize excited state charge separation (ΔG_CS) in these donor–acceptor conjugates as a function of different number of Fc-DPP entities. Formation of Fc⁺-DPP^.−-TPA charge separated states (CSS) in the case of 4 – 6 was evident. Using spectroelectrochemical studies, spectrum of CSS was deduced. Finally, femtosecond transient absorption spectral studies were performed to gather information on excited state charge separation. Increasing the number of Fc-DPP entities in 4 – 6 improved charge separation rates. Surprisingly, lifetime of the charge separated state, Fc⁺-DPP^.−-TPA was found to persist longer with an increase in the number of Fc-DPP entities in 4 – 6 as compared to Fc-DPP-control and simple DPP derived donor–acceptor conjugates in literature. This unprecedented result has been attributed to subtle changes in ΔG_CS and ΔG_CR and the associated electron coupling between different entities.     

Excited-State Electron Transfer in 1,1,4,4-Tetracyanobuta-1,3-diene (TCBD)- and Cyclohexa-2,5-diene-1,4-diylidene-Expanded TCBD-Substituted BODIPY-Phenothiazine Donor–Acceptor Conjugates

A new set of donor–acceptor (D–A) conjugates capable of undergoing ultrafast electron transfer were synthesized using 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY)-substituted phenothiazine, SM1–SM3 , by a Pd-catalyzed Sonogashira cross-coupling reaction and a [2+2] cycloaddition–electrocyclic ring-opening reaction. The incorporation of 1,1,4,4-tetracyanobuta-1,3-diene (TCBD) and cyclohexa-2,5-diene-1,4-diylidene-expanded TCBD (abbreviated as DCNQ=dicyanodiquinodimethane) in BODIPY-substituted phenothiazine resulted in significant perturbation of the optical and electronic properties. The absorption spectrum of both SM2 and SM3 showed red shifted absorption as compared to SM1 . Additionally, both SM2 and SM3 exhibited a distinct intramolecular charge-transfer (ICT) transition in the near-IR region more so for SM3 . The electrochemical study revealed multi-redox processes due to the presence of redox-active phenothiazine, BODIPY, TCBD or DCNQ entities. Using data from spectral, electrochemical and computational studies, an energy-level diagram was established to witness excited-state electron-transfer events. Finally, evidence of electron transfer and their kinetic information was secured from studies involving a femtosecond transient absorption technique. The time constants for excited-state electron-transfer events in the case of SM2 and SM3 were less than 5 ps revealing ultrafast processes.     

Visible-Light-Induced Insertion of Sulfur Dioxide Mediated by Electron Donor–Acceptor Complex: Synthesis and Photophysical Properties of 3-Sulfonyl Indolizines

This work investigates a light-driven 3-component sulfonylation reaction of indolizines without needing any external photocatalyst. The mechanistic investigations support the formation of an electron donor–acceptor (EDA) complex in situ. This transformation offers a mild and sustainable approach with high functional group tolerance for the synthesis of 3-sulfonylated indolizines. This compound class has valuable photophysical properties and represents promising candidates in various applications related to fluorescence.     

Understanding the Role of Solvents and Spin–Orbit Coupling in an Oxygen-Assisted SN2-Type Oxidative Transmetalation Reaction

The aerial oxidation of Pd^II to Pd^IV has emerged as an integral component of sustainable catalytic C−H functionalization processes. However, a proper understanding of the factors that control the viability of this oxidative process remains elusive. An investigation of the intricate mechanism of the transmetalation reaction of the aerial oxidative transformation of [(Me₃tacn)Pd^IIMe₂] (Me₃tacn=N,N′,N′′-trimethyl-1,4,7-triazacyclononane) to [(Me₃tacn)Pd^IVMe₃]⁺ has been conducted by using DFT, along with multireference methods, such as second-order n-electron valence-state perturbation theory (NEVPT2) with complete active space self-consistent field theory (CASSCF). The present endeavor predicts that the thermodynamics and kinetics of the oxygen activation step are primarily dictated by the polarity of the solvents, which determine the amount of charge transfer to the oxygen molecule from the Pd^II center. Additionally, it is observed that the presence of a protic solvent has a significant effect on the spin–orbit coupling term at the minimum energy crossing point of the triplet and singlet surfaces. Moreover, it is shown that the intermetal ligand-transfer phenomenon is an important instance of an oxygen-assisted S_N2 reaction.     

Manifestation of the Even–Odd Effect in the Spectral Properties of Solvated Electron and in the Probability of Positronium Formation in Alcohols

A change in the energy E _max of the solvated electron, which corresponds to the maximum intensity of its optical absorption spectrum in the homologous series of alcohols seems to be alternating in character. The effect is retained upon elevation of pressure up to 2 kbar but disappears in alcohols frozen at 77 K. Probably, the effect also holds for amines. The alternating character of variation is also observed for the intensity Y ₁ of the narrow components of the angular spectrum of -photons generated upon positron annihilation in alcohols and normal alkanes. The nature of alternation of E _max is associated with the mutual elimination of electric fields induced by the dipole moments of two neighboring CH₂ groups in each solvent molecule, including also the molecules forming the solvation shell of an excess electron. That fact that the E _max value correlates to Y ₁ led to the conclusion that Y ₁, rather than the intensity I ₃ of the long-lived component of the annihilation time spectrum generally used for the purpose, more adequately characterizes the positronium formation probability.